Clinical Focus

  • Neuroradiology

Academic Appointments

Honors & Awards

  • Distinguished Investigator Award, The Academy for Radiology & Biomedical Imaging Research (2016)
  • Scholar Award, Neuroradiology Education and Research Foundation (2009)
  • Executive Council Award, American Roentgen Ray Society (2006)
  • Resident/Fellow Research Award, Radiological Society of North America (2002)
  • Young Investigator Award in Stroke, American Heart Association (1998)
  • Young Investigator Finalist, International Society of Magnetic Resonance in Medicine (1998)
  • Phi Beta Kappa, Stanford University (1989)
  • Valedictorian, Materials Science and Engineering, Stanford University (1989)
  • Tau Beta Pi, Stanford University (1987)

Boards, Advisory Committees, Professional Organizations

  • Editorial Board, Radiology (2016 - Present)
  • Treasurer, American Society of Functional Neuroradiology (2016 - Present)
  • Scientific Program Committee, Neuroradiology/Head & Neck Subcommittee, Radiological Society of North America (RSNA) (2012 - Present)
  • Annual Meeting Program Committee, International Society of Magnetic Resonance in Medicine (2012 - 2015)
  • Special Consultant to the Editor - Physics, American Journal of Neuroradiology (2011 - Present)

Professional Education

  • Fellowship:Univ of California San Francisco (2006) CA
  • Residency:Univ of California San Francisco (2005) CA
  • Internship:Robert Wood Johnson University Hospital (2001) NJ
  • MD, Harvard Medical School, Medicine (2000)
  • PhD, Harvard University / Massachusetts Institute of Technology, Applied Physics (HST Program) (1999)
  • BS & BA, Stanford, Materials Science & Engineering/German Studies (1990)


  • Greg Zaharchuk, Enhao Gong, John Pauly. "United States Patent submitted Improving Quality of Medical Images Using Multi-Contrast and Deep Learning", Leland Stanford Junior University, Mar 6, 2017
  • Greg Zaharchuk, Roland Bammer. "United States Patent 8,929,972 Arterial Spin Labeling MRI-based Correction Factor for Improving Quantitative Accuracy of Blood Flow and Volume Images", Leland Stanford Junior University,, Jan 6, 2015
  • Greg Zaharchuk, Jean Brittain. "United States Patent 7,064,545 Method and Apparatus of Background Suppression in MR imaging using Spin Locking", General Electric Company, The Regents Of The University Of California, Jun 20, 2006
  • Kookrin Char, Stephen M. Garrison, Nathan Newman, Greg Zaharchuk. "United States Patent 5,157,466 Grain Boundary Junctions in High Temperature Superconductor Films", Conductus, Inc., Oct 20, 1992
  • Reed Busse, John Pauly, Greg Zaharchuk. "United States Patent 7,276,904 Method for Generating T1-weighted Magnetic Resonance Images and Quantitative T1 Maps", Leland Stanford Junior University, Oct 2, 0007

Research & Scholarship

Current Research and Scholarly Interests

Improving medical image quality using deep learning
Imaging of cerebral hemodynamics with MRI and CT
Noninvasive oxygenation measurement with MRI
Clinical imaging of cerebrovascular disease
Imaging of cervical artery dissection
MR/PET in Neuroradiology
Resting-state fMRI for perfusion imaging and stroke

Clinical Trials

  • Quantifying Collateral Perfusion in Cerebrovascular Disease-Moyamoya Disease and Stroke Patients Not Recruiting

    Quantifying Collateral Perfusion in Cerebrovascular Disease-Moyamoya disease and stroke patients

    Stanford is currently not accepting patients for this trial. For more information, please contact Sandra Dunn, 650-724-8278.

    View full details

  • Imaging Collaterals in Acute Stroke (iCAS) Recruiting

    Stroke is caused by a sudden blockage of a blood vessel that delivers blood to the brain. Unblocking the blood vessel with a blood clot removal device restores blood flow and if done quickly may prevent the disability that can be caused by a stroke. However, not all stroke patients benefit from having their blood vessel unblocked. The aim of this study is to determine if special brain imaging, called MRI, can be used to identify which stroke patients are most likely to benefit from attempts to unblock their blood vessel with a special blood clot removal device. In particular, we will assess in this trial whether a noncontrast MR imaging sequence, arterial spin labeling (ASL), can demonstrate the presence of collateral blood flow (compared with a gold standard of the angiogram) and whether it is useful to predict who will benefit from treatment.

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  • Computed Tomography Perfusion (CTP) to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Not Recruiting

    The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to develop a practical tool to identify acute stroke patients who are likely to benefit from endovascular therapy. The project has two main parts. During the first part, the investigators propose to develop a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will generate brain maps of the ischemic core and penumbra. There will be no patient enrollment in part one of this project. During the second part, the investigators aim to demonstrate that physicians in the emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can accurately predict response to recanalization in stroke patients undergoing revascularization. To achieve this aim the investigators will conduct a prospective cohort study of 240 consecutive stroke patients who will undergo a CTP scan prior to endovascular therapy. The study will be conducted at four sites (Stanford University, St Luke's Hospital, University of Pittsburgh Medical Center, and Emory University/Grady Hospital). Patients will have an early follow-up MRI scan within 12+/-6 hours to assess reperfusion and a late follow-up MRI scan at day 5 to determine the final infarct.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie M Kemp, BS, 650-723-4481.

    View full details


2016-17 Courses

Stanford Advisees


All Publications

  • 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


    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±2.4μm, 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 Web of Science ID 000332057400024

    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


    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


    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

  • 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


    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-?


    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

  • 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


    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. < 90%).Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7-43] on fluid-attenuated inversion recovery, and 23 ml [11-64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20-118] on fluid-attenuated inversion recovery, and 37 ml [16-91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [-1-13]), compared to <18 h (13 ml [2-47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12-57]; <18 h: 21 ml [5-57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8-57], fluid-attenuated inversion recovery: 41 ml [13-104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2-24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8-46]; p = 0.001).Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

    View details for PubMedID 27811306

  • 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


    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

  • 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


    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


    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


    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

  • 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


    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

  • 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
  • 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


    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

    View details for PubMedID 25965900

  • 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


    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 Web of Science ID 000363658700006

    View details for PubMedID 23228203

  • 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


    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 < 0·001). In patients who achieved reperfusion (n = 38), slower early diffusion-weighted imaging growth rates were associated with better clinical outcomes (P < 0·05) and a trend toward more penumbral salvage (n = 31, P = 0·103). A multivariate model demonstrated that initial diffusion-weighted imaging growth rate was an independent predictor of achieving a 90-day modified Rankin score of ≤2.The growth rate of early diffusion-weighted imaging lesions in acute stroke patients is highly variable; malignant profile patients have higher growth rates than patients with target mismatch. A slower rate of early diffusion-weighted imaging growth is associated with a greater degree of penumbral salvage and improved clinical outcomes following endovascular reperfusion.

    View details for DOI 10.1111/ijs.12436

    View details for Web of Science ID 000356718000025

  • 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


    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


    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 < 0.0001) and increased correlation coefficient with xeCT CBF imaging (from 0.07 to 0.62).We demonstrated that timing optimization, stimulated echo removal, and slice profile improvement have a large effect on image quality and robustness of VS-ASL in clinical imaging applications. J. Magn. Reson. Imaging 2015;41:1422-1431. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmri.24652

    View details for Web of Science ID 000353641600030

  • 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


    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 Web of Science ID 000351395300020

    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


    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


    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 Web of Science ID 000351306000012

  • 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


    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 Web of Science ID 000350279900037

    View details for PubMedID 24753286

  • 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


    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 Web of Science ID 000348850600018

  • 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
  • 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


    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

    View details for DOI 10.1002/mrm.25197

    View details for Web of Science ID 000346908800010

  • 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
  • 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


    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

    View details for DOI 10.1111/ijs.12271

    View details for Web of Science ID 000342581900013

  • 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


    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


    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

  • 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
  • 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

    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


    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 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


    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 Web of Science ID 000339138200010

  • 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


    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 Web of Science ID 000336260900012

    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


    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 Web of Science ID 000337297800004

    View details for PubMedID 24473366

  • Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort STROKE 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


    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 Web of Science ID 000333303400025

    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

  • Early Diffusion-Weighted Imaging Reversal After Endovascular Reperfusion Is Typically Transient in Patients Imaged 3 to 6 Hours After Onset STROKE 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


    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 Web of Science ID 000333303400026

    View details for PubMedID 24558095

  • Effect of Collateral Blood Flow on Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke STROKE 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


    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. Unique identifier: NCT01349946.

    View details for DOI 10.1161/STROKEAHA.113.004085

    View details for Web of Science ID 000333303400028

    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., Tamura, M. K., Zaharchuk, G. 2014; 9 (3)
  • 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)


    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

  • 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
  • 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

  • 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


    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


    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
  • 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

    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 AMERICAN JOURNAL OF NEURORADIOLOGY Christen, T., Bolar, D. S., Zaharchuk, G. 2013; 34 (6): 1113-1123


    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 Web of Science ID 000329847700008

  • 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


    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 Web of Science ID 000318394400013

  • 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


    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

  • 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


    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


    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 Web of Science ID 000309634300011

    View details for PubMedID 22954705

  • PRELIMINARY RESULTS UTILIZING VESSEL SIZE IMAGING AS A METRIC OF RESPONSE IN GLIOBLASTOMA MULTIFORME 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
  • 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


    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


    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

  • 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


    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


    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


    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

  • 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


    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

  • 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


    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
  • 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


    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

  • 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


    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

  • 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


    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

  • 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., Ni, W., Qiu, D., Schmiedeskamp, H., Bammer, R., Moseley, M., Zaharchuk, G. 2012


    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


    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

  • 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


    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


    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 Web of Science ID 000294342800031

    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


    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 (ISTU 2010) Townsend, K. A., King, R. L., Zaharchuk, G., Pauly, K. B. 2011; 1359: 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


    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 Web of Science ID 000278164400015

    View details for PubMedID 20512858

  • 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


    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 Web of Science ID 000271431200014

    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


    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 Web of Science ID 000270522900007

    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


    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


    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)


    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

  • SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke 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
  • 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


    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

  • 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


    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

  • 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


    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


    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


    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


    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., Borbély, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J., Nariai, T., Zaharchuk, G., Caillé, J., Dousset, V., Yonas, H. 2005; 36 (9): e83-99


    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
  • 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
  • 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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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

  • THIN-FILM HIGH-TEMPERATURE SUPERCONDUCTING FLUX TRANSFORMERS COUPLED TO SQUIDS SUPERCONDUCTING DEVICES AND THEIR APPLICATIONS Wellstood, F. C., Miklich, A. H., Kingston, J. J., Ferrari, M. J., Clarke, J., Colclough, M. S., Char, K., Zaharchuk, G. 1993; 64: 162-167
  • 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
  • HIGH-TC SUPERCONDUCTING MULTILAYERS FOR SQUID MAGNETOMETERS PHYSICA SCRIPTA Clarke, J., Kingston, J. J., Miklich, A. H., Wellstood, F. C., Char, K., Colclough, M. S., Lee, L. P., Zaharchuk, G. 1992; T42: 51-56
  • 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
  • MONOLITHIC 77K DC SQUID MAGNETOMETER APPLIED PHYSICS LETTERS Lee, L. P., Char, K., Colclough, M. S., Zaharchuk, G. 1991; 59 (23): 3051-3053
  • 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
  • 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