Dr. McNab is an MRI Physicist focused on the development of magnetic resonance imaging (MRI) contrast mechanisms and acquisition strategies that yield new and/or improved images of the in vivo human brain. Over the past decade, she has developed numerous MRI acquisition methods, with her primary contributions being in the field of diffusion MRI. Dr. McNab has extensive experience with the most cutting-edge MRI technology, including the world's strongest human-MRI gradients (300 mT/m), highly-parallelized phased-array RF coils (64-channels) and ultra-high magnetic field (7T).

Academic Appointments

Administrative Appointments

  • Director of Industry Collaborations, Department of Radiology, Stanford University (2020 - Present)

Honors & Awards

  • Senior Fellow, International Society for Magnetic Resonance in Medicine (2024)
  • Distinguished Investigator, The Academy for Radiology & Biomedical Imaging Research (2023)
  • Basic Scientist of the Year, Department of Radiology Stanford (2022)

Boards, Advisory Committees, Professional Organizations

  • Scientist from North America, Board of Trustees, International Society for Magnetic Resonance in Medicine (2024 - Present)
  • Faculty Evaluation Process Ad Hoc Committee Member, Department of Radiology, Stanford Unviersity (2022 - Present)
  • Instructor Review Committee Member, Department of Radiology, Stanford University (2023 - Present)
  • Ex Officio, Executive Committee Member, The AIMI Center at Stanford (2021 - Present)
  • Oversight Committee Member, Pre-Clinical MRI Lab at the Wu Tsai Neuroscience Institute at Stanford (2019 - Present)
  • Annual Meeting Program Committee Member, International Society for Magnetic Resonance in Medicine (2015 - 2017)
  • Chair of the Diffusion Study Group, International Society for Magnetic Resonance in Medicine (2018 - 2019)

Professional Education

  • Post-doc, Harvard Medical School, Massachusetts General Hospital, Radiology (2012)
  • PhD, University of Oxford, MRI Physics (2009)
  • MSc, University of Western Ontario, Medical Biophysics (2005)
  • BSc, University of British Columbia, Physics (2003)


  • McNab, Leuze. "United States Patent 11,291,852 Neuro-navigation device for localization of internal anatomical regions", Leland Stanford Junior University, Apr 5, 2022
  • McNab, Leuze, Sathyanarayana. "United States Patent 11,024,096 Improved Virtual-to-Real Alignment for Augmented Reality", Leland Stanford Junior University, Jun 1, 2021
  • Deisseroth, McNab, Ye, Tian. "United States Patent 10,641,782 Low Cost, High-Throughput CLARITY Imaging with Single-Cell Resolution and Axon Visualization", Leland Stanford Junior University, May 5, 2020

Current Research and Scholarly Interests

My research is focused on developing magnetic resonance imaging (MRI) methods that probe brain tissue microstructure. This requires new MRI contrast mechanisms, strategic encoding and reconstruction schemes, physiological monitoring, brain tissue modeling and validation. Applications of these methods include neuronavigation, neurosurgical planning and the development of improved biomarkers for brain development, degeneration, disease and injury.

Active projects include:
- development of q-space trajectory imaging methods for probing tissue microstructure
- development of diffusion MRI methods for mapping cortical fiber patterns
- comparisons of MRI with CLARITY 3D histology
- development of a mixed-reality neuronavigation system for TMS
- leveraging 7T MRI for predicting healthy versus pathological aging
- developing diffusion tractography-based neurosurgical targeting methods

2023-24 Courses

Stanford Advisees

Graduate and Fellowship Programs

All Publications

  • An orexigenic subnetwork within the human hippocampus. Nature Barbosa, D. A., Gattas, S., Salgado, J. S., Kuijper, F. M., Wang, A. R., Huang, Y., Kakusa, B., Leuze, C., Luczak, A., Rapp, P., Malenka, R. C., Hermes, D., Miller, K. J., Heifets, B. D., Bohon, C., McNab, J. A., Halpern, C. H. 2023


    Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1-4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

    View details for DOI 10.1038/s41586-023-06459-w

    View details for PubMedID 37648849

    View details for PubMedCentralID 6468104

  • Frequency-dependent diffusion kurtosis imaging in the human brain using an oscillating gradient spin echo sequence and a high-performance head-only gradient. NeuroImage Dai, E., Zhu, A., Yang, G. K., Quah, K., Tan, E. T., Fiveland, E., Foo, T. K., McNab, J. A. 2023: 120328


    Measuring the time/frequency dependence of diffusion MRI is a promising approach to distinguishing between the effects of different tissue microenvironments, such as membrane restriction, tissue heterogeneity, and compartmental water exchange. In this study, we measure the frequency dependence of diffusivity (D) and kurtosis (K) with the oscillating gradient diffusion encoding waveforms and diffusion kurtosis imaging (DKI) model in human brains in a high-performance, head-only MAGNUS gradient system, with a combination of b-values, oscillating frequencies (f), and echo time that has not been achieved in human studies before. Frequency dependence of diffusivity and kurtosis are observed in both global and regional white matter (WM) and gray matter (GM) regions and characterized with a power-law model ∼Λ*fθ. The frequency dependences of diffusivity and kurtosis (including changes between fmin and fmax, Λ, and θ) vary over different WM and GM regions, indicating potential microstructure changes over different regions. A trend of decreasing kurtosis over frequency in the short-time limit is successfully captured for in vivo human brains. The effects of gradient nonlinearity (GNL) on frequency-dependent diffusivity and kurtosis measurements are investigated and corrected. Our results show that the GNL has prominent scaling effects on the measured diffusivity values (3.5∼5.5% difference in the global WM and 6∼8% difference in the global cortex) and subsequently affects the corresponding power-law parameters (Λ, θ) while having a marginal influence on the measured kurtosis values (<0.05% difference) and power-law parameters (Λ, θ). This study expands previous OGSE studies and further demonstrates the translatability of frequency-dependent diffusivity and kurtosis measurements to human brains, which may provide new opportunities to probe human brain microstructure in health and disease.

    View details for DOI 10.1016/j.neuroimage.2023.120328

    View details for PubMedID 37586445

  • Quantitative MRI reveals widespread, network-specific myelination change during generalized epilepsy progression. NeuroImage Kung, G. C., Knowles, J. K., Batra, A., Ni, L., Rosenberg, J., McNab, J. A. 2023: 120312


    Activity-dependent myelination is a fundamentally important mode of brain plasticity which significantly influences function. We recently discovered that absence seizures, which occur in multiple forms of generalized epilepsy, can induce activity-dependent myelination, which in turn promotes further progression of epilepsy. Structural alterations of myelin are likely to be widespread, given that absence seizures arise from an extensive thalamocortical network involving frontoparietal regions of the bilateral hemispheres. However, the temporal course and spatial extent of myelin plasticity is unknown, due to limitations of gold-standard histological methods such as electron microscopy (EM). In this study, we leveraged magnetization transfer and diffusion MRI for estimation of g-ratios across major white matter tracts in a mouse model of generalized epilepsy with progressive absence seizures. Electron microscopy was performed on the same brains after MRI. After seizure progression, we found increased myelination (decreased g-ratios) throughout the anterior portion (genu-to-body) of the corpus callosum but not in the posterior portion (body-splenium) nor in the fornix or the internal capsule. Curves obtained from averaging g-ratio values at every longitudinal point of the corpus callosum were statistically different with p<0.0001. Seizure-associated myelin differences found in the corpus callosum body with MRI were statistically significant (p = 0.0027) and were concordant with EM in the same region (p = 0.01). Notably, these differences were not detected by diffusion tensor imaging. This study reveals widespread myelin structural change that is specific to the absence seizure network.Furthermore, our findings demonstrate the potential utility and importance of MRI-based g-ratio estimation to non-invasively detect myelin plasticity.

    View details for DOI 10.1016/j.neuroimage.2023.120312

    View details for PubMedID 37574120

  • Multi-band multi-shot diffusion MRI reconstruction with joint usage of structured low-rank constraints and explicit phase mapping. Magnetic resonance in medicine Dai, E., Mani, M., McNab, J. A. 2022


    To develop a joint reconstruction method for multi-band multi-shot diffusion MRI.Multi-band multi-shot EPI acquisition is an effective approach for high-resolution diffusion MRI, but requires specific algorithms to correct the inter-shot phase variations. The phase correction can be done by first estimating the explicit phase map and then feeding it into the k-space signal formulation model. Alternatively, the phase information can be used indirectly as structured low-rank constraints in k-space. The 2 methods differ in reconstruction accuracy and efficiency. We aim to combine the 2 different approaches for improved image quality and reconstruction efficiency simultaneously, termed "joint usage of structured low-rank constraints and explicit phase mapping" (JULEP). The proposed JULEP reconstruction is tested on both single-band and multi-band, multi-shot diffusion data, with different resolutions and b values. The results of JULEP are compared with conventional methods with explicit phase mapping (i.e., multiplexed sensitivity-encoding [MUSE]) and structured low-rank constraints (i.e., MUSSELS), and another joint reconstruction method (i.e., network estimated artifacts for tempered reconstruction [NEATR]).JULEP improves the quality of the navigator and subsequently facilitates the reconstruction of final diffusion images. Compared with all 3 other methods (MUSE, MUSSELS, and NEATR), JULEP mitigates residual structural bias and improves temporal SNRs in the final diffusion image, particularly at high multi-band factors. Compared with MUSSELS, JULEP also improves computational efficiency.The proposed JULEP method significantly improves the image quality and reconstruction efficiency of multi-band multi-shot diffusion MRI, which can promote a broader application of high-resolution diffusion MRI.

    View details for DOI 10.1002/mrm.29422

    View details for PubMedID 36063492

  • Distortion-Free Diffusion Imaging Using Self-Navigated Cartesian Echo-Planar Time Resolved Acquisition and Joint Magnitude and Phase Constrained Reconstruction IEEE TRANSACTIONS ON MEDICAL IMAGING Dai, E., Lee, P. K., Dong, Z., Fu, F., Setsompop, K., McNab, J. A. 2022; 41 (1): 63-74


    Echo-planar time resolved imaging (EPTI) is an effective approach for acquiring high-quality distortion-free images with a multi-shot EPI (ms-EPI) readout. As with traditional ms-EPI acquisitions, inter-shot phase variations present a main challenge when incorporating EPTI into a diffusion-prepared pulse sequence. The aim of this study is to develop a self-navigated Cartesian EPTI-based (scEPTI) acquisition together with a magnitude and phase constrained reconstruction for distortion-free diffusion imaging. A self-navigated Cartesian EPTI-based diffusion-prepared pulse sequence is designed. The different phase components in EPTI diffusion signal are analyzed and an approach to synthesize a fully phase-matched navigator for the inter-shot phase correction is demonstrated. Lastly, EPTI contains richer magnitude and phase information than conventional ms-EPI, such as the magnitude and phase correlations along the temporal dimension. The potential of these magnitude and phase correlations to enhance the reconstruction is explored. The reconstruction results with and without phase matching and with and without phase or magnitude constraints are compared. Compared with reconstruction without phase matching, the proposed phase matching method can improve the accuracy of inter-shot phase correction and reduce signal corruption in the final diffusion images. Magnitude constraints further improve image quality by suppressing the background noise and thereby increasing SNR, while phase constraints can mitigate possible image blurring from adding magnitude constraints. The high-quality distortion-free diffusion images and simultaneous diffusion-relaxometry imaging capacity provided by the proposed EPTI design represent a highly valuable tool for both clinical and neuroscientific assessments of tissue microstructure.

    View details for DOI 10.1109/TMI.2021.3104291

    View details for Web of Science ID 000736740900007

    View details for PubMedID 34383645

  • Diffusion MRI tractography guides investigation of the zona incerta: a novel target for deep brain stimulation. Biological psychiatry Saluja, S., Qiu, L., Wang, A. R., Campos, G., Selheimer, R., McNab, J. A., Haber, S. N., Barbosa, D. A., Halpern, C. H. 2024


    The zona incerta (ZI) is a subcortical structure primarily investigated in rodents, that is implicated in various behaviors from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In our study, we used diffusion MRI tractography to segment the ZI and gain insight into its connectivity in various circuits in humans.We performed probabilistic tractography in 7T on 178 subjects from the Human Connectome Project to validate the ZI's anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel's connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed.We identified two dominant clusters that delineated the whole ZI into rostral (ZIr) and caudal (ZIc) subregions. ZIc primarily connected with motor regions, while ZIr received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant's MRI for placement of stereoencephalographic leads for electrophysiology-guided DBS for treating their obsessive-compulsive disorder. ZIr stimulation improved the patient's core symptoms (mean improvement: 21%).We present a tractography-based atlas of the rostral and caudal ZI subregions, constructed using high resolution diffusion MRI from 178 healthy subjects. Our work provides an anatomic foundation to explore the ZIr as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry.

    View details for DOI 10.1016/j.biopsych.2024.02.1004

    View details for PubMedID 38401802

  • An Individualized Tractography Pipeline for the Nucleus Basalis of Meynert Lateral Tract. medRxiv : the preprint server for health sciences Crockett, R. A., Wilkins, K. B., Zeineh, M. M., McNab, J. A., Henderson, J. M., Buch, V. P., Brontë-Stewart, H. M. 2023


    At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in PD. Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function. However, precise tractography modelling is required to identify the optimal target for neurosurgical planning. Individualized tractography approaches have been shown to be highly effective for accurately identifying DBS targets but have yet to be developed for the NBM.Using structural and diffusion weighted imaging, we developed a tractography pipeline for precise individualized identification of the lateral NBM target tract. Using dice similarity coefficients, the reliability of the tractography outputs was assessed across three cohorts to investigate: 1) whether this manual pipeline is more reliable than an existing automated pipeline currently used in the literature; 2) the inter- and intra-rater reliability of our pipeline in research scans of patients with PD; and 3) the reliability and practicality of this pipeline in clinical scans of DBS patients.The individualized manual pipeline was found to be significantly more reliable than the existing automated pipeline for both the segmentation of the NBM region itself (p<0.001) and the reconstruction of the target lateral tract (p=0.002). There was also no significant difference between the reliability of two different raters in the PD cohort (p=0.25), which showed high inter- (mean Dice coefficient >0.6) and intra-rater (mean Dice coefficient >0.7) reliability across runs. Finally, the pipeline was shown to be highly reliable within the clinical scans (mean Dice coefficient = 0.77). However, accurate reconstruction was only evident in 7/10 tracts.We have developed a reliable tractography pipeline for the identification and analysis of the NBM lateral tract in research and clinical grade imaging of healthy young adult and PD patient scans.

    View details for DOI 10.1101/2023.08.31.23294922

    View details for PubMedID 37693520

    View details for PubMedCentralID PMC10491381

  • An orexigenic subnetwork within the human hippocampus NATURE Barbosa, D. N., Gattas, S., Salgado, J. S., Kuijper, F., Wang, A. R., Huang, Y., Kakusa, B., Leuze, C., Luczak, A., Rapp, P., Malenka, R. C., Hermes, D., Miller, K. J., Heifets, B. D., Bohon, C., Mcnab, J. A., Halpern, C. H. 2023
  • A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder. Journal of the American Academy of Child and Adolescent Psychiatry Hegarty, J. P., Monterrey, J. C., Tian, Q., Cleveland, S. C., Gong, X., Phillips, J. M., Wolke, O., McNab, J. A., Hallmayer, J., Reiss, A. L., Hardan, A. Y., Lazzeroni, L. C. 2023


    OBJECTIVE: White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD.METHOD: Diffusion-weighted MRIs were obtained from same-sex twin pairs (aged 6-15 years) in which at least one twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a new version of the twin-pair difference score analysis method that estimates the contribution of genetic and environmental factors to shared covariance between different brain and behavioral traits.RESULTS: Good quality data were available from 84 twin pairs, 50 ASD pairs [32 concordant for ASD (16 monozygotic; 16 dizygotic), 16 discordant for ASD (3 monozygotic; 13 dizygotic), and 2 pairs in which one twin had ASD and the other exhibited some subthreshold symptoms (1 monozygotic; 1 dizygotic)] and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A=0.80 [0.57,1.02]; A=0.80 [0.55,1.04]) and twins concordant for having ASD (A=0.71 [0.33,1.09]; A= 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD, e.g., our new twin-pair difference-scores analysis indicated that genetic factors may have contributed to 40-50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD, e.g., twin-pair difference-scores suggested that unique environmental factors may have contributed to 10-20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule.CONCLUSION: White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences.DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

    View details for DOI 10.1016/j.jaac.2023.05.030

    View details for PubMedID 37406770

  • Human habit neural circuitry may be perturbed in eating disorders. Science translational medicine Wang, A. R., Kuijper, F. M., Barbosa, D. A., Hagan, K. E., Lee, E., Tong, E., Choi, E. Y., McNab, J. A., Bohon, C., Halpern, C. H. 2023; 15 (689): eabo4919


    Circuit-based mechanisms mediating the development and execution of habitual behaviors involve complex cortical-striatal interactions that have been investigated in animal models and more recently in humans. However, how human brain circuits implicated in habit formation may be perturbed in psychiatric disorders remains unclear. First, we identified the locations of the sensorimotor putamen and associative caudate in the human brain using probabilistic tractography from Human Connectome Project data. We found that multivariate connectivity of the sensorimotor putamen was altered in humans with binge eating disorder and bulimia nervosa and that the degree of alteration correlated with severity of disordered eating behavior. Furthermore, the extent of this circuit aberration correlated with mean diffusivity in the sensorimotor putamen and decreased basal dopamine D2/3 receptor binding potential in the striatum, consistent with previously reported microstructural changes and dopamine signaling mediating habit learning in animal models. Our findings suggest a neural circuit that links habit learning and binge eating behavior in humans, which could, in part, explain the treatment-resistant behavior common to eating disorders and other psychiatric conditions.

    View details for DOI 10.1126/scitranslmed.abo4919

    View details for PubMedID 36989377

  • Audiovisual augmentation for coil positioning in transcranial magnetic stimulation COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING-IMAGING AND VISUALIZATION Schutz, L., Weber, E., Niu, W., Daniel, B., McNab, J., Navab, N., Leuze, C. 2022
  • High-resolution hippocampal diffusion tensor imaging of mesial temporal sclerosis in refractory epilepsy. Epilepsia Chau Loo Kung, G., Chiu, A., Davey, Z., Mouchawar, N., Carlson, M., Moein Taghavi, H., Martin, D., Graber, K., Razavi, B., McNab, J., Zeineh, M. 2022


    OBJECTIVE: We explore the possibility of using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to discern microstructural abnormalities in the hippocampus indicative of mesial temporal sclerosis (MTS) at the subfield level.METHODS: We analyzed data from 57 patients with refractory epilepsy who previously underwent 3.0-T magnetic resonance imaging (MRI) including DTI as a standard part of presurgical workup. We collected information about each subject's seizure semiology, conventional electroencephalography (EEG), high-density EEG, positron emission tomography reports, surgical outcome, and available histopathological findings to assign a final diagnostic category. We also reviewed the radiology MRI report to determine the radiographic category. DTI- and NODDI-based metrics were obtained in the hippocampal subfields.RESULTS: By examining diffusion characteristics among subfields in the final diagnostic categories, we found lower orientation dispersion indices and elevated axial diffusivity in the dentate gyrus in MTS compared to no MTS. By similarly examining among subfields in the different radiographic categories, we found all diffusion metrics were abnormal in the dentate gyrus and CA1. We finally examined whether diffusion imaging would better inform a radiographic diagnosis with respect to the final diagnosis, and found that dentate diffusivity suggested subtle changes that may help confirm a positive radiologic diagnosis.SIGNIFICANCE: The results suggest that diffusion metric analysis at the subfield level, especially in dentate gyrus and CA1, maybe useful for clinical confirmation of MTS.

    View details for DOI 10.1111/epi.17330

    View details for PubMedID 35751514

  • Aberrant impulse control circuitry in obesity. Molecular psychiatry Barbosa, D. A., Kuijper, F. M., Duda, J., Wang, A. R., Cartmell, S. C., Saluja, S., Cunningham, T., Shivacharan, R. S., Bhati, M. T., Safer, D. L., Lock, J. D., Malenka, R. C., de Oliveira-Souza, R., Williams, N. R., Grossman, M., Gee, J. C., McNab, J. A., Bohon, C., Halpern, C. H. 2022


    The ventromedial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) circuit has been implicated in impulsive reward-seeking. This disinhibition has been implicated in obesity and often manifests as binge eating, which is associated with worse treatment outcomes and comorbidities. It remains unclear whether the vmPFC-NAc circuit is perturbed in impulsive eaters with obesity. Initially, we analyzed publicly available, high-resolution, normative imaging data to localize where vmPFC structural connections converged within the NAc. These structural connections were found to converge ventromedially in the presumed NAc shell subregion. We then analyzed multimodal clinical and imaging data to test the a priori hypothesis that the vmPFC-NAc shell circuit is linked to obesity in a sample of female participants that regularly engaged in impulsive eating (i.e., binge eating). Functionally, vmPFC-NAc shell resting-state connectivity was inversely related to body mass index (BMI) and decreased in the obese state. Structurally, vmPFC-NAc shell structural connectivity and vmPFC thickness were inversely correlated with BMI; obese binge-prone participants exhibited decreased vmPFC-NAc structural connectivity and vmPFC thickness. Finally, to examine a causal link to binge eating, we directly probed this circuit in one binge-prone obese female using NAc deep brain stimulation in a first-in-human trial. Direct stimulation of the NAc shell subregion guided by local behaviorally relevant electrophysiology was associated with a decrease in number of weekly episodes of uncontrolled eating and decreased BMI. This study unraveled vmPFC-NAc shell circuit aberrations in obesity that can be modulated to restore control over eating behavior in obesity.

    View details for DOI 10.1038/s41380-022-01640-5

    View details for PubMedID 35697760

  • Changes In The Cerebello-thalamo-cortical Network After MR-guided Focused Ultrasound Thalamotomy. Brain connectivity Thaler, C., Tian, Q., WIntermark, M., Ghanouni, P., Halpern, C., Henderson, J., Airan, R., Zeineh, M., Goubran, M., Leuze, C., Fiehler, J., Butts Pauly, K., McNab, J. A. 2022


    Object In recent years, transcranial MR-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor. So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in essential tremor patients treated with tcMRgFUS thalamotomy. Methods Eleven patients diagnosed with essential tremor were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3T MRI including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed prior to the procedure as well as one year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus (ML) and the corticospinal tract (CST) in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p<0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r=-0.54, p=0.04; MD: r=0.57, p=0.04); RD: r=0.67, p=0.036). Furthermore, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r=0.58; p=0.062; MD: r=-0.52, p=0.64; RD: r=-0.61 p=0.090). Conclusions Microstructural changes were detected within the CTCT after tcMRgFUS and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism and ultimately to improve targeting prospectively.

    View details for DOI 10.1089/brain.2021.0157

    View details for PubMedID 35678063

  • Complex negative emotions induced by electrical stimulation of the human hypothalamus. Brain stimulation Parvizi, J., Veit, M. J., Barbosa, D. A., Kucyi, A., Perry, C., Parker, J. J., Shivacharan, R. S., Chen, F., Yih, J., Gross, J. J., Fisher, R., McNab, J. A., Falco-Walter, J., Halpern, C. H. 2022


    Stimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated.To examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions.We examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG).Recordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and tractography.This patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion and the importance of subcortical structures in processing emotions. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus ought to be seen as a causally important functional unit, within a broader human telencephalon, for our human subjective experience.

    View details for DOI 10.1016/j.brs.2022.04.008

    View details for PubMedID 35413481

  • Augmented Reality for Retrosigmoid Craniotomy Planning JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Leuze, C., Neves, C. A., Gomez, A. M., Navab, N., Blevins, N., Vaisbuch, Y., McNab, J. A. 2021
  • Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue. Nature communications Georgiadis, M., Schroeter, A., Gao, Z., Guizar-Sicairos, M., Liebi, M., Leuze, C., McNab, J. A., Balolia, A., Veraart, J., Ades-Aron, B., Kim, S., Shepherd, T., Lee, C. H., Walczak, P., Chodankar, S., DiGiacomo, P., David, G., Augath, M., Zerbi, V., Sommer, S., Rajkovic, I., Weiss, T., Bunk, O., Yang, L., Zhang, J., Novikov, D. S., Zeineh, M., Fieremans, E., Rudin, M. 2021; 12 (1): 2941


    Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin's nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method's sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.

    View details for DOI 10.1038/s41467-021-22719-7

    View details for PubMedID 34011929

  • Rapid computation of TMS-induced E-fields using a dipole-based magnetic stimulation profile approach. NeuroImage Daneshzand, M., Makarov, S. N., de Lara, L. I., Guerin, B., McNab, J., Rosen, B. R., Hamalainen, M. S., Raij, T., Nummenmaa, A. 2021: 118097


    BACKGROUND: TMS neuronavigation with on-line display of the induced electric field (E-field) has the potential to improve quantitative targeting and dosing of stimulation, but present commercially available solutions are limited by simplified approximations.OBJECTIVE: Developing a near real-time method for accurate approximation of TMS induced E-fields with subject-specific high-resolution surface-based head models that can be utilized for TMS navigation.METHODS: Magnetic dipoles are placed on a closed surface enclosing an MRI-based head model of the subject to define a set of basis functions for the incident and total E-fields that define the subject's Magnetic Stimulation Profile (MSP). The near real-time speed is achieved by recognizing that the total E-field of the coil only depends on the incident E-field and the conductivity boundary geometry. The total E-field for any coil position can be obtained by matching the incident field of the stationary dipole basis set with the incident E-field of the moving coil and applying the same basis coefficients to the total E-field basis functions.RESULTS: Comparison of the MSP-based approximation with an established TMS solver shows great agreement in the E-field amplitude (relative maximum error around 5%) and the spatial distribution patterns (correlation >98%). Computation of the E-field took 100 ms on a cortical surface mesh with 120k facets.CONCLUSION: The numerical accuracy and speed of the MSP approximation method make it well suited for a wide range of computational tasks including interactive planning, targeting, dosing, and visualization of the intracranial E-fields for near real-time guidance of coil positioning.

    View details for DOI 10.1016/j.neuroimage.2021.118097

    View details for PubMedID 33940151

  • Comparison of diffusion MRI and CLARITY fiber orientation estimates in both gray and white matter regions of human and primate brain. NeuroImage Leuze, C., Goubran, M., Barakovic, M., Aswendt, M., Tian, Q., Hsueh, B., Crow, A., Weber, E. M., Steinberg, G. K., Zeineh, M., Plowey, E. D., Daducci, A., Innocenti, G., Thiran, J., Deisseroth, K., McNab, J. A. 2020; 228: 117692


    Diffusion MRI (dMRI) represents one of the few methods for mapping brain fiber orientations non-invasively. Unfortunately, dMRI fiber mapping is an indirect method that relies on inference from measured diffusion patterns. Comparing dMRI results with other modalities is a way to improve the interpretation of dMRI data and help advance dMRI technologies. Here, we present methods for comparing dMRI fiber orientation estimates with optical imaging of fluorescently labeled neurofilaments and vasculature in 3D human and primate brain tissue cuboids cleared using CLARITY. The recent advancements in tissue clearing provide a new opportunity to histologically map fibers projecting in 3D, which represents a captivating complement to dMRI measurements. In this work, we demonstrate the capability to directly compare dMRI and CLARITY in the same human brain tissue and assess multiple approaches for extracting fiber orientation estimates from CLARITY data. We estimate the three-dimensional neuronal fiber and vasculature orientations from neurofilament and vasculature stained CLARITY images by calculating the tertiary eigenvector of structure tensors. We then extend CLARITY orientation estimates to an orientation distribution function (ODF) formalism by summing multiple sub-voxel structure tensor orientation estimates. In a sample containing part of the human thalamus, there is a mean angular difference of 19o±15o between the primary eigenvectors of the dMRI tensors and the tertiary eigenvectors from the CLARITY neurofilament stain. We also demonstrate evidence that vascular compartments do not affect the dMRI orientation estimates by showing an apparent lack of correspondence (mean angular difference=49o±23o) between the orientation of the dMRI tensors and the structure tensors in the vasculature stained CLARITY images. In a macaque brain dataset, we examine how the CLARITY feature extraction depends on the chosen feature extraction parameters. By varying the volume of tissue over which the structure tensor estimates are derived, we show that orientation estimates are noisier with more spurious ODF peaks for sub-voxels below 30m3 and that, for our data, the optimal gray matter sub-voxel size is between 62.5m3 and 125m3. The example experiments presented here represent an important advancement towards robust multi-modal MRI-CLARITY comparisons.

    View details for DOI 10.1016/j.neuroimage.2020.117692

    View details for PubMedID 33385546

  • Oscillating diffusion-encoding with a high gradient-amplitude and high slew-rate head-only gradient for human brain imaging. Magnetic resonance in medicine Tan, E. T., Shih, R. Y., Mitra, J., Sprenger, T., Hua, Y., Bhushan, C., Bernstein, M. A., McNab, J. A., DeMarco, J. K., Ho, V. B., Foo, T. K. 2020


    PURPOSE: We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate).METHODS: Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm2 . Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom.RESULTS: Simulations show that to achieve high frequency and b-value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8-19%, radial: 9-27%, parallel: 8-15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short-range disorder model provided radial long-term diffusivities of D,MD = 911 ± 72 m2 /s, D,PD = 1519 ± 164 m2 /s, and D,RD = 640 ± 111 m2 /s and correlation lengths of lc ,MD = 0.802 ± 0.156 m, lc ,PD = 0.837 ± 0.172 m, and lc ,RD = 0.780 ± 0.174 m. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected.CONCLUSION: The high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head-gradient enables OGSE acquisition for in vivo human brain imaging.

    View details for DOI 10.1002/mrm.28180

    View details for PubMedID 32011027

  • Evidence for the role of the dorsal ventral lateral posterior thalamic nucleus connectivity in deep brain stimulation for Gilles de la Tourette syndrome. Journal of psychiatric research Kakusa, B. n., Saluja, S. n., Barbosa, D. A., Cartmell, S. n., Espil, F. M., Williams, N. R., McNab, J. A., Halpern, C. H. 2020; 132: 60–64


    Gilles de la Tourette syndrome (GTS) can manifest as debilitating, medically-refractory tics for which deep brain stimulation (DBS) of the centromedian-parafascicular complex (CM) can provide effective treatment. However, patients have reported benefit with activation of contacts dorsal to the CM and likely in the ventro-lateral thalamus (VL). At our institution, a case of a robust and durable response in a GTS patient required stimulation in the CM and more dorsally. We explore the structural connectivity of thalamic subregions associated with GTS using diffusion MRI tractography. Diffusion weighted images from 40 healthy Human Connectome Project (HCP) subjects and our GTS patient were analyzed. The VL posterior nucleus (VLp) and the CM were used as seeds for whole-brain probabilistic tractography. Leads were localized via linear registration of pre-/post-operative imaging and cross-referenced with the DBS Intrinsic Template Atlas. Tractography revealed high streamline probability from the CM and VLp to the superior frontal gyrus, rostral middle frontal gyrus, brainstem, and ventral diencephalon. Given reported variable responses to DBS along the thalamus, we segmented the VLp based on its connectivity profile. Ventral and dorsal subdivisions emerged, with streamline probability patterns differing between the dorsal VLp and CM. The CM, the most reported DBS target for GTS, and the dorsal VLp have different but seemingly complimentary connectivity profiles as evidenced by our patient who, at 1-year post-operatively, had significant therapeutic benefit. Stimulation of both regions may better target reward and motor circuits, resulting in enhanced symptom control for GTS.

    View details for DOI 10.1016/j.jpsychires.2020.09.024

    View details for PubMedID 33045620

  • Landmark-based mixed-reality perceptual alignment of medical imaging data and accuracy validation in living subjects IEEE International Symposium on Mixed and Augmented Reality (ISMAR) Leuze, C., Sathyanarayana, S., Daniel, B. L., McNab, J. A. 2020
  • Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation. Frontiers in human neuroscience Saluja, S. n., Barbosa, D. A., Parker, J. J., Huang, Y. n., Jensen, M. R., Ngo, V. n., Santini, V. E., Pauly, K. B., Ghanouni, P. n., McNab, J. A., Halpern, C. H. 2020; 14: 191


    Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.

    View details for DOI 10.3389/fnhum.2020.00191

    View details for PubMedID 32676015

    View details for PubMedCentralID PMC7333679

  • Application of holographic augmented reality for external approaches to the frontal sinus. International forum of allergy & rhinology Neves, C. A., Vaisbuch, Y. n., Leuze, C. n., McNab, J. A., Daniel, B. n., Blevins, N. H., Hwang, P. H. 2020


    External approaches to the frontal sinus such as osteoplastic flaps are challenging because they require blind entry into the sinus, posing risks of injury to the brain or orbit. Intraoperative computed tomography (CT)-based navigation is the current standard for planning the approach, but still necessitates blind entry into the sinus. The aim of this work was to describe a novel technique for external approaches to the frontal sinus using a holographic augmented reality (AR) application.Our team developed an AR system to create a 3-dimensional (3D) hologram of key anatomical structures, based on CT scans images. Using Magic Leap AR goggles for visualization, the frontal sinus hologram was aligned to the surface anatomy in 6 fresh cadaveric heads' anatomic boundaries, and the boundaries of the frontal sinus were demarcated based on the margins of the fused image. Trephinations and osteoplastic flap approaches were performed. The specimens were re-scanned to assess the accuracy of the osteotomy with respect to the actual frontal sinus perimeter.Registration and surgery were completed successfully in all specimens. Registration required an average of 2 minutes. The postprocedure CT showed a mean difference of 1.4 ± 4.1 mm between the contour of the osteotomy and the contour of the frontal sinus. One surgical complication (posterior table perforation) occurred (16%).We describe proof of concept of a novel technique utilizing AR to enhance external approaches to the frontal sinus. Holographic AR-enhanced surgical navigation holds promise for enhanced visualization of target structures during surgical approaches to the sinuses.

    View details for DOI 10.1002/alr.22546

    View details for PubMedID 32362076

  • Comparison of head pose tracking methods for mixed-reality neuronavigation for transcranial magnetic stimulation SPIE Medical Imaging Sathyanarayana, S., Leuze, C., Hargreaves, B., Daniel, B. L., Wetzstein, G., Etkin, A., Bhati, M. T., McNab, J. A. 2020

    View details for DOI 10.1117/12.2547917

  • Multimodal characterization of the human nucleus accumbens NEUROIMAGE Cartmell, S. D., Tian, Q., Thio, B. J., Leuze, C., Ye, L., Williams, N. R., Yang, G., Ben-Dor, G., Deisseroth, K., Grill, W. M., McNab, J. A., Halpern, C. H. 2019; 198: 137–49
  • Generalized diffusion spectrum magnetic resonance imaging (GDSI) for model-free reconstruction of the ensemble average propagator NEUROIMAGE Tian, Q., Yang, G., Leuze, C., Rokem, A., Edlow, B. L., McNab, J. A. 2019; 189: 497–515
  • Eddy current nulled constrained optimization of isotropic diffusion encoding gradient waveforms MAGNETIC RESONANCE IN MEDICINE Yang, G., Mcnab, J. A. 2019; 81 (3): 1818–32

    View details for DOI 10.1002/mrm.27539

    View details for Web of Science ID 000462091200028

  • Motion-robust reconstruction of multishot diffusion-weighted images without phase estimation through locally low-rank regularization MAGNETIC RESONANCE IN MEDICINE Hu, Y., Levine, E. G., Tian, Q., Moran, C. J., Wang, X., Taviani, V., Vasanawala, S. S., Mcnab, J. A., Daniel, B. L., Hargreaves, B. A. 2019; 81 (2): 1181–90

    View details for DOI 10.1002/mrm.27488

    View details for Web of Science ID 000462086300038

  • Generalized diffusion spectrum magnetic resonance imaging (GDSI) for model-free reconstruction of the ensemble average propagator. NeuroImage Tian, Q., Yang, G., Leuze, C. W., Rokem, A., Edlow, B. L., McNab, J. A. 2019


    Diffusion spectrum MRI (DSI) provides model-free estimation of the diffusion ensemble average propagator (EAP) and orientation distribution function (ODF) but requires the diffusion data to be acquired on a Cartesian q-space grid. Multi-shell diffusion acquisitions are more flexible and more commonly acquired but have, thus far, only been compatible with model-based analysis methods. Here, we propose a generalized DSI (GDSI) framework to recover the EAP from multi-shell diffusion MRI data. The proposed GDSI approach corrects for q-space sampling density non-uniformity using a fast geometrical approach. The EAP is directly calculated in a preferable coordinate system by multiplying the sampling density corrected q-space signals by a discrete Fourier transform matrix, without any need for gridding. The EAP is demonstrated as a way to map diffusion patterns in brain regions such as the thalamus, cortex and brainstem where the tissue microstructure is not as well characterized as in white matter. Scalar metrics such as the zero displacement probability and displacement distances at different fractions of the zero displacement probability were computed from the recovered EAP to characterize the diffusion pattern within each voxel. The probability averaged across directions at a specific displacement distance provides a diffusion property based image contrast that clearly differentiates tissue types. The displacement distance at the first zero crossing of the EAP averaged across directions orthogonal to the primary fiber orientation in the corpus callosum is found to be larger in the body (5.65 ± 0.09 mum) than in the genu (5.55 ± 0.15 mum) and splenium (5.4 ± 0.15 mum) of the corpus callosum, which corresponds well to prior histological studies. The EAP also provides model-free representations of angular structure such as the diffusion ODF, which allows estimation and comparison of fiber orientations from both the model-free and model-based methods on the same multi-shell data. For the model-free methods, detection of crossing fibers is found to be strongly dependent on the maximum b-value and less sensitive compared to the model-based methods. In conclusion, our study provides a generalized DSI approach that allows flexible reconstruction of the diffusion EAP and ODF from multi-shell diffusion data and data acquired with other sampling patterns.

    View details for PubMedID 30684636

  • Multimodal image registration and connectivity analysis for integration of connectomic data from microscopy to MRI. Nature communications Goubran, M. n., Leuze, C. n., Hsueh, B. n., Aswendt, M. n., Ye, L. n., Tian, Q. n., Cheng, M. Y., Crow, A. n., Steinberg, G. K., McNab, J. A., Deisseroth, K. n., Zeineh, M. n. 2019; 10 (1): 5504


    3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation with in-vivo biomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.

    View details for DOI 10.1038/s41467-019-13374-0

    View details for PubMedID 31796741

  • High-gradient diffusion MRI reveals distinct estimates of axon diameter index within different white matter tracts in the in vivo human brain. Brain structure & function Huang, S. Y., Tian, Q. n., Fan, Q. n., Witzel, T. n., Wichtmann, B. n., McNab, J. A., Daniel Bireley, J. n., Machado, N. n., Klawiter, E. C., Mekkaoui, C. n., Wald, L. L., Nummenmaa, A. n. 2019


    Axon diameter and density are important microstructural metrics that offer valuable insight into the structural organization of white matter throughout the human brain. We report the systematic acquisition and analysis of a comprehensive diffusion MRI data set acquired with 300 mT/m maximum gradient strength in a cohort of 20 healthy human subjects that yields distinct and consistent patterns of axon diameter index in white matter tracts of arbitrary orientation. We use a straightforward, previously validated approach to estimating indices of axon diameter and volume fraction that involves interpolating the diffusion signal perpendicular to the principal fiber orientation and fitting a three-compartment model of intra-axonal, extra-axonal and free water diffusion. The resultant maps confirm the presence of larger diameter indices in the body of corpus callosum compared to the genu and splenium, as previously reported, and show larger axon diameter index in the corticospinal tracts compared to adjacent white matter tracts such as the cingulum. An anterior-to-posterior gradient in axon diameter index is also observed, with smaller diameter indices in the frontal lobes and larger diameter indices in the parieto-occipital white matter. These observations are consistent with known trends from prior histologic studies in humans and non-human primates. Rather than serving as fully quantitative measures of axon diameter and density, our results may be considered as axon diameter- and volume fraction-weighted images that appear to be modulated by the underlying microstructure and may capture broad trends in axonal size and packing density, acknowledging that the precise origin of such modulation requires further investigation that will be facilitated by the availability of high gradient strengths for in vivo human imaging.

    View details for DOI 10.1007/s00429-019-01961-2

    View details for PubMedID 31563995

  • Multi-shot diffusion-weighted MRI reconstruction with magnitude-based spatial-angular locally low-rank regularization (SPA-LLR). Magnetic resonance in medicine Hu, Y. n., Wang, X. n., Tian, Q. n., Yang, G. n., Daniel, B. n., McNab, J. n., Hargreaves, B. n. 2019


    To resolve the motion-induced phase variations in multi-shot multi-direction diffusion-weighted imaging (DWI) by applying regularization to magnitude images.A nonlinear model was developed to estimate phase and magnitude images separately. A locally low-rank regularization (LLR) term was applied to the magnitude images from all diffusion-encoding directions to exploit the spatial and angular correlation. In vivo experiments with different resolutions and b-values were performed to validate the proposed method.The proposed method significantly reduces the noise level compared to the conventional reconstruction method and achieves submillimeter (0.8mm and 0.9mm isotropic resolutions) DWI with a b-value of 1,000  s / mm 2 and 1-mm isotropic DWI with a b-value of 2,000  s / mm 2 without modification of the sequence.A joint reconstruction method with spatial-angular LLR regularization on magnitude images substantially improves multi-direction DWI reconstruction, simultaneously removes motion-induced phase artifacts, and denoises images.

    View details for DOI 10.1002/mrm.28025

    View details for PubMedID 31593337

  • Multimodal characterization of the human nucleus accumbens. NeuroImage Cartmell, S. C., Tian, Q. n., Thio, B. J., Leuze, C. n., Ye, L. n., Williams, N. R., Yang, G. n., Ben-Dor, G. n., Deisseroth, K. n., Grill, W. M., McNab, J. A., Halpern, C. H. 2019


    Dysregulation of the nucleus accumbens (NAc) is implicated in numerous neuropsychiatric disorders. Treatments targeting this area directly (e.g. deep brain stimulation) demonstrate variable efficacy, perhaps owing to non-specific targeting of a functionally heterogeneous nucleus. Here we provide support for this notion, first observing disparate behavioral effects in response to direct simulation of different locations within the NAc in a human patient. These observations motivate a segmentation of the NAc into subregions, which we produce from a diffusion-tractography based analysis of 245 young, unrelated healthy subjects. We further explore the mechanism of these stimulation-induced behavioral responses by identifying the most probable subset of axons activated using a patient-specific computational model. We validate our diffusion-based segmentation using evidence from several modalities, including MRI-based measures of function and microstructure, human post-mortem immunohistochemical staining, and cross-species comparison of cortical-NAc projections that are known to be conserved. Finally, we visualize the passage of individual axon bundles through one NAc subregion in a post-mortem human sample using CLARITY 3D histology corroborated by 7T tractography. Collectively, these findings extensively characterize human NAc subregions and provide insight into their structural and functional distinctions with implications for stereotactic treatments targeting this region.

    View details for PubMedID 31077843

  • Motion-robust reconstruction of multishot diffusion-weighted images without phase estimation through locally low-rank regularization. Magnetic resonance in medicine Hu, Y., Levine, E. G., Tian, Q., Moran, C. J., Wang, X., Taviani, V., Vasanawala, S. S., McNab, J. A., Daniel, B. A., Hargreaves, B. L. 2018


    PURPOSE: The goal of this work is to propose a motion robust reconstruction method for diffusion-weighted MRI that resolves shot-to-shot phase mismatches without using phase estimation.METHODS: Assuming that shot-to-shot phase variations are slowly varying, spatial-shot matrices can be formed using a local group of pixels to form columns, in which each column is from a different shot (excitation). A convex model with a locally low-rank constraint on the spatial-shot matrices is proposed. In vivo brain and breast experiments were performed to evaluate the performance of the proposed method.RESULTS: The proposed method shows significant benefits when the motion is severe, such as for breast imaging. Furthermore, the resulting images can be used for reliable phase estimation in the context of phase-estimation-based methods to achieve even higher image quality.CONCLUSION: We introduced the shot-locally low-rank method, a reconstruction technique for multishot diffusion-weighted MRI without explicit phase estimation. In addition, its motion robustness can be beneficial to neuroimaging and body imaging.

    View details for PubMedID 30346058

  • Increased white matter connectivity seen in young judo athletes with MRI CLINICAL RADIOLOGY Toh, Z. H., Gu, Q. L., Seah, T. C., Wong, W. H., McNab, J. A., Chuang, K., Hong, X., Tang, P. H. 2018; 73 (10)
  • RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke. Stroke Ito, M., Aswendt, M., Lee, A. G., Ishizaka, S., Cao, Z., Wang, E. H., Levy, S. L., Smerin, D. L., McNab, J. A., Zeineh, M., Leuze, C., Goubran, M., Cheng, M. Y., Steinberg, G. K. 2018; 49 (9): 2191-2199


    Background and Purpose- Many restorative therapies have been used to study brain repair after stroke. These therapeutic-induced changes have revealed important insights on brain repair and recovery mechanisms; however, the intrinsic changes that occur in spontaneously recovery after stroke is less clear. The goal of this study is to elucidate the intrinsic changes in spontaneous recovery after stroke, by directly investigating the transcriptome of primary motor cortex in mice that naturally recovered after stroke. Methods- Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion. Functional recovery was evaluated using the horizontal rotating beam test. A novel in-depth lesion mapping analysis was used to evaluate infarct size and locations. Ipsilesional and contralesional primary motor cortices (iM1 and cM1) were processed for RNA-sequencing transcriptome analysis. Results- Cluster analysis of the stroke mice behavior performance revealed 2 distinct recovery groups: a spontaneously recovered and a nonrecovered group. Both groups showed similar lesion profile, despite their differential recovery outcome. RNA-sequencing transcriptome analysis revealed distinct biological pathways in the spontaneously recovered stroke mice, in both iM1 and cM1. Correlation analysis revealed that 38 genes in the iM1 were significantly correlated with improved recovery, whereas 74 genes were correlated in the cM1. In particular, ingenuity pathway analysis highlighted the involvement of cAMP signaling in the cM1, with selective reduction of Adora2a (adenosine receptor A2A), Drd2 (dopamine receptor D2), and Pde10a (phosphodiesterase 10A) expression in recovered mice. Interestingly, the expressions of these genes in cM1 were negatively correlated with behavioral recovery. Conclusions- Our RNA-sequencing data revealed a panel of recovery-related genes in the motor cortex of spontaneously recovered stroke mice and highlighted the involvement of contralesional cortex in spontaneous recovery, particularly Adora2a, Drd2, and Pde10a-mediated cAMP signaling pathway. Developing drugs targeting these candidates after stroke may provide beneficial recovery outcome.

    View details for DOI 10.1161/STROKEAHA.118.021508

    View details for PubMedID 30354987

    View details for PubMedCentralID PMC6205731

  • RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke STROKE Ito, M., Aswendt, M., Lee, A. G., Ishizaka, S., Cao, Z., Wang, E. H., Levy, S. L., Smerin, D. L., McNab, J. A., Zeineh, M., Leuze, C., Goubran, M., Cheng, M. Y., Steinberg, G. K. 2018; 49 (9): 2191–99
  • Double diffusion encoding MRI for the clinic MAGNETIC RESONANCE IN MEDICINE Yang, G., Tian, Q., Leuze, C., Wintermark, M., McNab, J. A. 2018; 80 (2): 507–20


    The purpose of this study is to develop double diffusion encoding (DDE) MRI methods for clinical use. Microscopic diffusion anisotropy measurements from DDE promise greater specificity to changes in tissue microstructure compared with conventional diffusion tensor imaging, but implementation of DDE sequences on whole-body MRI scanners is challenging because of the limited gradient strengths and lengthy acquisition times.A custom single-refocused DDE sequence was implemented on a 3T whole-body scanner. The DDE gradient orientation scheme and sequence parameters were optimized based on a Gaussian diffusion assumption. Using an optimized 5-min DDE acquisition, microscopic fractional anisotropy (μFA) maps were acquired for the first time in multiple sclerosis patients.Based on simulations and in vivo human measurements, six parallel and six orthogonal diffusion gradient pairs were found to be the minimum number of diffusion gradient pairs necessary to produce a rotationally invariant measurement of μFA. Simulations showed that optimal precision and accuracy of μFA measurements were obtained using b-values between 1500 and 3000 s/mm2 . The μFA maps showed improved delineation of multiple sclerosis lesions compared with conventional fractional anisotropy and distinct contrast from T2 -weighted fluid attenuated inversion recovery and T1 -weighted imaging.The μFA maps can be measured using DDE in a clinical setting and may provide new opportunities for characterizing multiple sclerosis lesions and other types of tissue degeneration. Magn Reson Med 80:507-520, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for PubMedID 29266375

    View details for PubMedCentralID PMC5910247

  • Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project JOURNAL OF NEUROTRAUMA Edlow, B. L., Keene, C., Perl, D. P., Iacono, D., Folkerth, R. D., Stewart, W., Mac Donald, C. L., Augustinack, J., Diaz-Arrastia, R., Estrada, C., Flannery, E., Gordon, W. A., Grabowski, T. J., Hansen, K., Hoffman, J., Kroenke, C., Larson, E. B., Lee, P., Mareyam, A., McNab, J. A., McPhee, J., Moreau, A. L., Renz, A., Richmire, K., Stevens, A., Tang, C. Y., Tirrell, L. S., Trittschuh, E. H., van der Kouwe, A., Varjabedian, A., Wald, L. L., Wu, O., Yendiki, A., Young, L., Zollei, L., Fischl, B., Crane, P. K., Dams-O'Connor, K. 2018


    Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

    View details for PubMedID 29421973

  • Characterizing Signals within Lesions and Mapping Brain Network Connectivity After Traumatic Axonal Injury: A 7 Tesla Resting-State FMRI Study. Brain connectivity Lee, S., Polimeni, J. R., Price, C. M., Edlow, B. L., McNab, J. A. 2018


    Resting-state functional magnetic resonance imaging (RS-FMRI) has been widely used to map brain functional connectivity, but it is unclear how to probe connectivity within and around lesions. Here we characterize RS-FMRI signal time-course properties and evaluate different seed placements within and around hemorrhagic traumatic axonal injury lesions. RS-FMRI was performed on a 7 Tesla scanner in a patient who recovered consciousness after traumatic coma and in three healthy controls. Eleven lesions in the patient were characterized in terms of: 1) temporal signal-to-noise ratio (tSNR); 2) physiological noise, through comparison of noise regressors derived from the white matter (WM), cerebrospinal fluid (CSF) and gray matter (GM); and 3) seed-based functional connectivity. Temporal SNR at the center of the lesions was 38.3% and 74.1% lower compared to the same region in the contralesional hemisphere of the patient and in the ipsilesional hemispheres of the controls, respectively. Within the lesions, WM noise was more prominent than CSF and GM noise. Lesional seeds did not produce discernable networks, but seeds in the contralesional hemisphere revealed networks whose nodes appeared to be shifted or obscured due to overlapping or nearby lesions. Single-voxel seed analysis demonstrated that placing a seed within a lesion's periphery was necessary to identify networks associated with the lesion region. These findings provide evidence of resting-state network changes in the human brain after recovery from traumatic coma. Further, we show that seed placement within a lesion's periphery or in the contralesional hemisphere may be necessary for network identification in patients with hemorrhagic traumatic axonal injury.

    View details for PubMedID 29665699

  • Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY Kenney, K., Iacono, D., Edlow, B. L., Katz, D. I., Diaz-Arrastia, R., Dams-O'Connor, K., Daneshvar, D. H., Stevens, A., Moreau, A. L., Tirrell, L. S., Varjabedian, A., Yendiki, A., van der Kouwe, A., Mareyam, A., McNab, J. A., Gordon, W. A., Fischl, B., McKee, A. C., Perl, D. P. 2018; 77 (1): 50–63


    We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.

    View details for PubMedID 29155947

  • Eddy current nulled constrained optimization of isotropic diffusion encoding gradient waveforms. Magnetic resonance in medicine Yang, G. n., McNab, J. A. 2018


    Isotropic diffusion encoding efficiently encodes additional microstructural information in combination with conventional linear diffusion encoding. However, the gradient-intensive isotropic diffusion waveforms generate significant eddy currents, which cause image distortions. The purpose of this study is to present a method for designing isotropic diffusion encoding waveforms with intrinsic eddy current nulling.Eddy current nulled gradient waveforms were designed using a constrained optimization waveform for a 3T GE Premier MRI system. Encoding waveforms were designed for a variety of eddy current null times and sequence timings to evaluate the achievable b-value. Waveforms were also tested with both eddy current nulling and concomitant field compensation. Distortion reduction was tested in both phantoms and the in vivo human brain.The feasibility of isotropic diffusion encoding with intrinsic correction of eddy current distortion and signal bias from concomitant fields was demonstrated. The constrained optimization algorithm produced gradient waveforms with the specified eddy current null times. The reduction in the achievable diffusion weighting was dependent on the number of eddy current null times. A reduction in the eddy current-induced image distortions was observed in both phantoms and in vivo human subjects.The proposed framework allows the design of isotropic diffusion-encoding sequences with reduced image distortion.

    View details for PubMedID 30368913

  • Mixed-reality guidance for brain stimulation treatment of depression Leuze, C., Yang, G., Hargreaves, B., Daniel, B., Mcnab, J. A., IEEE IEEE. 2018: 377–80
  • Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor. NeuroImage. Clinical Tian, Q., Wintermark, M., Jeffrey Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K. B., McNab, J. A. 2018; 19: 572–80


    Purpose: To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET).Materials and methods: Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment.Results: The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = -0.929, -0.75, -0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = -0.719, -0.976, -0.707, -0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively).Conclusion: Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

    View details for PubMedID 29984165

  • The separate effects of lipids and proteins on brain MRI contrast revealed through tissue clearing. NeuroImage Leuze, C., Aswendt, M., Ferenczi, E., Liu, C. W., Hsueh, B., Goubran, M., Tian, Q., Steinberg, G., Zeineh, M. M., Deisseroth, K., McNab, J. A. 2017


    Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY. We monitor the temporal dynamics of tissue clearance via NMR spectroscopy, protein assays and optical emission spectroscopy. MRI of cleared brain tissue showed: 1) minimal contrast on standard MRI sequences; 2) increased relaxation times; and 3) diffusion rates close to free water. We conclude that lipids, present in myelin and membranes, are a dominant source of MRI contrast in brain tissue.

    View details for DOI 10.1016/j.neuroimage.2017.04.021

    View details for PubMedID 28411157

  • Accelerating Functional MRI Using Fixed-Rank Approximations and Radial-Cartesian Sampling MAGNETIC RESONANCE IN MEDICINE Chiew, M., Graedel, N. N., McNab, J. A., Smith, S. M., Miller, K. L. 2016; 76 (6): 1825-1836


    Recently, k-t FASTER (fMRI Accelerated in Space-time by means of Truncation of Effective Rank) was introduced for rank-constrained acceleration of fMRI data acquisition. Here we demonstrate improvements achieved through a hybrid three-dimensional radial-Cartesian sampling approach that allows posthoc selection of acceleration factors, as well as incorporation of coil sensitivity encoding in the reconstruction.The multicoil rank-constrained reconstruction used hard thresholding and shrinkage on matrix singular values of the space-time data matrix, using sensitivity encoding and the nonuniform Fast Fourier Transform to enforce data consistency in the multicoil non-Cartesian k-t domain. Variable acceleration factors were made possible using a radial increment based on the golden ratio. Both retrospective and prospectively under-sampled data were used to assess the fidelity of the enhancements to the k-t FASTER technique in resting and task-fMRI data.The improved k-t FASTER is capable of tailoring acceleration factors for recovery of different signal components, achieving up to R = 12.5 acceleration in visual-motor task data. The enhancements reduce data matrix reconstruction errors even at much higher acceleration factors when compared directly with the original k-t FASTER approach.We have shown that k-t FASTER can be used to significantly accelerate fMRI data acquisition with little penalty to data quality. Magn Reson Med, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26079

    View details for Web of Science ID 000389127200017

    View details for PubMedID 26777798

  • Motion correction for functional MRI with three-dimensional hybrid radial-Cartesian EPI. Magnetic resonance in medicine Graedel, N. N., McNab, J. A., Chiew, M., Miller, K. L. 2016


    Subject motion is a major source of image degradation for functional MRI (fMRI), especially when using multishot sequences like three-dimensional (3D EPI). We present a hybrid radial-Cartesian 3D EPI trajectory enabling motion correction in k-space for functional MRI.The EPI "blades" of the 3D hybrid radial-Cartesian EPI sequence, called TURBINE, are rotated about the phase-encoding axis to fill out a cylinder in 3D k-space. Angular blades are acquired over time using a golden-angle rotation increment, allowing reconstruction at flexible temporal resolution. The self-navigating properties of the sequence are used to determine motion parameters from a high temporal-resolution navigator time series. The motion is corrected in k-space as part of the image reconstruction, and evaluated for experiments with both cued and natural motion.We demonstrate that the motion correction works robustly and that we can achieve substantial artifact reduction as well as improvement in temporal signal-to-noise ratio and fMRI activation in the presence of both severe and subtle motion.We show the potential for hybrid radial-Cartesian 3D EPI to substantially reduce artifacts for application in fMRI, especially for subject groups with significant head motion. The motion correction approach does not prolong the scan, and no extra hardware is required. Magn Reson Med, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    View details for DOI 10.1002/mrm.26390

    View details for PubMedID 27604503

  • Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-GradientDiffusion MR Imaging RADIOLOGY Huang, S. Y., Tobyne, S. M., Nummenmaa, A., Witzel, T., Wald, L. L., McNab, J. A., Klawiter, E. C. 2016; 280 (1): 244-251


    Purpose To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing-remitting MS and six healthy control subjects underwent diffusion-weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intra-axonal, extra-axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results MS lesions showed increased mean axon diameter (10.3 vs 7.9 μm in the genu, 10.4 vs 9.3 μm in the body, and 10.6 vs 8.2 μm in the splenium; P < .05) and decreased axon density ([0.48 vs 1.1] × 10(10)/m(2) in the genu, [0.40 vs 0.70] × 10(10)/m(2) in the body, and [0.35 vs 1.1] × 10(10)/m(2) in the splenium; P < .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM. (©) RSNA, 2016 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2016151582

    View details for Web of Science ID 000378721900027

    View details for PubMedID 26859256

  • Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences CELL Ye, L., Allen, W. E., Thompson, K. R., Tian, Q., Hsueh, B., Ramakrishnan, C., Wang, A., Jennings, J. H., Adhikari, A., Halpern, C. H., Witten, I. B., Barth, A. L., Luo, L., McNab, J. A., Deisseroth, K. 2016; 165 (7): 1776-1788


    A major challenge in understanding the cellular diversity of the brain has been linking activity during behavior with standard cellular typology. For example, it has not been possible to determine whether principal neurons in prefrontal cortex active during distinct experiences represent separable cell types, and it is not known whether these differentially active cells exert distinct causal influences on behavior. Here, we develop quantitative hydrogel-based technologies to connect activity in cells reporting on behavioral experience with measures for both brain-wide wiring and molecular phenotype. We find that positive and negative-valence experiences in prefrontal cortex are represented by cell populations that differ in their causal impact on behavior, long-range wiring, and gene expression profiles, with the major discriminant being expression of the adaptation-linked gene NPAS4. These findings illuminate cellular logic of prefrontal cortex information processing and natural adaptive behavior and may point the way to cell-type-specific understanding and treatment of disease-associated states.

    View details for DOI 10.1016/j.cell.2016.05.010

    View details for PubMedID 27238022

  • The Structural Connectome of the Human Central Homeostatic Network. Brain connectivity Edlow, B. L., McNab, J. A., Witzel, T., Kinney, H. C. 2016; 6 (3): 187-200


    Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

    View details for DOI 10.1089/brain.2015.0378

    View details for PubMedID 26530629

  • Q-space truncation and sampling in diffusion spectrum imaging. Magnetic resonance in medicine Tian, Q., Rokem, A., Folkerth, R. D., Nummenmaa, A., Fan, Q., Edlow, B. L., McNab, J. A. 2016


    To characterize the q-space truncation and sampling on the spin-displacement probability density function (PDF) in diffusion spectrum imaging (DSI).DSI data were acquired using the MGH-USC connectome scanner (Gmax  = 300 mT/m) with bmax  = 30,000 s/mm(2) , 17 × 17 × 17, 15 × 15 × 15 and 11 × 11 × 11 grids in ex vivo human brains and bmax  = 10,000 s/mm(2) , 11 × 11 × 11 grid in vivo. An additional in vivo scan using bmax =7,000 s/mm(2) , 11 × 11 × 11 grid was performed with a derated gradient strength of 40 mT/m. PDFs and orientation distribution functions (ODFs) were reconstructed with different q-space filtering and PDF integration lengths, and from down-sampled data by factors of two and three.Both ex vivo and in vivo data showed Gibbs ringing in PDFs, which becomes the main source of artifact in the subsequently reconstructed ODFs. For down-sampled data, PDFs interfere with the first replicas or their ringing, leading to obscured orientations in ODFs.The minimum required q-space sampling density corresponds to a field-of-view approximately equal to twice the mean displacement distance (MDD) of the tissue. The 11 × 11 × 11 grid is suitable for both ex vivo and in vivo DSI experiments. To minimize the effects of Gibbs ringing, ODFs should be reconstructed from unfiltered q-space data with the integration length over the PDF constrained to around the MDD. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.26071

    View details for PubMedID 26762670

  • In vivo mapping of human spinal cord microstructure at 300 mT/m NEUROIMAGE Duval, T., McNab, J. A., Setsompop, K., Witzel, T., Schneider, T., Huang, S. Y., Keil, B., Klawiter, E. C., Wald, L. L., Cohen-Adad, J. 2015; 118: 494-507


    The ability to characterize white matter microstructure non-invasively has important applications for the diagnosis and follow-up of several neurological diseases. There exists a family of diffusion MRI techniques, such as AxCaliber, that provide indices of axon microstructure, such as axon diameter and density. However, to obtain accurate measurements of axons with small diameters (<5μm), these techniques require strong gradients, i.e. an order of magnitude higher than the 40-80mT/m currently available in clinical systems. In this study we acquired AxCaliber diffusion data at a variety of different q-values and diffusion times in the spinal cord of five healthy subjects using a 300mT/m whole body gradient system. Acquisition and processing were optimized using state-of-the-art methods (e.g., 64-channel coil, template-based analysis). Results consistently show an average axon diameter of 4.5+/-1.1μm in the spinal cord white matter. Diameters ranged from 3.0μm (gracilis) to 5.9μm (spinocerebellar tracts). Values were similar across laterality (left-right), but statistically different across spinal cord pathways (p<10(-5)). The observed trends are similar to those observed in animal histology. This study shows, for the first time, in vivo mapping of axon diameter in the spinal cord at 300mT/m, thus creating opportunities for applications in spinal cord diseases.

    View details for DOI 10.1016/j.neuroimage.2015.06.038

    View details for Web of Science ID 000360630200047

    View details for PubMedCentralID PMC4562035

  • The impact of gradient strength on in vivo diffusion MRI estimates of axon diameter. NeuroImage Huang, S. Y., Nummenmaa, A., Witzel, T., Duval, T., Cohen-Adad, J., Wald, L. L., McNab, J. A. 2015; 106: 464-472


    Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3T human MRI scanner with a maximum gradient strength of 300mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293mT/m and diffusion times encompassing short (16 and 25ms) and long (60 and 94ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners.

    View details for DOI 10.1016/j.neuroimage.2014.12.008

    View details for PubMedID 25498429

    View details for PubMedCentralID PMC4285777

  • Targeting of White Matter Tracts with Transcranial Magnetic Stimulation BRAIN STIMULATION Nummenmaa, A., McNab, J. A., Savadjiev, P., Okada, Y., Haemaelaeinen, M. S., Wang, R., Wald, L. L., Pascual-Leone, A., Wedeen, V. J., Raij, T. 2014; 7 (1): 80-84


    TMS activations of white matter depend not only on the distance from the coil, but also on the orientation of the axons relative to the TMS-induced electric field, and especially on axonal bends that create strong local field gradient maxima. Therefore, tractography contains potentially useful information for TMS targeting.Here, we utilized 1-mm resolution diffusion and structural T1-weighted MRI to construct large-scale tractography models, and localized TMS white matter activations in motor cortex using electromagnetic forward modeling in a boundary element model (BEM).As expected, in sulcal walls, pyramidal cell axonal bends created preferred sites of activation that were not found in gyral crowns. The model agreed with the well-known coil orientation sensitivity of motor cortex, and also suggested unexpected activation distributions emerging from the E-field and tract configurations. We further propose a novel method for computing the optimal coil location and orientation to maximally stimulate a pre-determined axonal bundle.Diffusion MRI tractography with electromagnetic modeling may improve spatial specificity and efficacy of TMS.

    View details for DOI 10.1016/j.brs.2013.10.001

    View details for Web of Science ID 000329947300012

    View details for PubMedID 24220599

    View details for PubMedCentralID PMC3938327

  • A 22-channel receive array with Helmholtz transmit coil for anesthetized macaque MRI at 3 T NMR IN BIOMEDICINE Janssens, T., Keil, B., Serano, P., Mareyam, A., McNab, J. A., Wald, L. L., Vanduffel, W. 2013; 26 (11): 1431-1440


    The macaque monkey is an important model for cognitive and sensory neuroscience that has been used extensively in behavioral, electrophysiological, molecular and, more recently, neuroimaging studies. However, macaque MRI has unique technical differences relative to human MRI, such as the geometry of highly parallel receive arrays, which must be addressed to optimize imaging performance. A 22-channel receive coil array was constructed specifically for rapid high-resolution anesthetized macaque monkey MRI at 3 T. A local Helmholtz transmit coil was used for excitation. Signal-to-noise ratios (SNRs) and noise amplification for parallel imaging were compared with those of single- and four-channel receive coils routinely used for macaque MRI. The 22-channel coil yielded significant improvements in SNR throughout the brain. Using this coil, the SNR in peripheral brain was 2.4 and 1.7 times greater than that obtained with single- or four-channel coils, respectively. In the central brain, the SNR gain was 1.5 times that of both the single- and four-channel coils. Finally, the performance of the array for functional, anatomical and diffusion-weighted imaging was evaluated. For all three modalities, the use of the 22-channel array allowed for high-resolution and accelerated image acquisition. Copyright © 2013 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/nbm.2970

    View details for Web of Science ID 000329225200011

    View details for PubMedID 23703859

  • Corrigendum to "Surface based analysis of diffusion orientation for identifying architectonic domains in the in vivo human cortex" [NeuroImage 69 (2013) 87-100]. NeuroImage McNab, J. A., Polimeni, J. R., Wang, R., Augustinack, J. C., Fujimoto, K., Stevens, A., Triantafyllou, C., Janssens, T., Farivar, R., Folkerth, R. D., Vanduffel, W., Wald, L. L. 2013; 81: 505

    View details for DOI 10.1016/j.neuroimage.2013.04.037

    View details for PubMedID 30180375

  • The Human Connectome Project and beyond: Initial applications of 300 mT/m gradients NEUROIMAGE McNab, J. A., Edlow, B. L., Witzel, T., Huang, S. Y., Bhat, H., Heberlein, K., Feiweier, T., Liu, K., Keil, B., Cohen-Adad, J., Tisdall, M. D., Folkerth, R. D., Kinney, H. C., Wald, L. L. 2013; 80: 234-245


    The engineering of a 3T human MRI scanner equipped with 300mT/m gradients - the strongest gradients ever built for an in vivo human MRI scanner - was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCP's goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients are rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease.

    View details for DOI 10.1016/j.neuroimage.2013.05.074

    View details for Web of Science ID 000322416000018

    View details for PubMedID 23711537

  • Pushing the limits of in vivo diffusion MRI for the Human Connectome Project. NeuroImage Setsompop, K., Kimmlingen, R., Eberlein, E., Witzel, T., Cohen-Adad, J., McNab, J. A., Keil, B., Tisdall, M. D., Hoecht, P., Dietz, P., Cauley, S. F., Tountcheva, V., Matschl, V., Lenz, V. H., Heberlein, K., Potthast, A., Thein, H., Van Horn, J., Toga, A., Schmitt, F., Lehne, D., Rosen, B. R., Wedeen, V., Wald, L. L. 2013


    Perhaps more than any other "-omics" endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depend on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an "image" of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain's structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with Gmax=300mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to achieve a DSI scan in less than 5min. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coils at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing.

    View details for DOI 10.1016/j.neuroimage.2013.05.078

    View details for PubMedID 23707579

  • Surface based analysis of diffusion orientation for identifying architectonic domains in the in vivo human cortex NEUROIMAGE McNab, J. A., Polimeni, J. R., Wang, R., Augustinack, J. C., Fujimoto, K., Stevens, A., Janssens, T., Farivar, R., Folkerth, R. D., Vanduffel, W., Wald, L. L. 2013; 69: 87-100


    Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in gray matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical gray matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1.

    View details for DOI 10.1016/j.neuroimage.2012.11.065

    View details for Web of Science ID 000314627800010

    View details for PubMedID 23247190

    View details for PubMedCentralID PMC3557597

  • A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology BRAIN Kolasinski, J., Stagg, C. J., Chance, S. A., DeLuca, G. C., Esiri, M. M., Chang, E., Palace, J. A., McNab, J. A., Jenkinson, M., Miller, K. L., Johansen-Berg, H. 2012; 135: 2938-2951


    Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a 'tract-specific' pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies.

    View details for DOI 10.1093/brain/aws242

    View details for Web of Science ID 000310156700005

    View details for PubMedID 23065787

  • An implanted 8-channel array coil for high-resolution macaque MRI at 3 T NEUROIMAGE Janssens, T., Keil, B., Farivar, R., McNab, J. A., Polimeni, J. R., Gerits, A., Arsenault, J. T., Wald, L. L., Vanduffel, W. 2012; 62 (3): 1529-1536


    An 8-channel receive coil array was constructed and implanted adjacent to the skull in a male rhesus monkey in order to improve the sensitivity of (functional) brain imaging. The permanent implant was part of an acrylic headpost assembly and only the coil element loop wires were implanted. The tuning, matching, and preamplifier circuitry was connected via a removable external assembly. Signal-to-noise ratio (SNR) and noise amplification for parallel imaging were compared to single-, 4-, and 8-channel external receive-only coils routinely used for macaque fMRI. In vivo measurements showed significantly improved SNR within the brain for the implanted versus the external coils. Within a region-of-interest covering the cerebral cortex, we observed a 5.4-, 3.6-fold, and 3.4-fold increase in SNR compared to the external single-, 4-, and 8-channel coils, respectively. In the center of the brain, the implanted array maintained a 2.4×, 2.5×, and 2.1× higher SNR, respectively compared to the external coils. The array performance was evaluated for anatomical, diffusion tensor and functional brain imaging. This study suggests that a stable implanted phased-array coil can be used in macaque MRI to substantially increase the spatial resolution for anatomical, diffusion tensor, and functional imaging.

    View details for DOI 10.1016/j.neuroimage.2012.05.028

    View details for Web of Science ID 000307369000021

    View details for PubMedID 22609793

  • T-2* mapping and B-o orientation-dependence at 7 T reveal cyto- and myeloarchitecture organization of the human cortex NEUROIMAGE Cohen-Adad, J., Polimeni, J. R., Helmer, K. G., Benner, T., McNab, J. A., Wald, L. L., Rosen, B. R., Mainero, C. 2012; 60 (2): 1006-1014


    Ultra-high field MRI (≥ 7 T) has recently shown great sensitivity to depict patterns of tissue microarchitecture. Moreover, recent studies have demonstrated a dependency between T₂* and orientation of white matter fibers with respect to the main magnetic field B₀. In this study we probed the potential of T₂* mapping at 7 T to provide new markers of cortical architecture. We acquired multi-echo measurements at 7 T and mapped T₂* over the entire cortex of eight healthy individuals using surface-based analysis. B₀ dependence was tested by computing the angle θ(z) between the normal of the surface and the direction of B₀, then fitting T₂*(θ(z)) using model from the literature. Average T₂* in the cortex was 32.20 +/- 1.35 ms. Patterns of lower T₂* were detected in the sensorimotor, visual and auditory cortices, likely reflecting higher myelin content. Significantly lower T₂* was detected in the left hemisphere of the auditory region (p<0.005), suggesting higher myelin content, in accordance with previous investigations. B₀ orientation dependence was detected in some areas of the cortex, the strongest being in the primary motor cortex (∆R₂*=4.10 Hz). This study demonstrates that quantitative T₂* measures at 7 T MRI can reveal patterns of cytoarchitectural organization of the human cortex in vivo and that B₀ orientation dependence can probe the coherency and orientation of gray matter fibers in the cortex, shedding light into the potential use of this type of contrast to characterize cyto-/myeloarchitecture and to understand the pathophysiology of diseases associated with changes in iron and/or myelin concentration.

    View details for DOI 10.1016/j.neuroimage.2012.01.053

    View details for Web of Science ID 000303272300018

    View details for PubMedID 22270354

  • Diffusion tractography of post-mortem human brains: Optimization and comparison of spin echo and steady-state free precession techniques NEUROIMAGE Miller, K. L., McNab, J. A., Jbabdi, S., Douaud, G. 2012; 59 (3): 2284-2297


    Diffusion imaging of post-mortem brains could provide valuable data for validation of diffusion tractography of white matter pathways. Long scans (e.g., overnight) may also enable high-resolution diffusion images for visualization of fine structures. However, alterations to post-mortem tissue (T2 and diffusion coefficient) present significant challenges to diffusion imaging with conventional diffusion-weighted spin echo (DW-SE) acquisitions, particularly for imaging human brains on clinical scanners. Diffusion-weighted steady-state free precession (DW-SSFP) has been proposed as an alternative acquisition technique to ameliorate this tradeoff in large-bore clinical scanners. In this study, both DWSE and DW-SSFP are optimized for use in fixed white matter on a clinical 3-Tesla scanner. Signal calculations predict superior performance from DW-SSFP across a broad range of protocols and conditions. DW-SE and DW-SSFP data in a whole, post-mortem human brain are compared for 6- and 12-hour scan durations. Tractography is performed in major projection, commissural and association tracts (corticospinal tract, corpus callosum, superior longitudinal fasciculus and cingulum bundle). The results demonstrate superior tract-tracing from DW-SSFP data, with 6-hour DW-SSFP data performing as well as or better than 12-hour DW-SE scans. These results suggest that DW-SSFP may be a preferred method for diffusion imaging of post-mortem human brains. The ability to estimate multiple fibers in imaging voxels is also demonstrated, again with greater success in DW-SSFP data.

    View details for DOI 10.1016/j.neuroimage.2011.09.054

    View details for Web of Science ID 000299494000030

    View details for PubMedID 22008372

  • Size-optimized 32-Channel Brain Arrays for 3 T Pediatric Imaging MAGNETIC RESONANCE IN MEDICINE Keil, B., Alagappan, V., Mareyam, A., McNab, J. A., Fujimoto, K., Tountcheva, V., Triantafyllou, C., Dilks, D. D., Kanwisher, N., Lin, W., Grant, P. E., Wald, L. L. 2011; 66 (6): 1777-1787


    Size-optimized 32-channel receive array coils were developed for five age groups, neonates, 6 months old, 1 year old, 4 years old, and 7 years old, and evaluated for pediatric brain imaging. The array consisted of overlapping circular surface coils laid out on a close-fitting coil-former. The two-section coil former design was obtained from surface contours of aligned three-dimensional MRI scans of each age group. Signal-to-noise ratio and noise amplification for parallel imaging were evaluated and compared to two coils routinely used for pediatric brain imaging; a commercially available 32-channel adult head coil and a pediatric-sized birdcage coil. Phantom measurements using the neonate, 6-month-old, 1-year-old, 4-year-old, and 7-year-old coils showed signal-to-noise ratio increases at all locations within the brain over the comparison coils. Within the brain cortex the five dedicated pediatric arrays increased signal-to-noise ratio by up to 3.6-, 3.0-, 2.6-, 2.3-, and 1.7-fold, respectively, compared to the 32-channel adult coil, as well as improved G-factor maps for accelerated imaging. This study suggests that a size-tailored approach can provide significant sensitivity gains for accelerated and unaccelerated pediatric brain imaging.

    View details for DOI 10.1002/mrm.22961

    View details for Web of Science ID 000297285000033

    View details for PubMedID 21656548

  • Diffusion imaging of whole, post-mortem human brains on a clinical MRI scanner NEUROIMAGE Miller, K. L., Stagg, C. J., Douaud, G., Jbabdi, S., Smith, S. M., Behrens, T. E., Jenkinson, M., Chance, S. A., Esiri, M. M., Voets, N. L., Jenkinson, N., Aziz, T. Z., Turner, M. R., Johansen-Berg, H., McNab, J. A. 2011; 57 (1): 167-181


    Diffusion imaging of post mortem brains has great potential both as a reference for brain specimens that undergo sectioning, and as a link between in vivo diffusion studies and "gold standard" histology/dissection. While there is a relatively mature literature on post mortem diffusion imaging of animals, human brains have proven more challenging due to their incompatibility with high-performance scanners. This study presents a method for post mortem diffusion imaging of whole, human brains using a clinical 3-Tesla scanner with a 3D segmented EPI spin-echo sequence. Results in eleven brains at 0.94 × 0.94 × 0.94 mm resolution are presented, and in a single brain at 0.73 × 0.73 × 0.73 mm resolution. Region-of-interest analysis of diffusion tensor parameters indicate that these properties are altered compared to in vivo (reduced diffusivity and anisotropy), with significant dependence on post mortem interval (time from death to fixation). Despite these alterations, diffusion tractography of several major tracts is successfully demonstrated at both resolutions. We also report novel findings of cortical anisotropy and partial volume effects.

    View details for DOI 10.1016/j.neuroimage.2011.03.070

    View details for Web of Science ID 000291624100020

    View details for PubMedID 21473920

  • Steady-state diffusion-weighted imaging: theory, acquisition and analysis NMR IN BIOMEDICINE McNab, J. A., Miller, K. L. 2010; 23 (7): 781-793


    Steady-state diffusion-weighted imaging (DWI) has long been recognized to offer potential benefits over conventional spin-echo methods. This family of pulse sequences is highly efficient and compatible with three-dimensional acquisitions, which could enable high-resolution, low-distortion images. However, the same properties that lead to its efficiency make steady-state imaging highly susceptible to motion and create a complicated signal with dependence on T(1), T(2) and flip angle. Recent developments in gradient hardware, motion-mitigation techniques and signal analysis offer potential solutions to these problems, reviving interest in steady-state DWI. This review offers a description of steady-state DWI signal formation and provides an overview of the current methods for steady-state DWI acquisition and analysis.

    View details for DOI 10.1002/nbm.1509

    View details for Web of Science ID 000283014300010

    View details for PubMedID 20886565

  • 3D Steady-State Diffusion-Weighted Imaging With Trajectory Using Radially Batched Internal Navigator Echoes (TURBINE) MAGNETIC RESONANCE IN MEDICINE McNab, J. A., Gallichan, D., Miller, K. L. 2010; 63 (1): 235-242


    While most diffusion-weighted imaging (DWI) is acquired using single-shot diffusion-weighted spin-echo echo-planar imaging, steady-state DWI is an alternative method with the potential to achieve higher-resolution images with less distortion. Steady-state DWI is, however, best suited to a segmented three-dimensional acquisition and thus requires three-dimensional navigation to fully correct for motion artifacts. In this paper, a method for three-dimensional motion-corrected steady-state DWI is presented. The method uses a unique acquisition and reconstruction scheme named trajectory using radially batched internal navigator echoes (TURBINE). Steady-state DWI with TURBINE uses slab-selection and a short echo-planar imaging (EPI) readout each pulse repetition time. Successive EPI readouts are rotated about the phase-encode axis. For image reconstruction, batches of cardiac-synchronized readouts are used to form three-dimensional navigators from a fully sampled central k-space cylinder. In vivo steady-state DWI with TURBINE is demonstrated in human brain. Motion artifacts are corrected using refocusing reconstruction and TURBINE images prove less distorted compared to two-dimensional single-shot diffusion-weighted-spin-EPI.

    View details for DOI 10.1002/mrm.22183

    View details for Web of Science ID 000273578600026

    View details for PubMedID 19859953

  • Reduced limbic connections may contraindicate subgenual cingulate deep brain stimulation for intractable depression Case report JOURNAL OF NEUROSURGERY McNab, J. A., Voets, N. L., Jenkinson, N., Squier, W., Miller, K. L., Goodwin, G. M., Aziz, T. Z. 2009; 111 (4): 780-784


    In this study, the authors performed deep brain stimulation (DBS) of the subgenual anterior cingulate cortex (SACC) in a patient with a history of bipolar disorder. After a right thalamic stroke, intractable depression without mood elevation or a mixed state developed in this patient. He underwent bilateral SACC DBS and died 16 months afterwards. Anatomical connections were studied in this patient preoperatively and postmortem using diffusion tractography (DT). A comparison of in vivo and high resolution ex vivo connectivity patterns was performed as a measure of the utility of in vivo DT in presurgical planning for DBS. Diagnostic measures included neuropsychological testing, preoperative and ex vivo DT, and macroscopic neuropathological assessment. Post-DBS depression rating scores did not improve. In vivo and ex vivo DT revealed markedly reduced limbic projections from the thalamus and SACC to the amygdala in the right (stroke-affected) hemisphere. A highly selective right mediothalamic lesion was associated with the onset of refractory depression. Reduced amygdalar-thalamic and amygdalar-SACC connections could be a contraindication to DBS for depression. Correspondence between preoperative and higher resolution ex vivo DT supports the validity of DT as a presurgical planning tool for DBS.

    View details for DOI 10.3171/2009.2.JNS081299

    View details for Web of Science ID 000270550000022

    View details for PubMedID 19284230

  • High resolution diffusion-weighted imaging in fixed human brain using diffusion-weighted steady state free precession NEUROIMAGE McNab, J. A., Jbabdi, S., Deoni, S. C., Douaud, G., Behrens, T. E., Miller, K. L. 2009; 46 (3): 775-785


    High resolution diffusion tensor imaging and tractography of ex vivo brain specimens has the potential to reveal detailed fibre architecture not visible on in vivo images. Previous ex vivo diffusion imaging experiments have focused on animal brains or small sections of human tissue since the unfavourable properties of fixed tissue (including short T(2) and low diffusion rates) demand the use of very powerful gradient coils that are too small to accommodate a whole, human brain. This study proposes the use of diffusion-weighted steady-state free precession (DW-SSFP) as a method of extending the benefits of ex vivo DTI and tractography to whole, human, fixed brains on a clinical 3 T scanner. DW-SSFP is a highly efficient pulse sequence; however, its complicated signal dependence precludes the use of standard diffusion tensor analysis and tractography. In this study, a method is presented for modelling anisotropy in the context of DW-SSFP. Markov Chain Monte Carlo sampling is used to estimate the posterior distributions of model parameters and it is shown that it is possible to estimate a tight distribution on the principal axis of diffusion at each voxel using DW-SSFP. Voxel-wise estimates are used to perform tractography in a whole, fixed human brain. A direct comparison between 3D diffusion-weighted spin echo EPI and 3D DW-SSFP-EPI reveals that the orientation of the principal diffusion axis can be inferred on with a higher degree of certainty using a 3D DW-SSFP-EPI even with a 68% shorter acquisition time.

    View details for DOI 10.1016/j.neuroimage.2009.01.008

    View details for Web of Science ID 000265938700024

    View details for PubMedID 19344686

  • Cortical and subcortical connections within the pedunculopontine nucleus of the primate Macaca mulatta determined using probabilistic diffusion tractography JOURNAL OF CLINICAL NEUROSCIENCE Aravamuthan, B. R., McNab, J. A., Miller, K. L., Rushworth, M., Jenkinson, N., Stein, J. F., Aziz, T. Z. 2009; 16 (3): 413-420


    The anatomical connections of the pedunculopontine nucleus (PPN), a brainstem structure associated with locomotion, have been determined recently in healthy humans using probabilistic diffusion tractography (PDT). In order to compare these with histologically demonstrated connections of the PPN in monkeys, and thus to support the use of PDT in humans, we have carried out PDT in a fixed rhesus monkey (Macaca mulatta) brain. Probabilistic diffusion tractography was carried out in a fixed post-mortem rhesus monkey brain using diffusion data acquired at 3T MRI (60 directions x 5 averages, b=3000 s/mm(2), matrix size=104 x 132 x 96, 720 x 720 x 720 microm voxels). We identified the major connections of the PPN from single seed voxels that could be confidently located within the nucleus on the diffusion images. The organisation of these connections within a 3 x 3 x 3 voxel ( approximately 10 mm(3)) region surrounding the initial seed voxel was then examined. PDT confirmed that the rhesus monkey PPN connections with the basal ganglia and motor cortical areas matched those previously demonstrated using conventional anatomical tracing techniques. Furthermore, although the organisation of subcortical connections within the PPN has not been extensively demonstrated in animals, we show here in a rhesus monkey that there are clearly separated connections of the PPN with the thalamus, substantia nigra, and subthalamic nucleus. Thus, in addition to increasing confidence in the accuracy of PDT for tracing PPN connections and determining the organisation of these connections within the PPN in vivo, our observations suggest that diffusion tractography will be a useful new technique to rapidly identify connections in animal brains pre-mortem and post-mortem.

    View details for DOI 10.1016/j.jocn.2008.03.018

    View details for Web of Science ID 000263762300011

    View details for PubMedID 19167229

  • Sensitivity of diffusion weighted steady state free precession to anisotropic diffusion MAGNETIC RESONANCE IN MEDICINE McNab, J. A., Miller, K. L. 2008; 60 (2): 405-413


    Diffusion-weighted steady-state free precession (DW-SSFP) accumulates signal from multiple echoes over several TRs yielding a strong sensitivity to diffusion with short gradient durations and imaging times. Although the DW-SSFP signal is well characterized for isotropic, Gaussian diffusion, it is unclear how the DW-SSFP signal propagates in inhomogeneous media such as brain tissue. This article presents a more general analytical expression for the DW-SSFP signal which accommodates Gaussian and non-Gaussian spin displacement probability density functions. This new framework for calculating the DW-SSFP signal is used to investigate signal behavior for a single fiber, crossing fibers, and reflective barriers. DW-SSFP measurements in the corpus callosum of a fixed brain are shown to be in good agreement with theoretical predictions. Further measurements in fixed brain tissue also demonstrate that 3D DW-SSFP out-performs 3D diffusion weighted spin echo in both SNR and CNR efficiency providing a compelling example of its potential to be used for high resolution diffusion tensor imaging.

    View details for DOI 10.1002/mrm.21668

    View details for Web of Science ID 000258105800021

    View details for PubMedID 18666106

  • Quantitative short echo-time H-1 LASER-CSI in human brain at 4T NMR IN BIOMEDICINE McNab, J. A., Bartha, R. 2006; 19 (8): 999-1009


    A novel short echo-time (1)H chemical shift imaging (CSI) pulse sequence is presented that incorporates localization by adiabatic selective refocusing (LASER) for FOV-reduction, k-space weighted averaging and macromolecule subtraction, to obtain quantitative concentration measurements of N-acetyl-aspartate, glutamate, glucose, myo-inositol, creatine and choline using a nominal voxel size of 0.56 cm(3). A comparison of spectral quality and metabolite concentration measurements was made between LASER-CSI and LASER-single voxel spectroscopy (SVS) in a region of homogeneous parietal white matter (N = 8). No significant differences were found in linewidths, signal-to-noise ratios or the effectiveness of the macromolecule subtraction between SVS and CSI. Water suppression was 45% more effective in SVS than in CSI (p < 0.05). A linear regression of all paired metabolite measurements resulted in a slope = 1.01 +/- 0.03 (r(2) = 0.73). LASER-CSI concentration measurements of N-acetyl-aspartate, glutamate, glucose, myo-inositol, creatine and choline were in agreement (within standard deviations) with LASER-SVS measurements. LASER-CSI is, therefore, a viable and attractive option for future (1)H CSI investigations.

    View details for DOI 10.1002/nbm.1053

    View details for Web of Science ID 000243168700001

    View details for PubMedID 16927396

  • Tissue oxygen tension measurements in the Shionogi model of prostate cancer using F-19 MRS and MRI 12th Annual Meeting of the ISMRM McNab, J. A., Yung, A. C., Kozlowski, P. SPRINGER. 2004: 288–95


    To investigate changes in tumour tissue oxygenation throughout the tumour growth-regression-relapse cycle in an androgen-dependent animal tumour model.19F T1 relaxometry of Perfluoro-15-Crown-5-Ether was used to measure in vivo partial oxygen pressure (pO2) of Shionogi tumours on a 2.35-T MR scanner. Perfluoro-15-Crown-5-Ether was administered as an emulsion injected intravenously or as a neat compound injected directly into the tumour. Non-localized, tumour 19F T1 measurements, made at multiple time points throughout the tumour cycle, were translated into pO2 levels.No correlation between tumour size and pO2 values was found. Values of pO2 for growing tumours (50 +/- 30 torr) were significantly lower than for regressing and relapsing tumours after 9 days post-castration (70 +/- 10 torr, p<0.05). Maximum pO2 values (90 +/- 30 torr) were reached between fifth and eighth day post-castration, when tumour pO2 was significantly higher than both pre-castration (p<0.001) and after 9 days post-castration (p<0.05).We demonstrate that longitudinal pO2 measurements in vivo are feasible. Values of pO2 for growing androgen-dependent tumours were significantly lower than for regressing and relapsing androgen-independent tumours. These results have potential clinical importance in optimizing the timing of chemotherapy and/or radiotherapy of hormone dependent tumours.

    View details for DOI 10.1007/s10334-004-0083-3

    View details for Web of Science ID 000227620700024

    View details for PubMedID 15605277