Academic Appointments

  • Instructor, Radiology


All Publications

  • PET/MRI of Metabolic Activity in Osteoarthritis: A Feasibility Study JOURNAL OF MAGNETIC RESONANCE IMAGING Kogan, F., Fan, A. P., McWalter, E. J., Oei, E. H., Quon, A., Gold, G. E. 2017; 45 (6): 1736-1745

    View details for DOI 10.1002/jmri.25529

    View details for Web of Science ID 000401259900018

  • Mitigation of Partial Volume Effects in Susceptibility-Based Oxygenation Measurements by Joint Utilization of Magnitude and Phase (JUMP) MAGNETIC RESONANCE IN MEDICINE McDaniel, P., Bilgic, B., Fan, A. P., Stout, J. N., Adalsteinsson, E. 2017; 77 (4): 1713-1727

    View details for DOI 10.1002/mrm.26227

    View details for Web of Science ID 000398085200035

  • Improved Quantification of Cerebral Vein Oxygenation Using Partial Volume Correction FRONTIERS IN NEUROSCIENCE Ward, P. G., Fan, A. P., Raniga, P., Barnes, D. G., Dowe, D. L., Ng, A. C., Egan, G. F. 2017; 11


    Purpose: Quantitative susceptibility mapping (QSM) enables cerebral venous characterization and physiological measurements, such as oxygen extraction fraction (OEF). The exquisite sensitivity of QSM to deoxygenated blood makes it possible to image small veins; however partial volume effects must be addressed for accurate quantification. We present a new method, Iterative Cylindrical Fitting (ICF), to estimate voxel-based partial volume effects for susceptibility maps and use it to improve OEF quantification of small veins with diameters between 1.5 and 4 voxels. Materials and Methods: Simulated QSM maps were generated to assess the performance of the ICF method over a range of vein geometries with varying echo times and noise levels. The ICF method was also applied to in vivo human brain data to assess the feasibility and behavior of OEF measurements compared to the maximum intensity voxel (MIV) method. Results: Improved quantification of OEF measurements was achieved for vessels with contrast to noise greater than 3.0 and vein radii greater than 0.75 voxels. The ICF method produced improved quantitative accuracy of OEF measurement compared to the MIV approach (mean OEF error 7.7 vs. 12.4%). The ICF method provided estimates of vein radius (mean error <27%) and partial volume maps (root mean-squared error <13%). In vivo results demonstrated consistent estimates of OEF along vein segments. Conclusion: OEF quantification in small veins (1.5-4 voxels in diameter) had lower error when using partial volume estimates from the ICF method.

    View details for DOI 10.3389/fnins.2017.00089

    View details for Web of Science ID 000394683900001

    View details for PubMedID 28289372

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


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

    View details for DOI 10.1177/0271678X17691784

    View details for PubMedID 28155582

  • Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease. Quantitative imaging in medicine and surgery Kogan, F., Fan, A. P., Gold, G. E. 2016; 6 (6): 756-771


    Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

    View details for DOI 10.21037/qims.2016.12.16

    View details for PubMedID 28090451

    View details for PubMedCentralID PMC5219958

  • PET/MRI of metabolic activity in osteoarthritis: A feasibility study. Journal of magnetic resonance imaging : JMRI Kogan, F., Fan, A. P., McWalter, E. J., Oei, E. H., Quon, A., Gold, G. E. 2016


    To evaluate positron emission tomography / magnetic resonance imaging (PET/MRI) knee imaging to detect and characterize osseous metabolic abnormalities and correlate PET radiotracer uptake with osseous abnormalities and cartilage degeneration observed on MRI.Both knees of 22 subjects with knee pain or injury were scanned at one timepoint, without gadolinium, on a hybrid 3.0T PET-MRI system following injection of (18) F-fluoride or (18) F-fluorodeoxyglucose (FDG). A musculoskeletal radiologist identified volumes of interest (VOIs) around bone abnormalities on MR images and scored bone marrow lesions (BMLs) and osteophytes using a MOAKS scoring system. Cartilage appearance adjacent to bone abnormalities was graded with MRI-modified Outerbridge classifications. On PET standardized uptake values (SUV) maps, VOIs with SUV greater than 5 times the SUV in normal-appearing bone were identified as high-uptake VOI (VOIHigh ). Differences in (18) F-fluoride uptake between bone abnormalities, BML, and osteophyte grades and adjacent cartilage grades on MRI were identified using Mann-Whitney U-tests.SUVmax in all subchondral bone lesions (BML, osteophytes, sclerosis) was significantly higher than that of normal-appearing bone on MRI (P < 0.001 for all). Of the 172 high-uptake regions on (18) F-fluoride PET, 63 (37%) corresponded to normal-appearing subchondral bone on MRI. Furthermore, many small grade 1 osteophytes (40 of 82 [49%]), often described as the earliest signs of osteoarthritis (OA), did not show high uptake. Lastly, PET SUVmax in subchondral bone adjacent to grade 0 cartilage was significantly lower compared to that of grades 1-2 (P < 0.05) and grades 3-4 cartilage (P < 0.001).PET/MRI can simultaneously assess multiple early metabolic and morphologic markers of knee OA across multiple tissues in the joint. Our findings suggest that PET/MR may detect metabolic abnormalities in subchondral bone, which appear normal on MRI.2 J. Magn. Reson. Imaging 2016.

    View details for DOI 10.1002/jmri.25529

    View details for PubMedID 27796082

  • 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

  • Mitigation of partial volume effects in susceptibility-based oxygenation measurements by joint utilization of magnitude and phase (JUMP). Magnetic resonance in medicine McDaniel, P., Bilgic, B., Fan, A. P., Stout, J. N., Adalsteinsson, E. 2016: -?


    Susceptibility-based blood oxygenation measurements in small vessels of the brain derive from gradient echo (GRE) phase and can provide localized assessment of brain function and pathology. However, when vessel diameter becomes smaller than the acquisition voxel size, partial volume effects compromise these measurements. The purpose of this study was to develop a technique to improve the reliability of vessel oxygenation estimates in the presence of partial volume effects.Intravoxel susceptibility variations are present when a vessel and parenchyma experience partial volume effects, modifying the voxel's GRE phase signal and attenuating the GRE magnitude signal. Using joint utilization of magnitude and phase (JUMP), both vessel susceptibility and voxel partial volume fraction can be estimated, providing measurements of venous oxygen saturation ( Yv) in straight, nearly vertical vessels that have improved robustness to partial volume effects.JUMP was demonstrated by estimating vessel Yv in numerical and in vivo experiments. Deviations from ground truth of Yv measurements in vessels tilted up to 30 from B0 were reduced by over 50% when using JUMP compared with phase-only techniques.JUMP exploits both magnitude and phase data in GRE imaging to mitigate partial volume effects in estimation of vessel oxygenation. Magn Reson Med, 2016. 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.26227

    View details for PubMedID 27059521

  • Baseline oxygenation in the brain: Correlation between respiratory-calibration and susceptibility methods NEUROIMAGE Fan, A. P., Schaefer, A., Huber, L., Lampe, L., von Smuda, S., Moeller, H. E., Villringer, A., Gauthier, C. J. 2016; 125: 920-931
  • Fast quantitative susceptibility mapping using 3D EPI and total generalized variation NEUROIMAGE Langkammer, C., Bredies, K., Poser, B. A., Barth, M., Reishofer, G., Fan, A. P., Bilgic, B., Fazekas, F., Mainero, C., Ropele, S. 2015; 111: 622-630


    Quantitative susceptibility mapping (QSM) allows new insights into tissue composition and organization by assessing its magnetic property. Previous QSM studies have already demonstrated that magnetic susceptibility is highly sensitive to myelin density and fiber orientation as well as to para- and diamagnetic trace elements. Image resolution in QSM with current approaches is limited by the long acquisition time of 3D scans and the need for high signal to noise ratio (SNR) to solve the dipole inversion problem. We here propose a new total-generalized-variation (TGV) based method for QSM reconstruction, which incorporates individual steps of phase unwrapping, background field removal and dipole inversion in a single iteration, thus yielding a robust solution to the reconstruction problem. This approach has beneficial characteristics for low SNR data, allowing for phase data to be rapidly acquired with a 3D echo planar imaging (EPI) sequence. The proposed method was evaluated with a numerical phantom and in vivo at 3 and 7 T. Compared to total variation (TV), TGV-QSM enforced higher order smoothness which yielded solutions closer to the ground truth and prevented stair-casing artifacts. The acquisition time for images with 1mm isotropic resolution and whole brain coverage was 10s on a clinical 3 Tesla scanner. In conclusion, 3D EPI acquisition combined with single-step TGV reconstruction yields reliable QSM images of the entire brain with 1mm isotropic resolution in seconds. The short acquisition time combined with the robust reconstruction may enable new QSM applications in less compliant populations, clinical susceptibility tensor imaging, and functional resting state examinations.

    View details for DOI 10.1016/j.neuroimage.2015.02.041

    View details for Web of Science ID 000352224100054

    View details for PubMedID 25731991

  • Regional quantification of cerebral venous oxygenation from MRI susceptibility during hypercapnia NEUROIMAGE Fan, A. P., Evans, K. C., Stout, J. N., Rosen, B. R., Adalsteinsson, E. 2015; 104: 146-155


    There is an unmet medical need for noninvasive imaging of regional brain oxygenation to manage stroke, tumor, and neurodegenerative diseases. Oxygenation imaging from magnetic susceptibility in MRI is a promising new technique to measure local venous oxygen extraction fraction (OEF) along the cerebral venous vasculature. However, this approach has not been tested in vivo at different levels of oxygenation. The primary goal of this study was to test whether susceptibility imaging of oxygenation can detect OEF changes induced by hypercapnia, via CO2 inhalation, within selected a priori brain regions. Ten healthy subjects were scanned at 3T with a 32-channel head coil. The end-tidal CO2 (ETCO2) was monitored continuously and inspired gases were adjusted to achieve steady-state conditions of eucapnia (413mmHg) and hypercapnia (504mmHg). Gradient echo phase images and pseudo-continuous arterial spin labeling (pcASL) images were acquired to measure regional OEF and CBF respectively during eucapnia and hypercapnia. By assuming constant cerebral oxygen consumption throughout both gas states, regional CBF values were computed to predict the local change in OEF in each brain region. Hypercapnia induced a relative decrease in OEF of -42.3% in the straight sinus, -39.9% in the internal cerebral veins, and approximately -50% in pial vessels draining each of the occipital, parietal, and frontal cortical areas. Across volunteers, regional changes in OEF correlated with changes in ETCO2. The reductions in regional OEF (via phase images) were significantly correlated (P<0.05) with predicted reductions in OEF derived from CBF data (via pcASL images). These findings suggest that susceptibility imaging is a promising technique for OEF measurements, and may serve as a clinical biomarker for brain conditions with aberrant regional oxygenation.

    View details for DOI 10.1016/j.neuroimage.2014.09.068

    View details for Web of Science ID 000345393800015

    View details for PubMedID 25300201

  • Quantitative oxygen extraction fraction from 7-Tesla MRI phase: reproducibility and application in multiple sclerosis JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Fan, A. P., Govindarajan, S. T., Kinkel, R. P., Madigan, N. K., Nielsen, A. S., Benner, T., Tinelli, E., Rosen, B. R., Adalsteinsson, E., Mainero, C. 2015; 35 (1): 131-139


    Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ~10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan-rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

    View details for DOI 10.1038/jcbfm.2014.187

    View details for Web of Science ID 000347392200016

    View details for PubMedID 25352043

  • Fast Quantitative Susceptibility Mapping with L1-Regularization and Automatic Parameter Selection MAGNETIC RESONANCE IN MEDICINE Bilgic, B., Fan, A. P., Polimeni, J. R., Cauley, S. F., Bianciardi, M., Adalsteinsson, E., Wald, L. L., Setsompop, K. 2014; 72 (5): 1444-1459


    To enable fast reconstruction of quantitative susceptibility maps with total variation penalty and automatic regularization parameter selection.?(1) -Regularized susceptibility mapping is accelerated by variable splitting, which allows closed-form evaluation of each iteration of the algorithm by soft thresholding and fast Fourier transforms. This fast algorithm also renders automatic regularization parameter estimation practical. A weighting mask derived from the magnitude signal can be incorporated to allow edge-aware regularization.Compared with the nonlinear conjugate gradient (CG) solver, the proposed method is 20 times faster. A complete pipeline including Laplacian phase unwrapping, background phase removal with SHARP filtering, and ?(1) -regularized dipole inversion at 0.6 mm isotropic resolution is completed in 1.2 min using MATLAB on a standard workstation compared with 22 min using the CG solver. This fast reconstruction allows estimation of regularization parameters with the L-curve method in 13 min, which would have taken 4 h with the CG algorithm. The proposed method also permits magnitude-weighted regularization, which prevents smoothing across edges identified on the magnitude signal. This more complicated optimization problem is solved 5 times faster than the nonlinear CG approach. Utility of the proposed method is also demonstrated in functional blood oxygen level-dependent susceptibility mapping, where processing of the massive time series dataset would otherwise be prohibitive with the CG solver.Online reconstruction of regularized susceptibility maps may become feasible with the proposed dipole inversion.

    View details for DOI 10.1002/mrm.25029

    View details for Web of Science ID 000343873900026

    View details for PubMedID 24259479

  • Quantitative Oxygenation Venography from MRI Phase MAGNETIC RESONANCE IN MEDICINE Fan, A. P., Bilgic, B., Gagnon, L., Witzel, T., Bhat, H., Rosen, B. R., Adalsteinsson, E. 2014; 72 (1): 149-159


    To demonstrate acquisition and processing methods for quantitative oxygenation venograms that map in vivo oxygen saturation (SvO2 ) along cerebral venous vasculature.Regularized quantitative susceptibility mapping (QSM) is used to reconstruct susceptibility values and estimate SvO2 in veins. QSM with ?1 and ?2 regularization are compared in numerical simulations of vessel structures with known magnetic susceptibility. Dual-echo, flow-compensated phase images are collected in three healthy volunteers to create QSM images. Bright veins in the susceptibility maps are vectorized and used to form a three-dimensional vascular mesh, or venogram, along which to display SvO2 values from QSM.Quantitative oxygenation venograms that map SvO2 along brain vessels of arbitrary orientation and geometry are shown in vivo. SvO2 values in major cerebral veins lie within the normal physiological range reported by (15) O positron emission tomography. SvO2 from QSM is consistent with previous MR susceptometry methods for vessel segments oriented parallel to the main magnetic field. In vessel simulations, ?1 regularization results in less than 10% SvO2 absolute error across all vessel tilt orientations and provides more accurate SvO2 estimation than ?2 regularization.The proposed analysis of susceptibility images enables reliable mapping of quantitative SvO2 along venograms and may facilitate clinical use of venous oxygenation imaging.

    View details for DOI 10.1002/mrm.24918

    View details for Web of Science ID 000337624400017

    View details for PubMedID 24006229

  • Phase-based regional oxygen metabolism (PROM) using MRI MAGNETIC RESONANCE IN MEDICINE Fan, A. P., Benner, T., Bolar, D. S., Rosen, B. R., Adalsteinsson, E. 2012; 67 (3): 669-678


    Venous oxygen saturation (Y(v) ) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO(2)) are important indicators for brain function and disease. Although MRI has been used for global measurements of these parameters, currently there is no recognized technique to quantify regional Y(v) and CMRO(2) using noninvasive imaging. This article proposes a technique to quantify CMRO(2) from independent MRI estimates of Y(v) and cerebral blood flow. The approach uses standard gradient-echo and arterial spin labeling acquisitions to make these measurements. Using MR susceptometry on gradient-echo phase images, Y(v) was quantified for candidate vein segments in gray matter that approximate a long cylinder parallel to the main magnetic field. Local cerebral blood flow for the identified vessel was determined from a corresponding region in the arterial spin labeling perfusion map. Fick's principle of arteriovenous difference was then used to quantify CMRO(2) locally around each vessel. Application of this method in young, healthy subjects provided gray matter averages of 59.6% 2.3% for Y(v), 51.7 6.4 mL/100 g/min for cerebral blood flow, and 158 18 ?mol/100 g/min for CMRO(2) (mean SD, n = 12), which is consistent with values previously reported by positron emission tomography and MRI.

    View details for DOI 10.1002/mrm.23050

    View details for Web of Science ID 000300683900011

    View details for PubMedID 21713981

  • MicroRNA Processing Pathway Regulates Olfactory Neuron Morphogenesis CURRENT BIOLOGY Berdnik, D., Fan, A. P., Potter, C. J., Luo, L. 2008; 18 (22): 1754-1759


    The microRNA (miRNA) processing pathway produces miRNAs as posttranscriptional regulators of gene expression. The nuclear RNase III Drosha catalyzes the first processing step together with the dsRNA binding protein DGCR8/Pasha generating pre-miRNAs [1, 2]. The next cleavage employs the cytoplasmic RNase III Dicer producing miRNA duplexes [3, 4]. Finally, Argonautes are recruited with miRNAs into an RNA-induced silencing complex for mRNA recognition (Figure 1A). Here, we identify two members of the miRNA pathway, Pasha and Dicer-1, in a forward genetic screen for mutations that disrupt wiring specificity of Drosophila olfactory projection neurons (PNs). The olfactory system is built as discrete map of highly stereotyped neuronal connections [5, 6]. Each PN targets dendrites to a specific glomerulus in the antennal lobe and projects axons stereotypically into higher brain centers [7-9]. In selected PN classes, pasha and Dicer-1 mutants cause specific PN dendrite mistargeting in the antennal lobe and altered axonal terminations in higher brain centers. Furthermore, Pasha and Dicer-1 act cell autonomously in postmitotic neurons to regulate dendrite and axon targeting during development. However, Argonaute-1 and Argonaute-2 are dispensable for PN morphogenesis. Our findings suggest a role for the miRNA processing pathway in establishing wiring specificity in the nervous system.

    View details for DOI 10.1016/j.cub.2008.09.045

    View details for Web of Science ID 000261244800025

    View details for PubMedID 19013069

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