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Artificial Intelligence Applications in Stroke. Stroke Mouridsen, K., Thurner, P., Zaharchuk, G. 2020: STROKEAHA119027479
View details for DOI 10.1161/STROKEAHA.119.027479

View details for PubMedID 32693750
Predicting PET Cerebrovascular Reserve with Deep Learning by Using Baseline MRI: A Pilot Investigation of a Drug-Free Brain Stress Test. Radiology Chen, D. Y., Ishii, Y., Fan, A. P., Guo, J., Zhao, M. Y., Steinberg, G. K., Zaharchuk, G. 2020: 192793
Abstract

Background Cerebrovascular reserve (CVR) may be measured by using an acetazolamide test to clinically evaluate patients with cerebrovascular disease. However, acetazolamide use may be contraindicated and/or undesirable in certain clinical settings. Purpose To predict CVR images generated from acetazolamide vasodilation with a deep learning network by using only images before acetazolamide administration. Materials and Methods Simultaneous oxygen 15 (15O)-labeled water PET/MRI before and after acetazolamide injection were retrospectively analyzed for patients with Moyamoya disease and healthy control participants from April 2017 to May 2019. Inputs to deep learning models were perfusion-based images (arterial spin labeling [ASL]), structural scans (T2 fluid-attenuated inversion-recovery, T1), and brain location. Two models, that is, 15O-labeled water PET cerebral blood flow (CBF) and MRI (PET-plus-MRI model) before acetazolamide administration and only MRI (MRI-only model) before acetazolamide administration, were trained and tested with sixfold cross-validation. The models learned to predict a voxelwise relative CBF change (rDeltaCBF) map by using rDeltaCBF measured with PET due to acetazolamide as ground truth. Quantitative analysis included image quality metrics (peak signal-to-noise ratio, root mean square error, and structural similarity index), as well as comparison between the various methods by using correlation and Bland-Altman analyses. Identification of vascular territories with impaired rDeltaCBF was evaluated by using receiver operating characteristic metrics. Results Thirty-six participants were included: 24 patients with Moyamoya disease (mean age � standard deviation, 41 years � 12; 17 women) and 12 age-matched healthy control participants (mean age, 39 years � 16; nine women). The rDeltaCBF maps predicted by both deep learning models demonstrated better image quality metrics than did ASL (all P < .001 in patients) and higher correlation coefficient with PET than with ASL (PET-plus-MRI model, 0.704; MRI-only model, 0.690 vs ASL, 0.432; both P < .001 in patients). Both models also achieved high diagnostic performance in identifying territories with impaired rDeltaCBF (area under receiver operating characteristic curve, 0.95 for PET-plus-MRI model [95% confidence interval: 0.90, 0.99] and 0.95 for MRI-only model [95% confidence interval: 0.91, 0.98]). Conclusion By using only images before acetazolamide administration, PET-plus-MRI and MRI-only deep learning models predicted cerebrovascular reserve images without the need for vasodilator injection. � RSNA, 2020 Online supplemental material is available for this article.

View details for DOI 10.1148/radiol.2020192793

View details for PubMedID 32662761
Use of Deep Learning to Predict Final Ischemic Stroke Lesions From Initial Magnetic Resonance Imaging. JAMA network open Yu, Y. n., Xie, Y. n., Thamm, T. n., Gong, E. n., Ouyang, J. n., Huang, C. n., Christensen, S. n., Marks, M. P., Lansberg, M. G., Albers, G. W., Zaharchuk, G. n. 2020; 3 (3): e200772
Abstract

Predicting infarct size and location is important for decision-making and prognosis in patients with acute stroke.To determine whether a deep learning model can predict final infarct lesions using magnetic resonance images (MRIs) acquired at initial presentation (baseline) and to compare the model with current clinical prediction methods.In this multicenter prognostic study, a specific type of neural network for image segmentation (U-net) was trained, validated, and tested using patients from the Imaging Collaterals in Acute Stroke (iCAS) study from April 14, 2014, to April 15, 2018, and the Diffusion Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) study from July 14, 2008, to September 17, 2011 (reported in October 2012). Patients underwent baseline perfusion-weighted and diffusion-weighted imaging and MRI at 3 to 7 days after baseline. Patients were grouped into unknown, minimal, partial, and major reperfusion status based on 24-hour imaging results. Baseline images acquired at presentation were inputs, and the final true infarct lesion at 3 to 7 days was considered the ground truth for the model. The model calculated the probability of infarction for every voxel, which can be thresholded to produce a prediction. Data were analyzed from July 1, 2018, to March 7, 2019.Area under the curve, Dice score coefficient (DSC) (a metric from 0-1 indicating the extent of overlap between the prediction and the ground truth; a DSC of ?0.5 represents significant overlap), and volume error. Current clinical methods were compared with model performance in subgroups of patients with minimal or major reperfusion.Among the 182 patients included in the model (97 women [53.3%]; mean [SD] age, 65?[16] years), the deep learning model achieved a median area under the curve of 0.92 (interquartile range [IQR], 0.87-0.96), DSC of 0.53 (IQR, 0.31-0.68), and volume error of 9 (IQR, -14 to 29) mL. In subgroups with minimal (DSC, 0.58 [IQR, 0.31-0.67] vs 0.55 [IQR, 0.40-0.65]; P?=?.37) or major (DSC, 0.48 [IQR, 0.29-0.65] vs 0.45 [IQR, 0.15-0.54]; P?=?.002) reperfusion for which comparison with existing clinical methods was possible, the deep learning model had comparable or better performance.The deep learning model appears to have successfully predicted infarct lesions from baseline imaging without reperfusion information and achieved comparable performance to existing clinical methods. Predicting the subacute infarct lesion may help clinicians prepare for decompression treatment and aid in patient selection for neuroprotective clinical trials.

View details for DOI 10.1001/jamanetworkopen.2020.0772

View details for PubMedID 32163165
Ultra-Low-Dose 18F-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs. Radiology Chen, K. T., Gong, E., de Carvalho Macruz, F. B., Xu, J., Boumis, A., Khalighi, M., Poston, K. L., Sha, S. J., Greicius, M. D., Mormino, E., Pauly, J. M., Srinivas, S., Zaharchuk, G. 2018: 180940
Abstract

Purpose To reduce radiotracer requirements for amyloid PET/MRI without sacrificing diagnostic quality by using deep learning methods. Materials and Methods Forty data sets from 39 patients (mean age � standard deviation [SD], 67 years � 8), including 16 male patients and 23 female patients (mean age, 66 years � 6 and 68 years � 9, respectively), who underwent simultaneous amyloid (fluorine 18 [18F]-florbetaben) PET/MRI examinations were acquired from March 2016 through October 2017 and retrospectively analyzed. One hundredth of the raw list-mode PET data were randomly chosen to simulate a low-dose (1%) acquisition. Convolutional neural networks were implemented with low-dose PET and multiple MR images (PET-plus-MR model) or with low-dose PET alone (PET-only) as inputs to predict full-dose PET images. Quality of the synthesized images was evaluated while Bland-Altman plots assessed the agreement of regional standard uptake value ratios (SUVRs) between image types. Two readers scored image quality on a five-point scale (5 = excellent) and determined amyloid status (positive or negative). Statistical analyses were carried out to assess the difference of image quality metrics and reader agreement and to determine confidence intervals (CIs) for reading results. Results The synthesized images (especially from the PET-plus-MR model) showed marked improvement on all quality metrics compared with the low-dose image. All PET-plus-MR images scored 3 or higher, with proportions of images rated greater than 3 similar to those for the full-dose images (-10% difference [eight of 80 readings], 95% CI: -15%, -5%). Accuracy for amyloid status was high (71 of 80 readings [89%]) and similar to intrareader reproducibility of full-dose images (73 of 80 [91%]). The PET-plus-MR model also had the smallest mean and variance for SUVR difference to full-dose images. Conclusion Simultaneously acquired MRI and ultra-low-dose PET data can be used to synthesize full-dose-like amyloid PET images. � RSNA, 2018 Online supplemental material is available for this article.

View details for PubMedID 30526350
Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine Albers, G. W., Marks, M. P., Kemp, S. n., Christensen, S. n., Tsai, J. P., Ortega-Gutierrez, S. n., McTaggart, R. A., Torbey, M. T., Kim-Tenser, M. n., Leslie-Mazwi, T. n., Sarraj, A. n., Kasner, S. E., Ansari, S. A., Yeatts, S. D., Hamilton, S. n., Mlynash, M. n., Heit, J. J., Zaharchuk, G. n., Kim, S. n., Carrozzella, J. n., Palesch, Y. Y., Demchuk, A. M., Bammer, R. n., Lavori, P. W., Broderick, J. P., Lansberg, M. G. 2018; 378 (8): 708?18
Abstract

Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms.We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

View details for PubMedID 29364767
Arterial Spin Labeling Perfusion of the Brain: Emerging Clinical Applications RADIOLOGY Haller, S., Zaharchuk, G., Thomas, D. L., Lovblad, K., Barkhof, F., Golay, X. 2016; 281 (2): 337-356
Abstract

Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain. This suggests that ASL might be considered as an alternative for FDG, reserving PET to be used for the molecular disease-specific amyloid and tau tracers. In stroke, ASL can be used to assess perfusion alterations both in the acute and the chronic phase. In arteriovenous malformations and dural arteriovenous fistulas, ASL is very sensitive to detect even small degrees of shunting. In epilepsy, ASL can be used to assess the epileptogenic focus, both in peri- and interictal period. In neoplasms, ASL is of particular interest in cases in which gadolinium-based perfusion is contraindicated (eg, allergy, renal impairment) and holds promise in differentiating tumor progression from benign causes of enhancement. Finally, various neurologic and psychiatric diseases including mild traumatic brain injury or posttraumatic stress disorder display alterations on ASL images in the absence of visualized structural changes. In the final part, current limitations and future developments of ASL techniques to improve clinical applicability, such as multiple inversion time ASL sequences to assess alterations of transit time, reproducibility and quantification of cerebral blood flow, and to measure cerebrovascular reserve, will be reviewed. (�) RSNA, 2016 Online supplemental material is available for this article.

View details for DOI 10.1148/radiol.2016150789

View details for Web of Science ID 000393199200003

View details for PubMedID 27755938
MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean vessel radius, and oxygenation maps in the human brain. NeuroImage Christen, T., Pannetier, N. A., Ni, W. W., Qiu, D., Moseley, M. E., Schuff, N., Zaharchuk, G. 2014; 89: 262-270
Abstract

In the present study, we describe a fingerprinting approach to analyze the time evolution of the MR signal and retrieve quantitative information about the microvascular network. We used a Gradient Echo Sampling of the Free Induction Decay and Spin Echo (GESFIDE) sequence and defined a fingerprint as the ratio of signals acquired pre- and post-injection of an iron-based contrast agent. We then simulated the same experiment with an advanced numerical tool that takes a virtual voxel containing blood vessels as input, then computes microscopic magnetic fields and water diffusion effects, and eventually derives the expected MR signal evolution. The parameter inputs of the simulations (cerebral blood volume [CBV], mean vessel radius [R], and blood oxygen saturation [SO2]) were varied to obtain a dictionary of all possible signal evolutions. The best fit between the observed fingerprint and the dictionary was then determined by using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained by using more conventional MR methods, steady-state contrast imaging for CBV and R and a global measure of oxygenation obtained from the superior sagittal sinus for SO2. The fingerprinting method enabled the creation of high-resolution parametric maps of the microvascular network showing expected contrast and fine details. Numerical values in gray matter (CBV=3.1�0.7%, R=12.6�2.4?m, SO2=59.5�4.7%) are consistent with literature reports and correlated with conventional MR approaches. SO2 values in white matter (53.0�4.0%) were slightly lower than expected. Numerous improvements can easily be made and the method should be useful to study brain pathologies.

View details for DOI 10.1016/j.neuroimage.2013.11.052

View details for PubMedID 24321559
Measuring brain oxygenation in humans using a multiparametric quantitative blood oxygenation level dependent MRI approach MAGNETIC RESONANCE IN MEDICINE Christen, T., Schmiedeskamp, H., Straka, M., Bammer, R., Zaharchuk, G. 2012; 68 (3): 905-911
Abstract

Quantitative blood oxygenation level dependent approaches have been designed to obtain quantitative oxygenation information using MRI. A mathematical model is usually fitted to the time signal decay of a gradient-echo and spin-echo measurements to derive hemodynamic parameters such as the blood oxygen saturation or the cerebral blood volume. Although the results in rats and human brain have been encouraging, recent studies have pointed out the need for independent estimation of one or more variables to increase the accuracy of the method. In this study, a multiparametric quantitative blood oxygenation level dependent approach is proposed. A combination of arterial spin labeling and dynamic susceptibility contrast methods were used to obtain quantitative estimates of cerebral blood volume and cerebral blood flow. These results were combined with T?2 and T(2) measurements to derive maps of blood oxygen saturation or cerebral metabolic rate of oxygen. In 12 normal subjects, a mean cerebral blood volume of 4.33 � 0.7%, cerebral blood flow of 43.8 � 5.7 mL/min/100 g, blood oxygen saturation of 60 � 6% and cerebral metabolic rate of oxygen 157 � 23 ?mol/100 g/min were found, which are in agreement with literature values. The results obtained in this study suggest that this methodology could be applied to study brain hypoxia in the setting of pathology.

View details for DOI 10.1002/mrm.23283

View details for Web of Science ID 000308098100029

View details for PubMedID 22162074
Comparison of Arterial Spin Labeling and Bolus Perfusion-Weighted Imaging for Detecting Mismatch in Acute Stroke STROKE Zaharchuk, G., El Mogy, I. S., Fischbein, N. J., Albers, G. W. 2012; 43 (7): 1843-1848
Abstract

The perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch paradigm is widely used in stroke imaging studies. Arterial spin labeling (ASL) is an alternative perfusion method that does not require contrast. This study compares the agreement of ASL-DWI and PWI-DWI mismatch classification in patients with stroke.This was a retrospective study drawn from all 1.5-T MRI studies performed in 2010 at a single institution. Inclusion criteria were: symptom onset<5 days, DWI lesion>10 mL, and acquisition of both PWI and ASL. DWI and PWI time to maximum>6 seconds lesion volumes were determined using automated software. Patients were classified into reperfused, matched, or mismatch groups. Two radiologists classified ASL-DWI qualitatively into the same categories blinded to DWI-PWI. Agreement between both individual readers and methods was assessed.Fifty-one studies met the inclusion criteria. Seven cases were excluded (1 due to PWI susceptibility artifact, 2 due to motion, and 4 due to severe ASL border zone sign), resulting in 44 studies for comparison. Interrater agreement for ASL-DWI mismatch status was high (?=0.92; 95% CI, 0.80-1.00). ASL-DWI and PWI-DWI mismatch categories agreed in 25 of 44 cases (57%). In the 16 of 19 discrepant cases (84%), ASL overestimated the PWI lesion size. In 34 of 44 cases (77%), they agreed regarding the presence of mismatch versus no mismatch.Mismatch classification based on ASL and PWI agrees frequently but not perfectly. ASL tends to overestimate the PWI time to maximum lesion volume. Improved ASL methodologies and/or higher field strength are necessary before ASL can be recommended for routine use in acute stroke.

View details for DOI 10.1161/STROKEAHA.111.639773

View details for Web of Science ID 000305882000030

View details for PubMedID 22539548

View details for PubMedCentralID PMC3383868
Identification of Venous Signal on Arterial Spin Labeling Improves Diagnosis of Dural Arteriovenous Fistulas and Small Arteriovenous Malformations AMERICAN JOURNAL OF NEURORADIOLOGY Le, T. T., Fischbein, N. J., Andre, J. B., Wijman, C., Rosenberg, J., Zaharchuk, G. 2012; 33 (1): 61-68
Abstract

DAVFs and small AVMs are difficult to detect on conventional MR imaging/MRA or CTA examinations and often require DSA for definitive diagnosis. The purpose of this study was to assess the value of venous signal intensity on ASL imaging for making this diagnosis.Two neuroradiologists and 1 neurologist reviewed MR imaging studies in 26 patients, 15 of whom had DSA-proved DAVFs or small (<2 cm) AVMs. Pseudocontinuous ASL was performed at 1.5T with background-suppressed 3D-FSE readout. Using a 5-point scale, these readers assessed the likelihood of positive findings on a DSA study before and after reviewing the ASL findings. Agreement on imaging findings, including venous ASL signal intensity, was performed by using ? statistics. Logistic regression and ROC analysis were performed to determine which imaging findings improved diagnosis.Venous ASL signal intensity was seen frequently in cases with positive findings on DSA. The sensitivity and specificity of venous ASL signal intensity for predicting positive findings on a DSA study were 78% and 85%, respectively. On ROC analysis, there was a significant increase in the AUC after review of the ASL images (AUC = 0.798 pre-ASL, AUC = 0.891 post-ASL; P = .02). Multivariate regression identified venous ASL signal intensity as the strongest predictor of positive findings on a DSA study, with an odds ratio of 17.3 (95% CI, 3.3-90.4).Identifying venous ASL signal intensity improved detection of DAVFs and small AVMs. Attention to this finding may improve triage to DSA in patients with suspected small vascular malformations.

View details for DOI 10.3174/ajnr.A2761

View details for Web of Science ID 000299491400012

View details for PubMedID 22158927
Arterial Spin Label Imaging of Acute Ischemic Stroke and Transient Ischemic Attack NEUROIMAGING CLINICS OF NORTH AMERICA Zaharchuk, G. 2011; 21 (2): 285-?
Abstract

Since acute stroke and transient ischemic attack (TIA) are disruptions of brain hemodynamics, perfusion neuroimaging might be of clinical utility. Recently, arterial spin labeling (ASL), a noncontrast perfusion method, has become clinically feasible. It has advantages compared to contrast bolus perfusion-weighted imaging (PWI) including lack of exposure to gadolinium, improved quantitation, and decreased sensitivity to susceptibility and motion. Drawbacks include reduced signal-to-noise and high sensitivity to arterial transit delays. However, this sensitivity can enable visualization of collateral flow. This article discusses ASL findings in patients with acute stroke and TIA, focusing on typical appearances, common artifacts, and comparisons with PWI.

View details for DOI 10.1016/j.nic.2011.01.003

View details for Web of Science ID 000292007900008

View details for PubMedID 21640300

View details for PubMedCentralID PMC3109302
COVID-19-induced anosmia associated with olfactory bulb atrophy. Neuroradiology Chiu, A., Fischbein, N., Wintermark, M., Zaharchuk, G., Yun, P. T., Zeineh, M. 2020
Abstract

As the global COVID-19 pandemic evolves, our knowledge of the respiratory and non-respiratory symptoms continues to grow. One such symptom, anosmia, may be a neurologic marker of coronavirus infection and the initial presentation of infected patients. Because this symptom is not routinely investigated by imaging, there is conflicting literature on neuroimaging abnormalities related to COVID-19-related anosmia. We present a novel case of COVID-19 anosmia with definitive olfactory bulb atrophy compared with pre-COVID imaging. The patient had prior MR imaging related to a history of prolactinoma that provided baseline volumes of her olfactory bulbs. After a positive diagnosis of COVID-19 and approximately 2 months duration of anosmia, an MRI was performed that showed clear interval olfactory bulb atrophy. This diagnostic finding is of prognostic importance and indicates that the olfactory entry point to the brain should be further investigated to improve our understanding of COVID infectious pathophysiology.

View details for DOI 10.1007/s00234-020-02554-1

View details for PubMedID 32930820
Simultaneous FDG-PET/MRI detects hippocampal subfield metabolic differences in AD/MCI. Scientific reports Carlson, M. L., DiGiacomo, P. S., Fan, A. P., Goubran, M., Khalighi, M. M., Chao, S. Z., Vasanawala, M., Wintermark, M., Mormino, E., Zaharchuk, G., James, M. L., Zeineh, M. M. 2020; 10 (1): 12064
Abstract

The medial temporal lobe is one of the most well-studied brain regions affected by Alzheimer's disease (AD). Although the spread of neurofibrillary pathology in the hippocampus throughout the progression of AD has been thoroughly characterized and staged using histology and other imaging techniques, it has not been precisely quantified in vivo at the subfield level using simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI). Here, we investigate alterations in metabolism and volume using [18F]fluoro-deoxyglucose (FDG) and simultaneous time-of-flight (TOF) PET/MRI with hippocampal subfield analysis of AD, mild cognitive impairment (MCI), and healthy subjects. We found significant structural and metabolic changes within the hippocampus that can be sensitively assessed at the subfield level in a small cohort. While no significant differences were found between groups for whole hippocampal SUVr values (p=0.166), we found a clear delineation in SUVr between groups in the dentate gyrus (p=0.009). Subfield analysis may be more sensitive for detecting pathological changes using PET-MRI in AD compared to global hippocampal assessment.

View details for DOI 10.1038/s41598-020-69065-0

View details for PubMedID 32694602
Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Rao, V. L., Mlynash, M., Christensen, S., Yennu, A., Kemp, S., Zaharchuk, G., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2020: 271678X20918816
Abstract

We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax>6s perfusion lesion predicts the infarct volume at 24h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32, p=0.006; CBV Index 0.78 vs. 0.85, p=0.001) and 24h (HIR 0.56 vs. 0.07, p=0.004; CBV Index 0.47 vs. 0.73, p=0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73, p=0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24h.

View details for DOI 10.1177/0271678X20918816

View details for PubMedID 32423329
Deep Flow-Net for EPI Distortion Estimation. NeuroImage Zahneisen, B., Baeumler, K., Zaharchuk, G., Fleischmann, D., Zeineh, M. 2020: 116886
Abstract

INTRODUCTION: Geometric distortions along the phase encoding direction caused by off-resonant spins are a major issue in EPI based functional and diffusion imaging. The widely used blip up/down approach estimates the underlying distortion field from a pair of images with inverted phase encoding direction. Typically, iterative methods are used to find a solution to the ill-posed problem of finding the displacement field that maps up/down acquisitions onto each other. Here, we explore the use of a deep convolutional network to estimate the displacement map from a pair of input images.METHODS: We trained a deep convolutional U-net architecture that was previously used to estimate optic flow between moving images to learn to predict the distortion map from an input pair of distorted EPI acquisitions. During the training step, the network minimizes a loss function (similarity metric) that is calculated from corrected input image pairs. This approach does not require the explicit knowledge of the ground truth distortion map, which is difficult to get for real life data.RESULTS: We used data from a total of Ntrain=22 healthy subjects to train our network. A separate dataset of Ntest=12 patients including some with abnormal findings and unseen acquisition modes, e.g. LR-encoding, coronal orientation) was reserved for testing and evaluation purposes. We compared our results to FSL's topup function with default parameters that served as the gold standard. We found that our approach results in a correction accuracy that is virtually identical to the optimum found by an iterative search, but with reduced computational time.CONCLUSION: By using a deep convolutional network, we can reduce the processing time to a few seconds per volume, which is significantly faster than iterative approaches like FSL's topup which takes around 10min on the same machine (but using only 1 CPU). This facilitates the use of a blip up/down scheme for all diffusion-weighted acquisitions and potential real-time EPI distortion correction without sacrificing accuracy.

View details for DOI 10.1016/j.neuroimage.2020.116886

View details for PubMedID 32389728
Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Fan, A. P., Khalil, A. A., Fiebach, J. B., Zaharchuk, G., Villringer, A., Villringer, K., Gauthier, C. J. 2020; 40 (3): 539?51
View details for DOI 10.1177/0271678X19827944

View details for Web of Science ID 000513378300007
Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment JOURNAL OF NEURORADIOLOGY Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2020; 47 (1): 13?19
View details for DOI 10.1016/j.neurad.2018.12.004

View details for Web of Science ID 000515216000004
Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI. NeuroImage Fan, A. P., An, H. n., Moradi, F. n., Rosenberg, J. n., Ishii, Y. n., Nariai, T. n., Okazawa, H. n., Zaharchuk, G. n. 2020: 117136
Abstract

Oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2) are key cerebral physiological parameters to identify at-risk cerebrovascular patients and understand brain health and function. PET imaging with [15O]-oxygen tracers, either through continuous or bolus inhalation, provides non-invasive assessment of OEF and CMRO2. Numerous tracer delivery, PET acquisition, and kinetic modeling approaches have been adopted to map brain oxygenation. The purpose of this technical review is to critically evaluate different methods for [15O]-gas PET and its impact on the accuracy and reproducibility of OEF and CMRO2 measurements. We perform a meta-analysis of brain oxygenation PET studies in healthy volunteers and compare between continuous and bolus inhalation techniques. We also describe OEF metrics that have been used to detect hemodynamic impairment in cerebrovascular disease. For these patients, advanced techniques to accelerate the PET scans and potential synthesis with MRI to avoid arterial blood sampling would facilitate broader use of [15O]-oxygen PET for brain physiological assessment.

View details for DOI 10.1016/j.neuroimage.2020.117136

View details for PubMedID 32634594
Generalization of deep learning models for ultra-low-count amyloid PET/MRI using transfer learning. European journal of nuclear medicine and molecular imaging Chen, K. T., Sch�rer, M. n., Ouyang, J. n., Koran, M. E., Davidzon, G. n., Mormino, E. n., Tiepolt, S. n., Hoffmann, K. T., Sabri, O. n., Zaharchuk, G. n., Barthel, H. n. 2020
Abstract

We aimed to evaluate the performance of deep learning-based generalization of ultra-low-count amyloid PET/MRI enhancement when applied to studies acquired with different scanning hardware and protocols.Eighty simultaneous [18F]florbetaben PET/MRI studies were acquired, split equally between two sites (site 1: Signa PET/MRI, GE Healthcare, 39 participants, 67?�?8�years, 23 females; site 2: mMR, Siemens Healthineers, 64?�?11�years, 23 females) with different MRI protocols. Twenty minutes of list-mode PET data (90-110�min post-injection) were reconstructed as ground-truth. Ultra-low-count data obtained from undersampling by a factor of 100 (site 1) or the first minute of PET acquisition (site 2) were reconstructed for ultra-low-dose/ultra-short-time (1% dose and 5% time, respectively) PET images. A deep convolution neural network was pre-trained with site 1 data and either (A) directly applied or (B) trained further on site 2 data using transfer learning. Networks were also trained from scratch based on (C) site 2 data or (D) all data. Certified physicians determined amyloid uptake (+/-) status for accuracy and scored the image quality. The peak signal-to-noise ratio, structural similarity, and root-mean-squared error were calculated between images and their ground-truth counterparts. Mean regional standardized uptake value ratios (SUVR, reference region: cerebellar cortex) from 37 successful site 2 FreeSurfer segmentations were analyzed.All network-synthesized images had reduced noise than their ultra-low-count reconstructions. Quantitatively, image metrics improved the most using method B, where SUVRs had the least variability from the ground-truth and the highest effect size to differentiate between positive and negative images. Method A images had lower accuracy and image quality than other methods; images synthesized from methods B-D scored similarly or better than the ground-truth images.Deep learning can successfully produce diagnostic amyloid PET images from short frame reconstructions. Data bias should be considered when applying pre-trained deep ultra-low-count amyloid PET/MRI networks for generalization.

View details for DOI 10.1007/s00259-020-04897-6

View details for PubMedID 32535655
Fellow in a Box: Combining AI and Domain Knowledge with Bayesian Networks for Differential Diagnosis in Neuroimaging. Radiology Zaharchuk, G. n. 2020: 200819
View details for DOI 10.1148/radiol.2020200819

View details for PubMedID 32267215
Deep Learning Enables Automatic Detection and Segmentation of Brain Metastases on Multisequence MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Grovik, E., Yi, D., Iv, M., Tong, E., Rubin, D., Zaharchuk, G. 2020; 51 (1): 175?82
View details for DOI 10.1002/jmri.26766

View details for Web of Science ID 000530627200017
Simultaneous Phase-Contrast MRI and PET for Noninvasive Quantification of Cerebral Blood Flow and Reactivity in Healthy Subjects and Patients With Cerebrovascular Disease JOURNAL OF MAGNETIC RESONANCE IMAGING Ishii, Y., Thamm, T., Guo, J., Khalighi, M., Wardak, M., Holley, D., Gandhi, H., Park, J., Shen, B., Steinberg, G. K., Chin, F. T., Zaharchuk, G., Fan, A. 2020; 51 (1): 183?94
View details for DOI 10.1002/jmri.26773

View details for Web of Science ID 000530627200018
Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases. European journal of nuclear medicine and molecular imaging Mormino, E. C., Toueg, T. N., Azevedo, C. n., Castillo, J. B., Guo, W. n., Nadiadwala, A. n., Corso, N. K., Hall, J. N., Fan, A. n., Trelle, A. N., Harrison, M. B., Hunt, M. P., Sha, S. J., Deutsch, G. n., James, M. n., Fredericks, C. A., Koran, M. E., Zeineh, M. n., Poston, K. n., Greicius, M. D., Khalighi, M. n., Davidzon, G. A., Shen, B. n., Zaharchuk, G. n., Wagner, A. D., Chin, F. T. 2020
Abstract

In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD).Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (A?+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.SUVRs in target regions were relatively stable 60 to 90�min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and A?+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

View details for DOI 10.1007/s00259-020-04923-7

View details for PubMedID 32572562
Deep Learning Detection of Penumbral Tissue on Arterial Spin Labeling in Stroke. Stroke Wang, K., Shou, Q., Ma, S. J., Liebeskind, D., Qiao, X. J., Saver, J., Salamon, N., Kim, H., Yu, Y., Xie, Y., Zaharchuk, G., Scalzo, F., Wang, D. J. 2019: STROKEAHA119027457
Abstract

Background and Purpose- Selection of patients with acute ischemic stroke for endovascular treatment generally relies on dynamic susceptibility contrast magnetic resonance imaging or computed tomography perfusion. Dynamic susceptibility contrast magnetic resonance imaging requires injection of contrast, whereas computed tomography perfusion requires high doses of ionizing radiation. The purpose of this work was to develop and evaluate a deep learning (DL)-based algorithm for assisting the selection of suitable patients with acute ischemic stroke for endovascular treatment based on 3-dimensional pseudo-continuous arterial spin labeling (pCASL). Methods- A total of 167 image sets of 3-dimensional pCASL data from 137 patients with acute ischemic stroke scanned on 1.5T and 3.0T Siemens MR systems were included for neural network training. The concurrently acquired dynamic susceptibility contrast magnetic resonance imaging was used to produce labels of hypoperfused brain regions, analyzed using commercial software. The DL and 6 machine learning (ML) algorithms were trained with 10-fold cross-validation. The eligibility for endovascular treatment was determined retrospectively based on the criteria of perfusion/diffusion mismatch in the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). The trained DL algorithm was further applied on twelve 3-dimensional pCASL data sets acquired on 1.5T and 3T General Electric MR systems, without fine-tuning of parameters. Results- The DL algorithm can predict the dynamic susceptibility contrast-defined hypoperfusion region in pCASL with a voxel-wise area under the curve of 0.958, while the 6 ML algorithms ranged from 0.897 to 0.933. For retrospective determination for subject-level endovascular treatment eligibility, the DL algorithm achieved an accuracy of 92%, with a sensitivity of 0.89 and specificity of 0.95. When applied to the GE pCASL data, the DL algorithm achieved a voxel-wise area under the curve of 0.94 and a subject-level accuracy of 92% for endovascular treatment eligibility. Conclusions- pCASL perfusion magnetic resonance imaging in conjunction with the DL algorithm provides a promising approach for assisting decision-making for endovascular treatment in patients with acute ischemic stroke.

View details for DOI 10.1161/STROKEAHA.119.027457

View details for PubMedID 31884904
Predicting 15O-Water PET cerebral blood flow maps from multi-contrast MRI using a deep convolutional neural network with evaluation of training cohort bias. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Guo, J., Gong, E., Fan, A. P., Goubran, M., Khalighi, M. M., Zaharchuk, G. 2019: 271678X19888123
View details for DOI 10.1177/0271678X19888123

View details for PubMedID 31722599
Applications of Deep Learning to Neuro-Imaging Techniques FRONTIERS IN NEUROLOGY Zhu, G., Jiang, B., Tong, L., Xie, Y., Zaharchuk, G., Wintermark, M. 2019; 10
View details for DOI 10.3389/fneur.2019.00869

View details for Web of Science ID 000480731000001
Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study. Journal of magnetic resonance imaging : JMRI Soman, S., Dai, W., Dong, L., Hitchner, E., Lee, K., Baughman, B. D., Holdsworth, S. J., Massaband, P., Bhat, J. V., Moseley, M. E., Rosen, A., Zhou, W., Zaharchuk, G. 2019
Abstract

BACKGROUND: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR).PURPOSE: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown.STUDY TYPE: Prospective longitudinal.SUBJECTS: Fifty-three subjects undergoing carotid endarterectomy or stenting.FIELD STRENGTH/SEQUENCE: 3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR).ASSESSMENT: We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery.STATISTICAL TESTS: PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P<0.05, while the voxel-level significance threshold was set for P<0.001.RESULTS: The entire group showed significant (cluster-level P<0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P>0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P<0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P>0.001) and cholesterol greater CBF decrease (P>0.001).DATA CONCLUSION: The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation.LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

View details for DOI 10.1002/jmri.26862

View details for PubMedID 31294898
Rigid Motion Correction for Brain PET/MR Imaging Using Optical Tracking IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Spangler-Bickell, M. G., Khalighi, M., Hoo, C., DiGiacomo, P., Maclaren, J., Aksoy, M., Rettmann, D., Bammer, R., Zaharchuk, G., Zeineh, M., Jansen, F. 2019; 3 (4): 498?503
View details for DOI 10.1109/TRPMS.2018.2878978

View details for Web of Science ID 000473623200012
Ultra-low-dose PET Reconstruction using Generative Adversarial Network with Feature Matching and Task-Specific Perceptual Loss. Medical physics Ouyang, J., Chen, K. T., Gong, E., Pauly, J., Zaharchuk, G. 2019
Abstract

PURPOSE: Our goal is to use a generative adversarial network (GAN) with feature matching and task-specific perceptual loss to synthesize standard-dose amyloid PET images of high quality and including accurate pathological features from ultra-low-dose PET images only.METHODS: 40 PET datasets from 39 participants were acquired with a simultaneous PET/MRI scanner following injection of 330�30 MBq of the amyloid radiotracer 18F-florbetaben. The raw list-mode PET data were reconstructed as the standard-dose ground truth and were randomly undersampled by a factor of 100 to reconstruct 1% low-dose PET scans. A 2D encoder-decoder network was implemented as the generator to synthesize a standard-dose image and a discriminator was used to evaluate them. The two networks contested with each other to achieve high visual quality PET from the ultra-low-dose PET. Multi-slice inputs were used to reduce noise by providing the network with 2.5D information. Feature matching was applied to reduce hallucinated structures. Task-specific perceptual loss was designed to maintain the correct pathological features. The image quality was evaluated by peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) metrics with and without each of these modules. Two expert radiologists were asked to score image quality on a five-point scale and identified the amyloid status (positive or negative).RESULTS: With only low-dose PET as input, the proposed method significantly outperformed Chen etal.'s method [9] (which shows the best performance in this task) with the same input (PET-only model) by 1.87 dB in PSNR, 2.04% in SSIM, and 24.75% in RMSE. It also achieved comparable results to Chen etal.'s method which used additional MRI inputs (PET-MR model). Experts' reading results showed that the proposed method could achieve better overall image quality and maintain better pathological features indicating amyloid status than both PET-only and PET-MR models proposed by Chen etal.CONCLUSION: Standard-dose amyloid PET images can be synthesized from ultra-low-dose images using GAN. Applying adversarial learning, feature matching, and task-specific perceptual loss are essential to ensure image quality and the preservation of pathological features. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/mp.13626

View details for PubMedID 31131901
State of the Art PET/MRI: Applications and Limitations - Summary of the First ISMRM/SNMMI Co-Provided Workshop on PET/MRI. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Hope, T. A., Fayad, Z. A., Fowler, K. J., Holley, D., Iagaru, A. H., McMillan, A., Veit-Haibach, P., Witte, R. J., Zaharchuk, G., Catana, C. 2019
Abstract

Since the introduction of simultaneous PET/MRI in 2011, there have been significant advancements. In this review, we highlight a number of the technical advancements that have been made primarily in attenuation correction and motion correction. Additionally, we review the status of multiple clinical applications using PET/MRI. This review was based on the experiences at the first ISMRM/SNMMI co-sponsored PET/MRI conference.

View details for DOI 10.2967/jnumed.119.227231

View details for PubMedID 31123099
Impact of attenuation correction on image-derived input functions and cerebral blood flow quantification with simultaneous [O-15]-water PET/MRI Hjoernevik, T., Khalighi, M., Kaushik, S., Ishii, Y., Zaharchuk, G., Fan, A. SOC NUCLEAR MEDICINE INC. 2019
View details for Web of Science ID 000473116800173
Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3 STROKE Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019; 50 (3): 626?31
View details for DOI 10.1161/STROKEAHA.118.023177

View details for Web of Science ID 000459699700023
Ultra-Low-Dose F-18-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs RADIOLOGY Chen, K. T., Gong, E., Macruz, F., Xu, J., Boumis, A., Khalighi, M., Poston, K. L., Sha, S. J., Greicius, M. D., Mormino, E., Pauly, J. M., Srinivas, S., Zaharchuk, G. 2019; 290 (3): 649?56
View details for DOI 10.1148/radiol.2018180940

View details for Web of Science ID 000459261900009
Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Fan, A. P., Khalil, A. A., Fiebach, J. B., Zaharchuk, G., Villringer, A., Villringer, K., Gauthier, C. J. 2019: 271678X19827944
Abstract

Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients. Absolute OEF was elevated in the affected (29.3�3.4%) versus the contralateral hemisphere (25.5�3.1%) of patients with large diffusion-perfusion lesion mismatch ( P=0.032). In these patients, OEF negatively correlated with relative CBF measured by dynamic susceptibility contrast MRI ( P=0.004), suggesting compensation for reduced flow. Patients with perfusion-diffusion match or no hypo-perfusion showed less OEF difference between hemispheres. Nine patients received longitudinal assessment and showed OEF ratio (affected to contralateral) of 1.2�0.1 at baseline that normalized (decreased) to 1.0�0.1 at follow-up three days later ( P=0.03). Our feasibility study demonstrates that QSM MRI can non-invasively quantify OEF in stroke patients, relates to perfusion status, and is sensitive to OEF changes over time. Clinical trial registration: Longitudinal MRI examinations of patients with brain ischemia and blood brain barrier permeability; clinicaltrials.org : NCT02077582.

View details for PubMedID 30732551
Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3. Stroke Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023177
Abstract

Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02586415.

View details for PubMedID 30727840
Identifying Hypoperfusion in Moyamoya Disease With Arterial Spin Labeling and an [O-15]-Water Positron Emission Tomography/Magnetic Resonance Imaging Normative Database STROKE Fan, A. P., Khalighi, M. M., Guo, J., Ishii, Y., Rosenberg, J., Wardak, M., Park, J., Shen, B., Holley, D., Gandhi, H., Haywood, T., Singh, P., Steinberg, G. K., Chin, F. T., Zaharchuk, G. 2019; 50 (2): 373?80
View details for DOI 10.1161/STROKEAHA.118.023426

View details for Web of Science ID 000469346800028
Prediction of Subacute Infarction in Acute Ischemic Stroke Using Baseline Multi-modal MRI and Deep Learning Yu Yannan, Xie, Y., Thamm, T., Chen, K. T., Gong Enhao, Zaharchuk, G. LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000478733401398
Union of Ischemic Core and Hypoperfusion Volume Correlates With 24-hour Infarct Size in DEFUSE 3 Rao, V., Christensen, S., Yennu, A., Mylnash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000478733402495
Identifying Hypoperfusion in Moyamoya Disease With Arterial Spin Labeling and an [15O]-Water Positron Emission Tomography/Magnetic Resonance Imaging Normative Database. Stroke Fan, A. P., Khalighi, M. M., Guo, J., Ishii, Y., Rosenberg, J., Wardak, M., Park, J. H., Shen, B., Holley, D., Gandhi, H., Haywood, T., Singh, P., Steinberg, G. K., Chin, F. T., Zaharchuk, G. 2019: STROKEAHA118023426
Abstract

Background and Purpose- Noninvasive imaging of brain perfusion has the potential to elucidate pathophysiological mechanisms underlying Moyamoya disease and enable clinical imaging of cerebral blood flow (CBF) to select revascularization therapies for patients. We used hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) technology to characterize the distribution of hypoperfusion in Moyamoya disease and its relationship to vessel stenosis severity, through comparisons with a normative perfusion database of healthy controls. Methods- To image CBF, we acquired [15O]-water PET as a reference and simultaneously acquired arterial spin labeling (ASL) MRI scans in 20 Moyamoya patients and 15 age-matched, healthy controls on a PET/MRI scanner. The ASL MRI scans included a standard single-delay ASL scan with postlabel delay of 2.0 s and a multidelay scan with 5 postlabel delays (0.7-3.0s) to estimate and account for arterial transit time in CBF quantification. The percent volume of hypoperfusion in patients (determined as the fifth percentile of CBF values in the healthy control database) was the outcome measure in a logistic regression model that included stenosis grade and location. Results- Logistic regression showed that anterior ( P<0.0001) and middle cerebral artery territory regions ( P=0.003) in Moyamoya patients were susceptible to hypoperfusion, whereas posterior regions were not. Cortical regions supplied by arteries with stenosis on MR angiography showed more hypoperfusion than normal arteries ( P=0.001), but the extent of hypoperfusion was not different between mild-moderate versus severe stenosis. Multidelay ASL did not perform differently from [15O]-water PET in detecting perfusion abnormalities, but standard ASL overestimated the extent of hypoperfusion in patients ( P=0.003). Conclusions- This simultaneous PET/MRI study supports the use of multidelay ASL MRI in clinical evaluation of Moyamoya disease in settings where nuclear medicine imaging is not available and application of a normative perfusion database to automatically identify abnormal CBF in patients.

View details for PubMedID 30636572
Deep learning enables automatic detection and segmentation of brain metastases on multisequence MRI. Journal of magnetic resonance imaging : JMRI Gr�vik, E. n., Yi, D. n., Iv, M. n., Tong, E. n., Rubin, D. n., Zaharchuk, G. n. 2019
Abstract

Detecting and segmenting brain metastases is a tedious and time-consuming task for many radiologists, particularly with the growing use of multisequence 3D imaging.To demonstrate automated detection and segmentation of brain metastases on multisequence MRI using a deep-learning approach based on a fully convolution neural network (CNN).Retrospective.In all, 156 patients with brain metastases from several primary cancers were included.5T and 3T.Pretherapy MR images included pre- and postgadolinium T1 -weighted 3D fast spin echo (CUBE), postgadolinium T1 -weighted 3D axial IR-prepped FSPGR (BRAVO), and 3D CUBE fluid attenuated inversion recovery (FLAIR).The ground truth was established by manual delineation by two experienced neuroradiologists. CNN training/development was performed using 100 and 5 patients, respectively, with a 2.5D network based on a GoogLeNet architecture. The results were evaluated in 51 patients, equally separated into those with few (1-3), multiple (4-10), and many (>10) lesions.Network performance was evaluated using precision, recall, Dice/F1 score, and receiver operating characteristic (ROC) curve statistics. For an optimal probability threshold, detection and segmentation performance was assessed on a per-metastasis basis. The Wilcoxon rank sum test was used to test the differences between patient subgroups.The area under the ROC curve (AUC), averaged across all patients, was 0.98 � 0.04. The AUC in the subgroups was 0.99 � 0.01, 0.97 � 0.05, and 0.97 � 0.03 for patients having 1-3, 4-10, and >10 metastases, respectively. Using an average optimal probability threshold determined by the development set, precision, recall, and Dice score were 0.79 � 0.20, 0.53 � 0.22, and 0.79 � 0.12, respectively. At the same probability threshold, the network showed an average false-positive rate of 8.3/patient (no lesion-size limit) and 3.4/patient (10 mm3 lesion size limit).A deep-learning approach using multisequence MRI can automatically detect and segment brain metastases with high accuracy.3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019.

View details for PubMedID 31050074
MRI safety and devices: An update and expert consensus. Journal of magnetic resonance imaging : JMRI Jabehdar Maralani, P. n., Schieda, N. n., Hecht, E. M., Litt, H. n., Hindman, N. n., Heyn, C. n., Davenport, M. S., Zaharchuk, G. n., Hess, C. P., Weinreb, J. n. 2019
Abstract

The use of magnetic resonance imaging (MRI) is increasing globally, and MRI safety issues regarding medical devices, which are constantly being developed or upgraded, represent an ongoing challenge for MRI personnel. To assist the MRI community, a panel of 10 radiologists with expertise in MRI safety from nine high-volume academic centers formed, with the objective of providing clarity on some of the MRI safety issues for the 10 most frequently questioned devices. Ten device categories were identified. The panel reviewed the literature, including key MRI safety issues regarding screening and adverse event reports, in addition to the manufacturer's Instructions For Use. Using a Delphi-inspired method, 36 practical recommendations were generated with 100% consensus that can aid the clinical MRI community. Level of Evidence: 5 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019.

View details for DOI 10.1002/jmri.26909

View details for PubMedID 31566852
Deep Generative Adversarial Neural Networks for Compressive Sensing MRI IEEE TRANSACTIONS ON MEDICAL IMAGING Mardani, M., Gong, E., Cheng, J. Y., Vasanawala, S. S., Zaharchuk, G., Xing, L., Pauly, J. M. 2019; 38 (1): 167?79
Abstract

Undersampled magnetic resonance image (MRI) reconstruction is typically an ill-posed linear inverse task. The time and resource intensive computations require tradeoffs between accuracy and speed. In addition, state-of-the-art compressed sensing (CS) analytics are not cognizant of the image diagnostic quality. To address these challenges, we propose a novel CS framework that uses generative adversarial networks (GAN) to model the (low-dimensional) manifold of high-quality MR images. Leveraging a mixture of least-squares (LS) GANs and pixel-wise l1/l2 cost, a deep residual network with skip connections is trained as the generator that learns to remove the aliasing artifacts by projecting onto the image manifold. The LSGAN learns the texture details, while the l1/l2 cost suppresses high-frequency noise. A discriminator network, which is a multilayer convolutional neural network (CNN), plays the role of a perceptual cost that is then jointly trained based on high-quality MR images to score the quality of retrieved images. In the operational phase, an initial aliased estimate (e.g., simply obtained by zero-filling) is propagated into the trained generator to output the desired reconstruction. This demands a very low computational overhead. Extensive evaluations are performed on a large contrast-enhanced MR dataset of pediatric patients. Images rated by expert radiologists corroborate that GANCS retrieves higher quality images with improved fine texture details compared with conventional Wavelet-based and dictionary-learning-based CS schemes as well as with deep-learning-based schemes using pixel-wise training. In addition, it offers reconstruction times of under a few milliseconds, which are two orders of magnitude faster than the current state-of-the-art CS-MRI schemes.

View details for DOI 10.1109/TMI.2018.2858752

View details for Web of Science ID 000455110500017

View details for PubMedID 30040634
Rigid Motion Correction for Brain PET/MR Imaging using Optical Tracking. IEEE transactions on radiation and plasma medical sciences Spangler-Bickell, M. G., Khalighi, M. M., Hoo, C. n., DiGiacomo, P. S., Maclaren, J. n., Aksoy, M. n., Rettmann, D. n., Bammer, R. n., Zaharchuk, G. n., Zeineh, M. n., Jansen, F. n. 2019; 3 (4): 498?503
Abstract

A significant challenge during high-resolution PET brain imaging on PET/MR scanners is patient head motion. This challenge is particularly significant for clinical patient populations who struggle to remain motionless in the scanner for long periods of time. Head motion also affects the MR scan data. An optical motion tracking technique, which has already been demonstrated to perform MR motion correction during acquisition, is used with a list-mode PET reconstruction algorithm to correct the motion for each recorded event and produce a corrected reconstruction. The technique is demonstrated on real Alzheimer's disease patient data for the GE SIGNA PET/MR scanner.

View details for DOI 10.1109/TRPMS.2018.2878978

View details for PubMedID 31396580

View details for PubMedCentralID PMC6686883
Arterial-Spin Labeling MRI Identifies Residual Cerebral Arteriovenous Malformation Following Stereotactic Radiosurgery Treatment. Journal of neuroradiology. Journal de neuroradiologie Heit, J. J., Thakur, N. H., Iv, M. n., Fischbein, N. J., Wintermark, M. n., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. n. 2019
Abstract

Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment.We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow?-?up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal.15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k?=?0.92; 95% CI: 0.8-1.0; p?
View details for PubMedID 30658138
Advantages of short repetition time resting-state functional MRI enabled by simultaneous multi-slice imaging JOURNAL OF NEUROSCIENCE METHODS Jahanian, H., Holdsworth, S., Christen, T., Wu, H., Zhu, K., Kerr, A. B., Middione, M. J., Dougherty, R. F., Moseley, M., Zaharchuk, G. 2019; 311: 122?32
View details for DOI 10.1016/j.jneumeth.2018.09.033

View details for Web of Science ID 000452935000015
Use of Gradient Boosting Machine Learning to Predict Patient Outcome in Acute Ischemic Stroke on the Basis of Imaging, Demographic, and Clinical Information AMERICAN JOURNAL OF ROENTGENOLOGY Xie, Y., Jiang, B., Gong, E., Li, Y., Zhu, G., Michel, P., Wintermark, M., Zaharchuk, G. 2019; 212 (1): 44?51
View details for DOI 10.2214/AJR.18.20260

View details for Web of Science ID 000453925000015
Next generation research applications for hybrid PET/MR and PET/CT imaging using deep learning. European journal of nuclear medicine and molecular imaging Zaharchuk, G. n. 2019
Abstract

Recently there have been significant advances in the field of machine learning and artificial intelligence (AI) centered around imaging-based applications such as computer vision. In particular, the tremendous power of deep learning algorithms, primarily based on convolutional neural network strategies, is becoming increasingly apparent and has already had direct impact on the fields of radiology and nuclear medicine. While most early applications of computer vision to radiological imaging have focused on classification of images into disease categories, it is also possible to use these methods to improve image quality. Hybrid imaging approaches, such as PET/MRI and PET/CT, are ideal for applying these methods.This review will give an overview of the application of AI to improve image quality for PET imaging directly and how the additional use of anatomic information from CT and MRI can lead to further benefits. For PET, these performance gains can be used to shorten imaging scan times, with improvement in patient comfort and motion artifacts, or to push towards lower radiotracer doses. It also opens the possibilities for dual tracer studies, more frequent follow-up examinations, and new imaging indications. How to assess quality and the potential effects of bias in training and testing sets will be discussed.Harnessing the power of these new technologies to extract maximal information from hybrid PET imaging will open up new vistas for both research and clinical applications with associated benefits in patient care.

View details for DOI 10.1007/s00259-019-04374-9

View details for PubMedID 31254036
Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke. Stroke Thamm, T. n., Guo, J. n., Rosenberg, J. n., Liang, T. n., Marks, M. P., Christensen, S. n., Do, H. M., Kemp, S. M., Adair, E. n., Eyngorn, I. n., Mlynash, M. n., Jovin, T. G., Keogh, B. P., Chen, H. J., Lansberg, M. G., Albers, G. W., Zaharchuk, G. n. 2019: STROKEAHA119026499
Abstract

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ?1, prestroke modified Rankin Scale score ?2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.

View details for DOI 10.1161/STROKEAHA.119.026499

View details for PubMedID 31619150
Simultaneous phase-contrast MRI and PET for noninvasive quantification of cerebral blood flow and reactivity in healthy subjects and patients with cerebrovascular disease. Journal of magnetic resonance imaging : JMRI Ishii, Y. n., Thamm, T. n., Guo, J. n., Khalighi, M. M., Wardak, M. n., Holley, D. n., Gandhi, H. n., Park, J. H., Shen, B. n., Steinberg, G. K., Chin, F. T., Zaharchuk, G. n., Fan, A. P. 2019
Abstract

H215 O-positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion.To demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood-free approach, called PC-PET, takes the spatial CBF distribution from a static H215 O-PET scan, and scales it to the whole-brain average CBF value measured by simultaneous phase-contrast MRI.Observational.Twelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease.3T/2D cardiac-gated phase-contrast MRI and H215 O-PET.PC-PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post-acetazolamide (vasodilator) scans, were measured by PC-PET in MM patients and HCs within cortical regions corresponding to major vascular territories. Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis.The mean CBF values in WB, GM, and WM in HC were 42 � 7 ml/100 g/min, 50 � 7 ml/100 g/min, and 23 � 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 � 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 � 17%, P = 0.011) and in severe/occluded areas (40 � 16%, P = 0.016). Data Conclusion: PC-PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC-PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H215 O-PET in future studies.3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019.

View details for PubMedID 31044459
Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? JOURNAL OF NEUROINTERVENTIONAL SURGERY Wolman, D. N., Iv, M., Wintermark, M., Zaharchuk, G., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018; 10 (12): 1132-+
View details for DOI 10.1136/neurintsurg-2018-013784

View details for Web of Science ID 000452800300012
Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI) MAGNETIC RESONANCE IN MEDICINE Terem, I., Ni, W. W., Goubran, M., Rahimi, M., Zaharchuk, G., Yeom, K. W., Moseley, M. E., Kurt, M., Holdsworth, S. J. 2018; 80 (6): 2549?59
View details for DOI 10.1002/mrm.27236

View details for Web of Science ID 000450220400021
Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent 11C-raclopride positron emission tomography and functional magnetic resonance imaging investigation. Translational psychiatry Hamilton, J. P., Sacchet, M. D., Hjornevik, T., Chin, F. T., Shen, B., Kampe, R., Park, J. H., Knutson, B. D., Williams, L. M., Borg, N., Zaharchuk, G., Camacho, M. C., Mackey, S., Heilig, M., Drevets, W. C., Glover, G. H., Gambhir, S. S., Gotlib, I. H. 2018; 8 (1): 264
Abstract

Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the cortico-striatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and 11C-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and 11C-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

View details for PubMedID 30504860
Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent C-11-raclopride positron emission tomography and functional magnetic resonance imaging investigation TRANSLATIONAL PSYCHIATRY Hamilton, J., Sacchet, M. D., Hjornevik, T., Chin, F. T., Shen, B., Kampe, R., Park, J., Knutson, B. D., Williams, L. M., Borg, N., Zaharchuk, G., Camacho, M., Mackey, S., Heilig, M., Drevets, W. C., Glover, G. H., Gambhir, S. S., Gotlib, I. H. 2018; 8
View details for DOI 10.1038/s41398-018-0316-2

View details for Web of Science ID 000452318900002
Advanced Neuroimaging of Acute Ischemic Stroke: Penumbra and Collateral Assessment. Neuroimaging clinics of North America Heit, J. J., Zaharchuk, G., Wintermark, M. 2018; 28 (4): 585?97
Abstract

Acute ischemic stroke (AIS) occurs when there is a sudden loss in cerebral blood flow due to embolic or thromboembolic occlusion of a cerebral or cervical artery. Patients with AIS require emergent neuroimaging to guide treatment, which includes intravenous thrombolysis and endovascular mechanical thrombectomy (EMT). Recent advances in AIS treatment by EMT has been driven in part by advances in computed tomography (CT) and MR imaging neuroimaging evaluation of ischemic penumbra and pial collateral vessels. The authors review advanced noninvasive brain imaging by CT and MR imaging for the evaluation of AIS focusing on penumbral and collateral imaging.

View details for DOI 10.1016/j.nic.2018.06.004

View details for PubMedID 30322595
Use of Gradient Boosting Machine Learning to Predict Patient Outcome in Acute Ischemic Stroke on the Basis of Imaging, Demographic, and Clinical Information. AJR. American journal of roentgenology Xie, Y., Jiang, B., Gong, E., Li, Y., Zhu, G., Michel, P., Wintermark, M., Zaharchuk, G. 2018: 1?7
Abstract

OBJECTIVE: When treatment decisions are being made for patients with acute ischemic stroke, timely and accurate outcome prediction plays an important role. The optimal rehabilitation strategy also relies on long-term outcome predictions. The decision-making process involves numerous biomarkers including imaging features and demographic information. The objective of this study was to integrate common stroke biomarkers using machine learning methods and predict patient recovery outcome at 90 days.MATERIALS AND METHODS: A total of 512 patients were enrolled in this retrospective study. Extreme gradient boosting (XGB) and gradient boosting machine (GBM) models were used to predict modified Rankin scale (mRS) scores at 90 days using biomarkers available at admission and 24 hours. Feature selections were performed using a greedy algorithm. Fivefold cross validation was applied to estimate model performance.RESULTS: For binary prediction of an mRS score of greater than 2 using biomarkers available at admission, XGB and GBM had an AUC of 0.746 and 0.748, respectively. Adding the National Institutes of Health Stroke Score at 24 hours and performing feature selection improved the AUC of XGB to 0.884 and the AUC of GBM to 0.877. With the addition of the recanalization outcome, XGB's AUC improved to 0.807 for nonrecanalized patients and dropped to 0.670 for recanalized patients. GBM's AUC improved to 0.781 for nonrecanalized patients and dropped to 0.655 for recanalized patients.CONCLUSION: Decision tree-based GBMs can predict the recovery outcome of stroke patients at admission with a high AUC. Breaking down the patient groups on the basis of recanalization and nonrecanalization can potentially help with the treatment decision process.

View details for PubMedID 30354266
Advantages of Short Repetition Time Resting-State Functional MRI Enabled by Simultaneous Multi-slice Imaging. Journal of neuroscience methods Jahanian, H., Holdsworth, S., Christen, T., Wu, H., Zhu, K., Kerr, A. B., Middione, M. J., Dougherty, R. F., Moseley, M., Zaharchuk, G. 2018
Abstract

BACKGROUND: Recent advancements in simultaneous multi-slice (SMS) imaging techniques have enabled whole-brain resting-state fMRI (rs-fMRI) scanning at sub-second temporal resolution, providing spectral ranges much wider than the typically used range of 0.01-0.1Hz. However, the advantages of this accelerated acquisition for rs-fMRI have not been evaluated.NEW METHOD: In this study, we used SMS Echo Planar Imaging (EPI) to probe whole-brain functional connectivity with a short repetition time (TR=350ms) and compared it with standard EPI with a longer TR of 2000ms. We determined the effect of scan length and investigated the temporal filtration strategies that optimize results based on metrics of signal-noise separation and test-retest reliability using both seed-based and independent component analysis (ICA).RESULTS: We found that use of either the entire frequency range of 0.01-1.4Hz or the entire frequency range with the exclusion of typical cardiac and respiratory frequency values tended to provide the best functional connectivity maps.COMPARISON WITH EXISTING METHODS: We found that the SMS-acquired rs-fMRI scans had improved the signal-noise separation, while preserving the same level of test-retest reliability compared to conventional EPI, and enabled the detection of reliable functional connectivity networks with scan times as short as 3minutes.CONCLUSIONS: Our findings suggest that whole-brain rs-fMRI studies may benefit from the increased temporal resolution enabled by the SMS-EPI acquisition, leading to drastic scan time reductions, which in turn should enable the more widespread use of rs-fMRI in clinical research protocols.

View details for PubMedID 30300699
Quantitative susceptibility mapping using deep neural network: QSMnet NEUROIMAGE Yoon, J., Gong, E., Chatnuntawech, I., Bilgic, B., Lee, J., Jung, W., Ko, J., Jung, H., Setsompop, K., Zaharchuk, G., Kim, E., Pauly, J., Lee, J. 2018; 179: 199?206
Abstract

Deep neural networks have demonstrated promising potential for the field of medical image reconstruction, successfully generating high quality images for CT, PET and MRI. In this work, an MRI reconstruction algorithm, which is referred to as quantitative susceptibility mapping (QSM), has been developed using a deep neural network in order to perform dipole deconvolution, which restores magnetic susceptibility source from an MRI field map. Previous approaches of QSM require multiple orientation data (e.g. Calculation of Susceptibility through Multiple Orientation Sampling or COSMOS) or regularization terms (e.g. Truncated K-space Division or TKD; Morphology Enabled Dipole Inversion or MEDI) to solve an ill-conditioned dipole deconvolution problem. Unfortunately, they either entail challenges in data acquisition (i.e. long scan time and multiple head orientations) or suffer from image artifacts. To overcome these shortcomings, a deep neural network, which is referred to as QSMnet, is constructed to generate a high quality susceptibility source map from single orientation data. The network has a modified U-net structure and is trained using COSMOS QSM maps, which are considered as gold standard. Five head orientation datasets from five subjects were employed for patch-wise network training after doubling the training data using a model-based data augmentation. Seven additional datasets of five head orientation images (i.e. total 35 images) were used for validation (one dataset) and test (six datasets). The QSMnet maps of the test dataset were compared with the maps from TKD and MEDI for their image quality and consistency with respect to multiple head orientations. Quantitative and qualitative image quality comparisons demonstrate that the QSMnet results have superior image quality to those of TKD or MEDI results and have comparable image quality to those of COSMOS. Additionally, QSMnet maps reveal substantially better consistency across the multiple head orientation data than those from TKD or MEDI. As a preliminary application, the network was further tested for three patients, one with microbleed, another with multiple sclerosis lesions, and the third with hemorrhage. The QSMnet maps showed similar lesion contrasts with those from MEDI, demonstrating potential for future applications.

View details for PubMedID 29894829
ISLES 2016 and 2017-Benchmarking Ischemic Stroke Lesion Outcome Prediction Based on Multispectral MRI FRONTIERS IN NEUROLOGY Winzeck, S., Hakim, A., McKinley, R., Pinto, J. R., Alves, V., Silva, C., Pisov, M., Krivov, E., Belyaev, M., Monteiro, M., Oliveira, A., Choi, Y., Palk, M., Kwon, Y., Lee, H., Kim, B., Won, J., Islam, M., Ren, H., Robben, D., Suetens, P., Gong, E., Niu, Y., Xu, J., Pauly, J. M., Lucas, C., Heinrich, M. P., Rivera', L. C., Castillo, L. S., Daza, L. A., Beers, A. L., Arbelaers, P., Maier, O., Chang, K., Brown, J. M., Kapalthy-Cramer, J., Zaharchuk, G., Wiest, R., Reyes, M. 2018; 9
View details for DOI 10.3389/fneur.2018.00679

View details for Web of Science ID 000444461500001
Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation Maralani, P., Das, S., Mainprize, T., Phan, N., Bharatha, A., Keith, J., Munoz, D. G., Sahgal, A., Symons, S., Ironside, S., Faraji-Dana, Z., Eilaghi, A., Chan, A., Alcaide-Leon, P., Shearkhani, O., Jakubovic, R., Atenafu, E. G., Zaharchuk, G., Mikulis, D. RADIOLOGICAL SOC NORTH AMERICA. 2018: 821?29
Abstract

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO2) maps. Two intratumoral sites were identified, one with low StO2 and one with high StO2. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO2). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1?, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO2 and PtO2, the ratios of low to high StO2 versus low to high PtO2 in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO2 versus high StO2. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.

View details for PubMedID 29944077
Consensus statement on current and emerging methods for the diagnosis and evaluation of cerebrovascular disease JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Donahue, M. J., Achten, E., Cogswell, P. M., De Leeuw, F., Derdeyn, C. P., Dijkhuizen, R. M., Fan, A. P., Ghaznawi, R., Heit, J. J., Ikram, M., Jezzard, P., Jordan, L. C., Jouvent, E., Knutsson, L., Leigh, R., Liebeskind, D. S., Lin, W., Okell, T. W., Qureshi, A. I., Stagg, C. J., van Osch, M. P., van Zijl, P. M., Watchmaker, J. M., Wintermark, M., Wu, O., Zaharchuk, G., Zhou, J., Hendrikse, J. 2018; 38 (9): 1391?1417
Abstract

Cerebrovascular disease (CVD) remains a leading cause of death and the leading cause of adult disability in most developed countries. This work summarizes state-of-the-art, and possible future, diagnostic and evaluation approaches in multiple stages of CVD, including (i) visualization of sub-clinical disease processes, (ii) acute stroke theranostics, and (iii) characterization of post-stroke recovery mechanisms. Underlying pathophysiology as it relates to large vessel steno-occlusive disease and the impact of this macrovascular disease on tissue-level viability, hemodynamics (cerebral blood flow, cerebral blood volume, and mean transit time), and metabolism (cerebral metabolic rate of oxygen consumption and pH) are also discussed in the context of emerging neuroimaging protocols with sensitivity to these factors. The overall purpose is to highlight advancements in stroke care and diagnostics and to provide a general overview of emerging research topics that have potential for reducing morbidity in multiple areas of CVD.

View details for PubMedID 28816594
Erroneous Resting-State fMRI Connectivity Maps Due to Prolonged Arterial Arrival Time and How to Fix Them BRAIN CONNECTIVITY Jahanian, H., Christen, T., Moseley, M. E., Zaharchuk, G. 2018; 8 (6): 362?70
Abstract

In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.

View details for PubMedID 29886781

View details for PubMedCentralID PMC6103249
Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Gong, E., Pauly, J. M., Wintermark, M., Zaharchuk, G. 2018; 48 (2): 330?40
View details for DOI 10.1002/jmri.25970

View details for Web of Science ID 000440926000003
The vast potential and bright future of neuroimaging. The British journal of radiology Wintermark, M., Colen, R., Whitlow, C. T., Zaharchuk, G. 2018: 20170505
Abstract

Significant advances in anatomical and functional neuroimaging techniques have allowed researchers and clinicians to visualize the brain in action. The field of neuroimaging currently includes newer and faster scanners, improved image quality, higher spatial and temporal resolution and diverse methods of acquisition and analysis. Beyond simply imaging brain structures, these developments enable quantitative assessment of the microstructural and functional architecture, perfusion and metabolism of the brain. The resultant highly granular data have the potential to greatly improve characterization of neurological, neurosurgical and psychiatric disorders without invasive neurosurgery. However, the surge in neuroimaging data that can be collected over a relatively short acquisition period has led to a "big data" problem, where novel methods are needed to appropriately extract and analyze information and integrate data with other types of big data, such as genomic and proteomic data. Another challenge is the translation of these new technologies from basic science into clinical practice, so that they can be leveraged to improve patient outcomes and alleviate human disease. Critical to this endeavor is research comparing the effectiveness and outcomes of these advancements to allow widespread acceptance in the modern, economically constrained healthcare system. This review aims to illustrate the different facets of cutting edge neuroimaging techniques, as well as the potential role of these methods as clinical tools for evaluating the breadth of diseases that affect the brain.

View details for PubMedID 29848016
Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI). Magnetic resonance in medicine Terem, I., Ni, W. W., Goubran, M., Rahimi, M. S., Zaharchuk, G., Yeom, K. W., Moseley, M. E., Kurt, M., Holdsworth, S. J. 2018
Abstract

PURPOSE: Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian video magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here, we strive to improve aMRI by incorporating a phase-based motion amplification algorithm.METHODS: Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output.RESULTS: Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient.CONCLUSION: Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion and may reveal subtle physiological variations of the brain as a result of pathology using processing of the fundamental harmonic or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

View details for PubMedID 29845645
Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke STROKE Tsai, J. P., Mlynash, M., Christensen, S., Kemp, S., Kim, S., Mishra, N. K., Federau, C., Nogueira, R. G., Jovin, T. G., Devlin, T. G., Akhtar, N., Yavagal, D. R., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W., Lansberg, M. G., CRISP Investigators 2018; 49 (4): 952-+
Abstract

This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke.We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5.Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001).Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

View details for PubMedID 29581341
Comparing accuracy and reproducibility of sequential and Hadamard-encoded multidelay pseudocontinuous arterial spin labeling for measuring cerebral blood flow and arterial transit time in healthy subjects: A simulation and in vivo study JOURNAL OF MAGNETIC RESONANCE IMAGING Guo, J., Holdsworth, S. J., Fan, A. P., Lebel, M. R., Zun, Z., Shankaranarayanan, A., Zaharchuk, G. 2018; 47 (4): 1119?32
Abstract

To compare performance of sequential and Hadamard-encoded pseudocontinuous arterial spin labeling (PCASL).Monte Carlo simulations and in vivo experiments were performed in 10 healthy subjects. Field strength and sequence: 5-delay sequential (5-del. Seq.), 7-delay Hadamard-encoded (7-del. Had.), and a single-delay (1-del.) PCASL, without and with vascular crushing at 3.0T. The errors and variations of cerebral blood flow (CBF) and arterial transit time (ATT) from simulations and the CBF and ATT estimates and variations in gray matter (GM) with different ATT ranges were compared. Pairwise t-tests with Bonferroni correction were used.The simulations and in vivo experiments showed that 1-del. PCASL underestimated GM CBF due to insufficient postlabeling delay (PLD) (37.2?�?8.1 vs. 47.3?�?8.5 and 47.3?�?9.0?ml/100g/min, P ? 6.5 � 10-6 ), while 5-del. Seq. and 7-del. Had. yielded comparable GM CBF (P ? 0.49). 5-del. Seq. was more reproducible for CBF (P?=?4.7 � 10-4 ), while 7-del. Had. was more reproducible for ATT (P?=?0.033). 5-del. Seq. was more prone to intravascular artifacts and yielded lower GM ATTs compared to 7-del. Had. without crushing (1.13?�?0.18 vs. 1.23?�?0.13 seconds, P?=?2.3 � 10-3 ), but they gave comparable ATTs with crushing (P?=?0.12). ATTs measured with crushing were longer than those without crushing (P ? 6.7 � 10-4 ), but CBF was not affected (P ? 0.16).The theoretical signal-to-noise ratio (SNR) gain through Hadamard encoding was confirmed experimentally. For 1-del., a PLD of 1.8 seconds is recommended for healthy subjects. With current parameters, 5-del. Seq. was more reproducible for CBF, and 7-del. Had. for ATT. Vascular crushing may help reduce variations in multidelay experiments without compromising tissue CBF or ATT measurements.1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1119-1132.

View details for PubMedID 28792653

View details for PubMedCentralID PMC5807238
Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI. Journal of magnetic resonance imaging : JMRI Gong, E., Pauly, J. M., Wintermark, M., Zaharchuk, G. 2018
Abstract

BACKGROUND: There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration.PURPOSE: To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method.STUDY TYPE: Retrospective, crossover.POPULATION: Sixty patients receiving clinically indicated contrast-enhanced brain MRI.SEQUENCE: 3D T1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma.ASSESSMENT: For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images.STATISTICAL ANALYSIS: Results were assessed using paired t-tests and noninferiority tests.RESULTS: The proposed deep learning method yielded significant (n=50, P<0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n=20, P=0.003) and contrast enhancement (n=20, P<0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n=20, P=0.083) and contrast enhancement (n=20, P=0.068). Slightly better (n=20, P=0.039) motion-artifact suppression was noted in the synthesized images. The noninferiority test rejects the inferiority of the synthesized to true full-dose images for image quality (95% CI: -14-9%), artifacts suppression (95% CI: -5-20%), and contrast enhancement (95% CI: -13-6%).DATA CONCLUSION: With the proposed deep learning method, gadolinium dose can be reduced 10-fold while preserving contrast information and avoiding significant image quality degradation.LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

View details for PubMedID 29437269
Clinical Evaluation of Silent T1-Weighted MRI and Silent MR Angiography of the Brain AMERICAN JOURNAL OF ROENTGENOLOGY Holdsworth, S. J., Macpherson, S. J., Yeom, K. W., Wintermark, M., Zaharchuk, G. 2018; 210 (2): 404?11
Abstract

New MRI sequences based on rapid radial acquisition have reduced gradient noise. The purpose of this study was to compare Silent T1-weighted and unenhanced MR angiography (MRA) against conventional sequences in a clinical population.The study cohort consisted of 40 patients with suspected brain metastases (median age, 60 years; range, 23-91 years) who underwent T1-weighted contrast-enhanced MRI and 51 patients with suspected vascular lesions or cerebral ischemia (median age, 60 years; range, 16-94 years) who underwent unenhanced intracranial MRA. Three neuroradiologists reviewed the images blindly and rated several measures of image quality on a 5-point Likert scale. Reviewers recorded the number of enhancing lesions and whether Silent images were better than, worse than, or equivalent to conventional images.For T1-weighted MR images, ratings were slightly lower for Silent versus conventional images, except for diagnostic confidence. Although more lesions were detected on conventional images, this difference was not statistically significant; agreement was seen in 88% of cases. In 48% of cases, T1-weighted scans were deemed equivalent, but when a preference existed, it was usually for conventional images (38% vs 14%). Conventional MRA images were rated higher on all image quality metrics and were strongly preferred (reviewers preferred conventional images in 69% of cases, rated the images as equivalent in 27% of cases, and preferred Silent images in 4% of cases). In some cases, artifacts on Silent images caused reduced vessel caliber, vessel irregularities, and even absent vessels.Although conventional T1-weighted images were preferred overall, most Silent T1-weighted images were rated as equivalent to or better than conventional images and represent a potential alternative for imaging of noise-averse patients. Silent MRA scored significantly worse and could not be recommended at this time, suggesting that it requires additional refinement before routine clinical use.

View details for PubMedID 29112472
Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M. n., Wintermark, M. n., Zaharchuk, G. n., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018
Abstract

Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (?=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; ?=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; ?=0.830; P=0.529).AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

View details for PubMedID 29555872
ISLES 2016 and 2017-Benchmarking Ischemic Stroke Lesion Outcome Prediction Based on Multispectral MRI. Frontiers in neurology Winzeck, S. n., Hakim, A. n., McKinley, R. n., Pinto, J. A., Alves, V. n., Silva, C. n., Pisov, M. n., Krivov, E. n., Belyaev, M. n., Monteiro, M. n., Oliveira, A. n., Choi, Y. n., Paik, M. C., Kwon, Y. n., Lee, H. n., Kim, B. J., Won, J. H., Islam, M. n., Ren, H. n., Robben, D. n., Suetens, P. n., Gong, E. n., Niu, Y. n., Xu, J. n., Pauly, J. M., Lucas, C. n., Heinrich, M. P., Rivera, L. C., Castillo, L. S., Daza, L. A., Beers, A. L., Arbelaezs, P. n., Maier, O. n., Chang, K. n., Brown, J. M., Kalpathy-Cramer, J. n., Zaharchuk, G. n., Wiest, R. n., Reyes, M. n. 2018; 9: 679
Abstract

Performance of models highly depend not only on the used algorithm but also the data set it was applied to. This makes the comparison of newly developed tools to previously published approaches difficult. Either researchers need to implement others' algorithms first, to establish an adequate benchmark on their data, or a direct comparison of new and old techniques is infeasible. The Ischemic Stroke Lesion Segmentation (ISLES) challenge, which has ran now consecutively for 3 years, aims to address this problem of comparability. ISLES 2016 and 2017 focused on lesion outcome prediction after ischemic stroke: By providing a uniformly pre-processed data set, researchers from all over the world could apply their algorithm directly. A total of nine teams participated in ISLES 2015, and 15 teams participated in ISLES 2016. Their performance was evaluated in a fair and transparent way to identify the state-of-the-art among all submissions. Top ranked teams almost always employed deep learning tools, which were predominately convolutional neural networks (CNNs). Despite the great efforts, lesion outcome prediction persists challenging. The annotated data set remains publicly available and new approaches can be compared directly via the online evaluation system, serving as a continuing benchmark (www.isles-challenge.org).

View details for PubMedID 30271370
The vast potential and bright future of neuroimaging BRITISH JOURNAL OF RADIOLOGY Wintermark, M., Colen, R., Whitlow, C. T., Zaharchuk, G. 2018; 91 (1087)
View details for DOI 10.1259/bjr.20170505

View details for Web of Science ID 000436607600003
Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture. Stroke Heit, J. J., Wintermark, M. n., Martin, B. W., Zhu, G. n., Marks, M. P., Zaharchuk, G. n., Dodd, R. L., Do, H. M., Steinberg, G. K., Lansberg, M. G., Albers, G. W., Federau, C. n. 2018
Abstract

Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.Sixteen patients (11 females, 69%;P=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI- group). Compared with DCI- patients, DCI+ patients had decreased IVIM perfusion fractionf(0.09�0.03 versus 0.13�0.01;P=0.03), reduced diffusion coefficientD(0.82�0.05 versus 0.92�0.07�10-3mm2/s;P=0.003), and reduced blood flow-related parameterfD* (1.18�0.40 versus 1.83�0.40�10-3mm2/s;P=0.009). IVIM pseudodiffusion coefficientD* did not differ between DCI- (0.011�0.002) and DCI+ (0.013�0.005 mm2/s;P=0.4) patients. No differences in mortality or clinical outcome were identified.Decreased IVIM perfusion fractionfand blood flow-related parameterfD* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.

View details for DOI 10.1161/STROKEAHA.117.020395

View details for PubMedID 29439196
Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI SCIENTIFIC REPORTS Zun, Z., Zaharchuk, G., Andescavage, N. N., Donofrio, M. T., Limperopoulos, C. 2017; 7: 16126
Abstract

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental perfusion imaging was performed using velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with whole-placenta coverage. In pregnancies with fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age; however, no such correlation was found in healthy pregnancies. Also, global placental perfusion was significantly higher in fetal CHD versus controls, in the lateral side-lying patient position versus supine, and in the posterior placental position versus anterior placental position. This study reports for the first time non-invasive whole-placenta perfusion imaging in utero. These data suggest that placental VSASL may serve as a potential biomarker of placental dysfunction in fetuses diagnosed with CHD.

View details for PubMedID 29170468
Semiquantitative Assessment of F-18-FDG Uptake in the Normal Skeleton: Comparison Between PET/CT and Time-of-Flight Simultaneous PET/MRI AMERICAN JOURNAL OF ROENTGENOLOGY Minamimoto, R., Xu, G., Jamali, M., Holley, D., Barkhodari, A., Zaharchuk, G., lagaru, A. 2017; 209 (5): 1136?42
Abstract

Differences in the attenuation correction methods used in PET/CT scanners versus the newly introduced whole-body simultaneous PET/MRI reportedly result in differences in standardized uptake values (SUVs) in the normal skeleton. The aim of the study was to compare the semiquantitative FDG uptake in the normal skeleton using time-of-flight (TOF) PET/MRI versus PET/CT with and without TOF.Participants received a single FDG injection and underwent non-TOF and TOF PET/CT (n = 23) or non-TOF PET/CT and TOF PET/MRI (n = 50). Mean SUV (SUVmean) and maximum SUV (SUVmax) were measured from all PET scans for nine normal regions of the skeleton. Pearson correlation coefficients (r) were used to evaluate the SUVmax and SUVmean of normal skeleton between non-TOF and TOF PET/CT, as well as between non-TOF PET/CT and TOF PET/MRI. In addition, percentage differences in SUVmax and SUVmean of the normal skeleton between non-TOF and TOF PET/CT and between non-TOF PET/CT and TOF PET/MRI were evaluated.The SUVmax and SUVmean in the normal skeleton significantly increased between non-TOF and TOF PET/CT, but they significantly decreased between non-TOF PET/CT and TOF PET/MRI. The SUVmax and SUVmean in normal skeleton showed good correlation between non-TOF PET/CT and TOF PET/MRI (SUVmax, r = 0.88; SUVmean, r = 0.91) and showed a similar trend between non-TOF and TOF PET/CT (SUVmax, r = 0.88; SUVmean, r = 0.94).In the normal skeleton, SUVmax and SUVmean showed high correlations between PET/MRI and PET/CT. The MRI attenuation correction used in TOF PET/MRI provides reliable semiquantitative measurements in the normal skeleton.

View details for PubMedID 28777652
CEREBRAL BLOW FLOW AND SUV TRENDS IN PET/MRI FOLLOWING BEVACIZUMAB ADMINISTRATION IN GLIOBLASTOMA Corbin, Z. A., Zaharchuk, G., Spielman, D. M., Recht, L. D. OXFORD UNIV PRESS INC. 2017: 158
View details for Web of Science ID 000415152503007
Clinical evaluation of TOF versus non-TOF on PET artifacts in simultaneous PET/MR: a dual centre experience. European journal of nuclear medicine and molecular imaging Ter Voert, E. E., Veit-Haibach, P., Ahn, S., Wiesinger, F., Khalighi, M. M., Levin, C. S., Iagaru, A. H., Zaharchuk, G., Huellner, M., Delso, G. 2017; 44 (7): 1223-1233
Abstract

Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning.A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact).A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 � 0.82 for non-TOF PET images and 0.53 � 0.66 for TOF images (p?
View details for DOI 10.1007/s00259-017-3619-2

View details for PubMedID 28124091
Further Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan Response RADIOLOGY Haller, S., Barkhof, F., Thomas, D., Lovblad, K., Golay, X., Zaharchuk, G. 2017; 284 (1): 302?3
View details for Web of Science ID 000403562200037
F-FTC-146 in humans. Journal of nuclear medicine Hj�rnevik, T., Cipriano, P. W., Shen, B., Hyung Park, J., Gulaka, P., Holley, D., Gandhi, H., Yoon, D., Mittra, E. S., Zaharchuk, G., Gambhir, S. S., McCurdy, C. R., Chin, F. T., Biswal, S. 2017
Abstract

The purpose of this study is to assess safety, biodistribution and radiation dosimetry in humans for the highly selective sigma-1 receptor (S1R) positron emission tomography (PET) agent (18)F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ((18)F-FTC-146). Methods: Ten healthy volunteers (HV; five female, five male; age: 34.3 � 6.5 years) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/magnetic resonance imaging (PET/MRI) examinations were acquired for up to three hours after injection (357.2 � 48.8 MBq). Blood samples were collected and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions-of-interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry was estimated using PMOD 3.7 and Organ Linear Internal Dose Assessment (OLINDA). Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to (18)F-FTC-146 were reported. High accumulation of (18)F-FTC-146 was observed in S1R dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose (ED) of (18)F-FTC-146 was 0.0259 � 0.0034 mSv/MBq (range: 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade (18)F-FTC-146 were successful. Injection of (18)F-FTC-146 is safe, and absorbed doses are acceptable. The potential of (18)F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.

View details for DOI 10.2967/jnumed.117.192641

View details for PubMedID 28572487
CT Perfusion to Predict Response to Recanalization in Ischemic Stroke. Annals of neurology Lansberg, M. G., Christensen, S., Kemp, S., Mlynash, M., Mishra, N., Federau, C., Tsai, J. P., Kim, S., Nogueria, R. G., Jovin, T., Devlin, T. G., Akhtar, N., Yavagal, D. R., Haussen, D., Dehkharghani, S., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W. 2017
Abstract

To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging.Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age?=?66 years, median NIH Stroke Scale [NIHSS]?=?16, median time from symptom onset to endovascular therapy?=?5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n?=?131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ?8 points on the NIHSS (83% vs 44%; p?=?0.002, adjusted odds ratio [OR]?=?6.6, 95% confidence interval [CI]?=?2.1-20.9). This association did not differ between patients treated within 6 hours (OR?=?6.4, 95% CI?=?1.5-27.8) and those treated?>?6 hours after symptom onset (OR?=?13.7, 95% CI?=?1.4-140).The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.

View details for DOI 10.1002/ana.24953

View details for PubMedID 28486789
Resting-State BOLD MRI for Perfusion and Ischemia. Topics in magnetic resonance imaging Kroll, H., Zaharchuk, G., Christen, T., Heit, J. J., Iv, M. 2017; 26 (2): 91-96
Abstract

Advanced imaging techniques including computed tomography (CT) angiography, CT perfusion, magnetic resonance (MR) angiography, MR with diffusion- and perfusion-weighted imaging, and, more recently, resting-state BOLD (Blood Oxygen Level Dependent) functional MRI (rs-fMRI) are increasingly used to evaluate patients with acute ischemic stroke. Advanced imaging allows for identification of patients with ischemic stroke and determination of the size of infarcted and potentially salvageable tissue, all of which yield crucial information for proper stroke management. The addition of rs-fMRI for ischemia adds information at the microvascular level, thereby improving the understanding of pathophysiologic mechanisms of impaired cerebral perfusion and tissue oxygenation beyond the known concepts at the macrovascular level. As such, it may further delineate functional and dysfunctional neuronal networks, guide stroke interventions, and improve prognosis and monitoring of patient outcomes.

View details for DOI 10.1097/RMR.0000000000000119

View details for PubMedID 28277456
Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Ni, W. W., Christen, T., Rosenberg, J., Zun, Z., Moseley, M. E., Zaharchuk, G. 2017; 37 (4): 1213-1222
Abstract

This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49?�?12 vs. 48?�?11?mL/100?g/min, p?=?0.44). However, baseline R2' differed between these regions (3.2?�?0.7 vs. 2.9?�?0.6?s(-1), p?
View details for DOI 10.1177/0271678X16651088

View details for Web of Science ID 000400234000004
Benchmarking transverse spin relaxation based oxygenation measurements in the brain during hypercapnia and hypoxia. Journal of magnetic resonance imaging : JMRI Ni, W. W., Christen, T., Zaharchuk, G. 2017
Abstract

To simultaneously assess reproducibility of three MRI transverse relaxation parameters ( R2', R2*, and R2 ) for brain tissue oxygenation mapping and to assess changes in these parameters with inhalation of gases that increase and decrease oxygenation, to identify the most sensitive parameter for imaging brain oxygenation.Forty-eight healthy subjects (25 male, ages 35?�?8 years) were scanned at 3.0 Tesla, each with one of four gases (mildly and strongly hypercapnic and hypoxic) administered in a challenge paradigm, using a gas delivery setup designed for patient use. Cerebral blood flow mapping with arterial spin labeling, and simultaneous R2', R2*, and R2 mapping with gradient-echo sampling of free induction decay and echo (GESFIDE) were performed. Reproducibility in air and gas-induced changes were evaluated using nonparametric analysis with correction for multiple comparisons.Our gas delivery setup achieved stable gas challenges as shown by physiological monitoring. Test-retest variability of R2', R2*, and R2 were found to be 0.24 s(-1) (8.6% of mean), 0.24 s(-1) (1.3% of mean), and 0.15 s(-1) (1.0% of mean), respectively. Strong hypoxia produced the most conclusive oxygenation-driven relaxation change, inducing increases in R2' (25?�?13%, P?=?0.03), R2* (5?�?2%, P?=?0.02), and R2 (2?�?2%, NS).We benchmarked the intra-scan test-retest variability in GESFIDE-based transverse relaxation rate mapping. Using a reliable framework for gas challenge paradigms, we recommend strong hypoxia for validating oxygenation mapping methods, and the use of tissue R2' change, instead of R2* or R2 , as a metric for studying brain tissue oxygenation using transverse relaxation methods.1 J. Magn. Reson. Imaging 2017.

View details for DOI 10.1002/jmri.25582

View details for PubMedID 28306210
Conspicuity of Malignant Lesions on PET/CT and Simultaneous Time-Of-Flight PET/MRI PLOS ONE Minamimoto, R., Iagaru, A., Jamali, M., Holley, D., Barkhodari, A., Vasanawala, S., Zaharchuk, G. 2017; 12 (1)
Abstract

To compare the conspicuity of malignant lesions between FDG PET/CT and a new simultaneous, time-of-flight (TOF) enabled PET/MRI scanner.All patients underwent a single-injection of FDG, followed by a dual imaging protocol consisting of PET/CT followed by TOF PET/MRI. PET/CT and PET/MRI images were evaluated by two readers independently for areas of FDG uptake compatible with malignancy, and then categorized into 5 groups (1: PET/MRI and PET/CT positive; 2: PET/MRI positive, PET/CT positive in retrospect; 3: PET/CT positive, PET/MRI positive in retrospect; 4: PET/MRI positive, PET/CT negative; 5: PET/MRI negative, PET/CT positive) by consensus. Patients with no lesions on either study or greater than 10 lesions based on either modality were excluded from the study.Fifty-two patients (mean�SD age: 58�14 years) underwent the dual imaging protocol; of these, 29 patients with a total of 93 FDG-avid lesions met the inclusion criteria. The majority of lesions (56%) were recorded prospectively in the same location on PET/CT and PET/MRI. About an equal small fraction of lesions were seen on PET/CT but only retrospectively on PET/MRI (9%) and vice versa (12%). More lesions were identified only on PET/MRI but not on PET/CT, even in retrospect (96% vs. 81%, respectively; p = 0.003). Discrepant lesions had lower maximum standardized uptake value (SUVmax) than concordant lesions on both modalities (p<0.001).While most lesions were identified prospectively on both modalities, significantly more lesions were identified with PET/MRI than with PET/CT.

View details for DOI 10.1371/journal.pone.0167262

View details for Web of Science ID 000392381100001

View details for PubMedID 28103230

View details for PubMedCentralID PMC5245859
Cerebral blood flow, transit time, and apparent diffusion coefficient in moyamoya disease before and after acetazolamide NEURORADIOLOGY Federau, C., Christensen, S., Zun, Z., Park, S., Ni, W., Moseley, M., Zaharchuk, G. 2017; 59 (1): 5-12
Abstract

The goal of this study was to assess the changes in arterial spin labeling (ASL) cerebral blood flow (CBF) and arterial transit time (ATT), and in apparent diffusion coefficient (ADC), before and after an acetazolamide challenge in moyamoya patients, as function of arterial stenosis severity.Pre-operative patients diagnosed with moyamoya disease who could undergo MRI at 3.0T were recruited for this study. A multi-delay pseudo-continuous ASL and a diffusion-weighted sequence were acquired before and 15�min after acetazolamide injection. The severity of anterior, middle, and posterior cerebral artery pathology was graded on time-of-flight MR angiographic images. CBF, ATT, and ADC were measured on standardized regions of interest as function of the vessel stenosis severity.Thirty patients were included. Fifty-four percent of all vessels were normal, 28% mildly/moderately stenosed, and 18% severely stenosed/occluded. Post-acetazolamide, a significantly larger CBF (ml/100�g/min) increase was observed in territories of normal (+19.6��14.9) compared to mildly/moderately stenosed (+14.2��27.2, p�=�0.007), and severely stenosed/occluded arteries (+9.9��24.2, p�<�0.0001). ATT was longer in territories of vessel anomalies compared with normal regions at baseline. ATT decreases were observed in all territories post-acetazolamide. ADC did not decrease after acetazolamide in any regions, and no correlation was found between ADC changes and baseline ATT, change in ATT, or CVR.The hemodynamic response in moyamoya disease, as measured with ASL CBF, is impaired mostly in territories with severe arterial stenosis/occlusion, while ATT was prolonged in all non-normal regions. No significant changes in ADC were observed after acetazolamide.

View details for DOI 10.1007/s00234-016-1766-y

View details for Web of Science ID 000392306400003

View details for PubMedID 27913820
Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous Anomalies. Journal of neuroimaging : official journal of the American Society of Neuroimaging Zhang, M. n., Telischak, N. A., Fischbein, N. J., Steinberg, G. K., Marks, M. n., Zaharchuk, G. n., Heit, J. J., Iv, M. n. 2017
Abstract

Transitional venous anomalies (TVAs) are rare cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but demonstrate early arteriovenous shunting on digital subtraction angiography (DSA) without the parenchymal nidus of arteriovenous malformations (AVMs). We investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) can distinguish brain TVAs from DVAs and guide their clinical management.We conducted a single-center retrospective review of patients with brain parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories and follow-up information were obtained. Two readers assessed ASL signal location relative to the vascular lesion on MRI and, if available, the presence of arteriovenous shunting on DSA.Thirty patients with DVA-like lesions with increased ASL signal were identified. Clinical symptoms prompted MRI evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten percent presented with acute symptoms, only one of whom presented with hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50% in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater agreement was very good (? = .81-1.0, P < .001).A DVA-like lesion with increased ASL signal likely represents a TVA with arteriovenous shunting. Our study indicates that these lesions are usually incidentally detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful tool to identify TVAs and guide further management of patients with TVAs.

View details for PubMedID 29205641
Image-derived input function estimation on a TOF-enabled PET/MR for cerebral blood flow mapping. Journal of cerebral blood flow and metabolism Khalighi, M. M., Deller, T. W., Fan, A. P., Gulaka, P. K., Shen, B., Singh, P., Park, J., Chin, F. T., Zaharchuk, G. 2017: 271678X17691784-?
Abstract

(15)O-H2O PET imaging is an accurate method to measure cerebral blood flow (CBF) but it requires an arterial input function (AIF). Historically, image-derived AIF estimation suffers from low temporal resolution, spill-in, and spill-over problems. Here, we optimized tracer dose on a time-of-flight PET/MR according to the acquisition-specific noise-equivalent count rate curve. An optimized dose of 850?MBq of (15)O-H2O was determined, which allowed sufficient counts to reconstruct a short time-frame PET angiogram (PETA) during the arterial phase. This PETA enabled the measurement of the extent of spill-over, while an MR angiogram was used to measure the true arterial volume for AIF estimation. A segment of the high cervical arteries outside the brain was chosen, where the measured spill-in effects were minimal. CBF studies were performed twice with separate [15O]-H2O injections in 10 healthy subjects, yielding values of 88?�?16, 44?�?9, and 58?�?11?mL/min/100?g for gray matter, white matter, and whole brain, with intra-subject CBF differences of 5.0?�?4.0%, 4.1?�?3.3%, and 4.5?�?3.7%, respectively. A third CBF measurement after the administration of 1?g of acetazolamide showed 35?�?23%, 29?�?20%, and 33?�?22% increase in gray matter, white matter, and whole brain, respectively. Based on these findings, the proposed noninvasive AIF method provides robust CBF measurement with (15)O-H2O PET.

View details for DOI 10.1177/0271678X17691784

View details for PubMedID 28155582
Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow Measurements in Moyamoya Patients: A Simultaneous Positron Emission Tomography/MRI Study. Stroke Fan, A. P., Guo, J. n., Khalighi, M. M., Gulaka, P. K., Shen, B. n., Park, J. H., Gandhi, H. n., Holley, D. n., Rutledge, O. n., Singh, P. n., Haywood, T. n., Steinberg, G. K., Chin, F. T., Zaharchuk, G. n. 2017; 48 (9): 2441?49
Abstract

Arterial spin labeling (ASL) MRI is a promising, noninvasive technique to image cerebral blood flow (CBF) but is difficult to use in cerebrovascular patients with abnormal, long arterial transit times through collateral pathways. To be clinically adopted, ASL must first be optimized and validated against a reference standard in these challenging patient cases.We compared standard-delay ASL (post-label delay=2.025 seconds), multidelay ASL (post-label delay=0.7-3.0 seconds), and long-label long-delay ASL acquisitions (post-label delay=4.0 seconds) against simultaneous [15O]-positron emission tomography (PET) CBF maps in 15 Moyamoya patients on a hybrid PET/MRI scanner. Dynamic susceptibility contrast was performed in each patient to identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays. Relative CBF measurements by each ASL scan in 20 cortical regions were compared with the PET reference standard, and correlations were calculated for areas with moderate and severe Tmax delays.Standard-delay ASL underestimated relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and middle territories commonly affected by Moyamoya disease (P<0.001). Arterial transit times correction by multidelay acquisitions led to improved consistency with PET, but still underestimated CBF in the presence of long transit delays (P=0.02). Long-label long-delay ASL scans showed the strongest correlation relative to PET, and there was no difference in mean relative CBF between the modalities, even in areas of severe delays.Post-label delay times of ?4 seconds are needed and may be combined with multidelay strategies for robust ASL assessment of CBF in Moyamoya disease.

View details for PubMedID 28765286
Studying GABA Neurophysiology by Simultaneous [18F]Flumazenil-Positron Emission Tomography and Magnetic Resonance Spectroscopy Fung, L., Gu, M., Leuze, C., Hjoernevik, T., Shen, B., Park, J., Flores, R., Reyes, S., Holley, D., Gandhi, H., Jung, J., Lee, B., Kim, S., Khalighi, M., Gulaka, P., Zaharchuk, G., McNab, J., Quon, A., Spielman, D., Chin, F. NATURE PUBLISHING GROUP. 2016: S209
View details for Web of Science ID 000440365600366
MR Vascular Fingerprinting in Stroke and Brain Tumors Models SCIENTIFIC REPORTS LeMasson, B., Pannetier, N., Coquery, N., Boisserand, L. S., Collomb, N., Schuff, N., Moseley, M., Zaharchuk, G., Barbier, E. L., Christen, T. 2016; 6
Abstract

In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n?=?115), divided in 3 models: brain tumors (9?L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9?L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9?L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

View details for DOI 10.1038/srep37071

View details for Web of Science ID 000388795600001

View details for PubMedID 27883015

View details for PubMedCentralID PMC5121626
Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy. International journal of stroke Federau, C., Christensen, S., Mlynash, M., Tsai, J., Kim, S., Zaharchuk, G., Inoue, M., Straka, M., Mishra, N. K., Kemp, S., Lansberg, M. G., Albers, G. W. 2016
Abstract

To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy.We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18?h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (?18?h vs. <18?h), and the degree of reperfusion (on Tmax>6?s; ??90% vs.?
View details for PubMedID 27811306
CHANGES IN ACUTE FDG-PET FOLLOWING BEVACIZUMAB ADMINISTRATION IN GLIOBLASTOMA Corbin, Z., Zaharchuk, G., Spielman, D., Recht, L. OXFORD UNIV PRESS INC. 2016: 140
View details for Web of Science ID 000398604103098
Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI. Molecular imaging and biology Minamimoto, R., Levin, C., Jamali, M., Holley, D., Barkhodari, A., Zaharchuk, G., Iagaru, A. 2016; 18 (5): 776-781
Abstract

An integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner with time of flight (TOF) technology is now available for clinical use. The aim of this study is to evaluate the potential of TOF PET in PET/MRI to reduce artifacts in PET images when compared to non-TOF PET/MRI, TOF PET/X-ray computed tomography (CT), and non-TOF PET/CT.All patients underwent a single 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) injection, followed first by PET/CT, and subsequently by PET/MRI. PET/CT exams were requested as standard-of-care for oncological indications. Using the PET acquisitions datasets, 4 series of images (TOF PET/CT, non-TOF PET/CT, TOF PET/MRI, and non-TOF PET/MRI) were reconstructed. These image series were visually evaluated for: (1) dental metal artifacts, (2) breathing artifacts, and (3) pelvic artifacts due to scatter correction errors from high bladder [(18)F]FDG concentration. PET image quality was assessed by a 3-point scale (1-clinically significant artifact, 2-non clinically significant artifact, and 3-no artifact).Twenty-five patients (mean?�?SD age: 56?�?13�years old; female: 10, male: 15) were enrolled. TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT scores 2.8, 2.5, 2.4, and 2.3, respectively for the presence of dental artifacts, 2.8, 2.5, 2.2, and 1.9, respectively, for the presence of breathing artifacts, and 2.7, 1.7, 2.0, and 1.3, respectively, for the presence of pelvic artifacts TOF PET/MRI images showed the highest image quality scores among the 4 datasets of PET images.The superior timing resolution and resulting TOF capability of the new PET/MRI scanner improved PET image quality in this cohort by reducing artifacts compared to non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT.

View details for DOI 10.1007/s11307-016-0939-8

View details for PubMedID 26884058
Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge? Journal of cerebral blood flow and metabolism Jahanian, H., Christen, T., Moseley, M. E., Pajewski, N. M., Wright, C. B., Tamura, M. K., Zaharchuk, G. 2016
Abstract

Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69?�?7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R(2?)=?0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

View details for PubMedID 27683452
Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology Leigh, R., Christensen, S., Campbell, B. C., Marks, M. P., Albers, G. W., Lansberg, M. G. 2016; 87 (3): 263-269
Abstract

This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy.The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p = 0.004). BBB disruption on the pretreatment scan was associated with PH (p = 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified.The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment.

View details for DOI 10.1212/WNL.0000000000002862

View details for PubMedID 27316247
Evolution of Volume and Signal Intensity on Fluid-attenuated Inversion Recovery MR Images after Endovascular Stroke Therapy RADIOLOGY Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Lansberg, M. G., Wintermark, M., Albers, G. W. 2016; 280 (1): 184-192
Abstract

Purpose To analyze both volume and signal evolution on magnetic resonance (MR) fluid-attenuated inversion recovery (FLAIR) images between the images after endovascular therapy and day 5 (which was the prespecified end point for infarct volume in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution [DEFUSE 2] trial) in a subset of patients enrolled in the DEFUSE 2 study. Materials and Methods This study was approved by the local ethics committee at all participating sites. Informed written consent was obtained from all patients. In this post hoc analysis of the DEFUSE 2 study, 35 patients with FLAIR images acquired both after endovascular therapy (median time after symptom onset, 12 hours) and at day 5 were identified. Patients were separated into two groups based on the degree of reperfusion achieved on time to maximum greater than 6-second perfusion imaging (?90% vs <90%). After coregistration and signal normalization, lesion volumes and signal intensity were assessed by using FLAIR imaging for the initial lesion (ie, visible after endovascular therapy) and the recruited lesion (the additional lesion visible on day 5, but not visible after endovascular therapy). Statistical significance was assessed by using Wilcoxon signed-rank, Mann-Whitney U, and Fisher exact tests. Results All 35 patients had FLAIR lesion growth between the after-revascularization examination and day 5. Median lesion growth was significantly larger in patients with <90% reperfusion (27.85 mL) compared with ?90% (8.12 mL; P = .003). In the initial lesion, normalized signal did not change between after endovascular therapy (median, 1.60) and day 5 (median, 1.58) in the ?90% reperfusion group (P = .97), but increased in the <90% reperfusion group (from 1.60 to 1.73; P = .01). In the recruited lesion, median normalized signal increased significantly in both groups between after endovascular therapy and day 5 (after endovascular therapy, from 1.19 to 1.56, P < .001; and day 5, from 1.18 to 1.63, P < .001). Conclusion Patients with ?90% reperfusion after endovascular therapy have significantly less lesion growth on FLAIR images between after therapy and day 5 compared with patients who have <90% reperfusion. Therefore, the effect of reperfusion therapies on lesion volumes are likely more apparent at day 5 than after therapy. (�) RSNA, 2016.

View details for DOI 10.1148/radiol.2015151586

View details for Web of Science ID 000378721900020

View details for PubMedID 26761721
Non-Relative Value Unit-Generating Activities Represent One-Fifth of Academic Neuroradiologist Productivity. AJNR. American journal of neuroradiology Wintermark, M., Zeineh, M., Zaharchuk, G., Srivastava, A., Fischbein, N. 2016; 37 (7): 1206-1208
Abstract

A neuroradiologist's activity includes many tasks beyond interpreting relative value unit-generating imaging studies. Our aim was to test a simple method to record and quantify the non-relative value unit-generating clinical activity represented by consults and clinical conferences, including tumor boards.Four full-time neuroradiologists, working an average of 50% clinical and 50% academic activity, systematically recorded all the non-relative value unit-generating consults and conferences in which they were involved during 3 months by using a simple, Web-based, computer-based application accessible from smartphones, tablets, or computers. The number and type of imaging studies they interpreted during the same period and the associated relative value units were extracted from our billing system.During 3 months, the 4 neuroradiologists working an average of 50% clinical activity interpreted 4241 relative value unit-generating imaging studies, representing 8152 work relative value units. During the same period, they recorded 792 non-relative value unit-generating study reviews as part of consults and conferences (not including reading room consults), representing 19% of the interpreted relative value unit-generating imaging studies.We propose a simple Web-based smartphone app to record and quantify non-relative value unit-generating activities including consults, clinical conferences, and tumor boards. The quantification of non-relative value unit-generating activities is paramount in this time of a paradigm shift from volume to value. It also represents an important tool for determining staffing levels, which cannot be performed on the basis of relative value unit only, considering the importance of time spent by radiologists on non-relative value unit-generating activities. It may also influence payment models from medical centers to radiology departments or practices.

View details for DOI 10.3174/ajnr.A4701

View details for PubMedID 26939630
Amplified magnetic resonance imaging (aMRI). Magnetic resonance in medicine Holdsworth, S. J., Rahimi, M. S., Ni, W. W., Zaharchuk, G., Moseley, M. E. 2016; 75 (6): 2245-2254
Abstract

This work describes a new method called amplified MRI (aMRI), which uses Eulerian video magnification to amplify the subtle spatial variations in cardiac-gated brain MRI scans and enables better visualization of brain motion.The aMRI method takes retrospective cardiac-gated cine MRI data as input, applies a spatial decomposition, followed by temporal filtering and frequency-selective amplification of the MRI cardiac-gated frames before synthesizing a motion-amplified cine data set.This approach reveals deformations of the brain parenchyma and displacements of arteries due to cardiac pulsatility, especially in the brainstem, cerebellum, and spinal cord.aMRI has the potential for widespread neuro- and non-neuro clinical use because it can amplify and characterize small, often barely perceptible motion and can visualize the biomechanical response of tissues using the heartbeat as an endogenous mechanical driver. Magn Reson Med 75:2245-2254, 2016. � 2016 Wiley Periodicals, Inc.

View details for DOI 10.1002/mrm.26142

View details for PubMedID 26888418
Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease. Journal of cerebral blood flow and metabolism Ni, W. W., Christen, T., Rosenberg, J., Zun, Z., Moseley, M. E., Zaharchuk, G. 2016
Abstract

This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49?�?12 vs. 48?�?11?mL/100?g/min, p?=?0.44). However, baseline R2' differed between these regions (3.2?�?0.7 vs. 2.9?�?0.6?s(-1), p?
View details for PubMedID 27207169
Comparison of cerebral blood flow measurement with [O-15]-water positron emission tomography and arterial spin labeling magnetic resonance imaging: A systematic review JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Fan, A. P., Jahanian, H., Holdsworth, S. J., Zaharchuk, G. 2016; 36 (5): 842-861
Abstract

Noninvasive imaging of cerebral blood flow provides critical information to understand normal brain physiology as well as to identify and manage patients with neurological disorders. To date, the reference standard for cerebral blood flow measurements is considered to be positron emission tomography using injection of the [(15)O]-water radiotracer. Although [(15)O]-water has been used to study brain perfusion under normal and pathological conditions, it is not widely used in clinical settings due to the need for an on-site cyclotron, the invasive nature of arterial blood sampling, and experimental complexity. As an alternative, arterial spin labeling is a promising magnetic resonance imaging technique that magnetically labels arterial blood as it flows into the brain to map cerebral blood flow. As arterial spin labeling becomes more widely adopted in research and clinical settings, efforts have sought to standardize the method and validate its cerebral blood flow values against positron emission tomography-based cerebral blood flow measurements. The purpose of this work is to critically review studies that performed both [(15)O]-water positron emission tomography and arterial spin labeling to measure brain perfusion, with the aim of better understanding the accuracy and reproducibility of arterial spin labeling relative to the positron emission tomography reference standard.

View details for DOI 10.1177/0271678X16636393

View details for Web of Science ID 000375261800002

View details for PubMedID 26945019

View details for PubMedCentralID PMC4853843
Image-based arterial input function estimation for cerebral blood flow measurement on a PET/MR scanner Khalighi, M., Fan, A., Delso, G., Singh, P., Park, J., Hoehne, A., Shen, B., Chin, F., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2016
View details for Web of Science ID 000442211002285
Optimization of 15O-H2O dose for cerebral blood flow imaging on a time-of-flight PET/MR scanner Deller, T., Khalighi, M., Fan, A., Singh, P., Park, J., Hoehne, A., Shen, B., Chin, F., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2016
View details for Web of Science ID 000442211003016
Cerebral Blood Flow Imaging with 15O-H2O PET/MR-Review and Workflow Optimization Gandhi, H., Holley, D., Fan, A., Gulaka, P., Mittra, E., Shen, B., Singh, P., Park, J., Chin, F., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2016
View details for Web of Science ID 000442211003172
Clinical Research Review of Scheduled vs. Completed PET/MRI Scans Holley, D., Gandhi, H., Zaharchuk, G., Gulaka, P., Gold, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2016
View details for Web of Science ID 000442211003264
Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398
Abstract

The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

View details for DOI 10.1161/STROKEAHA.115.012364

View details for PubMedID 27073243
Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults NEUROLOGY Tamura, M. K., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216
Abstract

To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ?50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ?30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ?60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ?30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

View details for DOI 10.1212/WNL.0000000000002527

View details for Web of Science ID 000372853000007

View details for PubMedCentralID PMC4818564
Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults. Neurology Kurella Tamura, M., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216
Abstract

To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ?50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ?30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ?60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ?30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

View details for DOI 10.1212/WNL.0000000000002527

View details for PubMedID 26920359
Acute Preoperative Infarcts and Poor Cerebrovascular Reserve Are Independent Risk Factors for Severe Ischemic Complications following Direct Extracranial-Intracranial Bypass for Moyamoya Disease AMERICAN JOURNAL OF NEURORADIOLOGY Antonucci, M. U., Burns, T. C., Pulling, T. M., Rosenberg, J., Marks, M. P., Steinberg, G. K., Zaharchuk, G. 2016; 37 (2): 228-235
Abstract

Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to MCA bypass in patients with Moyamoya disease. This study was undertaken to determine whether preoperative MR imaging and/or cerebrovascular reserve assessment by using reference standard stable xenon-enhanced CT could predict such complications.Among all adult patients undergoing direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xenon-enhanced CT examination, we identified index cases (patients with >15-mL postoperative infarcts) and control cases (patients without postoperative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated by using the Mann-Whitney U test. Univariate and multivariate generalized linear model regression was used to test predictors of postoperative infarct.Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95 � 55 mL. Four of 6 index cases (67%), but no control patients, had preoperative acute infarcts. Baseline CBF was similar, but cerebrovascular reserve was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median cerebrovascular reserve was -0.4% (range, -38.0%-16.6%) in index versus 26.3% (range, -8.2%-60.5%) in control patients (P = .003). Multivariate analysis demonstrated that the presence of a small preoperative infarct (regardless of location) and impaired cerebrovascular reserve were independent, significant predictors of severe postoperative ischemic injury.Acute infarcts and impaired cerebrovascular reserve on preoperative imaging are independent risk factors for severe ischemic complications following superficial temporal artery to MCA bypass in Moyamoya disease.

View details for DOI 10.3174/ajnr.A4535

View details for Web of Science ID 000369111200013

View details for PubMedCentralID PMC4752884
The Malignant CTP Imaging Profile Predicts Worse Functional Outcomes Mlynash, M., Christensen, S., Kemp, S. M., Mishra, N., Federau, C., Tsai, J. P., Kim, S., Frankel, M., Dehkharghani, S., Devlin, T. G., Yavagal, D. R., Akhtar, N., Jovin, T., Nogueira, R., Bammer, R., Straka, M., Zaharchuk, G., Albers, G. W., Marks, M. P., Lansberg, M. G., CRISP Investigators LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956100155
Arterial Occlusive Lesion Location Does Not Impact Functional Outcome in Patients with Endovascular Reperfusion Kim, S., Christensen, S., Mlynash, M., Tsai, J. P., Federau, C., Kemp, S. M., Mishra, N., Frankel, M., Dehkharghani, S., Devlin, T. G., Yavagal, D. R., Akhtar, N., Tudor, J., Nogueira, R., Bammer, R., Straka, M., Zaharchuk, G., Albers, G. W., Marks, M., Lansberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956102122
Severe CT Perfusion Bolus Delays Predict Infarct Growth Despite Reperfusion Christensen, S., Tsai, J., Kemp, S., Mishra, N., Kim, S., Mlynash, M., Federau, C., Bammer, R., Frankel, M., Dehkharghani, S., Devlin, T., Yavagal, D., Straka, M., Zaharchuk, G., Akhtar, N., Haussen, D., Marks, M., Jovin, T., Nogueira, R., Albers, G., Lansberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956102139
Evolution of FLAIR Volume and Signal Intensity Following Endovascular Stroke Therapy Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Wintermark, M., Lansberg, M., Albers, G., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956103281
Patient Selection is a Better Predictor of Good Outcome Than Time to Reperfusion in Acute Ischemic Stroke. Tsai, J. P., Mlynash, M., Christensen, S., Kemp, S., Mishra, N., Federau, C., Kim, S., Frankel, M., Dehkharghani, S., Devlin, T. G., Yavagal, D. R., Akhtar, N., Jovin, T., Nogueira, R. G., Bammer, R., Straka, M., Zaharchuk, G., Gregory, W., Marks, M. P., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956100005
Main Results of the CTP to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Lansberg, M. G., Christensen, S., Kemp, S., Mlynash, M., Mishra, N., Federau, C., Tsai, J. P., Kim, S., Haussen, D. C., Dehkharghani, S., Devlin, T. G., Yavagal, D. R., Akhtar, N., Jovin, T., Nogueira, R. G., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956100055
Associations Between CTP Ischemic Core Volume, ASPECTS Scores and Clinical Outcomes After Endovascular Reperfusion Marks, M. P., Christensen, S., Tsai, J. P., Mlynash, M., Kemp, S., Mishra, N., Federau, C., Kim, S., Haussen, D. C., Dehkharghani, S., Devlin, T. G., Yavagal, D. R., Akhtar, N., Jovin, T., Nogueira, R. G., Bammer, R., Straka, M., Zaharchuk, G., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000399956103167
Evaluation of diagnostic accuracy in CT perfusion analysis in moyamoya disease JAPANESE JOURNAL OF RADIOLOGY Ohno, T., Kudo, K., Zaharchuk, G., Fujima, N., Shirato, H. 2016; 34 (1): 28-34
Abstract

The purpose of the present study was to determine optimal threshold of vascular pixel elimination (VPE) for CT perfusion (CTP) and to assess diagnostic accuracy of CTP by comparing with xenon enhanced CT (XeCT) in moyamoya disease.Twenty-three patients underwent XeCT and CTP. Cerebral blood flow (CBF) images were generated for XeCT and CTP using nine types of software. Region of interest (ROI) measurement was performed on XeCT-CBF and CTP-CBF. Linear regression analysis was performed between XeCT-CBF and CTP-CBF in all software, without and with VPE. The Pearson correlation coefficient was calculated, and an optimal threshold was determined based on maximum correlation coefficients. Correlation coefficients at various VPE thresholds including data of no-VPE were compared with each other. The maximum correlation coefficient at the optimal threshold was also compared.Optimal thresholds varied among software types (0.8-2.2 and 7-14�ml/100�g in relative and absolute VPE, respectively). There were significant differences between correlation coefficients at a range of VPE thresholds compared to no-VPE in most software types. There were significant differences in maximum correlation coefficient at optimal threshold among various software types.Optimal threshold of VPE for CTP could be determined and diagnostic accuracy of CTP varied among software types in moyamoya disease.

View details for DOI 10.1007/s11604-015-0497-z

View details for Web of Science ID 000368698200005
Evaluation of Zero-TE-based Attenuation Correction Methods on PET Quantification of PET/MRI Head and Neck Lesions Lee, K., Zaharchuk, G., Gulaka, P. K., Levin, C. S., IEEE IEEE. 2016
View details for Web of Science ID 000432419500009
Monitoring Cerebrovascular Reactivity through the Use of Arterial Spin Labeling in Patients with Moyamoya Disease. Radiology Yun, T. J., Paeng, J. C., Sohn, C. H., Kim, J. E., Kang, H. S., Yoon, B. W., Choi, S. H., Kim, J. H., Lee, H. Y., Han, M. H., Zaharchuk, G. n. 2016; 278 (1): 205?13
Abstract

To assess arterial spin labeling in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease.The institutional review board approved this prospective study, and written informed consent was obtained from all patients. A prospective study was conducted in 78 subjects with moyamoya disease (of whom 31 underwent unilateral direct arterial anastomosis). The concordance between the cerebrovascular reactivity index values from arterial spin labeling and single photon emission computed tomography (SPECT) was assessed by using Bland-Altman analysis, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin labeling to depict impaired cerebrovascular reactivity (in which the cerebrovascular reactivity index value is less than 0% on SPECT images).The cerebrovascular reactivity index from arterial spin labeling had a lower value than that from SPECT (mean difference, -4.2%). The area under the receiver operating characteristic curve for arterial spin labeling in the detection of impaired cerebrovascular reactivity was at least 0.85. On the anastomotic side, a significant increase was found between the cerebrovascular reactivity index values on arterial spin labeling images obtained preoperatively and those obtained 6 months after surgery, as well as on SPECT images (mean � standard deviation values of cerebrovascular reactivity index increased by 5.9% � 10.9 and 3.0% � 6.3 for arterial spin labeling and SPECT, respectively).Arterial spin labeling has excellent performance in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease, and it has the potential to serve as a noninvasive imaging tool to monitor cerebrovascular reactivity in patients with moyamoya disease.

View details for PubMedID 26197057
Acute Preoperative Infarcts and Poor Cerebrovascular Reserve Are Independent Risk Factors for Severe Ischemic Complications following Direct Extracranial-Intracranial Bypass for Moyamoya Disease. AJNR. American journal of neuroradiology Antonucci, M. U., Burns, T. C., Pulling, T. M., Rosenberg, J. n., Marks, M. P., Steinberg, G. K., Zaharchuk, G. n. 2016; 37 (2): 228?35
Abstract

Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to MCA bypass in patients with Moyamoya disease. This study was undertaken to determine whether preoperative MR imaging and/or cerebrovascular reserve assessment by using reference standard stable xenon-enhanced CT could predict such complications.Among all adult patients undergoing direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xenon-enhanced CT examination, we identified index cases (patients with >15-mL postoperative infarcts) and control cases (patients without postoperative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated by using the Mann-Whitney U test. Univariate and multivariate generalized linear model regression was used to test predictors of postoperative infarct.Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95 � 55 mL. Four of 6 index cases (67%), but no control patients, had preoperative acute infarcts. Baseline CBF was similar, but cerebrovascular reserve was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median cerebrovascular reserve was -0.4% (range, -38.0%-16.6%) in index versus 26.3% (range, -8.2%-60.5%) in control patients (P = .003). Multivariate analysis demonstrated that the presence of a small preoperative infarct (regardless of location) and impaired cerebrovascular reserve were independent, significant predictors of severe postoperative ischemic injury.Acute infarcts and impaired cerebrovascular reserve on preoperative imaging are independent risk factors for severe ischemic complications following superficial temporal artery to MCA bypass in Moyamoya disease.

View details for PubMedID 26564435
Monitoring Cerebrovascular Reactivity through the Use of Arterial Spin Labeling in Patients with Moyamoya Disease RADIOLOGY Yun, T. J., Paeng, J. C., Sohn, C., Kim, J. E., Kang, H., Yoon, B., Choi, S. H., Kim, J., Lee, H., Han, M. H., Zaharchuk, G. 2016; 278 (1): 205-213
Abstract

To assess arterial spin labeling in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease.The institutional review board approved this prospective study, and written informed consent was obtained from all patients. A prospective study was conducted in 78 subjects with moyamoya disease (of whom 31 underwent unilateral direct arterial anastomosis). The concordance between the cerebrovascular reactivity index values from arterial spin labeling and single photon emission computed tomography (SPECT) was assessed by using Bland-Altman analysis, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin labeling to depict impaired cerebrovascular reactivity (in which the cerebrovascular reactivity index value is less than 0% on SPECT images).The cerebrovascular reactivity index from arterial spin labeling had a lower value than that from SPECT (mean difference, -4.2%). The area under the receiver operating characteristic curve for arterial spin labeling in the detection of impaired cerebrovascular reactivity was at least 0.85. On the anastomotic side, a significant increase was found between the cerebrovascular reactivity index values on arterial spin labeling images obtained preoperatively and those obtained 6 months after surgery, as well as on SPECT images (mean � standard deviation values of cerebrovascular reactivity index increased by 5.9% � 10.9 and 3.0% � 6.3 for arterial spin labeling and SPECT, respectively).Arterial spin labeling has excellent performance in the identification of impaired cerebrovascular reactivity in patients with moyamoya disease, and it has the potential to serve as a noninvasive imaging tool to monitor cerebrovascular reactivity in patients with moyamoya disease.

View details for DOI 10.1148/radiol.2015141865

View details for Web of Science ID 000372519500022
3D Pseudocontinuous arterial spin labeling in routine clinical practice: A review of clinically significant artifacts. Journal of magnetic resonance imaging Amukotuwa, S. A., Yu, C., Zaharchuk, G. 2016; 43 (1): 11-27
Abstract

Arterial spin labeling (ASL) is a completely noninvasive magnetic resonance imaging (MRI) perfusion method for quantitatively measuring cerebral blood flow utilizing magnetically labeled arterial water. Advances in the technique have enabled the major MRI vendors to make the sequence available to the clinical neuroimaging community. Consequently, ASL is being increasingly incorporated into the routine neuroimaging protocol. Although a variety of ASL techniques are available, the ISMRM Perfusion Study Group and the European ASL in Dementia Consortium have released consensus guidelines recommending standardized implementation of 3D pseudocontinuous ASL with background suppression. The purpose of this review, aimed at the large number of neuroimaging clinicians who have either no or limited experience with this 3D pseudocontinuous ASL, is to discuss the common and clinically significant artifacts that may be encountered with this technique. While some of these artifacts hinder accurate interpretation of studies, either by degrading the images or mimicking pathology, there are other artifacts that are of clinical utility, because they increase the conspicuity of pathology. Cognizance of these artifacts will help the physician interpreting ASL to avoid potential diagnostic pitfalls, and increase their level of comfort with the technique.

View details for DOI 10.1002/jmri.24873

View details for PubMedID 25857715
Evaluation of diagnostic accuracy in CT perfusion analysis in moyamoya disease. Japanese journal of radiology Ohno, T. n., Kudo, K. n., Zaharchuk, G. n., Fujima, N. n., Shirato, H. n. 2016; 34 (1): 28?34
Abstract

The purpose of the present study was to determine optimal threshold of vascular pixel elimination (VPE) for CT perfusion (CTP) and to assess diagnostic accuracy of CTP by comparing with xenon enhanced CT (XeCT) in moyamoya disease.Twenty-three patients underwent XeCT and CTP. Cerebral blood flow (CBF) images were generated for XeCT and CTP using nine types of software. Region of interest (ROI) measurement was performed on XeCT-CBF and CTP-CBF. Linear regression analysis was performed between XeCT-CBF and CTP-CBF in all software, without and with VPE. The Pearson correlation coefficient was calculated, and an optimal threshold was determined based on maximum correlation coefficients. Correlation coefficients at various VPE thresholds including data of no-VPE were compared with each other. The maximum correlation coefficient at the optimal threshold was also compared.Optimal thresholds varied among software types (0.8-2.2 and 7-14�ml/100�g in relative and absolute VPE, respectively). There were significant differences between correlation coefficients at a range of VPE thresholds compared to no-VPE in most software types. There were significant differences in maximum correlation coefficient at optimal threshold among various software types.Optimal threshold of VPE for CTP could be determined and diagnostic accuracy of CTP varied among software types in moyamoya disease.

View details for PubMedID 26553201
Correlation between arterial spin labeling MRI and dynamic FDG on PET-MR in Alzheimer's disease and non-Alzhiemer's disease patients. EJNMMI physics Douglas, D., Goubran, M., Wilson, E., Xu, G., Tripathi, P., Holley, D., Chao, S., Wintermark, M., Quon, A., Zeineh, M., Vasanawala, M., Zaharchuk, G. 2015; 2: A83-?
View details for DOI 10.1186/2197-7364-2-S1-A83

View details for PubMedID 26956345
Assessment of PET & ASL metabolism in the hippocampal subfields of MCI and AD using simultaneous PET-MR. EJNMMI physics Goubran, M., Douglas, D., Chao, S., Quon, A., Tripathi, P., Holley, D., Vasanawala, M., Zaharchuk, G., Zeineh, M. 2015; 2: A73-?
View details for DOI 10.1186/2197-7364-2-S1-A73

View details for PubMedID 26956334
Dynamic brain PET/MR using TOF reconstruction. EJNMMI physics Khalighi, M. M., Delso, G., Tohme, M., Iagaru, A., Zaharchuk, G. 2015; 2: A60-?
View details for DOI 10.1186/2197-7364-2-S1-A60

View details for PubMedID 26956320
Whole-body simultaneous time-of-flight PET-MRI: early experience with clinical studies. EJNMMI physics Minamimoto, R., Iagaru, A., Jamali, M., Barkodhodari, A., Holley, D., Vasanawala, S., Zaharchuk, G. 2015; 2: A64-?
View details for DOI 10.1186/2197-7364-2-S1-A64

View details for PubMedID 26956324

View details for PubMedCentralID PMC4798693
The potential of TOF PET-MRI for reducing artifacts in PET images. EJNMMI physics Iagaru, A., Minamimoto, R., Levin, C., Barkhodari, A., Jamali, M., Holley, D., Greg, Z. 2015; 2: A77-?
View details for DOI 10.1186/2197-7364-2-S1-A77

View details for PubMedID 26956338

View details for PubMedCentralID PMC4798707
Glioblastoma Multiforme Recurrence: An Exploratory Study of F-18 FPPRGD(2) PET/CT1 RADIOLOGY Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2015; 277 (2): 497-506
Abstract

Purpose To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). Materials and Methods The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUVmax) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUVmax. Results A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. Conclusion (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings. (�) RSNA, 2015 Online supplemental material is available for this article.

View details for DOI 10.1148/radiol.2015141550

View details for Web of Science ID 000368435100026
Yield of CT perfusion for the evaluation of transient ischaemic attack. International journal of stroke Kleinman, J. T., Mlynash, M., Zaharchuk, G., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Singh, P., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2015; 10: 25-29
Abstract

BACKGROUND: Magnetic resonance diffusion-weighted imaging and perfusion-weighted imaging are able to identify ischaemic 'footprints' in transient ischaemic attack. Computed tomography perfusion (CTP) may be useful for patient triage and subsequent management. To date, less than 100 cases have been reported, and none have compared computed tomography perfusion to perfusion-weighted imaging (PWI). We sought to define the yield of computed tomography perfusion for the evaluation of transient ischaemic attack. METHODS: Consecutive patients with a discharge diagnosis of possible or definite transient ischaemic event who underwent computed tomography perfusion were included in this study. The presence of an ischaemic lesion was assessed on noncontrast computed tomography, automatically deconvolved CTP(TMax) (Time till the residue function reaches its maximum), and when available on diffusion-weighted imaging and PWI(TMax) maps. RESULTS: Thirty-four patients were included and 17 underwent magnetic resonance imaging. Median delay between onset and computed tomography perfusion was 4�4?h (Interquartile range [IQR]: 1�9-9�6), and between computed tomography perfusion and magnetic resonance imaging was 11?h (Interquartile range: 3�8-22). Noncontrast computed tomography was negative in all cases, while CTP(TMax) identified an ischaemic lesion in 12/34 patients (35%). In the subgroup of patients with multimodal magnetic resonance imaging, an ischaemic lesion was found in six (35%) patients using CTP(TMax) versus nine (53%) on magnetic resonance imaging (five diffusion-weighted imaging, nine perfusion-weighted imaging). The additional yield of CTP(TMax) over computed tomography angiography was significant in the evaluation of transient ischaemic attack (12 vs. 3, McNemar, P?=?0�004). CONCLUSIONS: CTP(TMax) found an ischaemic lesion in one-third of acute transient ischaemic attack patients. Computed tomography perfusion may be an acceptable substitute when magnetic resonance imaging is unavailable or contraindicated, and has additional yield over computed tomography angiography. Further studies evaluating the outcome of patients with computed tomography perfusion lesions in transient ischaemic attack are justified at this time.

View details for DOI 10.1111/j.1747-4949.2012.00941.x

View details for PubMedID 23228203
Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology Lansberg, M. G., Cereda, C. W., Mlynash, M., Mishra, N. K., Inoue, M., Kemp, S., Christensen, S., Straka, M., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2015; 85 (8): 708-714
Abstract

To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI.Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ?2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes.Among 78 patients with the target mismatch profile (mean age 66 � 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time � reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2).The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.

View details for DOI 10.1212/WNL.0000000000001853

View details for PubMedID 26224727
Glioblastoma Multiforme: Exploratory Radiogenomic Analysis by Using Quantitative Image Features. Radiology Gevaert, O., Mitchell, L. A., Achrol, A. S., Xu, J., Echegaray, S., Steinberg, G. K., Cheshier, S. H., Napel, S., Zaharchuk, G., Plevritis, S. K. 2015; 276 (1): 313-?
View details for DOI 10.1148/radiol.2015154019

View details for PubMedID 26101929
The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion INTERNATIONAL JOURNAL OF STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirnini, A., Liggins, J., Bammer, R., Lansberg, M. G., Kemp, S., Zaharchuk, G., Straka, M., Albers, G. W. 2015; 10 (5): 723-729
Abstract

The degree of variability in the rate of early diffusion-weighted imaging expansion in acute stroke has not been well characterized.We hypothesized that patients with slowly expanding diffusion-weighted imaging lesions would have more penumbral salvage and better clinical outcomes following endovascular reperfusion than patients with rapidly expanding diffusion-weighted imaging lesions.In the first part of this substudy of DEFUSE 2, growth curves were constructed for patients with >90% reperfusion and <10% reperfusion. Next, the initial growth rate was determined in all patients with a clearly established time of symptom onset, assuming a lesion volume of 0?ml just prior to symptom onset. Patients who achieved reperfusion (>50% reduction in perfusion-weighted imaging after endovascular therapy) were categorized into tertiles according to their initial diffusion-weighted imaging growth rates. For each tertile, penumbral salvage [comparison of final volume to the volume of perfusion-weighted imaging (Tmax?>?6?s)/diffusion-weighted imaging mismatch prior to endovascular therapy], favorable clinical response (National Institutes of Health Stroke Scale improvement of ?8 points or 0-1 at 30 days), and good functional outcome (90-day modified Rankin score of ?2) were calculated. A multivariate model assessed whether infarct growth rates were an independent predictor of clinical outcomes.Sixty-five patients were eligible for this study; the median initial growth rate was 3�1?ml/h (interquartile range 0�7-10�7). Target mismatch patients (n?=?42) had initial growth rates that were significantly slower than the growth rates in malignant profile (n?=?9 patients, P?
View details for DOI 10.1111/ijs.12436

View details for Web of Science ID 000356718000025

View details for PubMedID 25580662

View details for PubMedCentralID PMC4478123
Arterial Spin Labeling MRI: Clinical Applications in the Brain JOURNAL OF MAGNETIC RESONANCE IMAGING Telischak, N. A., Detre, J. A., Zaharchuk, G. 2015; 41 (5): 1165-1180
Abstract

Visualization of cerebral blood flow (CBF) has become an important part of neuroimaging for a wide range of diseases. Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) sequences are increasingly being used to provide MR-based CBF quantification without the need for contrast administration, and can be obtained in conjunction with a structural MRI study. ASL MRI is useful for evaluating cerebrovascular disease including arterio-occlusive disease, vascular shunts, for assessing primary and secondary malignancy, and as a biomarker for neuronal metabolism in other disorders such as seizures and neurodegeneration. In this review we briefly outline the various ASL techniques including advantages and disadvantages of each, methodology for clinical interpretation, and clinical applications with specific examples.

View details for DOI 10.1002/jmri.24751

View details for Web of Science ID 000353641600003

View details for PubMedID 25236477
Improved multislice perfusion imaging with velocity-selective arterial spin labeling. Journal of magnetic resonance imaging Zun, Z., Hargreaves, B. A., Rosenberg, J., Zaharchuk, G. 2015; 41 (5): 1422-1431
Abstract

To improve the multislice performance of velocity-selective arterial spin labeling (VS-ASL) imaging for cerebral blood flow (CBF) measurement such that it might be routinely applied for clinical applications with whole brain coverage.VS-ASL was performed with improvements such as timing optimization, stimulated echo removal, and slice profile sharpening. Each improvement was evaluated in volunteers by measuring temporal noise in the CBF measurement. VS-ASL with all these improvements was performed in 20 patients with Moyamoya disease some of whom also underwent xenon-enhanced CT (xeCT) imaging which was the reference standard for CBF measurement.Sequence timing optimization and inter-slice crosstalk reduction using stimulated echo removal and slice profile sharpening all contributed to reduction of temporal noise. VS-ASL imaging with all these improvements performed in Moyamoya disease patients showed significant reduction of temporal noise (P?
View details for DOI 10.1002/jmri.24652

View details for PubMedID 24797337
TIA triage in emergency department using acute MRI (TIA-TEAM): A feasibility and safety study. International journal of stroke Vora, N., Tung, C. E., Mlynash, M., Garcia, M., Kemp, S., Kleinman, J., Zaharchuk, G., Albers, G., Olivot, J. 2015; 10 (3): 343-347
Abstract

Positive diffusion weighted imaging (DWI) on MRI is associated with increased recurrent stroke risk in TIA patients. Acute MRI aids in TIA risk stratification and diagnosis.To evaluate the feasibility and safety of TIA triage directly from the emergency department (ED) with acute MRI and neurological consultation.Consecutive ED TIA patients assessed by a neurologist underwent acute MRI/MRA of head/neck per protocol and were hospitalized if positive DWI, symptomatic vessel stenosis, or per clinical judgment. Stroke neurologist adjudicated the final TIA diagnosis as definite, possible, or not a cerebrovascular event. Stroke recurrence rates were calculated at 7, 90, 365 days and compared with predicted stroke rates derived from historical DWI and ABCD(2) score data.One hundred twenty-nine enrolled patients had a mean age of 69 years (�17) and median ABCD(2) score of 3 (interquartile range [IQR] 3-4). During triage, 112 (87%) patients underwent acute MRI after a median of 16?h (IQR 10-23) from symptom onset. No patients experienced a recurrent event before imaging. Twenty-four (21%) had positive DWI and 8 (7%) had symptomatic vessel stenosis. Of the total cohort, 83 (64%) were discharged and 46 (36%) were hospitalized. By one-year follow-up, one patient in each group had experienced a stroke. Of 92 patients with MRI and index cerebrovascular event, recurrent stroke rates were 1�1% at 7 and 90 days. These were similar to predicted recurrence rates.TIA triage in the ED using a protocol with neurological consultation and acute MRI is feasible and safe. The majority of patients were discharged without hospitalization and rates of recurrent stroke were not higher than predicted.

View details for DOI 10.1111/ijs.12390

View details for PubMedID 25367837
Cerebral Blood Flow Changes in Glioblastoma Patients Undergoing Bevacizumab Treatment Are Seen in Both Tumor and Normal Brain. The neuroradiology journal Andre, J. B., Nagpal, S., Hippe, D. S., Ravanpay, A. C., Schmiedeskamp, H., Bammer, R., Palagallo, G. J., Recht, L., Zaharchuk, G. 2015; 28 (2): 112-119
Abstract

Bevacizumab (BEV) is increasingly used to treat recurrent glioblastoma (GBM) with some reported improvement in neurocognitive function despite potential neurotoxicities. We examined the effects of BEV on cerebral blood flow (CBF) within recurrent GBM tumor and in the contralateral middle cerebral artery (MCA) territory.Post-chemoradiation patients with histologically confirmed GBM were treated with BEV and underwent routine, serial tumor imaging with additional pseudocontinuous arterial spin labeling (pcASL) following informed consent. Circular regions-of-interest were placed on pcASL images directly over the recurrent tumor and in the contralateral MCA territory. CBF changes before and during BEV treatment were evaluated in tumor and normal tissue. Linear mixed models were used to assess statistical significance.Fifty-three pcASL studies in 18 patients were acquired. Evaluation yielded lower mean tumoral CBF during BEV treatment compared with pre-treatment (45 � 27 vs. 65 � 27?ml/100?g/min, p?=?0.002), and in the contralateral MCA territory during, compared with pre-BEV treatment (35 � 8.4 vs. 41 � 8.4 ml/100 g/min, p = 0.03). The decrease in mean CBF tended to be greater in the tumoral region than in the contralateral MCA, though the difference did not reach statistical significance (31% vs. 13%; p = 0.082).BEV administration results in statistically significant global CBF decrease with a potentially preferential decrease in tumor perfusion compared with normal brain tissue.

View details for DOI 10.1177/1971400915576641

View details for PubMedID 25923677
Association of developmental venous anomalies with perfusion abnormalities on arterial spin labeling and bolus perfusion-weighted imaging. Journal of neuroimaging Iv, M., Fischbein, N. J., Zaharchuk, G. 2015; 25 (2): 243-250
Abstract

To investigate the frequency and characteristics of developmental venous anomaly (DVA)-associated perfusion abnormalities on arterial spin labeling (ASL) and bolus perfusion-weighted imaging (PWI) and discuss their potential causes.We reviewed brain MR reports to identify all DVAs reported on studies performed between 2009 and 2012. DVA location and findings on PWI and/or ASL imaging were assessed by visual inspection. Sizes of DVAs were categorized as small (<15 mm), medium (15-25 mm), and large (>25 mm). For ASL, signal in the DVA, surrounding parenchyma, or associated draining vein was recorded. For PWI, changes on hemodynamic maps (cerebral blood volume [CBV], cerebral blood flow [CBF], mean transit time [MTT], and normalized time-to-peak of the residue function [Tmax]) were evaluated. Coexisting vascular malformations in association with DVAs were also identified.Six hundred and fifty-two DVAs were identified in 632 subjects. Of these, 121 underwent both perfusion modalities, 15 only PWI, and 127 only ASL. ASL abnormalities were seen in 21/248 (8%), including signal in a draining vein (2/21, 10%), in the DVA (11/21, 52%), and in the parenchyma (8/21, 38%). On PWI, the majority of DVAs demonstrated abnormalities (108/136, 79%), typically increased CBF, CBV, MTT, and Tmax. There was no association between DVA size and presence of ASL signal (P = .836). Borderline statistical significance was found between DVA size and presence of PWI abnormality (P = .046). No relationship was found between the presence of a coexisting vascular malformation and presence of ASL (P = .468) or PWI abnormality (P = .745).Perfusion changes with DVAs are common on PWI but uncommon on ASL. PWI findings are expected based on the anatomy and physiology of DVAs and are accentuated by gradient echo acquisition. DVAs with intrinsic ASL signal or signal in draining veins may be associated with arteriovenous shunting (transitional lesions).

View details for DOI 10.1111/jon.12119

View details for PubMedID 24717021
Comparison of R2' measurement methods in the normal brain at 3 tesla. Magnetic resonance in medicine Ni, W., Christen, T., Zun, Z., Zaharchuk, G. 2015; 73 (3): 1228-1236
Abstract

R2', the reversible component of transverse relaxation, is an important susceptibility measurement for studies of brain physiology and pathologies. In existing literature, different R2' measurement methods are used with assumption of equivalency. This study explores the choice of measurement method in healthy, young subjects at 3T.In this study, a modified gradient-echo sampling of free induction decay and echo (GESFIDE) sequence was used to compare four standard R2' measurement methods: asymmetric spin echo (ASE), standard GESFIDE, gradient echo sampling of the spin echo (GESSE), and separate R2 and R2* mapping.GESSE returned lower R2' measurements than other methods (P < 0.05). Intersubject mean R2' in gray matter was found to be 2.7 s(-1) using standard GESFIDE and GESSE, versus 3.4-3.8 s(-1) using other methods. In white matter, mean R2' from GESSE was 2.3 s(-1) while other methods produced 3.7-4.3 s(-1) . R2 correction was applied to partially reduce the discrepancies between the methods, but significant differences remained, likely due to violation of the fundamental assumption of a single-compartmental tissue model, and hence monoexponential decay.R2' measurements are influenced significantly by the choice of method. Awareness of this issue is important when designing and interpreting studies that involve R2' measurements. Magn Reson Med 73:1228-1236, 2015. � 2014 Wiley Periodicals, Inc.

View details for DOI 10.1002/mrm.25232

View details for PubMedID 24753286

View details for PubMedCentralID PMC4308575
Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: A study in Moyamoya patients. Journal of magnetic resonance imaging Christen, T., Jahanian, H., Ni, W. W., Qiu, D., Moseley, M. E., Zaharchuk, G. 2015; 41 (2): 424-430
Abstract

To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) signal can be used to create maps similar to time-to-maximum of the residue function (Tmax) in Moyamoya patients and to determine whether sfBOLD delays affect the results of brain connectivity mapping.Ten patients were scanned at 3 Tesla using a gradient-echo echo planar imaging sequence for sfBOLD imaging. Cross correlation analysis was performed between each brain voxel signal and a reference signal comprised of either the superior sagittal sinus (SSS) or whole brain (WB) average time course. sfBOLD delay maps were created based on the time shift necessary to maximize the correlation coefficient, and compared with dynamic susceptibility contrast Tmax maps. Standard and time-shifted resting-state BOLD connectivity analyses of the default mode network were compared.Good linear correlations were found between sfBOLD delays and Tmax using the SSS as reference (r(2) ?=?0.8, slope?=?1.4, intercept?=?-4.6) or WB (r(2) ?=?0.7, slope?=?0.8, intercept?=?-3.2). New nodes of connectivity were found in delayed regions when accounting for delays in the analysis.Resting-state sfBOLD imaging can create delay maps similar to Tmax maps without the use of contrast agents in Moyamoya patients. Accounting for these delays may affect the results of functional connectivity maps.J. Magn. Reson. Imaging 2014. � 2014 Wiley Periodicals, Inc.

View details for DOI 10.1002/jmri.24558

View details for PubMedID 24419985
Simultaneous Whole-Body Time-of-Flight F-18-FDG PET/MRI A Pilot Study Comparing SUVmax With PET/CT and Assessment of MR Image Quality CLINICAL NUCLEAR MEDICINE Iagaru, A., Mittra, E., Minamimoto, R., Jamali, M., Levin, C., Quon, A., Gold, G., Herfkens, R., Vasanawala, S., Gambhir, S. S., Zaharchuk, G. 2015; 14 (1): 1-8
Abstract

The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF.We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality.Thirty-six patients (19 men, 17 women, mean [�standard deviation] age of 61 � 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (�standard deviation) of 74 � 14 minutes (range: 49-100 minutes) after injection of 10 � 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 � 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed.The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

View details for Web of Science ID 000346633400023
Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magnetic resonance in medicine Alsop, D. C., Detre, J. A., Golay, X. n., G�nther, M. n., Hendrikse, J. n., Hernandez-Garcia, L. n., Lu, H. n., MacIntosh, B. J., Parkes, L. M., Smits, M. n., van Osch, M. J., Wang, D. J., Wong, E. C., Zaharchuk, G. n. 2015; 73 (1): 102?16
Abstract

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model.

View details for PubMedID 24715426
Glioblastoma Multiforme Recurrence: An Exploratory Study of (18)F FPPRGD2 PET/CT. Radiology Iagaru, A. n., Mosci, C. n., Mittra, E. n., Zaharchuk, G. n., Fischbein, N. n., Harsh, G. n., Li, G. n., Nagpal, S. n., Recht, L. n., Gambhir, S. S. 2015: 141550
Abstract

Purpose To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). Materials and Methods The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUVmax) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUVmax. Results A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. Conclusion (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings. (�) RSNA, 2015 Online supplemental material is available for this article.

View details for PubMedID 25965900
Simultaneous whole-body time-of-flight 18F-FDG PET/MRI: a pilot study comparing SUVmax with PET/CT and assessment of MR image quality. Clinical nuclear medicine Iagaru, A., Mittra, E., Minamimoto, R., Jamali, M., Levin, C., Quon, A., Gold, G., Herfkens, R., Vasanawala, S., Gambhir, S. S., Zaharchuk, G. 2015; 40 (1): 1-8
Abstract

The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF.We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality.Thirty-six patients (19 men, 17 women, mean [�standard deviation] age of 61 � 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (�standard deviation) of 74 � 14 minutes (range: 49-100 minutes) after injection of 10 � 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 � 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed.The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

View details for DOI 10.1097/RLU.0000000000000611

View details for PubMedID 25489952
Recommended Implementation of Arterial Spin-Labeled Perfusion MRI for Clinical Applications: A Consensus of the ISMRM Perfusion Study Group and the European Consortium for ASL in Dementia MAGNETIC RESONANCE IN MEDICINE Alsop, D. C., Detre, J. A., Golay, X., Guenther, M., Hendrikse, J., Hernandez-Garcia, L., Lu, H., MacIntosh, B. J., Parkes, L. M., Smits, M., van Osch, M. J., Wang, D. J., Wong, E. C., Zaharchuk, G. 2015; 73 (1): 102-116
Abstract

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model.

View details for DOI 10.1002/mrm.25197

View details for Web of Science ID 000346908800010

View details for PubMedCentralID PMC4190138
Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome JOURNAL OF NEUROINTERVENTIONAL SURGERY Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728
Abstract

To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth.Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12?h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2.Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3.TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

View details for DOI 10.1136/neurintsurg-2013-010973

View details for Web of Science ID 000344939800007

View details for PubMedCentralID PMC4090292
Assessment and modulation of resting-state neural networks after stroke CURRENT OPINION IN NEUROLOGY Dijkhuizen, R. M., Zaharchuk, G., Otte, W. M. 2014; 27 (6): 637?43
Abstract

Stroke is a major cause of disability; however, most patients experience spontaneous partial recovery of functions in subacute to chronic phases. Poststroke loss and recovery of functions have been increasingly correlated with brain-wide alterations in the connectivity of neural networks, which is described in this review. Elucidation of the mechanisms of functional brain remodeling could reveal targets and strategies for more effective neurorehabilitation.Data from recent resting-state functional MRI, electroencephalography, magnetoencephalography, and optical imaging studies in patients and animal models have demonstrated that loss of function after stroke is closely associated with disrupted connectivity in large-scale networks beyond the lesion territory. Restoration of functional connectivity in the surviving networks appears to be critical for functional recovery, and this may be promoted with specific therapeutic strategies, such as robot-assisted training and noninvasive brain stimulation. The adaptability of functional networks relies on the structural integrity of neuronal pathways, but the relationship between the two remains incompletely understood. Furthermore, disturbed neurovascular coupling after stroke can confound hemodynamically based measurements of functional connectivity.Identification of key network processes in adaptive brain plasticity can aid in the prediction of functional outcome and the development of therapeutic interventions to support and promote recovery after stroke.

View details for PubMedID 25333606
Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome. Journal of neurointerventional surgery Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728
Abstract

To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth.Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12?h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2.Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3.TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

View details for DOI 10.1136/neurintsurg-2013-010973

View details for PubMedID 24353330
Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial INTERNATIONAL JOURNAL OF STROKE Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865
Abstract

DEFUSE 2 demonstrated that patients with magnetic resonance imaging mismatch had a favorable clinical response to tissue reperfusion assessed by magnetic resonance imaging. This study reports the endovascular results and correlates angiographic reperfusion with clinical and imaging outcomes.Prospectively enrolled ischemic stroke patients underwent baseline magnetic resonance imaging and started endovascular therapy within 12?h of onset. Patients were classified as either target mismatch or no target mismatch using magnetic resonance imaging. The pre- and postprocedure angiogram was evaluated to determine thrombolysis in cerebral infarction scores. Favorable clinical response was determined at day 30, and good functional outcome was defined as a modified Rankin Scale 0-2 at day 90.One-hundred patients had attempted endovascular treatment. At procedure end, 23% were thrombolysis in cerebral infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More favorable thrombolysis in cerebral infarction-reperfusion scores were associated with greater magnetic resonance imaging reperfusion (P<0�001). thrombolysis in cerebral infarction scores correlated with 30-day favorable clinical response (P=0�041) and 90-day modified Rankin Scale 0-2 (P=0�008). These correlations were significant for target mismatch patients at 30 days (P=0�034) and 90 days (P=0�003). Infarct growth was strongly associated with poorer thrombolysis in cerebral infarction scores in target mismatch patients (P<0�001). Patients with thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic resonance imaging reperfusion (P=0�004) and poorer clinical outcome at 90 days (P=0�01) compared with thrombolysis in cerebral infarction 2B-3 patients.Thrombolysis in cerebral infarction reperfusion following endovascular therapy for ischemic stroke is highly correlated with magnetic resonance imaging reperfusion, infarct growth, and clinical outcome.

View details for DOI 10.1111/ijs.12271

View details for Web of Science ID 000342581900013

View details for PubMedCentralID PMC4411961
Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. Radiology Gevaert, O., Mitchell, L. A., Achrol, A. S., Xu, J., Echegaray, S., Steinberg, G. K., Cheshier, S. H., Napel, S., Zaharchuk, G., Plevritis, S. K. 2014; 273 (1): 168-174
Abstract

To derive quantitative image features from magnetic resonance (MR) images that characterize the radiographic phenotype of glioblastoma multiforme (GBM) lesions and to create radiogenomic maps associating these features with various molecular data.Clinical, molecular, and MR imaging data for GBMs in 55 patients were obtained from the Cancer Genome Atlas and the Cancer Imaging Archive after local ethics committee and institutional review board approval. Regions of interest (ROIs) corresponding to enhancing necrotic portions of tumor and peritumoral edema were drawn, and quantitative image features were derived from these ROIs. Robust quantitative image features were defined on the basis of an intraclass correlation coefficient of 0.6 for a digital algorithmic modification and a test-retest analysis. The robust features were visualized by using hierarchic clustering and were correlated with survival by using Cox proportional hazards modeling. Next, these robust image features were correlated with manual radiologist annotations from the Visually Accessible Rembrandt Images (VASARI) feature set and GBM molecular subgroups by using nonparametric statistical tests. A bioinformatic algorithm was used to create gene expression modules, defined as a set of coexpressed genes together with a multivariate model of cancer driver genes predictive of the module's expression pattern. Modules were correlated with robust image features by using the Spearman correlation test to create radiogenomic maps and to link robust image features with molecular pathways.Eighteen image features passed the robustness analysis and were further analyzed for the three types of ROIs, for a total of 54 image features. Three enhancement features were significantly correlated with survival, 77 significant correlations were found between robust quantitative features and the VASARI feature set, and seven image features were correlated with molecular subgroups (P < .05 for all). A radiogenomics map was created to link image features with gene expression modules and allowed linkage of 56% (30 of 54) of the image features with biologic processes.Radiogenomic approaches in GBM have the potential to predict clinical and molecular characteristics of tumors noninvasively. Online supplemental material is available for this article.

View details for DOI 10.1148/radiol.14131731

View details for PubMedID 24827998
Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial. International journal of stroke Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865
Abstract

DEFUSE 2 demonstrated that patients with magnetic resonance imaging mismatch had a favorable clinical response to tissue reperfusion assessed by magnetic resonance imaging. This study reports the endovascular results and correlates angiographic reperfusion with clinical and imaging outcomes.Prospectively enrolled ischemic stroke patients underwent baseline magnetic resonance imaging and started endovascular therapy within 12?h of onset. Patients were classified as either target mismatch or no target mismatch using magnetic resonance imaging. The pre- and postprocedure angiogram was evaluated to determine thrombolysis in cerebral infarction scores. Favorable clinical response was determined at day 30, and good functional outcome was defined as a modified Rankin Scale 0-2 at day 90.One-hundred patients had attempted endovascular treatment. At procedure end, 23% were thrombolysis in cerebral infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More favorable thrombolysis in cerebral infarction-reperfusion scores were associated with greater magnetic resonance imaging reperfusion (P<0�001). thrombolysis in cerebral infarction scores correlated with 30-day favorable clinical response (P=0�041) and 90-day modified Rankin Scale 0-2 (P=0�008). These correlations were significant for target mismatch patients at 30 days (P=0�034) and 90 days (P=0�003). Infarct growth was strongly associated with poorer thrombolysis in cerebral infarction scores in target mismatch patients (P<0�001). Patients with thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic resonance imaging reperfusion (P=0�004) and poorer clinical outcome at 90 days (P=0�01) compared with thrombolysis in cerebral infarction 2B-3 patients.Thrombolysis in cerebral infarction reperfusion following endovascular therapy for ischemic stroke is highly correlated with magnetic resonance imaging reperfusion, infarct growth, and clinical outcome.

View details for DOI 10.1111/ijs.12271

View details for PubMedID 24684804
Pseudocontinuous Arterial Spin Labeling with Prospective Motion Correction (PCASL-PROMO) MAGNETIC RESONANCE IN MEDICINE Zun, Z., Shankaranarayanan, A., Zaharchuk, G. 2014; 72 (4): 1049-1056
Abstract

Arterial spin labeling (ASL) perfusion imaging with a segmented three-dimensional (3D) readout is becoming increasing popular, yet conventional motion correction approaches cannot be applied in segmented imaging. The purpose of this study was to demonstrate the integration of 3D pseudocontinuous ASL (PCASL) and PROMO (PROspective MOtion correction) for cerebral blood flow measurements.PROMO was integrated into 3D PCASL without increasing repetition time. PCASL was performed with and without PROMO in the absence of motion. The performance of PCASL-PROMO was then evaluated with controlled motions using separate scans with and without PROMO and also with random motion using an interleaved scan where every repetition time is repeated twice, once with and once without PROMO.The difference in the average ASL signal of the 3D volume between conventional and PROMO implementations was negligible (<0.2%). ASL image artifacts from both controlled and random motions were removed significantly with PROMO, showing improved correlation with reference images. Multiple combinations of data acquired using the interleaved scan revealed that PROMO with real-time motion updating alone reduces motion artifact significantly and that rescanning of corrupted segments is more critical in tagged images than control images.This study demonstrates that PROMO is a successful approach to motion correction for PCASL cerebral blood flow imaging.

View details for DOI 10.1002/mrm.25024

View details for Web of Science ID 000342342300016

View details for PubMedID 24243585

View details for PubMedCentralID PMC4048655
Glioblastoma Multiforme: Exploratory Radiogenomic Analysis by Using Quantitative Image Features RADIOLOGY Gevaert, O., Mitchell, L. A., Achrol, A. S., Xu, J., Echegaray, S., Steinberg, G. K., Cheshier, S. H., Napel, S., Zaharchuk, G., Plevritis, S. K. 2014; 273 (1): 168-174
Abstract

To derive quantitative image features from magnetic resonance (MR) images that characterize the radiographic phenotype of glioblastoma multiforme (GBM) lesions and to create radiogenomic maps associating these features with various molecular data.Clinical, molecular, and MR imaging data for GBMs in 55 patients were obtained from the Cancer Genome Atlas and the Cancer Imaging Archive after local ethics committee and institutional review board approval. Regions of interest (ROIs) corresponding to enhancing necrotic portions of tumor and peritumoral edema were drawn, and quantitative image features were derived from these ROIs. Robust quantitative image features were defined on the basis of an intraclass correlation coefficient of 0.6 for a digital algorithmic modification and a test-retest analysis. The robust features were visualized by using hierarchic clustering and were correlated with survival by using Cox proportional hazards modeling. Next, these robust image features were correlated with manual radiologist annotations from the Visually Accessible Rembrandt Images (VASARI) feature set and GBM molecular subgroups by using nonparametric statistical tests. A bioinformatic algorithm was used to create gene expression modules, defined as a set of coexpressed genes together with a multivariate model of cancer driver genes predictive of the module's expression pattern. Modules were correlated with robust image features by using the Spearman correlation test to create radiogenomic maps and to link robust image features with molecular pathways.Eighteen image features passed the robustness analysis and were further analyzed for the three types of ROIs, for a total of 54 image features. Three enhancement features were significantly correlated with survival, 77 significant correlations were found between robust quantitative features and the VASARI feature set, and seven image features were correlated with molecular subgroups (P < .05 for all). A radiogenomics map was created to link image features with gene expression modules and allowed linkage of 56% (30 of 54) of the image features with biologic processes.Radiogenomic approaches in GBM have the potential to predict clinical and molecular characteristics of tumors noninvasively. Online supplemental material is available for this article.

View details for DOI 10.1148/radiol.14131731

View details for Web of Science ID 000344232100019

View details for PubMedCentralID PMC4263772
Multimodality Evaluation of Dural Arteriovenous Fistula with CT Angiography, MR with Arterial Spin Labeling, and Digital Subtraction Angiography: Case Report JOURNAL OF NEUROIMAGING Alexander, M., McTaggart, R., Santarelli, J., Fischbein, N., Marks, M., Zaharchuk, G., Do, H. 2014; 24 (5): 520-523
Abstract

Dural arteriovenous fistulae (DAVF) are cerebrovascular lesions with pathologic shunting into the venous system from arterial feeders. Digital subtraction angiography (DSA) has long been considered the gold standard for diagnosis, but advances in noninvasive imaging techniques now play a role in the diagnosis of these complex lesions. Herein, we describe the case of a patient with right-side pulsatile tinnitus and DAVF diagnosed using computed tomography angiography, magnetic resonance with arterial spin labeling, and DSA. Implications for imaging analysis of DAVFs and further research are discussed.

View details for DOI 10.1111/jon.12032

View details for Web of Science ID 000341990200015
Multimodality evaluation of dural arteriovenous fistula with CT angiography, MR with arterial spin labeling, and digital subtraction angiography: case report. Journal of neuroimaging Alexander, M., McTaggart, R., Santarelli, J., Fischbein, N., Marks, M., Zaharchuk, G., Do, H. 2014; 24 (5): 520-523
Abstract

Dural arteriovenous fistulae (DAVF) are cerebrovascular lesions with pathologic shunting into the venous system from arterial feeders. Digital subtraction angiography (DSA) has long been considered the gold standard for diagnosis, but advances in noninvasive imaging techniques now play a role in the diagnosis of these complex lesions. Herein, we describe the case of a patient with right-side pulsatile tinnitus and DAVF diagnosed using computed tomography angiography, magnetic resonance with arterial spin labeling, and DSA. Implications for imaging analysis of DAVFs and further research are discussed.

View details for DOI 10.1111/jon.12032

View details for PubMedID 23746119
Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke. AJNR. American journal of neuroradiology Holdsworth, S. J., Yeom, K. W., Antonucci, M. U., Andre, J. B., Rosenberg, J., Aksoy, M., Straka, M., Fischbein, N. J., Bammer, R., Moseley, M. E., Zaharchuk, G., Skare, S. 2014; 35 (7): 1293-1302
Abstract

Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging.Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information.Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts.Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.

View details for DOI 10.3174/ajnr.A3921

View details for PubMedID 24763417
Near-contiguous spin echo imaging using matched-phase RF and its application in velocity-selective arterial spin labeling. Magnetic resonance in medicine Zun, Z., Hargreaves, B. A., Pauly, J., Zaharchuk, G. 2014; 71 (6): 2043-2050
Abstract

The minimum slice spacing in multislice imaging is limited by inter-slice crosstalk due to an imperfect slice profile. This study sought to minimize the slice spacing using matched-phase RF pulses and demonstrate its application in cerebral blood flow imaging using velocity-selective arterial spin labeling.A spin-echo matched-phase 90�-180� RF pair was designed using Shinnar-Le Roux algorithm in order to improve the slice profile of longitudinal magnetization, which plays a more critical role in creating interslice crosstalk than transverse magnetization. Both transverse and longitudinal slice profiles were compared between matched-phase RF and sinc-based RF pulses in simulations and measurements. Velocity-selective arterial spin labeling was performed in normal volunteers using both RF pulses and standard deviation of cerebral blood flow time series was calculated to examine ASL signal stability.Using designed matched-phase RF, the longitudinal slice profile was sharpened without signal-to-noise ratio loss. In velocity-selective arterial spin labeling imaging, the temporal standard deviation of cerebral blood flow measurements was reduced from 48 mL/100 g/min to 32 mL/100 g/min by 33% using matched-phase RF pulses, and as a result, cerebral blood flow image quality improved.This study reports that near-contiguous multislice imaging can be achieved using matched-phase RF pulses without compromising signal-to-noise ratio and signal stability. Magn Reson Med, 2013. � 2013 Wiley Periodicals, Inc.

View details for DOI 10.1002/mrm.24866

View details for PubMedID 23857667
Ultrahigh-resolution imaging of the human brain with phase-cycled balanced steady-state free precession at 7 T. Investigative radiology Zeineh, M. M., Parekh, M. B., Zaharchuk, G., Su, J. H., Rosenberg, J., Fischbein, N. J., Rutt, B. K. 2014; 49 (5): 278-289
Abstract

The objectives of this study were to acquire ultra-high resolution images of the brain using balanced steady-state free precession (bSSFP) at 7.0 T and to identify the potential utility of this sequence.Eight volunteers participated in this study after providing informed consent. Each volunteer was scanned with 8 phase cycles of bSSFP at 0.4-mm isotropic resolution using 0.5 number of excitations and 2-dimensional parallel acceleration of 1.75 � 1.75. Each phase cycle required 5 minutes of scanning, with pauses between the phase cycles allowing short periods of rest. The individual phase cycles were aligned and then averaged. The same volunteers underwent scanning using 3-dimensional (3D) multiecho gradient recalled echo at 0.8-mm isotropic resolution, 3D Cube T2 at 0.7-mm isotropic resolution, and thin-section coronal oblique T2-weighted fast spin echo at 0.22 � 0.22 � 2.0-mm resolution for comparison. Two neuroradiologists assessed image quality and potential research and clinical utility.The volunteers generally tolerated the scan sessions well, and composite high-resolution bSSFP images were produced for each volunteer. Rater analysis demonstrated that bSSFP had a superior 3D visualization of the microarchitecture of the hippocampus, very good contrast to delineate the borders of the subthalamic nucleus, and relatively good B1 homogeneity throughout. In addition to an excellent visualization of the cerebellum, subtle details of the brain and skull base anatomy were also easier to identify on the bSSFP images, including the line of Gennari, membrane of Liliequist, and cranial nerves. Balanced steady-state free precession had a strong iron contrast similar to or better than the comparison sequences. However, cortical gray-white contrast was significantly better with Cube T2 and T2-weighted fast spin echo.Balanced steady-state free precession can facilitate ultrahigh-resolution imaging of the brain. Although total imaging times are long, the individually short phase cycles can be acquired separately, improving examination tolerability. These images may be beneficial for studies of the hippocampus, iron-containing structures such as the subthalamic nucleus and line of Gennari, and the basal cisterns and their contents.

View details for DOI 10.1097/RLI.0000000000000015

View details for PubMedID 24473366
Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort. Stroke; a journal of cerebral circulation Olivot, J. M., Mlynash, M., Inoue, M., Marks, M. P., Wheeler, H. M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1018-1023
Abstract

We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ?2 at 90 days.Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014.HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

View details for DOI 10.1161/STROKEAHA.113.003857

View details for PubMedID 24595591
Arterial Spin-Labeled Perfusion Imaging in Acute Ischemic Stroke STROKE Zaharchuk, G. 2014; 45 (4): 1202-1207
View details for DOI 10.1161/STROKEAHA.113.003612

View details for Web of Science ID 000333303400059

View details for PubMedID 24603069

View details for PubMedCentralID PMC3967005
Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Christensen, S., Wheeler, H. M., Straka, M., Tipirneni, A., Kemp, S. M., Zaharchuk, G., Olivot, J., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1024-1028
Abstract

The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient.MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed.A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion.Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

View details for DOI 10.1161/STROKEAHA.113.002135

View details for PubMedID 24558095
Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke; a journal of cerebral circulation Marks, M. P., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Kemp, S., McTaggart, R., Inoue, M., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 45 (4): 1035-1039
Abstract

Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke.Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ?6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90.Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ?6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06).Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score.http://www.clinicaltrials.gov. Unique identifier: NCT01349946.

View details for DOI 10.1161/STROKEAHA.113.004085

View details for PubMedID 24569816
Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)
View details for DOI 10.1371/journal.pone.0092539

View details for PubMedID 24651703
Spontaneous BOLD signal fluctuations in young healthy subjects and elderly patients with chronic kidney disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)
Abstract

Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity. We compared the coefficient of variation (CV) of the time series (defined as the temporal standard deviation of the time series divided by the mean signal intensity) in two populations: 1) Ten young healthy adults and 2) Ten hypertensive elderly subjects with chronic kidney disease (CKD). We found a statistically significant increase (P<0.01) in the CV values for the CKD patients compared with the young healthy adults in both gray matter (GM) and white matter (WM). The difference was independent of the exact segmentation method, became more significant after correcting for physiological signals using RETROICOR, and mainly arose from very low frequency components of the BOLD signal fluctuation (f<0.025 Hz). Furthermore, there was a strong relationship between WM and GM signal fluctuation CV's (R2?=?0.87) in individuals, with a ratio of about 1?3. These results suggest that amplitude of the spontaneous BOLD signal fluctuations may be used to assess the cerebrovascular reactivity mechanisms and provide valuable information about variations with age and different disease states.

View details for DOI 10.1371/journal.pone.0092539

View details for PubMedID 24651703

View details for PubMedCentralID PMC3961376
Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J. A., Derdeyn, C. P., Hetts, S. W., Johnson, M. H., Kidwell, C. S., Lev, M. H., Liebeskind, D. S., Rowley, H. A., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 10 (11): 828-832
Abstract

In the article entitled "Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution.

View details for DOI 10.1016/j.jacr.2013.06.019

View details for Web of Science ID 000327418100009
CREATING A RADIOGENOMICS MAP OF MULTI-OMICS AND QUANTITATIVE IMAGE FEATURES IN GLIOBLASTOMA MULTIFORME Gevaert, O., Mitchell, L., Achrol, A., Xu, J., Steinberg, G., Cheshier, S., Napel, S., Zaharchuk, G., Plevritis, S. OXFORD UNIV PRESS INC. 2013: 140?41
View details for Web of Science ID 000327456200564
Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J., Derdeyn, C., Hetts, S. W., Johnson, M. H., Kidwell, C., Lev, M. H., Liebeskind, D. S., Rowley, H., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 34 (11): E117-E127
View details for DOI 10.3174/ajnr.A3690

View details for Web of Science ID 000330234700001

View details for PubMedID 23907247
Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery. Journal of the American College of Radiology Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J. A., Derdeyn, C. P., Hetts, S. W., Johnson, M. H., Kidwell, C. S., Lev, M. H., Liebeskind, D. S., Rowley, H. A., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 10 (11): 828-832
Abstract

In the article entitled "Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution.

View details for DOI 10.1016/j.jacr.2013.06.019

View details for PubMedID 23948676
Imaging recommendations for acute stroke and transient ischemic attack patients: A joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery. AJNR. American journal of neuroradiology Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J., Derdeyn, C., Hetts, S. W., Johnson, M. H., Kidwell, C., Lev, M. H., Liebeskind, D. S., Rowley, H., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 34 (11): E117-27
Abstract

Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

View details for DOI 10.3174/ajnr.A3690

View details for PubMedID 23907247
Acute Stroke Imaging Research Roadmap II STROKE Wintermark, M., Albers, G. W., Broderick, J. P., Demchuk, A. M., Fiebach, J. B., Fiehler, J., Grotta, J. C., Houser, G., Jovin, T. G., Lees, K. R., Lev, M. H., Liebeskind, D. S., Luby, M., Muir, K. W., Parsons, M. W., von Kummer, R., Wardlaw, J. M., Wu, O., Yoo, A. J., Alexandrov, A. V., Alger, J. R., Aviv, R. I., Bammer, R., Baron, J., Calamante, F., Campbell, B. C., Carpenter, T. C., Christensen, S., Copen, W. A., Derdeyn, C. P., Haley, C., Khatri, P., Kudo, K., Lansberg, M. G., Latour, L. L., Lee, T., Leigh, R., Lin, W., Lyden, P., Mair, G., Menon, B. K., Michel, P., Mikulik, R., Nogueira, R. G., Ostergaard, L., Pedraza, S., Riedel, C. H., Rowley, H. A., Sanelli, P. C., Sasaki, M., Saver, J. L., Schaefer, P. W., Schellinger, P. D., Tsivgoulis, G., Wechsler, L. R., White, P. M., Zaharchuk, G., Zaidat, O. O., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Kang, D., Kidwell, C., Thijs, V. N., Thomalla, G., Warach, S. J. 2013; 44 (9): 2628-2639
View details for DOI 10.1161/STROKEAHA.113.002015

View details for Web of Science ID 000329982500063

View details for PubMedID 23860298
High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol MAGNETIC RESONANCE IN MEDICINE Christen, T., Ni, W., Qiu, D., Schmiedeskamp, H., Bammer, R., Moseley, M., Zaharchuk, G. 2013; 70 (3): 705-710
Abstract

Cerebral blood volume maps are usually acquired using dynamic susceptibility contrast imaging which inherently limits the spatial resolution and signal to noise ratio of the images. In this study, we used ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA), an FDA-approved compound, to obtain high-resolution cerebral blood volume maps with a steady-state approach in seven healthy volunteers. R?2* maps (0.8 � 0.8 � 1 mm(3) ) were acquired before and after injection of ferumoxytol and an intraindividual normalization protocol was used to obtain quantitative values. The results show excellent contrast between white and gray matter as well as fine highly detailed vascular structures. An average blood volume of 4% was found in the brain of all volunteers, consistent with prior literature values. A linear relationship was found between ferumoxytol dose (mg/kg) and ?R?2* (1/s) in gray (R(2) = 0.98) and white matter (R(2) = 0.98). A quadratic relationship was found in the sagittal sinus (R(2) = 0.98). The cerebral blood volume maps compare well with lower resolution dynamic susceptibility contrast-MRI and their use should improve the evaluation of small and heterogeneous lesions and facilitate intrapatient and interpatient comparisons. Magn Reson Med, 2012. � 2012 Wiley Periodicals, Inc.

View details for DOI 10.1002/mrm.24500

View details for Web of Science ID 000323543600012
Imaging brain oxygenation with MRI using blood oxygenation approaches: methods, validation, and clinical applications. AJNR. American journal of neuroradiology Christen, T., Bolar, D. S., Zaharchuk, G. 2013; 34 (6): 1113-1123
Abstract

In many pathophysiologic situations, including brain neoplasms, neurodegenerative disease, and chronic and acute ischemia, an imbalance exists between oxygen tissue consumption and delivery. Furthermore, oxygenation changes following a stress challenge, such as with carbogen gas or acetazolamide, can yield information about cerebrovascular reactivity. The unique sensitivity of the BOLD effect to the presence of deoxyhemoglobin has led to its widespread use in the field of cognitive neurosciences. However, the high spatial and temporal resolution afforded by BOLD imaging does not need to be limited to the study of healthy brains. While the complex relationship between the MR imaging signal and tissue oxygenation hinders a direct approach, many different methods have been developed during the past decade to obtain specific oxygenation measurements. These include qBOLD, phase- and susceptibility-based imaging, and intravascular T2-based approaches. The aim of this review is to give an overview of the theoretic basis of these methods as well as their application to measure oxygenation in both healthy subjects and those with disease.

View details for DOI 10.3174/ajnr.A3070

View details for PubMedID 22859287
Simultaneous perfusion and permeability measurements using combined spin- and gradient-echo MRI. Journal of cerebral blood flow and metabolism Schmiedeskamp, H., Andre, J. B., Straka, M., Christen, T., Nagpal, S., Recht, L., Thomas, R. P., Zaharchuk, G., Bammer, R. 2013; 33 (5): 732-743
Abstract

The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T1-, T2-, and -related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.

View details for DOI 10.1038/jcbfm.2013.10

View details for PubMedID 23462570
Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2 STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (3): 681-685
Abstract

It is hypothesized that early diffusion-weighted imaging (DWI) lesions accurately estimate the size of the irreversibly injured core and thresholded perfusion-weighted imaging (PWI) lesions (time to maximum of tissue residue function [Tmax] >6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and posttreatment PWI is hypothesized to predict infarct volume.This is a substudy of Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2); all patients with technically adequate MRI scans at 3 time points were included. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program. Final infarct volumes were assessed with 5-day fluid-attenuated inversion recovery and were corrected for edema. Reperfusion was defined on the basis of the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes.Seventy-three patients were eligible. Twenty-six patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r=0.95; P<0.001). Nine patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 seconds) volume and final infarct volume (r=0.86; P=0.002). Using all 73 patients, the union of baseline DWI and early follow-up PWI is highly correlated with final infarct volume (r=0.94; P<0.001). The median absolute difference between observed and predicted final volumes is 15 mL (interquartile range, 5.5-30.2).Baseline DWI and early follow-up PWI (Tmax >6 seconds) volumes provide a reasonable approximation of final infarct volume after endovascular therapy.

View details for DOI 10.1161/STROKEAHA.111.000135

View details for Web of Science ID 000315447400024

View details for PubMedID 23390119

View details for PubMedCentralID PMC3625664
Hypoperfusion Severity Is Associated With Poor Collaterals And Progresses Over Time Olivot, J., Marks, M. P., Mlynash, M., Wheeler, H. M., Inoue, M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540200242
Correlation of AOL Recanalization, TIMI Reperfusion and TICI Reperfusion with Infarct Growth and Clinical Outcome in the DEFUSE 2 Trial Marks, M. P., Lansberg, M. G., Mlynash, M., Straka, M., Kemp, S., Inoue, M., Tipirneni, A., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540200064
Impact of Collateral Blood Flow on Clinical Presentation, Diffusion and Perfusion Imaging, Infarct Growth and Clinical Outcome in the DEFUSE 2 Trial Marks, M. P., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Kemp, S., McTaggart, R., Inoue, M., Tipirneni, A., Zaharchuk, G., Bammer, R., Albers, G. W., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540201129
Early Diffusion Weighted Imaging and Perfusion Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2 Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540200036
The Growth Rate of Early DWI Lesions is Highly Variable and Associated with Penumbral Salvage and Clinical Outcomes Following Endovascular Reperfusion Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Mishra, N. K., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540200179
Early DWI Reversal Following Endovascular Reperfusion Is Typically Transient Inoue, M., Wheeler, H. M., Mlynash, M., Tipirneni, A., Straka, M., Kemp, S. M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540201137
An ASL Collateral Score Can Identify Improved Quantitative Cerebral Blood Flow in Acute Stroke Patients Christen, T., Zhao, C., Coram, M. A., Straka, M., Bammer, R., Albers, G. W., Zaharchuk, G. LIPPINCOTT WILLIAMS & WILKINS. 2013
View details for Web of Science ID 000330540201265
Imaging of brain oxygenation CLINICAL PERFUSION MRI: TECHNIQUES AND APPLICATIONS Lin, W., An, H., Ford, A. D., Vo, K. L., Lee, J., Zaharchuk, G., Barker, B. P., Golay, Zaharchuk, G. 2013: 75?88
View details for Web of Science ID 000337680600007
MR perfusion imaging in neurovascular disease CLINICAL PERFUSION MRI: TECHNIQUES AND APPLICATIONS Zaharchuk, G., Barker, B. P., Golay, Zaharchuk, G. 2013: 127?63
View details for Web of Science ID 000337680600010
Clinical Evaluation of Reduced Field-of-View Diffusion-Weighted Imaging of the Cervical and Thoracic Spine and Spinal Cord AMERICAN JOURNAL OF NEURORADIOLOGY Andre, J. B., Zaharchuk, G., Saritas, E., Komakula, S., Shankaranarayan, A., Banerjee, S., Rosenberg, J., Nishimura, D. G., Fischbein, N. J. 2012; 33 (10): 1860-1866
Abstract

DWI has the potential to improve the detection and evaluation of spine and spinal cord pathologies. This study assessed whether a recently described method (rFOV DWI) adds diagnostic value in clinical patients.Consecutive patients undergoing clinically indicated cervical and/or thoracic spine imaging received standard anatomic sequences supplemented with sagittal rFOV DWI by using a b-value of 500 s/mm(2). Two neuroradiologists blinded to clinical history evaluated the standard anatomic sequences only for pathology and provided their level of confidence in their diagnosis. These readers then rescored the examinations after reviewing the rFOV DWI study and indicated whether this sequence altered findings or confidence levels.Two hundred twenty-three patients were included in this study. One hundred eighty patient scans (80.7%) demonstrated at least 1 pathologic finding. Interobserver agreement for identifying pathology (? = 0.77) and in assessing the added value of the rFOV DWI sequence (? = 0.77) was high. In pathologic cases, the rFOV DWI sequence added clinical utility in 33% of cases (P < .00001, Fisher exact test). The rFOV DWI sequence was found to be helpful in the evaluation of acute infarction, demyelination, infection, neoplasm, and intradural and epidural collections (P < .001, ?(2) test) and provided a significant increase in clinical confidence in the evaluation of 11 of the 15 pathologic subtypes assessed (P < .05, 1-sided paired Wilcoxon test).rFOV diffusion-weighted imaging of the cervical and thoracic spine is feasible in a clinical population and increases clinical confidence in the diagnosis of numerous common spinal pathologies.

View details for DOI 10.3174/ajnr.A3134

View details for Web of Science ID 000311711400006

View details for PubMedID 22555576
MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study LANCET NEUROLOGY Lansberg, M. G., Straka, M., Kemp, S., Mlynash, M., Wechsler, L. R., Jovin, T. G., Wilder, M. J., Lutsep, H. L., Czartoski, T. J., Bernstein, R. A., Chang, C. W., Warach, S., Fazekas, F., Inoue, M., Tipirneni, A., Hamilton, S. A., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2012; 11 (10): 860-867
Abstract

Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8�8 (95% CI 2�7-29�0) in the target mismatch group and 0�2 (0�0-1�6) in the no target mismatch group (p=0�003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4�0, 95% CI 1�3-12�2) in the target mismatch group, but not in the no target mismatch group (1�9, 0�2-18�7).Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.National Institute for Neurological Disorders and Stroke.

View details for DOI 10.1016/S1474-4422(12)70203-X

View details for PubMedID 22954705
PRELIMINARY RESULTS UTILIZING VESSEL SIZE IMAGING AS A METRIC OF RESPONSE IN GLIOBLASTOMA MULTIFORME 17th Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) Andre, J. B., Schmiedeskamp, H., Thomas, R. P., Feroze, A., Nagpal, S., Zaharchuk, G., Straka, M., Recht, L., Bammer, R. OXFORD UNIV PRESS INC. 2012: 127?127
View details for Web of Science ID 000310971300503
Extracranial Venous Drainage Patterns in Patients with Multiple Sclerosis and Healthy Controls AMERICAN JOURNAL OF NEURORADIOLOGY McTaggart, R. A., Fischbein, N. J., Elkins, C. J., Hsiao, A., Cutalo, M. J., Rosenberg, J., Dake, M. D., Zaharchuk, G. 2012; 33 (8): 1615-1620
Abstract

CCSVI hypothesizes an association between impaired extracranial venous drainage and MS. Published sonographic criteria for CCSVI are controversial, and no MR imaging data exist to support the CCSVI hypothesis. Our purpose was to evaluate possible differences in the extracranial venous drainage of MS and healthy controls using both TOF and contrast-enhanced TRICKS MRV.Healthy subjects (n = 20) and patients with MS (n = 19) underwent axial 2D-TOF neck MRV (to assess flattening) and TRICKS MRV (to assess collaterals) at 3T. Two neuroradiologists blinded to cohort status scored IJV flattening and the severity of non-IJV collaterals by using a 4-point qualitative scale (normal = 0, mild = 1, moderate = 2, severe = 3). ? was used to assess reader agreement. Comparisons between groups were performed by using the Wilcoxon rank sum test. The Spearman rank correlation was used to assess the relationship between IJV flattening and collateral scores and, in patients with MS, EDSS scores.The 2 groups were matched for age and sex (MS, 45 � 8 years, 79% female; healthy controls, 47 � 10 years, 65% female). Reader agreement for IJV flattening and collateral severity was good (? = 0.74) and moderate (? = 0.58), respectively. While IJV flattening was seen in both patients with MS and healthy controls, scores for the patients with MS were significantly higher (P = .002). Despite a trend, there was no significant difference in collateral scores between groups (P = .063). There was a significant positive correlation between flattening and collateral scores (? = 0.32, P = .005) and EDSS and flattening scores (? = 0.45, P = .004) but not between EDSS and collateral scores (? = 0.01, P = .97).These results indicate that patients with MS have greater IJV flattening and a trend toward more non-IJV collaterals than healthy subjects. The role that this finding plays in the pathogenesis or progression of MS, if any, requires further study.

View details for DOI 10.3174/ajnr.A3097

View details for Web of Science ID 000309489800034

View details for PubMedID 22517280
Contrast-enhanced functional blood volume imaging (CE-fBVI): Enhanced sensitivity for brain activation in humans using the ultrasmall superparamagnetic iron oxide agent ferumoxytol NEUROIMAGE Qiu, D., Zaharchuk, G., Christen, T., Ni, W. W., Moseley, M. E. 2012; 62 (3): 1726-1731
Abstract

Functional MRI (fMRI) brain studies performed in the presence of a steady-state or "blood pool" contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise ratio (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional blood volume imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood-oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8�1.3 s) and a slow (75.3�27.5 s) component of CBV response to stimuli. A significant CNR gain of approximately 2-3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping.

View details for DOI 10.1016/j.neuroimage.2012.05.010

View details for Web of Science ID 000307369000040

View details for PubMedID 22584230

View details for PubMedCentralID PMC3477511
Patients With the Malignant Profile Within 3 Hours of Symptom Onset Have Very Poor Outcomes After Intravenous Tissue-Type Plasminogen Activator Therapy STROKE Inoue, M., Mlynash, M., Straka, M., Lansberg, M. G., Zaharchuk, G., Bammer, R., Albers, G. W. 2012; 43 (9): 2494-2496
Abstract

The malignant profile has been associated with poor outcomes after reperfusion in the 3- to 6-hour time window. The aim of this study was to estimate the incidence and prognostic implications of the malignant profile, as identified by CT perfusion, in intravenous tissue-type plasminogen activator-treated patients who were imaged <3 hours from stroke onset.The incidence of the malignant profile, based on the previously published optimal perfusion-weighted imaging definition, was assessed in consecutive patients using a fully automated software program (RApid processing of Perfusion and Diffusion [RAPID]). A receiver operating characteristic curve analysis was done to identify time to maximum and core volume thresholds that optimally identify patients with poor outcome (modified Rankin Scale 5-6).Forty-two patients had an interpretable CT perfusion performed within 3 hours of symptom onset. Mean age was 74�14 years and median (interquartile range) National Institutes of Stroke Scale score was 13 (6-19). Four patients (9.5%) met the prespecified criteria for the malignant profile and all 4 had poor outcome. Receiver operating characteristic analysis determined that the best CT perfusion measure to identify patients with poor outcome was a cerebral blood flow based infarct core >53 mL (100% specificity and 67% sensitivity). This criterion identified 5 patients as malignant (12%). The poor outcome rate in these patients was 100% versus 7.1% in the 37 nonmalignant patients (P<0.001).The incidence of the malignant profile on CT perfusion is approximately 10% in tissue-type plasminogen activator-eligible patients imaged within 3 hours of symptom onset. The clinical outcome of these patients is very poor despite intravenous tissue-type plasminogen activator therapy.

View details for DOI 10.1161/STROKEAHA.112.653329

View details for Web of Science ID 000308416300050

View details for PubMedID 22811464
Clinical Assessment of Standard and Generalized Autocalibrating Partially Parallel Acquisition Diffusion Imaging: Effects of Reduction Factor and Spatial Resolution AMERICAN JOURNAL OF NEURORADIOLOGY Andre, J. B., Zaharchuk, G., Fischbein, N. J., Augustin, M., Skare, S., Straka, M., Rosenberg, J., Lansberg, M. G., Kemp, S., Wijman, C. A., Albers, G. W., Schwartz, N. E., Bammer, R. 2012; 33 (7): 1337-1342
Abstract

PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique.Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence.Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 � 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions.PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

View details for DOI 10.3174/ajnr.A2980

View details for Web of Science ID 000307628200025

View details for PubMedID 22403781
Combined spin- and gradient-echo perfusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Schmiedeskamp, H., Straka, M., Newbould, R. D., Zaharchuk, G., Andre, J. B., Olivot, J., Moseley, M. E., Albers, G. W., Bammer, R. 2012; 68 (1): 30-40
Abstract

In this study, a spin- and gradient-echo echo-planar imaging (SAGE EPI) MRI pulse sequence is presented that allows simultaneous measurements of gradient-echo and spin-echo dynamic susceptibility-contrast perfusion-weighted imaging data. Following signal excitation, five readout trains were acquired using spin- and gradient-echo echo-planar imaging, all of them with echo times of less than 100 ms. Contrast agent concentrations in brain tissue were determined based on absolute R2* and R(2) estimates rather than relative changes in the signals of individual echo trains, producing T(1)-independent dynamic susceptibility-contrast perfusion-weighted imaging data. Moreover, this acquisition technique enabled vessel size imaging through the simultaneous quantification of R2* and R(2), without an increase in acquisition time. In this work, the concepts of SAGE EPI pulse sequence and results in stroke and tumor imaging are presented. Overall, SAGE EPI combined the advantages of higher sensitivity to contrast agent passage of gradient-echo perfusion-weighted imaging with better microvascular selectivity of spin-echo perfusion-weighted imaging.

View details for DOI 10.1002/mrm.23195

View details for Web of Science ID 000305119100004

View details for PubMedID 22114040

View details for PubMedCentralID PMC3374915
CBF measurements using multidelay pseudocontinuous and velocity-selective arterial spin labeling in patients with long arterial transit delays: Comparison with xenon CT CBF JOURNAL OF MAGNETIC RESONANCE IMAGING Qiu, D., Straka, M., Zun, Z., Bammer, R., Moseley, M. E., Zaharchuk, G. 2012; 36 (1): 110-119
Abstract

To test the theory that velocity-selective arterial spin labeling (VSASL) is insensitive to transit delay.Cerebral blood flow (CBF) was measured in ten Moyamoya disease patients using xenon computed tomography (xeCT) and magnetic resonance imaging (MRI), which included multiple pseudo-continuous ASL (pcASL) with different postlabel delays, VSASL, and dynamic susceptibility contrast (DSC) imaging. Correlation coefficient, root-mean-square difference, mean CBF error between ASL, and gold-standard xeCT CBF measurements as well the dependence of this error on transit delay (TD) as estimated by DSC time-to-peak of the residue function (Tmax) were determined.For pcASL with different postlabel delay time (PLD), CBF measurement with short PLD (1.5-2 sec) had the strongest correlations with xeCT; VSASL had a lower but still significant correlation with a mean coefficient of 0.55. We noted the theoretically predicted dependence of CBF error on Tmax and on PLD for pcASL; VSASL CBF measurements had the least dependence of the error on TD. We also noted effects suggesting that the location of the label decay (blood vs. tissue) impacted the measurement, which was worse for pcASL than for VSASL.We conclude that VSASL is less sensitive to TD than conventional ASL techniques and holds promise for CBF measurements in cerebrovascular diseases with slow flow.

View details for DOI 10.1002/jmri.23613

View details for Web of Science ID 000305185700009

View details for PubMedID 22359345

View details for PubMedCentralID PMC3368036
Automated Perfusion Imaging for the Evaluation of Transient Ischemic Attack STROKE Kleinman, J. T., Zaharchuk, G., Mlynash, M., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2012; 43 (6): 1556-1560
Abstract

Diffusion-weighted imaging (DWI) is recommended for the evaluation of transient ischemic attack. Perfusion imaging can increase the yield of MRI in transient ischemic attack. We evaluated automated bolus perfusion (the time when the residue function reaches its maximum [TMax] and mean transit time [MTT]) and arterial spin labeling (ASL) sequences for the detection of ischemic lesions in patients with transient ischemic attack.We enrolled consecutive patients evaluated for suspicion of acute transient ischemic attack by multimodal MRI within 36 hours of symptom onset. Two independent raters assessed the presence and location of ischemic lesions blinded to the clinical presentation. The prevalence of ischemic lesions and the interrater agreement were 1,410 assessed.From January 2010 to 2011, 93 patients were enrolled and 90 underwent perfusion imaging (69 bolus perfusion and 76 ASL). Overall, 25 of 93 patients (27%) were DWI-positive and 14 (15%) were perfusion-positive but DWI-negative (ASL n=9; TMax n=9; MTT n=2). MTT revealed an ischemic lesion in fewer patients than TMax (7 versus 20, P=0.004). Raters agreed on 89% of diffusion-weighted imaging cases, 89% of TMax, 87% o10f010 MTT, and 90% of ASL cases. The interrater agreement was good for DWI, TMax, and ASL (?=0.73, 0.72, and 0.74, respectively) and fair for MTT (?=0.43). Diffusion and/or perfusion were positive in 39 of 69 (57%) patients with a discharge diagnosis of possible ischemic event.Our results suggest that in patients referred for suspicion of transient ischemic attack, automated TMax is more sensitive than MTT, and both ASL and TMax increase the yield of MRI for the detection of ischemic lesions.

View details for DOI 10.1161/STROKEAHA.111.644971

View details for Web of Science ID 000304523800025

View details for PubMedID 22474058
Arterial Spin Labeling for Acute Stroke: Practical Considerations TRANSLATIONAL STROKE RESEARCH Zaharchuk, G. 2012; 3 (2): 228-235
Abstract

Arterial spin labeling (ASL) is a non-contrast method of measuring cerebral perfusion with MRI. It has several advantages over traditional contrast-based perfusion-weighted imaging, including non-invasiveness, more straightforward cerebral blood flow (CBF) quantification, and repeatability. However, because of its lower signal-to-noise ratio (SNR) per unit time and its high sensitivity to arterial transit delays, it has not been used frequently in acute stroke, where arterial delays and time-efficiency are of the essence. This is beginning to change, driven by higher SNR implementations of ASL and the increasing use of 3T scanners. Furthermore, velocity-selective ASL sequences that are largely insensitive to arrival times are beginning to be applied to patients with cerebrovascular disease and promise the ability to quantify CBF even in regions supplied by late-arriving collateral flow. Despite these advances, many practical issues must be addressed to optimize ASL for its use in acute stroke studies. These include optimizing the trade-off between time, SNR, imaging resolution, and sensitivity to slow flow. Rapid and robust post-processing of image data must be made routine, such that CBF maps are available in real time so that they can be considered when making treatment decisions. Lastly, automated software needs to be developed in order to delineate hypoperfused tissue volumes, which is challenging due to the inherent differences between gray and white matter CBF. Attention to these details is critical to translate this promising research tool into mainstream clinical trials and practice in acute stroke.

View details for DOI 10.1007/s12975-012-0159-8

View details for Web of Science ID 000304625200008

View details for PubMedCentralID PMC4040499
Quantitative MR estimates of blood oxygenation based on T2*: A numerical study of the impact of model assumptions MAGNETIC RESONANCE IN MEDICINE Christen, T., Zaharchuk, G., Pannetier, N., Serduc, R., Joudiou, N., Vial, J., Remy, C., Barbier, E. L. 2012; 67 (5): 1458-1468
Abstract

Several MR methods have been proposed over the last decade to obtain quantitative estimates of the tissue blood oxygen saturation (StO2) using a quantification of the blood oxygen level dependent effect. These approaches are all based on mathematical models describing the time evolution of the MR signal in biological tissues in the presence of magnetic field inhomogeneities. Although the experimental results are very encouraging, possible biases induced by the model assumptions have not been extensively studied. In this study, a numerical approach was used to examine the influence on T(2)*, blood volume fraction, and StO2 estimates of possible confounding factors such as water diffusion, intravascular signal, and presence of arterial blood in the voxel. To evaluate the impact of the vessel geometry, straight cylinders and realistic data from two-photon microscopy for microvascular geometry were compared. Our results indicate that the models are sufficiently realistic, based on a good correlation between ground truth and MR estimates of StO2.

View details for DOI 10.1002/mrm.23094

View details for Web of Science ID 000302619400027

View details for PubMedID 22183768
Radiogenomic analysis indicates MR images are potentially predictive of EGFR mutation status in glioblastoma multiforme Gevaert, O., Mitchell, L., Xu, J., Yu, C., Rubin, D., Zaharchuk, G., Napel, S., Plevritis, S. AMER ASSOC CANCER RESEARCH. 2012
View details for DOI 10.1158/1538-7445.AM2012-5561

View details for Web of Science ID 000209701601072
Better Late than Never The Long Journey for Noncontrast Arterial Spin Labeling Perfusion Imaging in Acute Stroke STROKE Zaharchuk, G. 2012; 43 (4): 931-932
View details for DOI 10.1161/STROKEAHA.111.644344

View details for Web of Science ID 000302124200007

View details for PubMedID 22328550
Is T2*Enough to Assess Oxygenation? Quantitative Blood Oxygen Level-Dependent Analysis in Brain Tumor RADIOLOGY Christen, T., Lemasson, B., Pannetier, N., Farion, R., Remy, C., Zaharchuk, G., Barbier, E. L. 2012; 262 (2): 495-502
Abstract

To analyze the contribution of the transverse relaxation parameter (T2), macroscopic field inhomogeneities (B0), and blood volume fraction (BVf) to blood oxygen level-dependent (BOLD)-based magnetic resonance (MR) measurements of blood oxygen saturation (SO2) obtained in a brain tumor model.This study was approved by the local committee for animal care and use. Experiments were performed in accordance with permit 380?820 from the French Ministry of Agriculture. The 9L gliosarcoma cells were implanted in the brain of eight rats. Fifteen days later, 4.7-T MR examinations were performed to estimate T2*, T2, BVf, and T2*?B0corrected in the tumor and contralateral regions. MR estimates of SO2 were derived by combining T2, BVf, and T2*?B0corrected according to a recently described quantitative BOLD approach. Scatterplots and linear regression analysis were used to identify correlation between parameters. Paired Student t tests were used to compare the tumor region with the contralateral region.No significant correlations were found between T2* and any parameter in either tumor tissue or healthy tissue. T2* in the tumor and T2* in the uninvolved contralateral brain were the same (36 msec�4 [standard deviation] vs 36 msec�5, respectively), which might suggest similar oxygenation. Adding T2 information (98 msec�7 vs 68 msec�2, respectively) alone yields results that suggest apparent hypo-oxygenation of the tumor, while incorporating BVf (5.3%�0.6 vs 2.6%�0.3, respectively) alone yields results that suggest apparent hyperoxygenation. MR estimates of SO2 obtained with a complete quantitative BOLD analysis, although not correlated with T2* values, suggest normal oxygenation (68%�3 vs 65%�4, respectively). MR estimates of SO2 obtained in the contralateral tissue agree with previously reported values.Additional measurements, such as BVf, T2, and B0, are needed to obtain reliable information on oxygenation with BOLD MR imaging. The proposed quantitative BOLD approach, which includes these measurements, appears to be a promising tool with which to map tumor oxygenation.

View details for DOI 10.1148/radiol.11110518

View details for Web of Science ID 000300300200015

View details for PubMedID 22156990

View details for PubMedCentralID PMC3267079
Arterial Spin Labeling Imaging Findings in Transient Ischemic Attack Patients: Comparison with Diffusion- and Bolus Perfusion-Weighted Imaging CEREBROVASCULAR DISEASES Zaharchuk, G., Olivot, J., Fischbein, N. J., Bammer, R., Straka, M., Kleinman, J. T., Albers, G. W. 2012; 34 (3): 221-228
Abstract

Since transient ischemic attacks (TIAs) can predict future stroke, it is important to distinguish true vascular events from non-vascular etiologies. Arterial spin labeling (ASL) is a non-contrast magnetic resonance (MR) method that is sensitive to cerebral perfusion and arterial arrival delays. Due to its high sensitivity to minor perfusion alterations, we hypothesized that ASL abnormalities would be identified frequently in TIA patients, and could therefore help increase clinicians' confidence in the diagnosis.We acquired diffusion-weighted imaging (DWI), intracranial MR angiography (MRA), and ASL in a prospective cohort of TIA patients. A subset of these patients also received bolus contrast perfusion-weighted imaging (PWI). Two neuroradiologists evaluated the images in a blinded fashion to determine the frequency of abnormalities on each imaging sequence. Kappa (?) statistics were used to assess agreement, and the ?(2) test was used to detect differences in the proportions of abnormal studies.76 patients met the inclusion criteria, 48 (63%) of whom received PWI. ASL was abnormal in 62%, a much higher frequency compared with DWI (24%) and intracranial MRA (13%). ASL significantly increased the MR imaging yield above the combined DWI and MRA yield (62 vs. 32%, p < 0.05). Arterial transit artifact in vascular borderzones was the most common ASL abnormality (present in 51%); other abnormalities included focal high or low ASL signal (11%). PWI was abnormal in 31% of patients, and in these, ASL was abnormal in 14 out of 15 cases (93%). In hemispheric TIA patients, both PWI and ASL findings were more common in the symptomatic hemisphere. Agreement between neuroradiologists regarding abnormal studies was good for ASL and PWI [? = 0.69 (95% CI 0.53-0.86) and ? = 0.66 (95% CI 0.43-0.89), respectively].In TIA patients, perfusion-related alterations on ASL were more frequently detected compared with PWI or intracranial MRA and were most frequently associated with the symptomatic hemisphere. Almost all cases with a PWI lesion also had an ASL lesion. These results suggest that ASL may aid in the workup and triage of TIA patients, particularly those who cannot undergo a contrast study.

View details for DOI 10.1159/000339682

View details for Web of Science ID 000313654100007

View details for PubMedID 23006669
Arterial spin labeling for acute stroke: practical considerations. Translational stroke research Zaharchuk, G. n. 2012; 3 (2): 228?35
Abstract

Arterial spin labeling (ASL) is a non-contrast method of measuring cerebral perfusion with MRI. It has several advantages over traditional contrast-based perfusion-weighted imaging, including non-invasiveness, more straightforward cerebral blood flow (CBF) quantification, and repeatability. However, because of its lower signal-to-noise ratio (SNR) per unit time and its high sensitivity to arterial transit delays, it has not been used frequently in acute stroke, where arterial delays and time-efficiency are of the essence. This is beginning to change, driven by higher SNR implementations of ASL and the increasing use of 3T scanners. Furthermore, velocity-selective ASL sequences that are largely insensitive to arrival times are beginning to be applied to patients with cerebrovascular disease and promise the ability to quantify CBF even in regions supplied by late-arriving collateral flow. Despite these advances, many practical issues must be addressed to optimize ASL for its use in acute stroke studies. These include optimizing the trade-off between time, SNR, imaging resolution, and sensitivity to slow flow. Rapid and robust post-processing of image data must be made routine, such that CBF maps are available in real time so that they can be considered when making treatment decisions. Lastly, automated software needs to be developed in order to delineate hypoperfused tissue volumes, which is challenging due to the inherent differences between gray and white matter CBF. Attention to these details is critical to translate this promising research tool into mainstream clinical trials and practice in acute stroke.

View details for PubMedID 24323778

View details for PubMedCentralID PMC4040499
High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Christen, T. n., Ni, W. n., Qiu, D. n., Schmiedeskamp, H. n., Bammer, R. n., Moseley, M. n., Zaharchuk, G. n. 2012
Abstract

Cerebral blood volume maps are usually acquired using dynamic susceptibility contrast imaging which inherently limits the spatial resolution and signal to noise ratio of the images. In this study, we used ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA), an FDA-approved compound, to obtain high-resolution cerebral blood volume maps with a steady-state approach in seven healthy volunteers. R?2* maps (0.8 � 0.8 � 1 mm(3) ) were acquired before and after injection of ferumoxytol and an intraindividual normalization protocol was used to obtain quantitative values. The results show excellent contrast between white and gray matter as well as fine highly detailed vascular structures. An average blood volume of 4% was found in the brain of all volunteers, consistent with prior literature values. A linear relationship was found between ferumoxytol dose (mg/kg) and ?R?2* (1/s) in gray (R(2) = 0.98) and white matter (R(2) = 0.98). A quadratic relationship was found in the sagittal sinus (R(2) = 0.98). The cerebral blood volume maps compare well with lower resolution dynamic susceptibility contrast-MRI and their use should improve the evaluation of small and heterogeneous lesions and facilitate intrapatient and interpatient comparisons. Magn Reson Med, 2012. � 2012 Wiley Periodicals, Inc.

View details for PubMedID 23001902
Cerebral CT Perfusion Using an Interventional C-Arm Imaging System: Cerebral Blood Flow Measurements AMERICAN JOURNAL OF NEURORADIOLOGY Ganguly, A., Fieselmann, A., Marks, M., Rosenberg, J., Boese, J., Deuerling-Zheng, Y., Straka, M., Zaharchuk, G., Bammer, R., Fahrig, R. 2011; 32 (8): 1525-1531
Abstract

CTP imaging in the interventional suite could reduce delays to the start of image-guided interventions and help determine the treatment progress and end point. However, C-arms rotate slower than clinical CT scanners, making CTP challenging. We developed a cerebral CTP protocol for C-arm CBCT and evaluated it in an animal study.Five anesthetized swine were imaged by using C-arm CBCT and conventional CT. The C-arm rotates in 4.3 seconds plus a 1.25-second turnaround, compared with 0.5 seconds for clinical CT. Each C-arm scan had 6 continuous bidirectional sweeps. Multiple scans each with a different delay to the start of an aortic arch iodinated contrast injection and a novel image reconstruction algorithm were used to increase temporal resolution. Three different scan sets (consisting of 6, 3, or 2 scans) and 3 injection protocols (3-mL/s 100%, 3-mL/s 67%, and 6-mL/s 50% contrast concentration) were studied. CBF maps for each scan set and injection were generated. The concordance and Pearson correlation coefficients (? and r) were calculated to determine the injection providing the best match between the following: the left and right hemispheres, and CT and C-arm CBCT.The highest ? and r values (both 0.92) for the left and right hemispheres were obtained by using the 6-mL 50% iodinated contrast concentration injection. The same injection gave the best match for CT and C-arm CBCT for the 6-scan set (? = 0.77, r = 0.89). Some of the 3-scan and 2-scan protocols provided matches similar to those in CT.This study demonstrated that C-arm CBCT can produce CBF maps that correlate well with those from CTP.

View details for DOI 10.3174/ajnr.A2518

View details for Web of Science ID 000295706200027

View details for PubMedID 21757522

View details for PubMedCentralID PMC3171629
Comparison of MR and Contrast Venography of the Cervical Venous System in Multiple Sclerosis AMERICAN JOURNAL OF NEURORADIOLOGY Zaharchuk, G., Fischbein, N. J., Rosenberg, J., Herfkens, R. J., Dake, M. D. 2011; 32 (8): 1482-1489
Abstract

MRV has been proposed as a possible screening method to identify chronic cerebrospinal venous insufficiency, which may play a role in MS. We report our initial experience comparing MRV and CV in MS patients to evaluate venous stenosis and collateral venous drainage.Time-of-flight and time-resolved imaging of contrast kinetics MRV and CV were performed in 39 MS patients. The presence and severity of both IJ vein caliber changes and non-IJ collaterals were graded by using a 4-point scale by 2 radiologists in an independent and blinded manner.Both studies frequently showed venous abnormalities, most commonly IJ flattening at the C1 level and in the lower neck. There was moderate-to-good agreement between the modalities (? = 0.55; 95% CI, 0.45%-0.65%). For collaterals, agreement was only fair (? = 0.30; 95% CI, 0.09%-0.50%). The prevalence of IJ segments graded mild or worse on CV was 54%. If CV was considered a standard, the sensitivity and specificity of MRV was 0.79 (0.71-0.86) and 0.76 (0.67-0.83), respectively. Degree of stenosis was related to the severity of collaterals for CV but not for MRV.IJ caliber changes were seen in characteristic locations on both MRV and CV in MS patients. Agreement between modalities was higher for stenosis than for collaterals. If CV is considered a standard, MRV performance is good but may require additional improvement before MRV can be used for screening.

View details for DOI 10.3174/ajnr.A2549

View details for Web of Science ID 000295706200021

View details for PubMedID 21757521
Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Perfusion in Patients With Moyamoya Disease STROKE Zaharchuk, G., Do, H. M., Marks, M. P., Rosenberg, J., Moseley, M. E., Steinberg, G. K. 2011; 42 (9): 2485-U183
Abstract

Determining the presence and adequacy of collateral blood flow is important in cerebrovascular disease. Therefore, we explored whether a noninvasive imaging modality, arterial spin labeling (ASL) MRI, could be used to detect the presence and intensity of collateral flow using digital subtraction angiography (DSA) and stable xenon CT cerebral blood flow as gold standards for collaterals and cerebral blood flow, respectively.ASL and DSA were obtained within 4 days of each other in 18 patients with Moyamoya disease. Two neurointerventionalists scored DSA images using a collateral grading scale in regions of interest corresponding to ASPECTS methodology. Two neuroradiologists similarly scored ASL images based on the presence of arterial transit artifact. Agreement of ASL and DSA consensus scores was determined, including kappa statistics. In 15 patients, additional quantitative xenon CT cerebral blood flow measurements were performed and compared with collateral grades.The agreement between ASL and DSA consensus readings was moderate to strong, with a weighted kappa value of 0.58 (95% confidence interval, 0.52-0.64), but there was better agreement between readers for ASL compared with DSA. Sensitivity and specificity for identifying collaterals with ASL were 0.83 (95% confidence interval, 0.77-0.88) and 0.82 (95% confidence interval, 0.76-0.87), respectively. Xenon CT cerebral blood flow increased with increasing DSA and ASL collateral grade (P<0.05).ASL can noninvasively predict the presence and intensity of collateral flow in patients with Moyamoya disease using DSA as a gold standard. Further study of other cerebrovascular diseases, including acute ischemic stroke, is warranted.

View details for DOI 10.1161/STROKEAHA.111.61646

View details for PubMedID 21799169
Reduced Field-of-View Diffusion Imaging of the Human Spinal Cord: Comparison with Conventional Single-Shot Echo-Planar Imaging AMERICAN JOURNAL OF NEURORADIOLOGY Zaharchuk, G., Saritas, E. U., Andre, J. B., CHIN, C. T., Rosenberg, J., Brosnan, T. J., Shankaranarayan, A., Nishimura, D. G., Fischbein, N. J. 2011; 32 (5): 813-820
Abstract

DWI of the spinal cord is challenging because of its small size and artifacts associated with the most commonly used clinical imaging method, SS-EPI. We evaluated the performance of rFOV spinal cord DWI and compared it with the routine fFOV SS-EPI in a clinical population.Thirty-six clinical patients underwent 1.5T MR imaging examination that included rFOV SS-EPI DWI of the cervical spinal cord as well as 2 comparison diffusion sequences: fFOV SS-EPI DWI normalized for either image readout time (low-resolution fFOV) or spatial resolution (high-resolution fFOV). ADC maps were created and compared between the methods by using single-factor analysis of variance. Two neuroradiologists blinded to sequence type rated the 3 DWI methods, based on susceptibility artifacts, perceived spatial resolution, signal intensity-to-noise ratio, anatomic detail, and clinical utility.ADC values for the rFOV and both fFOV sequences were not statistically different (rFOV: 1.01 � 0.18 � 10(-3) mm(2)/s; low-resolution fFOV: 1.12 � 0.22 � 10(-3) mm(2)/s; high-resolution fFOV: 1.10 � 0.21 � 10(-3) mm(2)/s; F = 2.747, P > .05). The neuroradiologist reviewers rated the rFOV diffusion images superior in terms of all assessed measures (P < 0.0001). Particular improvements were noted in patients with metal hardware, degenerative disease, or both.rFOV DWI of the spinal cord overcomes many of the problems associated with conventional fFOV SS-EPI and is feasible in a clinical population. From a clinical standpoint, images were deemed superior to those created by using standard fFOV methods.

View details for DOI 10.3174/ajnr.A2418

View details for Web of Science ID 000291117600006

View details for PubMedID 21454408
MR-Guided Unfocused Ultrasound Disruption of the Rat Blood-Brain Barrier 10th International Symposium on Therapeutic Ultrasound Townsend, K. A., King, R. L., Zaharchuk, G., Pauly, K. B. AMER INST PHYSICS. 2011: 356?360
View details for DOI 10.1063/1.3607933

View details for Web of Science ID 000295944900059
Combined Arterial Spin Label and Dynamic Susceptibility Contrast Measurement of Cerebral Blood Flow MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Straka, M., Marks, M. P., Albers, G. W., Moseley, M. E., Bammer, R. 2010; 63 (6): 1548-1556
Abstract

Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial- volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient-specific correction factor, the ratio of ASL- and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 +/- 30% (33%) for combined ASL and DSC CBF, 43 +/- 21% (47%) for DSC, and 91 +/- 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

View details for DOI 10.1002/mrm.22329

View details for PubMedID 20512858
MIGRAINE-LIKE HEADACHE WITH VISUAL DEFICIT AND PERFUSION ABNORMALITY ON MRI NEUROLOGY Kapinos, G., Fischbein, N. J., Zaharchuk, G., Venkatasubramanian, C. 2010; 74 (21): 1743-1745
View details for Web of Science ID 000278018400014

View details for PubMedID 20498443

View details for PubMedCentralID PMC2882211
Optimizing Saturation-Recovery Measurements of the Longitudinal Relaxation Rate Under Time Constraints MAGNETIC RESONANCE IN MEDICINE Hsu, J., Glover, G. H., Zaharchuk, G. 2009; 62 (5): 1202-1210
Abstract

The saturation-recovery method using two and three recovery times is studied for conditions in which the sum of recovery times is 1.5T(1) to 3T(1), where T(1) is the longitudinal relaxation time. These conditions can reduce scan time considerably for long T(1) species and make longitudinal relaxation rate R(1) (R(1) = 1/T(1)) mapping for body fluids clinically feasible. Monte Carlo computer simulation is carried out to determine the ideal set of recovery times under various constraints of the sum of recovery times. The ideal set is found to be approximately invariant to the signal-to-noise ratio. For the three-point method, two of the recovery times should be set the same or approximately the same and should be shorter than the third one. Only marginal improvements in accuracy and precision can be achieved by the three-point method over the two-point method under a common constraint of the sum of recovery times. Three-dimensional, high resolution, whole-brain saturation-recovery scans on volunteers with a fast-spin-echo technique (XETA) and completed in a scan time of 10 min generated R(1) measurements of cerebrospinal fluid (T(1) approximately 4 s) in agreement with the computer simulation and literature results, which demonstrates the clinical feasibility of applying the two-point saturation-recovery method for R(1) mapping for long relaxation components.

View details for DOI 10.1002/mrm.22111

View details for PubMedID 19780164
Improving Dynamic Susceptibility Contrast MRI Measurement of Quantitative Cerebral Blood Flow using Corrections for Partial Volume and Nonlinear Contrast Relaxivity: A Xenon Computed Tomographic Comparative Study JOURNAL OF MAGNETIC RESONANCE IMAGING Zaharchuk, G., Bammer, R., Straka, M., Newbould, R. D., Rosenberg, J., Olivot, J., Mlynash, M., Lansberg, M. G., Schwartz, N. E., Marks, M. M., Albers, G. W., Moseley, M. E. 2009; 30 (4): 743-752
Abstract

To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT).Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.Mean xeCT CBF was 43.3 +/- 13.7 mL/100g/min (mean +/- SD). BB correction decreased CBF by a factor of 4.7 +/- 0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8 +/- 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 +/- 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

View details for DOI 10.1002/jmri.21908

View details for PubMedID 19787719
Arterial Spin-Label Imaging in Patients with Normal Bolus Perfusion-weighted MR Imaging Findings: Pilot Identification of the Borderzone Sign RADIOLOGY Zaharchuk, G., Bammer, R., Straka, M., Shankaranarayan, A., Alsop, D. C., Fischbein, N. J., Atlas, S. W., Moseley, M. E. 2009; 252 (3): 797-807
Abstract

To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images obtained in patients with normal bolus perfusion-weighted (PW) magnetic resonance (MR) imaging findings.Institutional review board approval and written informed patient consent were obtained. This study was HIPAA compliant. Consecutive patients suspected or known to have cerebrovascular disease underwent 1.5-T brain MR imaging, including MR angiography, gradient-echo PW imaging, and pseudocontinuous ASL imaging, between October 2007 and January 2008. Patients with normal bolus PW imaging findings were retrospectively identified, and two neuroradiologists subsequently evaluated the ASL images for focal abnormalities. The severity of the borderzone sign-that is, bilateral ASL signal dropout with surrounding cortical areas of hyperintensity in the middle cerebral artery borderzone regions-was classified by using a four-point scale. For each group, the ASL-measured mean mixed cortical cerebral blood flow (CBF) at the level of the centrum semiovale was evaluated by using the Jonckheere-Terpstra test.One hundred thirty-nine patients met the study inclusion criteria, and 41 (30%) of them had normal bolus PW imaging findings. Twenty-three (56%) of these 41 patients also had normal ASL imaging findings. The remaining 18 (44%) patients had the ASL borderzone sign; these patients were older (mean age, 71 years +/- 11 [standard deviation] vs 57 years +/- 16; P < .005) and had lower mean CBF (30 mL/100 g/min +/- 12 vs 46 mL/100 g/min +/- 12, P < .003) compared with the patients who had normal ASL imaging findings. Five patients had additional focal ASL findings that were related to either slow blood flow in a vascular structure or postsurgical perfusion defects and were not visible on the PW images.Approximately half of the patients with normal bolus PW imaging findings had abnormal ASL findings-most commonly the borderzone sign. Results of this pilot study suggest that ASL imaging in patients who have this sign and are suspected of having cerebrovascular disease yields additional and complementary hemodynamic information.

View details for DOI 10.1148/radiol.2523082018

View details for Web of Science ID 000270809500022

View details for PubMedID 19703858
Rapid Methods for Concurrent Measurement of the RF-Pulse Flip Angle and the Longitudinal Relaxation Time MAGNETIC RESONANCE IN MEDICINE Hsu, J., Zaharchuk, G., Glover, G. H. 2009; 61 (6): 1319-1325
Abstract

Measuring both the flip angle (FA) and the longitudinal relaxation time T(1) is essential in quantitative and longitudinal studies because the signal amplitude is dependent on these quantities. Conventional methods can only measure one of them at a time and require long scan times. In this work, two mutually consistent methods are developed; each can acquire multislice data for determining both the FA and T(1) in a scan time about half the time needed for a conventional FA measurement. On the basis of a recent development of longitudinal-relaxation measurement (Hsu and Lowe, J Magn Reson 2004;169:270-278; Hsu and Glover, J Magn Reson 2006;181:98-106), one of the methods uses RF pulse trains of two FAs whereas the other uses pulse trains of different pulse spacing. When only the FA or T(1) is needed, the present methods can still be faster than conventional methods for the needed quantity. In benchmarking with a uniform-density sample, both methods generate precise T(1) values independent of the FA chosen (except at and near 90 degrees ). In the demonstration with three normal volunteers at 3 T, the T(1) values of frontal and occipital white matter, putamen, and caudate are compared; the T(1) values are in agreement with literature values and the intrasubject deviation is 0.2%-2.8%.

View details for DOI 10.1002/mrm.21900

View details for Web of Science ID 000266429900007

View details for PubMedID 19267342
Quantitative hemodynamic studies in moyamoya disease NEUROSURGICAL FOCUS Lee, M., Zaharchuk, G., Guzman, R., Achrol, A., Bell-Stephens, T., Steinberg, G. K. 2009; 26 (4)
Abstract

Moyamoya disease is characterized by a chronic stenoocclusive vasculopathy affecting the terminal internal carotid arteries. The clinical presentation and outcome of moyamoya disease remain varied based on angiographic studies alone, and much work has been done to study cerebral hemodynamics in this group of patients. The ability to measure cerebral blood flow (CBF) accurately continues to improve with time, and with it a better understanding of the pathophysiological mechanisms in patients with moyamoya disease. The main imaging techniques used to evaluate cerebral hemodynamics include PET, SPECT, xenon-enhanced CT, dynamic perfusion CT, MR imaging with dynamic susceptibility contrast and with arterial spin labeling, and Doppler ultrasonography. More invasive techniques include intraoperative ultrasonography. The authors review the current knowledge of CBF in this group of patients and the role each main quantitative method has played in evaluating them, both in the disease state and after surgical intervention.

View details for DOI 10.3171/2009.1.FOCUS08300

View details for Web of Science ID 000265656400005

View details for PubMedID 19335131

View details for PubMedCentralID PMC2905646
SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke American-Association-International-Stroke Conference 2009 Schwartz, N. E., Newbould, R. D., Skare, S., Zaharchuk, G., Mlynash, M., Olivot, J., Lansberg, M. G., Eyngorn, I., Thai, D., Albers, G. W., Bammer, R. LIPPINCOTT WILLIAMS & WILKINS. 2009: E115?E115
View details for Web of Science ID 000264709500133
Perfusion MRI (Tmax and MTT) correlation with xenon CT cerebral blood flow in stroke patients NEUROLOGY Olivot, J., Mlynash, M., Zaharchuk, G., Straka, M., Bammer, R., Schwartz, N., Lansberg, M. G., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1140-1145
Abstract

While stable xenon CT (Xe-CT) cerebral blood flow (CBF) is an accepted standard for quantitative assessment of cerebral hemodynamics, the accuracy of magnetic resonance perfusion-weighted imaging (PWI-MRI) is unclear. The Improved PWI Methodology in Acute Clinical Stroke Study compares PWI findings with Xe-CT CBF values in patients experiencing symptomatic severe cerebral hypoperfusion.We compared mean transit time (MTT) and Tmax PWI-MRI with the corresponding Xe-CT CBF values in 25 coregistered regions of interest (ROIs) of multiple sizes and locations in nine subacute stroke patients. Comparisons were performed with Pearson correlation coefficients (R). We performed receiver operating characteristic (ROC) curve analyses to define the threshold of Tmax and absolute MTT that could best predict a Xe-CT CBF <20 mL/100 g/minute.The subjects' mean (SD) age was 50 (15) years, the median (interquartile range [IQR]) NIH Stroke Scale score was 2 (2-6), and the median (IQR) time between MRI and Xe-CT was 12 (-7-19) hours. The total number of ROIs was 225, and the median (IQR) ROI size was 550 (360-960) pixels. Tmax correlation with Xe-CT CBF (R = 0.63, p < 0.001) was stronger than absolute MTT (R = 0.55, p < 0.001), p = 0.049. ROC curve analysis found that Tmax >4 seconds had 68% sensitivity, 80% specificity, and 77% accuracy and MTT >10 seconds had 68% sensitivity, 77% specificity, and 75% accuracy for predicting ROIs with Xe-CT CBF <20 mL/100 g/minute.Our results suggest that in subacute ischemic stroke patients, Tmax correlates better than absolute mean transit time (MTT) with xenon CT cerebral blood flow (Xe-CT CBF) and that both Tmax >4 seconds and MTT >10 seconds are strongly associated with Xe-CT CBF <20 mL/100 g/minute. CBF = cerebral blood flow; DBP = diastolic blood pressure; DEFUSE = Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution; DWI = diffusion-weighted imaging; EPITHET = Echoplanar Imaging Thrombolytic Evaluation Trial; FOV = field of view; ICA = internal carotid artery; IQR = interquartile range; MCA = middle cerebral artery; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; PWI-MRI = magnetic resonance perfusion-weighted imaging; ROC = receiver operating characteristic; ROI = region of interest; SBP = systolic blood pressure; SVD = singular value decomposition; Xe-CT = xenon CT.

View details for DOI 10.1212/01.wnl.0000345372.49233.e3

View details for Web of Science ID 000264709000007

View details for PubMedID 19332690

View details for PubMedCentralID PMC2680065
Urinary Oxygen Tension Measurement in Humans Using Magnetic Resonance Imaging ACADEMIC RADIOLOGY Wang, Z. J., Joe, B. N., Coakley, F. V., Zaharchuk, G., Busse, R., Yeh, B. M. 2008; 15 (11): 1467-1473
Abstract

Renal medullary hypoxia is frequently implicated in renal dysfunction, and urinary oxygen tension (PO(2)) in the renal pelvis can be used as a surrogate for the adjacent renal medullary oxygenation. We sought to assess the feasibility of magnetic resonance (MR) quantification of urinary PO(2) in humans.The longitudinal relaxivity (R1) of fluids is linearly related to PO(2), allowing MR quantification of urinary PO(2). We imaged urine phantoms with a range of PO(2) using a real-time saturation recovery T2-prepped single-shot fast spin-echo sequence to calibrate urine R1 values to PO(2). Following institutional review board approval, we imaged the urinary bladders of seven healthy subjects while they were breathing room air and the renal pelvis of nine healthy subjects while they were breathing room air or 100% oxygen via facemask. The renal pelvic urine PO(2) was compared before, during, and after 100% oxygen breathing.Our phantom study confirmed that urine R1 is linearly related to PO(2): PO(2) (mm Hg) = (R1 - 0.2253 s(-1))/(2.61e(-4) s(-1)/mm Hg). The mean bladder urine PO(2) ranged from 23 to 45 mm Hg among the seven subjects. Successful MR measurements of renal pelvic urine PO(2) were obtained in seven of nine healthy subjects. Following 100% O(2) breathing, the renal pelvic urine PO(2) showed a significant mean increase of 29 mm Hg (P < .05).We show that MR quantification of urinary PO(2) is feasible. Noninvasive renal pelvic urine PO(2) determinations could serve as a valuable indirect measure for renal medullary oxygenation, allowing for clinical investigations of the role of renal medullary hypoxia in renal disease.

View details for DOI 10.1016/j.acra.2008.04.013

View details for Web of Science ID 000260707600014

View details for PubMedID 18995198

View details for PubMedCentralID PMC2605795
Comparison of Multidetector CT Angiography and MR Imaging of Cervical Artery Dissection AMERICAN JOURNAL OF NEURORADIOLOGY Vertinsky, A. T., Schwartz, N. E., Fischbein, N. J., Rosenberg, J., Albers, G. W., Zaharchuk, G. 2008; 29 (9): 1753-1760
Abstract

Conventional angiography has been historically considered the gold standard for the diagnosis of cervical artery dissection, but MR imaging/MR angiography (MRA) and CT/CT angiography (CTA) are commonly used noninvasive alternatives. The goal of this study was to compare the ability of multidetector CT/CTA and MR imaging/MRA to detect common imaging findings of dissection.Patients in the data base of our Stroke Center between 2003 and 2007 with dissections who had CT/CTA and MR imaging/MRA on initial work-up were reviewed retrospectively. Two neuroradiologists evaluated the images for associated findings of dissection, including acute ischemic stroke, luminal narrowing, vessel irregularity, wall thickening/hematoma, pseudoaneurysm, and intimal flap. The readers also subjectively rated each vessel on the basis of whether the imaging findings were more clearly displayed with CT/CTA or MR imaging/MRA or were equally apparent.Eighteen patients with 25 dissected vessels (15 internal carotid arteries [ICA] and 10 vertebral arteries [VA]) met the inclusion criteria. CT/CTA identified more intimal flaps, pseudoaneurysms, and high-grade stenoses than MR imaging/MRA. CT/CTA was preferred for diagnosis in 13 vessels (5 ICA, 8 VA), whereas MR imaging/MRA was preferred in 1 vessel (ICA). The 2 techniques were deemed equal in the remaining 11 vessels (9 ICA, 2 VA). A significant preference for CT/CTA was noted for VA dissections (P < .05), but not for ICA dissections.Multidetector CT/CTA visualized more features of cervical artery dissection than MR imaging/MRA. CT/CTA was subjectively favored for vertebral dissection, whereas there was no technique preference for ICA dissection. In many cases, MR imaging/MRA provided complementary or confirmatory information, particularly given its better depiction of ischemic complications.

View details for DOI 10.3174/ajnr.A1189

View details for Web of Science ID 000260023800029

View details for PubMedID 18635617
Noninvasive imaging of quantitative cerebral blood flow changes during 100% oxygen inhalation using arterial spin-labeling MR imaging AMERICAN JOURNAL OF NEURORADIOLOGY Zaharchuk, G., Martin, A. J., Dillon, W. P. 2008; 29 (4): 663-667
Abstract

Tracer studies have demonstrated that 100% oxygen inhalation causes a small cerebral blood flow (CBF) decrease. This study was performed to determine whether arterial spin-labeling (ASL), a noninvasive MR imaging technique, could image these changes with clinically reasonable imaging durations.Continuous ASL imaging was performed in 7 healthy subjects before, during, and after 100% oxygen inhalation. ASL difference signal intensity (DeltaM, control - label), CBF, and CBF percentage change were measured. A test-retest paradigm was used to calculate the variability of the initial and final room air CBF measurements.During oxygen inhalation, DeltaM decreased significantly in all regions (eg, global DeltaM decreased by 23 +/- 11%, P < .01, all values mean +/- SD). Accounting for the reduced T1 of hyperoxygenated blood, we found a smaller CBF decrease, which did not reach significance in any of the regions. Global CBF dropped from 50 +/- 10 mL per 100 g/minute to 47 +/- 10 mL per 100 g/minute following 100% oxygen inhalation, a decrease of 5 +/- 14% (P > .17). The root-mean-square variability of the initial and final room air CBF measurements was 7-8 mL per 100 g/minute.The DeltaM signal intensity decreased significantly with oxygen inhalation; however, after accounting for changes in blood T1 with oxygen, CBF decreases were small. Such measurements support the use of hyperoxia as an MR imaging contrast agent and may be helpful to interpret hyperoxia-based stroke trials.

View details for DOI 10.3174/ajnr.A0896

View details for Web of Science ID 000255129700009

View details for PubMedID 18397966
Theoritical basis of hemodynamic MR imaging techniques to measure cerebral blood volume, cerebral blood how, and permeability AMERICAN JOURNAL OF NEURORADIOLOGY Zaharchuk, G. 2007; 28 (10): 1850-1858
Abstract

Cerebrovascular hemodynamic assessment adds new information to standard anatomic MR imaging and improves patient care. This article reviews the theoretic underpinnings of several potentially quantitative MR imaging-based methods that shed light on the hemodynamic status of the brain, including cerebral blood flow (CBF), cerebral blood volume (CBV), and contrast agent permeability. Techniques addressed include dynamic susceptibility contrast (which most simply and accurately estimates CBV), arterial spin labeling (a powerful method to measure CBF), and contrast-enhanced methods to derive permeability parameters such as the transport constant Ktrans.

View details for DOI 10.3174/ainr.A0831

View details for Web of Science ID 000251198600011

View details for PubMedID 17998415
Noninvasive oxygen partial pressure measurement of human body fluids in vivo using magnetic resonance imaging ACADEMIC RADIOLOGY Zaharchuk, G., Busse, R. F., Rosenthal, G., Manley, G. T., Glenn, O. A., Dillon, W. P. 2006; 13 (8): 1016-1024
Abstract

The oxygen partial pressure (pO2) of human body fluids reflects the oxygenation status of surrounding tissues. All existing fluid pO2 measurements are invasive, requiring either microelectrode/optode placement or fluid removal. The purpose of this study is to develop a noninvasive magnetic resonance imaging method to measure the pO2 of human body fluids.We developed an imaging paradigm that exploits the paramagnetism of molecular oxygen to create quantitative images of fluid oxygenation. A single-shot fast spin echo pulse sequence was modified to minimize artifacts from motion, fluid flow, and partial volume. Longitudinal relaxation rate (R1 = 1/T1) was measured with a time-efficient nonequilibrium saturation recovery method and correlated with pO2 measured in phantoms.pO2 images of human and fetal cerebrospinal fluid, bladder urine, and vitreous humor are presented and quantitative oxygenation levels are compared with prior literature estimates, where available. Significant pO2 increases are shown in cerebrospinal fluid and vitreous following 100% oxygen inhalation. Potential errors due to temperature, fluid flow, and partial volume are discussed.Noninvasive measurements of human body fluid pO2 in vivo are presented, which yield reasonable values based on prior literature estimates. This rapid imaging-based measurement of fluid oxygenation may provide insight into normal physiology as well as changes due to disease or during treatment.

View details for DOI 10.1016/j.acra.2006.04.016

View details for Web of Science ID 000239234600012

View details for PubMedID 16843855
Comparative overview of brain perfusion imaging techniques. Stroke; a journal of cerebral circulation Wintermark, M., Sesay, M., Barbier, E., Borb�ly, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J., Nariai, T., Zaharchuk, G., Caill�, J., Dousset, V., Yonas, H. 2005; 36 (9): e83-99
Abstract

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks.This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques.For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting.

View details for PubMedID 16100027
Comparative overview of brain perfusion imaging techniques STROKE Wintermark, M., Sesay, M., Barbier, E., Borbely, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J. F., Nariai, T., Zaharchuk, G., Caille, J. M., Dousset, V., Yonas, H. 2005; 36 (9): E83-E99
View details for DOI 10.1161/01.STR.0000177884.72657.8b

View details for Web of Science ID 000231441200063
Comparative overview of brain perfusion imaging techniques STROKE Wintermark, M., Sesay, M., Barbier, E., Borbely, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J. F., Nariai, T., Zaharchuk, G., Caille, J. M., Dousset, V., Yonas, H. 2005; 36 (9): 2032-2033
View details for DOI 10.1161/01.STR.0000177839.03321.25

View details for Web of Science ID 000231441200051
Measurement of cerebrospinal fluid oxygen partial pressure in humans using MRI MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Martin, A. J., Rosenthal, G., Manley, G. T., Dillon, W. P. 2005; 54 (1): 113-121
Abstract

Fluid-attenuated inversion recovery (FLAIR) images obtained during the administration of supplemental oxygen demonstrate a hyperintense signal within the cerebrospinal fluid (CSF) that is likely caused by T1 changes induced by paramagnetic molecular oxygen. Previous studies demonstrated a linear relationship between the longitudinal relaxation rate (R1 = 1/T1) and oxygen content, which permits quantification of the CSF oxygen partial pressure (P(csf)O2). In the current study, CSF T1 was measured at 1.5 T in the lateral ventricles, third ventricle, cortical sulci, and basilar cisterns of eight normal subjects breathing room air or 100% oxygen. Phantom studies performed with artificial CSF enabled absolute P(csf)O2 quantitation. Regional P(csf)O2 differences on room air were observed, from 65 +/- 27 mmHg in the basilar cisterns to 130 +/- 49 mmHg in the third ventricle. During 100% oxygen, P(csf)O2 increases of 155 +/- 45 and 124 +/- 34 mmHg were measured in the basilar cisterns and cortical sulci, respectively, with no change observed in the lateral or third ventricles. P(csf)O2 measurements in humans breathing room air or 100% oxygen using a T1 method are comparable to results from invasive human and animal studies. Similar approaches could be applied to noninvasively monitor oxygenation in many acellular, low-protein body fluids.

View details for DOI 10.1002/mrm.20546

View details for Web of Science ID 000230013800015

View details for PubMedID 15968660
Is all perfusion-weighted magnetic resonance imaging for stroke equal? The temporal evolution of multiple hemodynamic parameters after focal ischemia in rats correlated with evidence of infarction JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Zaharchuk, G., Yamada, M., Sasamata, M., Jenkins, B. G., Moskowitz, M. A., Rosen, B. R. 2000; 20 (9): 1341-1351
Abstract

Although perfusion-weighted imaging techniques are increasingly used to study stroke, no particular hemodynamic variable has emerged as a standard marker for accumulated ischemic damage. To better characterize the hemodynamic signature of infarction. the authors have assessed the severity and temporal evolution of ischemic hemodynamics in a middle cerebral artery occlusion model in the rat. Cerebral blood flow (CBF) and total and microvascular cerebral blood volume (CBV) changes were measured with arterial spin labeling and steady-state susceptibility contrast magnetic resonance imaging (MRI), respectively, and analyzed in regions corresponding to infarcted and spared ipsilateral tissue, based on 2,3,5-triphenyltetrazolium chloride histology sections after 24 hours ischemia. Spin echo susceptibility contrast was used to measure microvascular-weighted CBV, which had a maximum sensitivity for vessels with radii between 4 and 30 microm. Serial measurements between 1 and 3 hours after occlusion showed no change in CBF (22 +/- 20% of contralateral, mean +/- SD) or in total CBV (78 +/- 13% of contralateral) in regions destined to infarct. However, microvascular CBV progressively declined from 72 +/- 5% to 64 +/- 11% (P < 0.01) during this same period. Microvascular CBV changes with time were entirely due to decreases in subcortical infarcted zones (from 73 +/- 9% to 57 +/- 14%. P < 0.001) without changes in the cortical infarcted territory. The hemodynamic variables showed differences in magnitude and temporal response, and these changes varied based on histologic outcome and brain architecture. Such factors should be considered when designing imaging studies for human stroke.

View details for Web of Science ID 000089069800009

View details for PubMedID 10994856
Cerebrovascular dynamics of autoregulation and hypoperfusion - An MRI study of CBF and changes in total and microvascular cerebral blood volume during hemorrhagic hypotension STROKE Zaharchuk, G., Mandeville, J. B., Bogdanov, A. A., Weissleder, R., Rosen, B. R., Marota, J. J. 1999; 30 (10): 2197-2204
Abstract

To determine how cerebral blood flow (CBF), total and microvascular cerebral blood volume (CBV), and blood oxygenation level-dependent (BOLD) contrast change during autoregulation and hypotension using hemodynamic MRI.Using arterial spin labeling and steady-state susceptibility contrast, we measured CBF and changes in both total and microvascular CBV during hemorrhagic hypotension in the rat (n=9).We observed CBF autoregulation for mean arterial blood pressure (MABP) between 50 and 140 mm Hg, at which average CBF was 1.27+/-0.44 mL. g(-1). min(-1) (mean+/-SD). During autoregulation, total and microvascular CBV changes were small and not significantly different from CBF changes. Consistent with this, no significant BOLD changes were observed. For MABP between 10 and 40 mm Hg, total CBV in the striatum increased slightly (+7+/-12%, P<0.05) whereas microvascular CBV decreased (-15+/-17%, P<0.01); on the cortical surface, total CBV increases were larger (+21+/-18%, P<0.01) and microvascular CBV was unchanged (3+/-22%, P>0.05). With severe hypotension, both total and microvascular CBV decreased significantly. Over the entire range of graded global hypoperfusion, there were increases in the CBV/CBF ratio.Parenchymal CBV changes are smaller than those of previous reports but are consistent with the small arteriolar fraction of total blood volume. Such measurements allow a framework for understanding effective compensatory vasodilation during autoregulation and volume-flow relationships during hypoperfusion.

View details for Web of Science ID 000082983200035

View details for PubMedID 10512929
Multislice perfusion and perfusion territory imaging in humans with separate label and image coils MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Ledden, P. J., Kwong, K. K., Reese, T. G., Rosen, B. R., Wald, L. L. 1999; 41 (6): 1093-1098
Abstract

An arterial spin labeling technique using separate RF labeling and imaging coils was used to obtain multislice perfusion images of the human brain at 3 T. Continuous RF irradiation at a peak power of 0.3 W was applied to the carotid arteries to adiabatically invert spins. Labeling was achieved without producing magnetization transfer effects since the B1 field of the labeling coil did not extend into the imaging region or couple significant power into the imaging coil. Eliminating magnetization transfer allowed the acquisition of multislice perfusion images of arbitrary orientation. Combining surface coil labeling with a reduced RF duty cycle permitted significantly lower SAR than single coil approaches. The technique was also found to allow selective labeling of blood in either carotid, providing an assessment of the artery's perfusion territory. In normal subjects, these territories were well-defined and localized to the ipsilateral hemisphere.

View details for Web of Science ID 000081422500004

View details for PubMedID 10371440
Evidence of a cerebrovascular postarteriole windkessel with delayed compliance JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Mandeville, J. B., Marota, J. J., Ayata, C., Zaharchuk, G., Moskowitz, M. A., Rosen, B. R., Weisskoff, R. M. 1999; 19 (6): 679-689
Abstract

A pronounced temporal mismatch was observed between the responses of relative cerebral blood volume (rCBV) measured by magnetic resonance imaging and relative cerebral blood flow measured by laser-Doppler flowmetry in rat somatosensory cortex after electrical forepaw stimulation. The increase of relative cerebral blood flow after stimulus onset and decrease after stimulus cessation were accurately described with a single exponential time constant of 2.4 +/- 0.8 seconds. In contrast, rCBV exhibited two distinct and nearly sequential processes after both onset and cessation of stimulation. A rapid change of rCBV (1.5 +/- 0.8 seconds) occurring immediately after onset and cessation was not statistically different from the time constant for relative cerebral blood flow. However, a slow phase of increase (onset) and decrease (cessation) with an exponential time constant of 14 +/- 13 seconds began approximately 8 seconds after the rapid phase of CBV change. A modified windkessel model was developed to describe the temporal evolution of rCBV as a rapid elastic response of capillaries and veins followed by slow venous relaxation of stress. Venous delayed compliance was suggested as the mechanism for the poststimulus undershoot in blood oxygen-sensitive magnetic resonance imaging signal that has been observed in this animal model and in human data.

View details for Web of Science ID 000084948700012

View details for PubMedID 10366199
Delivery of imaging agents into brain ADVANCED DRUG DELIVERY REVIEWS Abbott, N. J., Chugani, D. C., Zaharchuk, G., Rosen, B. R., Lo, E. H. 1999; 37 (1-3): 253-277
Abstract

Delivery of diagnostic agents to the central nervous system (CNS) poses several challenges as a result of the special features of CNS blood vessels and tissue fluids. Diffusion barriers exist between blood and neural tissue, in the endothelium of parenchymal vessels (blood-brain barrier, BBB), and in the epithelia of the choroid plexuses and arachnoid membrane (blood-CSF barriers), which severely restrict penetration of several diagnostic imaging agents. The anatomy of large vessels can be imaged using bolus injection of X-ray contrast agents to identify sites of malformation or occlusion, and blood flow measured using MRI and CT, while new techniques permit analysis of capillary perfusion and blood volume. Absolute quantities can be derived, although relative measures in different CNS regions may be as useful in diagnosis. Local blood flow, blood volume, and their ratio (mean transit time) can be measured with high speed tomographic imaging using MRI and CT. Intravascular contrast agents for MRI are based on high magnetic susceptibility agents such as gadolinium, dysprosium and iron. Steady-state imaging using agents that cross the BBB including (123)I- and (99m)Tc-labelled lipophilic agents with SPECT, gives a 'snapshot' of perfusion at the time of injection. Cerebral perfusion can also be measured with PET, using H(2)(15)O, (11)C- or (15)O-butanol, and (18)F-fluoromethane, and cerebral blood volume measured with C(15)O. Recent advances in MRI permit the non-invasive 'labelling' of endogenous water protons in flowing blood, with subsequent detection as a measure of blood flow. Imaging the BBB most commonly involves detecting disruptions of the barrier, allowing contrast agents to leak out of the vascular system. Gd-DTPA is useful in imaging leaky vessels as in some cerebral tumors, while the shortening of T(1) by MR contrast agents can be used to detect more subtle changes in BBB permeability to water as in cerebral ischemia. Techniques for imaging the dynamic activity of the brain parenchyma mainly involve PET, using a variety of radiopharmaceuticals to image glucose transport and metabolism, neurotransmitter binding and uptake, protein synthesis and DNA dynamics. PET methods permit detailed analysis of regional function by comparing resting and task-related images, important in improving understanding of both normal and pathological brain function.

View details for Web of Science ID 000079979400017

View details for PubMedID 10837739
Continuous assessment of perfusion by tagging including volume and water extraction (CAPTIVE): A steady-state contrast agent technique for measuring blood flow, relative blood volume fraction, and the water extraction fraction MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Bogdanov, A. A., Marota, J. J., Shimizu-Sasamata, M., Weisskoff, R. M., Kwong, K. K., Jenkins, B. G., Weissleder, R., Rosen, B. R. 1998; 40 (5): 666-678
Abstract

A new technique, CAPTIVE, that is a synthesis of arterial spin labeling (ASL) blood flow and steady-state susceptibility contrast relative blood volume imaging is described. Using a single injection of a novel, long half-life intravascular magnetopharmaceutical with a high tissue:blood susceptibility difference (deltachi) to deltaR1 ratio, changes in tissue transverse relaxivity (deltaR2 or deltaR2*) that arise from changes in blood volume were measured, while preserving the ability to measure blood flow using traditional T1-based ASL techniques. This modification permits the continuous measurement of both blood flow and blood volume. Also, because the contrast agent can be used to remove the signal from intravascular spins, it is possible to measure the first-pass water extraction fraction. Contrast-to-noise is easily traded off with repetition rate, allowing the use of non-EPI scanners and more flexible imaging paradigms. The basic theory of these measurements, several experimental scenarios, and validating results are presented. Specifically, the PaCO2-reactivity of microvascular and total relative cerebral blood volume (rCBV), cerebral blood flow (CBF), and the water extraction-flow product (EF) in rats with the new contrast agent MPEG-PL-DyDTPA is measured, and the values are concordant with those of previous literature. As an example of one possible application, continuous flow and volume measurements during transient focal ischemia are presented. It is believed that CAPTIVE imaging will yield a more complete picture of the hemodynamic state of an organ, and has further application for understanding the origins of the BOLD effect.

View details for Web of Science ID 000076496700003

View details for PubMedID 9797148
Mismatch between cerebral blood volume and flow index during transient focal ischemia studied with MRI and Gd-BOPTA MAGNETIC RESONANCE IMAGING Caramia, F., Huang, Z., Hamberg, L. M., Weisskoff, R. M., Zaharchuk, G., Moskowitz, M. A., Cavagna, F. M., Rosen, B. R. 1998; 16 (2): 97-103
Abstract

We investigated the regional and temporal changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and vascular transit time in seven mongrel cats during 30 min transient focal ischemia, caused by occlusion of the middle cerebral artery. Dynamic susceptibility contrast magnetic resonance imaging was done at 4.7 T, using fast gradient echo T2* weighted imaging and intravenous injection of gadolinium-BOPTA/Dimeglumine. During occlusion, the areas showing a blood volume change were predominantly within the middle cerebral artery territory and could be divided into areas showing either CBV increases or decreases. The area with decreased blood volume also had decreased blood flow as measured by our flow-based index (p < 0.05) and was located in the central territory of the middle cerebral artery. Peripheral to this region was an area showing increased blood volume but without significant CBF changes (p > 0.05). During reperfusion, the CBF increased in the entire zone showing changes in blood volume during occlusion, and remained significantly elevated until 45 min post-occlusion, while CBV remained elevated in the hyperemic rim for at least 2 h. The presence of a peri-ischemic zone showing flow/volume mismatch identified a region wherein baseline CBF is maintained by means of compensatory vasodilatation, but where the ratio of CBF to CBV is decreased. Dynamic susceptibility contrast magnetic resonance imaging with gadolinium-BOPTA/Dimeglumine may be a valuable technique for the investigation of regional and temporal perturbations of hemodynamics during ischemia and reperfusion.

View details for Web of Science ID 000072063800001

View details for PubMedID 9508266
Measurement of changes in cerebral blood volume in spontaneously hypertensive rats following L-arginine infusion using dynamic susceptibility contrast MRI MAGNETIC RESONANCE IN MEDICINE Caramia, F., Yoshida, T., Hamberg, L. M., Huang, Z. H., Hunter, G., Wanke, I., Zaharchuk, G., Moskowitz, M. A., Rosen, B. R. 1998; 39 (1): 160-163
Abstract

To understand whether the NO-dependent vasodilator L-arginine was effective upon a chronically hypertensive cerebral capillary endothelium, dynamic susceptibility contrast MRI was used to measure the relative cerebral blood volume (rCBV) changes in nonischemic spontaneously hypertensive rats (SHRs). rCBV was measured in 11 rats at 4.7 T using fast gradient echo imaging with intravenous injection of Gd-DTPA. Images were acquired before, immediately after, and up to 90 min after the infusion of 300 mg/kg L-arginine (n = 7) or of an equivalent volume of saline (n = 4). L-arginine increased rCBV in cortex beginning 10 min after infusion and reached significance after 30 min (P < 0.01), reached a peak of 1.24 +/- 0.06 (mean +/- SEM) times pre-injection level after 50 min, and was sustained throughout the 90 min observation period. In contrast, the rCBV in the deeper gray matter (striatum) showed no statistically significant change over the 90 min observation period. While this is consistent with previous studies showing that L-arginine infusion can directly modulate vascular tone and cerebral hemodynamics, it demonstrates that the effect is present only in cortex, and that it can occur also in the setting of a disturbed capillary endothelium.

View details for Web of Science ID 000071161400022

View details for PubMedID 9438450
Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient changes in the peri-infarct zone during focal cerebral ischemia MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Hara, H., Huang, P. L., Fishman, M. C., Moskowitz, M. A., Jenkins, B. G., Rosen, B. R. 1997; 37 (2): 170-175
Abstract

Diffusion-weighted MRI at 2 T was used to monitor and assess tissue damage after permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and mice deficient in nitric oxide synthase gene expression (nNOS-). The ischemic lesion was evaluated 3 h after occlusion and subdivided into the lesion core and peri-infarct zone based on the magnitude of the apparent diffusion coefficient (ADC) change. Infarct volume, measured by using histochemical staining 24 h after MCA occlusion, correlated best with MRI infarct volume as assessed by an ADC threshold of 25% decrease from baseline at 3 h. For ADC thresholds of greater than 25% decrease, lesion size was not significantly different in nNOS- and WT mice. However, brain tissue showing ADC decreases of 10-25% was significantly smaller in the ipsilateral hemisphere of mutants (27 +/- 2% and 21 +/- 2% in WT and nNOS-, respectively; P < 0.05). These findings occurred independently of infarct volume and are consistent with a smaller peri-infarct zone in nNOS- mice. We postulate that the smaller peri-infarct zone is a reflection of less severe metabolic disturbance after ischemia in nNOS- mice, possibly related to diminished production of nitric oxide (NO) or a related product. We conclude that magnetic resonance techniques previously used to assess ischemic damage in larger animals can be extended to the mouse, raising the possibility that the molecular mechanisms leading to ischemic damage can be examined by using genetically engineered mice.

View details for Web of Science ID A1997WD27200003

View details for PubMedID 9001139
PROGRESS TOWARDS AN INTEGRATED HTS SQUID MAGNETOMETER 4TH INTERNATIONAL CONFERENCE on Superconducting and Quantum Effect Devices and Their Applications (SQUID 91) Char, K., Colclough, M. S., Lee, L. P., Zaharchuk, G. SPRINGER-VERLAG BERLIN. 1993: 172?179
View details for Web of Science ID A1993BA73R00029
THIN-FILM HIGH-TEMPERATURE SUPERCONDUCTING FLUX TRANSFORMERS COUPLED TO SQUIDS 4th International Conference on Superconducting and Quantum Effect Devices and Their Applications (SQUID 91) Wellstood, F. C., Miklich, A. H., Kingston, J. J., Ferrari, M. J., Clarke, J., Colclough, M. S., Char, K., Zaharchuk, G. SPRINGER-VERLAG BERLIN. 1993: 162?167
View details for Web of Science ID A1993BA73R00027
LARGE-AREA YBA2CU3O7-DELTA THIN-FILMS ON SAPPHIRE FOR MICROWAVE APPLICATIONS APPLIED PHYSICS LETTERS Cole, B. F., Liang, G. C., Newman, N., Char, K., Zaharchuk, G. 1992; 61 (14): 1727-1729
View details for Web of Science ID A1992JQ65200040
MICROSTRUCTURE OF BIEPITAXIAL GRAIN-BOUNDARY JUNCTIONS IN YBA2CU3O7 APPLIED PHYSICS LETTERS Rosner, S. J., Char, K., Zaharchuk, G. 1992; 60 (8): 1010-1012
View details for Web of Science ID A1992HE66100031
MULTILAYER SUPERCONDUCTING DEVICES MADE USING BI-EPITAXIAL GRAIN-BOUNDARY JOSEPHSON-JUNCTIONS IN YBA2CU3O7 CONF ON PROGRESS IN HIGH-TEMPERATURE SUPERCONDUCTING TRANSISTORS AND OTHER DEVICES Char, K., Colclough, M. S., Lee, L. P., Zaharchuk, G. SPIE - INT SOC OPTICAL ENGINEERING. 1992: 90?100
View details for Web of Science ID A1992BV53P00012
HIGH-TC SUPERCONDUCTING MULTILAYERS FOR SQUID MAGNETOMETERS NOBEL JUBILEE SYMP Clarke, J., Kingston, J. J., Miklich, A. H., Wellstood, F. C., Char, K., Colclough, M. S., Lee, L. P., Zaharchuk, G. IOP PUBLISHING LTD. 1992: 51?56
View details for Web of Science ID A1992JQ22400011
FLUX FOCUSING EFFECTS IN PLANAR THIN-FILM GRAIN-BOUNDARY JOSEPHSON-JUNCTIONS APPLIED PHYSICS LETTERS Rosenthal, P. A., Beasley, M. R., Char, K., Colclough, M. S., Zaharchuk, G. 1991; 59 (26): 3482-3484
View details for Web of Science ID A1991GW01800045
MONOLITHIC 77K DC SQUID MAGNETOMETER APPLIED PHYSICS LETTERS Lee, L. P., Char, K., Colclough, M. S., Zaharchuk, G. 1991; 59 (23): 3051-3053
View details for Web of Science ID A1991GT01700044
GRAIN-BOUNDARY JOSEPHSON-JUNCTIONS CREATED BY BI-EPITAXIAL PROCESSES INTERNATIONAL CONF ON MATERIALS AND MECHANISMS OF SUPERCONDUCTIVITY HIGH TEMPERATURE SUPERCONDUCTORS 3 Char, K., Colclough, M. S., Lee, L. P., Zaharchuk, G. ELSEVIER SCIENCE BV. 1991: 2561?2562
View details for Web of Science ID A1991GX30900213
EXTENSION OF THE BI-EPITAXIAL JOSEPHSON JUNCTION PROCESS TO VARIOUS SUBSTRATES APPLIED PHYSICS LETTERS Char, K., Colclough, M. S., Lee, L. P., Zaharchuk, G. 1991; 59 (17): 2177-2179
View details for Web of Science ID A1991GK72700038
SENSITIVE YBA2CU3O7-X THIN-FILM MAGNETOMETER APPLIED PHYSICS LETTERS Miklich, A. H., Kingston, J. J., Wellstood, F. C., Clarke, J., Colclough, M. S., Char, K., Zaharchuk, G. 1991; 59 (8): 988-990
View details for Web of Science ID A1991GB29600036
BI-EPITAXIAL GRAIN-BOUNDARY JUNCTIONS IN YBA2CU3O7 APPLIED PHYSICS LETTERS Char, K., Colclough, M. S., GARRISON, S. M., Newman, N., Zaharchuk, G. 1991; 59 (6): 733-735
View details for Web of Science ID A1991FZ35000039

Greg Zaharchuk

Professor of Radiology (Neuroimaging and Neurointervention)

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