Jonathan R. Polimeni
Associate Professor of Radiology (Radiological Sciences Laboratory)
Contact
https://orcid.org/0000-0002-1348-11792024-25 Courses
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Independent Studies (2)
- Directed Investigation
BIOE 392 (Sum) - Directed Study
BIOE 391 (Spr)
- Directed Investigation
Stanford Advisees
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Postdoctoral Faculty Sponsor
Zhangxuan Hu, Sébastien Proulx, Nadira Yusif Rodriguez -
Doctoral Dissertation Advisor (AC)
Megan Martin
All Publications
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Imaging of the pial arterial vasculature of the human brain in vivo using high-resolution 7T time-of-flight angiography
ELIFE
2022; 11
Abstract
The pial arterial vasculature of the human brain is the only blood supply to the neocortex, but quantitative data on the morphology and topology of these mesoscopic arteries (diameter 50-300 µm) remains scarce. Because it is commonly assumed that blood flow velocities in these vessels are prohibitively slow, non-invasive time-of-flight magnetic resonance angiography (TOF-MRA)-which is well suited to high 3D imaging resolutions-has not been applied to imaging the pial arteries. Here, we provide a theoretical framework that outlines how TOF-MRA can visualize small pial arteries in vivo, by employing extremely small voxels at the size of individual vessels. We then provide evidence for this theory by imaging the pial arteries at 140 µm isotropic resolution using a 7 Tesla (T) magnetic resonance imaging (MRI) scanner and prospective motion correction, and show that pial arteries one voxel width in diameter can be detected. We conclude that imaging pial arteries is not limited by slow blood flow, but instead by achievable image resolution. This study represents the first targeted, comprehensive account of imaging pial arteries in vivo in the human brain. This ultra-high-resolution angiography will enable the characterization of pial vascular anatomy across the brain to investigate patterns of blood supply and relationships between vascular and functional architecture.
View details for DOI 10.7554/eLife.71186
View details for Web of Science ID 000806033800001
View details for PubMedID 35486089
View details for PubMedCentralID PMC9150892
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Probing in vivo cortical myeloarchitecture in humans via line-scan diffusion acquisitions at 7 T with 250-500 micron radial resolution
MAGNETIC RESONANCE IN MEDICINE
2021; 85 (1): 42-55
Abstract
The goal of this study was to measure diffusion signals within the cerebral cortex using the line-scan technique to achieve extremely high resolution in the radial direction (ie, perpendicular to the cortical surface) and to demonstrate the utility of these measurements for investigating laminar architecture in the living human brain.Line-scan diffusion data with 250-500 micron radial resolution were acquired at 7 T on 8 healthy volunteers, with each line prescribed perpendicularly to primary somatosensory cortex (S1) and primary motor cortex (M1). Apparent diffusion coefficients, fractional anisotropy values, and radiality indices were measured as a function of cortical depth.In the deep layers of S1, we found evidence for high anisotropy and predominantly tangential diffusion, with low anisotropy observed in superficial S1. In M1, moderate anisotropy and predominantly radial diffusion was seen at almost all cortical depths. These patterns were consistent across subjects and were conspicuous without averaging data across different locations on the cortical sheet.Our results are in accord with the myeloarchitecture of S1 and M1, known from prior histology studies: in S1, dense bands of tangential myelinated fibers run through the deep layers but not the superficial ones, and in M1, radial myelinated fibers are prominent at most cortical depths. This work therefore provides support for the idea that high-resolution diffusion signals, measured with the line-scan technique and receiving a boost in SNR at 7 T, may serve as a sensitive probe of in vivo laminar architecture.
View details for DOI 10.1002/mrm.28419
View details for Web of Science ID 000558847800001
View details for PubMedID 32738088
View details for PubMedCentralID PMC7951328
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Ultra-high spatial resolution BOLD fMRI in humans using combined segmented-accelerated VFA-FLEET with a recursive RF pulse design
MAGNETIC RESONANCE IN MEDICINE
2020
Abstract
To alleviate the spatial encoding limitations of single-shot echo-planar imaging (EPI) by developing multi-shot segmented EPI for ultra-high-resolution functional MRI (fMRI) with reduced ghosting artifacts from subject motion and respiration.Segmented EPI can reduce readout duration and reduce acceleration factors, however, the time elapsed between segment acquisitions (on the order of seconds) can result in intermittent ghosting, limiting its use for fMRI. Here, "FLEET" segment ordering, where segments are looped over before slices, was combined with a variable flip angle progression (VFA-FLEET) to improve inter-segment fidelity and maximize signal for fMRI. Scaling a sinc pulse's flip angle for each segment (VFA-FLEET-Sinc) produced inconsistent slice profiles and ghosting, therefore, a recursive Shinnar-Le Roux (SLR) radiofrequency (RF) pulse design was developed (VFA-FLEET-SLR) to generate unique pulses for every segment that together produce consistent slice profiles and signals.The temporal stability of VFA-FLEET-SLR was compared against conventional-segmented EPI and VFA-FLEET-Sinc at 3T and 7T. VFA-FLEET-SLR showed reductions in both intermittent and stable ghosting compared to conventional-segmented and VFA-FLEET-Sinc, resulting in improved image quality with a minor trade-off in temporal SNR. Combining VFA-FLEET-SLR with acceleration, we achieved a 0.6-mm isotropic acquisition at 7T, without zoomed imaging or partial Fourier, demonstrating reliable detection of blood oxygenation level-dependent (BOLD) responses to a visual stimulus. To counteract the increased repetition time from segmentation, simultaneous multi-slice VFA-FLEET-SLR was demonstrated using RF-encoded controlled aliasing.VFA-FLEET with a recursive RF pulse design supports acquisitions with low levels of artifact and spatial blur, enabling fMRI at previously inaccessible spatial resolutions with a "full-brain" field of view.
View details for DOI 10.1002/mrm.28415
View details for Web of Science ID 000551431800001
View details for PubMedID 32705723
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Laminar (f)MRI: A short history and future prospects
NEUROIMAGE
2019; 197: 643-649
View details for DOI 10.1016/j.neuroimage.2019.04.082
View details for Web of Science ID 000472161500059
View details for PubMedID 31059800
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Using PINS pulses to saturate inflow effects on fMRI data at 3 and 7 T.
Magnetic resonance in medicine
2025
Abstract
To suppress inflow effects by saturating the magnetization within slice gaps.Power independent of number of slices (PINS) pulses was designed to saturate the magnetization in all slice gaps at once. The PINS saturation module was played before every excitation. The saturation and excitation profiles were validated in simulation and phantom experiments. To demonstrate the efficacy of the method to suppress inflow, experiments were performed using a flow phantom. As an example use-case, fMRI experiments with and without PINS inflow saturation were performed at 3 T and 7 T.Simulations and phantom experiments showed that the PINS saturation module successfully saturated the magnetization in the slice gaps without degrading the slice profile of the imaging slices. Flow phantom experiments showed that the PINS saturation module suppresses through-plane inflow better than no-gap acquisitions. In vivo fMRI experiments demonstrated that the PINS saturation module can be used to modulate the spin-echo BOLD signal. At 3 T application of PINS pulses to saturate the magnetization in the slice gaps resulted in approximately 25% fewer activated voxels (PINS-ON vs. PINS-OFF). Interestingly, at 7 T the activation patterns remained more similar and only approximately 10% fewer activated voxels were detected. The observed difference between 3 and 7 T may be linked to the relative shortening of the blood T2.Using PINS pulses, inflow effects from slice gaps were effectively and efficiently saturated. The proposed PINS saturation module can be used to further study the contribution of inflow effects in fMRI data.
View details for DOI 10.1002/mrm.30584
View details for PubMedID 40391598
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Multilayer network analysis across cortical depths in 7-T resting-state fMRI.
Network neuroscience (Cambridge, Mass.)
2025; 9 (2): 475-503
Abstract
In graph theory, "multilayer networks" represent systems involving several interconnected topological levels. One example in neuroscience is the stratification of connections between different cortical depths or "laminae," which is becoming noninvasively accessible in humans using ultrahigh-resolution functional MRI (fMRI). Here, we applied multilayer graph theory to examine functional connectivity across different cortical depths in humans, using 7-T fMRI (1-mm3 voxels; 30 participants). Blood oxygenation level dependent (BOLD) signals were derived from five depths between the white matter and pial surface. We compared networks where the interregional connections were limited to a single cortical depth only ("layer-by-layer matrices") with those considering all possible connections between areas and cortical depths ("multilayer matrix"). We utilized global and local graph theory features that quantitatively characterize network attributes including network composition, nodal centrality, path-based measures, and hub segregation. Detecting functional differences between cortical depths was improved using multilayer connectomics compared with the layer-by-layer versions. Superficial depths of the cortex dominated information transfer, and deeper depths drove clustering. These differences were largest in frontotemporal and limbic regions. fMRI functional connectivity across different cortical depths may contain neurophysiologically relevant information; thus, multilayer connectomics could provide a methodological framework for studies on how information flows across this stratification.
View details for DOI 10.1162/netn_a_00436
View details for PubMedID 40497141
View details for PubMedCentralID PMC12151305
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Multilayer network analysis across cortical depths in 7-T resting-state fMRI
NETWORK NEUROSCIENCE
2025; 9 (2): 475-503
View details for DOI 10.1162/netn_a_00436
View details for Web of Science ID 001489278300004
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Romer-EPTI: Rotating-view motion-robust super-resolution EPTI for SNR-efficient distortion-free in-vivo mesoscale diffusion MRI and microstructure imaging
MAGNETIC RESONANCE IN MEDICINE
2025; 93 (4): 1535-1555
Abstract
To overcome the major challenges in diffusion MRI (dMRI) acquisition, including limited SNR, distortion/blurring, and susceptibility to motion artifacts.A novel Romer-EPTI technique is developed to achieve SNR-efficient acquisition while providing distortion-free imaging, minimal spatial blurring, high motion robustness, and simultaneous multi-TE imaging. It introduces a ROtating-view Motion-robust supEr-Resolution technique (Romer) combined with a distortion/blurring-free Echo Planar Time-resolved Imaging (EPTI) readout. Romer enhances SNR through simultaneous multi-thick-slice acquisition with rotating-view encoding, while providing high motion-robustness via a high-fidelity, motion-aware super-resolution reconstruction. Instead of EPI, the in-plane encoding is performed using EPTI readout to prevent geometric distortion, T2/T2*-blurring, and importantly, dynamic distortions that could introduce additional blurring/artifacts after super-resolution reconstruction due to combining volumes with inconsistent geometries. This further improves effective spatial resolution and motion robustness. Additional developments include strategies to address slab-boundary artifacts, achieve minimized TE and optimized readout for additional SNR gain, and increase robustness to strong phase variations at high b-values.Using Romer-EPTI, we demonstrated distortion-free whole-brain mesoscale in-vivo dMRI at both 3T (500-μm isotropic [iso] resolution) and 7T (485-μm iso resolution) for the first time. Motion experiments demonstrated the technique's motion robustness and its ability to obtain high-resolution diffusion images in the presence of subject motion. Romer-EPTI also demonstrated high SNR gain and robustness in high b-value (b = 5000 s/mm2) and time-dependent dMRI.The high SNR efficiency, improved image quality, and motion robustness of Romer-EPTI make it a highly efficient acquisition for high-resolution dMRI and microstructure imaging.
View details for DOI 10.1002/mrm.30365
View details for Web of Science ID 001356889300001
View details for PubMedID 39552568
View details for PubMedCentralID PMC11782731
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Single-shot echo planar time-resolved imaging for multi-echo functional MRI and distortion-free diffusion imaging
MAGNETIC RESONANCE IN MEDICINE
2025; 93 (3): 993-1013
Abstract
To develop a single-shot SNR-efficient distortion-free multi-echo imaging technique for dynamic imaging applications.Echo planar time-resolved imaging (EPTI) was first introduced as a multi-shot technique for distortion-free multi-echo imaging. This work aims to develop single-shot EPTI (ss-EPTI) to achieve improved robustness to motion/physiological noise, increased temporal resolution, and higher SNR efficiency. A new spatiotemporal encoding that enables reduced phase-encoding blips and minimized echo spacing under the single-shot regime was developed, which improves sampling efficiency and enhances spatiotemporal correlation in the k-TE space for improved reconstruction. A continuous readout with minimized deadtime was employed to optimize SNR efficiency. Moreover, k-TE partial Fourier and simultaneous multi-slice acquisition were integrated for further acceleration.ss-EPTI provided distortion-free imaging with densely sampled multi-echo images at standard resolutions (e.g., ˜1.25 to 3 mm) in a single-shot. Improved SNR efficiency was observed in ss-EPTI due to improved motion/physiological-noise robustness and efficient continuous readout. Its ability to eliminate dynamic distortions-geometric changes across dynamics due to field changes induced by physiological variations or eddy currents-further improved the data's temporal stability. For multi-echo fMRI, ss-EPTI's multi-echo images recovered signal dropout in short- T 2 * $$ {\mathrm{T}}_2^{\ast } $$ regions and provided TE-dependent functional information to distinguish non-BOLD noise for further tSNR improvement. For diffusion MRI, it achieved shortened TEs for improved SNR and provided images free from both B0-induced and diffusion-encoding-dependent eddy-current-induced distortions with multi-TE diffusion metrics.ss-EPTI provides SNR-efficient distortion-free multi-echo imaging with comparable temporal resolutions to ss-EPI, offering a new acquisition tool for dynamic imaging.
View details for DOI 10.1002/mrm.30327
View details for Web of Science ID 001337941500001
View details for PubMedID 39428674
View details for PubMedCentralID PMC11680730
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Reduced physiology-induced temporal instability achieved with variable-flip-angle fast low-angle excitation echo-planar technique with multishot echo planar time-resolved imaging
MAGNETIC RESONANCE IN MEDICINE
2024: 597-614
Abstract
Echo planar time-resolved imaging (EPTI) is a new imaging approach that addresses the limitations of EPI by providing high-resolution, distortion- and T2/ T 2 * $$ {\mathrm{T}}_2^{\ast } $$ blurring-free imaging for functional MRI (fMRI). However, as in all multishot sequences, intershot phase variations induced by physiological processes can introduce temporal instabilities to the reconstructed time-series data. This study aims to reduce these instabilities in multishot EPTI.In conventional multishot EPTI, the time intervals between the shots comprising each slice can introduce intershot phase variations. Here, the fast low-angle excitation echo-planar technique (FLEET), in which all shots of each slice are acquired consecutively with minimal time delays, was combined with a variable flip angle (VFA) technique to improve intershot consistency and maximize signal. A recursive Shinnar-Le Roux RF pulse design algorithm was used to generate pulses for different shots to produce consistent slice profiles and signal intensities across shots. Blipped controlled aliasing in parallel imaging simultaneous multislice was also combined with the proposed VFA-FLEET EPTI to improve temporal resolution and increase spatial coverage.The temporal stability of VFA-FLEET EPTI was compared with conventional EPTI at 7 T. The results demonstrated that VFA-FLEET can provide spatial-specific increase of temporal stability. We performed high-resolution task-fMRI experiments at 7 T using VFA-FLEET EPTI, and reliable BOLD responses to a visual stimulus were detected.The intershot phase variations induced by physiological processes in multishot EPTI can manifest as specific spatial patterns of physiological noise enhancement and lead to reduced temporal stability. The VFA-FLEET technique can substantially reduce these physiology-induced instabilities in multishot EPTI acquisitions. The proposed method provides sufficient stability and sensitivity for high-resolution fMRI studies.
View details for DOI 10.1002/mrm.30301
View details for Web of Science ID 001320190700001
View details for PubMedID 39323238
View details for PubMedCentralID PMC11661687
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Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging - A Symposium Review
NEUROINFORMATICS
2024; 22 (4): 679-706
Abstract
Advances in the spatiotemporal resolution and field-of-view of neuroimaging tools are driving mesoscale studies for translational neuroscience. On October 10, 2023, the Center for Mesoscale Mapping (CMM) at the Massachusetts General Hospital (MGH) Athinoula A. Martinos Center for Biomedical Imaging and the Massachusetts Institute of Technology (MIT) Health Sciences Technology based Neuroimaging Training Program (NTP) hosted a symposium exploring the state-of-the-art in this rapidly growing area of research. "Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging" brought together researchers who use a broad range of imaging techniques to study brain structure and function at the convergence of the microscopic and macroscopic scales. The day-long event centered on areas in which the CMM has established expertise, including the development of emerging technologies and their application to clinical translational needs and basic neuroscience questions. The in-person symposium welcomed more than 150 attendees, including 57 faculty members, 61 postdoctoral fellows, 35 students, and four industry professionals, who represented institutions at the local, regional, and international levels. The symposium also served the training goals of both the CMM and the NTP. The event content, organization, and format were planned collaboratively by the faculty and trainees. Many CMM faculty presented or participated in a panel discussion, thus contributing to the dissemination of both the technologies they have developed under the auspices of the CMM and the findings they have obtained using those technologies. NTP trainees who benefited from the symposium included those who helped to organize the symposium and/or presented posters and gave "flash" oral presentations. In addition to gaining experience from presenting their work, they had opportunities throughout the day to engage in one-on-one discussions with visiting scientists and other faculty, potentially opening the door to future collaborations. The symposium presentations provided a deep exploration of the many technological advances enabling progress in structural and functional mesoscale brain imaging. Finally, students worked closely with the presenting faculty to develop this report summarizing the content of the symposium and putting it in the broader context of the current state of the field to share with the scientific community. We note that the references cited here include conference abstracts corresponding to the symposium poster presentations.
View details for DOI 10.1007/s12021-024-09686-2
View details for Web of Science ID 001318931700001
View details for PubMedID 39312131
View details for PubMedCentralID PMC11579116
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Individual connectivity-based parcellations reflect functional properties of human auditory cortex.
bioRxiv : the preprint server for biology
2024
Abstract
Neuroimaging studies of the functional organization of human auditory cortex have focused on group-level analyses to identify tendencies that represent the typical brain. Here, we mapped auditory areas of the human superior temporal cortex (STC) in 30 participants by combining functional network analysis and 1-mm isotropic resolution 7T functional magnetic resonance imaging (fMRI). Two resting-state fMRI sessions, and one or two auditory and audiovisual speech localizer sessions, were collected on 3-4 separate days. We generated a set of functional network-based parcellations from these data. Solutions with 4, 6, and 11 networks were selected for closer examination based on local maxima of Dice and Silhouette values. The resulting parcellation of auditory cortices showed high intraindividual reproducibility both between resting state sessions (Dice coefficient: 69-78%) and between resting state and task sessions (Dice coefficient: 62-73%). This demonstrates that auditory areas in STC can be reliably segmented into functional subareas. The interindividual variability was significantly larger than intraindividual variability (Dice coefficient: 57%-68%, p<0.001), indicating that the parcellations also captured meaningful interindividual variability. The individual-specific parcellations yielded the highest alignment with task response topographies, suggesting that individual variability in parcellations reflects individual variability in auditory function. Connectional homogeneity within networks was also highest for the individual-specific parcellations. Furthermore, the similarity in the functional parcellations was not explainable by the similarity of macroanatomical properties of auditory cortex. Our findings suggest that individual-level parcellations capture meaningful idiosyncrasies in auditory cortex organization.
View details for DOI 10.1101/2024.01.20.576475
View details for PubMedID 38293021
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Impact of repeated blast exposure on active- duty United States Special Operations Forces
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2024; 121 (19): e2313568121
Abstract
United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.
View details for DOI 10.1073/pnas.2313568121
View details for Web of Science ID 001230171600003
View details for PubMedID 38648470
View details for PubMedCentralID PMC11087753
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Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.
Nature methods
2023
Abstract
To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.
View details for DOI 10.1038/s41592-023-02068-7
View details for PubMedID 38012321
View details for PubMedCentralID 2492463
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Role of articulatory motor networks in perceptual categorization of speech signals: a 7T fMRI study
CEREBRAL CORTEX
2023; 33 (24): 11517-11525
Abstract
Speech and language processing involve complex interactions between cortical areas necessary for articulatory movements and auditory perception and a range of areas through which these are connected and interact. Despite their fundamental importance, the precise mechanisms underlying these processes are not fully elucidated. We measured BOLD signals from normal hearing participants using high-field 7 Tesla fMRI with 1-mm isotropic voxel resolution. The subjects performed 2 speech perception tasks (discrimination and classification) and a speech production task during the scan. By employing univariate and multivariate pattern analyses, we identified the neural signatures associated with speech production and perception. The left precentral, premotor, and inferior frontal cortex regions showed significant activations that correlated with phoneme category variability during perceptual discrimination tasks. In addition, the perceived sound categories could be decoded from signals in a region of interest defined based on activation related to production task. The results support the hypothesis that articulatory motor networks in the left hemisphere, typically associated with speech production, may also play a critical role in the perceptual categorization of syllables. The study provides valuable insights into the intricate neural mechanisms that underlie speech processing.
View details for DOI 10.1093/cercor/bhad384
View details for Web of Science ID 001085666000001
View details for PubMedID 37851854
View details for PubMedCentralID PMC10724868
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Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy
FRONTIERS IN NEUROSCIENCE
2023; 17: 1141007
Abstract
Cerebral Amyloid Angiopathy (CAA) is a cerebral small vessel disease that can lead to microstructural disruption of white matter (WM), which can be measured by the Peak Width of Skeletonized Mean Diffusivity (PSMD). We hypothesized that PSMD measures would be increased in patients with CAA compared to healthy controls (HC), and increased PSMD is associated with lower cognitive scores in patients with CAA.Eighty-one probable CAA patients without cognitive impairment who were diagnosed with Boston criteria and 23 HCs were included. All subjects underwent an advanced brain MRI with high-resolution diffusion-weighted imaging (DWI). PSMD scores were quantified from a probabilistic skeleton of the WM tracts in the mean diffusivity (MD) image using a combination of fractional anisotropy (FA) and the FSL Tract-Based Spatial Statistics (TBSS) algorithm (www.psmd-marker.com). Within CAA cohort, standardized z-scores of processing speed, executive functioning and memory were obtained.The mean of age and sex were similar between CAA patients (69.6 ± 7.3, 59.3% male) and HCs (70.6 ± 8.5, 56.5% male) (p = 0.581 and p = 0.814). PSMD was higher in the CAA group [(4.13 ± 0.94) × 10-4 mm2/s] compared to HCs [(3.28 ± 0.51) × 10-4 mm2/s] (p < 0.001). In a linear regression model corrected for relevant variables, diagnosis of CAA was independently associated with increased PSMD compared to HCs (ß = 0.45, 95% CI 0.13-0.76, p = 0.006). Within CAA cohort, higher PSMD was associated with lower scores in processing speed (p < 0.001), executive functioning (p = 0.004), and memory (0.047). Finally, PSMD outperformed all other MRI markers of CAA by explaining most of the variance in models predicting lower scores in each cognitive domain.Peak Width of Skeletonized Mean Diffusivity is increased in CAA, and it is associated with worse cognitive scores supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA. As a robust marker, PSMD can be used in clinical trials or practice.
View details for DOI 10.3389/fnins.2023.1141007
View details for Web of Science ID 000971919500001
View details for PubMedID 37077322
View details for PubMedCentralID PMC10106761
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High-resolution quantitative and functional MRI indicate lower myelination of thin and thick stripes in human secondary visual cortex
ELIFE
2023; 12
Abstract
The characterization of cortical myelination is essential for the study of structure-function relationships in the human brain. However, knowledge about cortical myelination is largely based on post-mortem histology, which generally renders direct comparison to function impossible. The repeating pattern of pale-thin-pale-thick stripes of cytochrome oxidase (CO) activity in the primate secondary visual cortex (V2) is a prominent columnar system, in which histology also indicates different myelination of thin/thick versus pale stripes. We used quantitative magnetic resonance imaging (qMRI) in conjunction with functional magnetic resonance imaging (fMRI) at ultra-high field strength (7 T) to localize and study myelination of stripes in four human participants at sub-millimeter resolution in vivo. Thin and thick stripes were functionally localized by exploiting their sensitivity to color and binocular disparity, respectively. Resulting functional activation maps showed robust stripe patterns in V2 which enabled further comparison of quantitative relaxation parameters between stripe types. Thereby, we found lower longitudinal relaxation rates (R1) of thin and thick stripes compared to surrounding gray matter in the order of 1-2%, indicating higher myelination of pale stripes. No consistent differences were found for effective transverse relaxation rates (R2*). The study demonstrates the feasibility to investigate structure-function relationships in living humans within one cortical area at the level of columnar systems using qMRI.
View details for DOI 10.7554/eLife.78756
View details for Web of Science ID 000946354400001
View details for PubMedID 36888685
View details for PubMedCentralID PMC9995117
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Diffusion MRI data analysis assisted by deep learning synthesized anatomical images (DeepAnat)
MEDICAL IMAGE ANALYSIS
2023; 86: 102744
Abstract
Diffusion MRI is a useful neuroimaging tool for non-invasive mapping of human brain microstructure and structural connections. The analysis of diffusion MRI data often requires brain segmentation, including volumetric segmentation and cerebral cortical surfaces, from additional high-resolution T1-weighted (T1w) anatomical MRI data, which may be unacquired, corrupted by subject motion or hardware failure, or cannot be accurately co-registered to the diffusion data that are not corrected for susceptibility-induced geometric distortion. To address these challenges, this study proposes to synthesize high-quality T1w anatomical images directly from diffusion data using convolutional neural networks (CNNs) (entitled "DeepAnat"), including a U-Net and a hybrid generative adversarial network (GAN), and perform brain segmentation on synthesized T1w images or assist the co-registration using synthesized T1w images. The quantitative and systematic evaluations using data of 60 young subjects provided by the Human Connectome Project (HCP) show that the synthesized T1w images and results for brain segmentation and comprehensive diffusion analysis tasks are highly similar to those from native T1w data. The brain segmentation accuracy is slightly higher for the U-Net than the GAN. The efficacy of DeepAnat is further validated on a larger dataset of 300 more elderly subjects provided by the UK Biobank. Moreover, the U-Nets trained and validated on the HCP and UK Biobank data are shown to be highly generalizable to the diffusion data from Massachusetts General Hospital Connectome Diffusion Microstructure Dataset (MGH CDMD) acquired with different hardware systems and imaging protocols and therefore can be used directly without retraining or with fine-tuning for further improved performance. Finally, it is quantitatively demonstrated that the alignment between native T1w images and diffusion images uncorrected for geometric distortion assisted by synthesized T1w images substantially improves upon that by directly co-registering the diffusion and T1w images using the data of 20 subjects from MGH CDMD. In summary, our study demonstrates the benefits and practical feasibility of DeepAnat for assisting various diffusion MRI data analyses and supports its use in neuroscientific applications.
View details for DOI 10.1016/j.media.2023.102744
View details for Web of Science ID 000952326500001
View details for PubMedID 36867912
View details for PubMedCentralID PMC10517382
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High-resolution motion- and phase-corrected functional MRI at 7 T using shuttered multishot echo-planar imaging.
Magnetic resonance in medicine
2023
Abstract
PURPOSE: To achieve high-resolution multishot echo-planar imaging (EPI) for functional MRI (fMRI) with reduced sensitivity to in-plane motion and between-shot phase variations.METHODS: Two-dimensional radiofrequency pulses were incorporated in a multishot EPI sequence at 7T which selectively excited a set of in-plane bands (shutters) in the phase encoding direction, which moved between shots to cover the entire slice. A phase- and motion-corrected reconstruction was implemented for the acquisition. Brain imaging experiments were performed with instructed motion to evaluate image quality for conventional multishot and shuttered EPI. Temporal stability was assessed in three subjects by quantifying temporal SNR (tSNR) and artifact levels, and fMRI activation experiments using visual stimulation were performed to assess the strength and distribution of activation, using both conventional multishot and shuttered EPI.RESULTS: In the instructed motion experiment, ghosting was lower in shuttered EPI images without or with corrections and image quality metrics were improved with motion correction. tSNR was improved by phase correction in both conventional multishot and shuttered EPI and the acquisitions had similar tSNR without and with phase correction. However, while phase correction was necessary to maximize tSNR in conventional multishot EPI, it also increased intermittent ghosting, but did not increase intermittent ghosting in shuttered EPI. Phase correction increased activation strength in both conventional multishot and shuttered EPI, but caused increased spurious activation outside the brain and in frontal brain regions in conventional multishot EPI.CONCLUSION: Shuttered EPI supports multishot segmented EPI acquisitions with lower sensitivity to artifacts from motion for high-resolution fMRI.
View details for DOI 10.1002/mrm.29608
View details for PubMedID 36708203
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Real-time shimming with FID navigators.
Magnetic resonance in medicine
2022; 88 (6): 2548-2563
Abstract
To implement a method for real-time field control using rapid FID navigator (FIDnav) measurements and evaluate the efficacy of the proposed approach for mitigating dynamic field perturbations and improving T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted image quality.FIDnavs were embedded in a gradient echo sequence and a subject-specific linear calibration model was generated on the scanner to facilitate rapid shim updates in response to measured FIDnav signals. To confirm the accuracy of FID-navigated field updates, phantom and volunteer scans were performed with online updates of the scanner B0 shim settings. To evaluate improvement in T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted image quality with real-time shimming, 10 volunteers were scanned at 3T while performing deep-breathing and nose-touching tasks designed to modulate the B0 field. Quantitative image quality metrics were compared with and without FID-navigated field control. An additional volunteer was scanned at 7T to evaluate performance at ultra-high field.Applying measured FIDnav shim updates successfully compensated for applied global and linear field offsets in phantoms and across all volunteers. FID-navigated real-time shimming led to a substantial reduction in field fluctuations and a consequent improvement in T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted image quality in volunteers performing deep-breathing and nose-touching tasks, with 7.57% ± 6.01% and 8.21% ± 10.90% improvement in peak SNR and structural similarity, respectively.FIDnavs facilitate rapid measurement and application of field coefficients for slice-wise B0 shimming. The proposed approach can successfully counteract spatiotemporal field perturbations and substantially improves T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted image quality, which is important for a variety of clinical and research applications, particularly at ultra-high field.
View details for DOI 10.1002/mrm.29421
View details for PubMedID 36093989
View details for PubMedCentralID PMC9529812
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T1 relaxation time of ISMRM/NIST T1 phantom spheres at 7 T
NMR IN BIOMEDICINE
2023; 36 (5): e4873
Abstract
T1 relaxation times of the 14 T1 phantom spheres that make up the standard International Society for Magnetic Resonance in Medicine (ISMRM)/National Institute of Standards and Technology (NIST) system phantom are reported at 7 T. T1 values of six of the 14 T1 spheres at 7 T (with T1 > 270 ms) have been reported previously, but, to the best of our knowledge, not all of the T1s of the 14 T1 spheres at 7 T have been reported before. Given the increasing number of 7-T MRI systems in clinical settings and the increasing need for T1 phantoms that cover a wide range of T1 relaxation times to evaluate rapid T1 mapping techniques at 7 T, it is of high interest to obtain accurate T1 values for all the ISMRM/NIST T1 spheres at 7 T. In this work, T1 relaxation time was measured on a 7-T MRI scanner using an inversion-recovery spin-echo pulse sequence and derived by curve fitting to a signal equation that exhibits insensitivity to B 1 + inhomogeneity. Day-to-day reproducibility was within 0.4% and differences between two different RF coils within 1.5%. T1s of a subset of the 14 spheres were also measured by NMR at 7 T for comparison, and the T1 results were consistent between the MRI and NMR measurements. T1 measurements performed at 3 T on the same 14 spheres using the same sequence and fitting method yielded good agreement (mean percentage difference of -0.4%) with the reference T1 values available from the NIST, reflecting the accuracy of the reported technique despite being without the standard phantom housing. We found that the T1 values of all 14 NiCl2 spheres are consistently lower at 7 T than at 3 T. Although our results were well reproduced, this study represents initial work to quantify the 7-T T1 values of all 14 NIST T1 spheres outside of the standard housing and does not warrant reproducibility of the ISMRM/NIST system phantom as a whole. A future study to assess the T1 values of a version of the ISMRM/NIST system phantom that fits inside typical commercial coils at 7 T will be very helpful. Nonetheless, the details on our acquisition and curve-fitting methods reported here allow the T1 measurements to be reproduced elsewhere. The T1 values of all 14 spheres reported here will be valuable for the development of quantitative MR fingerprinting and rapid T1 mapping for a large variety of research projects, not only in neuroimaging but also in body MRI, musculoskeletal MRI, and gadolinium contrast-enhanced MRI, each of which is concerned with much shortened T1.
View details for DOI 10.1002/nbm.4873
View details for Web of Science ID 000888119600001
View details for PubMedID 36347826
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Slice-direction geometric distortion evaluation and correction with reversed slice-select gradient acquisitions
NEUROIMAGE
2022; 264: 119701
Abstract
Accurate spatial alignment of MRI data acquired across multiple contrasts in the same subject is often crucial for data analysis and interpretation, but can be challenging in the presence of geometric distortions that differ between acquisitions. It is well known that single-shot echo-planar imaging (EPI) acquisitions suffer from distortion in the phase-encoding direction due to B0 field inhomogeneities arising from tissue magnetic susceptibility differences and other sources, however there can be distortion in other encoding directions as well in the presence of strong field inhomogeneities. High-resolution ultrahigh-field MRI typically uses low bandwidth in the slice-encoding direction to acquire thin slices and, when combined with the pronounced B0 inhomogeneities, is prone to an additional geometric distortion in the slice direction as well. Here we demonstrate the presence of this slice distortion in high-resolution 7T EPI acquired with a novel pulse sequence allowing for the reversal of the slice-encoding gradient polarity that enables the acquisition of pairs of images with equal magnitudes of distortion in the slice direction but with opposing polarities. We also show that the slice-direction distortion can be corrected using gradient reversal-based method applying the same software used for conventional corrections of phase-encoding direction distortion.
View details for DOI 10.1016/j.neuroimage.2022.119701
View details for Web of Science ID 000886063700006
View details for PubMedID 36283542
View details for PubMedCentralID PMC9910288
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A temporal sequence of thalamic activity unfolds at transitions in behavioral arousal state
NATURE COMMUNICATIONS
2022; 13 (1): 5442
Abstract
Awakening from sleep reflects a profound transformation in neural activity and behavior. The thalamus is a key controller of arousal state, but whether its diverse nuclei exhibit coordinated or distinct activity at transitions in behavioral arousal state is unknown. Using fast fMRI at ultra-high field (7 Tesla), we measured sub-second activity across thalamocortical networks and within nine thalamic nuclei to delineate these dynamics during spontaneous transitions in behavioral arousal state. We discovered a stereotyped sequence of activity across thalamic nuclei and cingulate cortex that preceded behavioral arousal after a period of inactivity, followed by widespread deactivation. These thalamic dynamics were linked to whether participants subsequently fell back into unresponsiveness, with unified thalamic activation reflecting maintenance of behavior. These results provide an outline of the complex interactions across thalamocortical circuits that orchestrate behavioral arousal state transitions, and additionally, demonstrate that fast fMRI can resolve sub-second subcortical dynamics in the human brain.
View details for DOI 10.1038/s41467-022-33010-8
View details for Web of Science ID 000854793700013
View details for PubMedID 36114170
View details for PubMedCentralID PMC9481532
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Cortical depth profiles of auditory and visual 7 T functional MRI responses in human superior temporal areas
HUMAN BRAIN MAPPING
2023; 44 (2): 362-372
Abstract
Invasive neurophysiological studies in nonhuman primates have shown different laminar activation profiles to auditory vs. visual stimuli in auditory cortices and adjacent polymodal areas. Means to examine the underlying feedforward vs. feedback type influences noninvasively have been limited in humans. Here, using 1-mm isotropic resolution 3D echo-planar imaging at 7 T, we studied the intracortical depth profiles of functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals to brief auditory (noise bursts) and visual (checkerboard) stimuli. BOLD percent-signal-changes were estimated at 11 equally spaced intracortical depths, within regions-of-interest encompassing auditory (Heschl's gyrus, Heschl's sulcus, planum temporale, and posterior superior temporal gyrus) and polymodal (middle and posterior superior temporal sulcus) areas. Effects of differing BOLD signal strengths for auditory and visual stimuli were controlled via normalization and statistical modeling. The BOLD depth profile shapes, modeled with quadratic regression, were significantly different for auditory vs. visual stimuli in auditory cortices, but not in polymodal areas. The different depth profiles could reflect sensory-specific feedforward versus cross-sensory feedback influences, previously shown in laminar recordings in nonhuman primates. The results suggest that intracortical BOLD profiles can help distinguish between feedforward and feedback type influences in the human brain. Further experimental studies are still needed to clarify how underlying signal strength influences BOLD depth profiles under different stimulus conditions.
View details for DOI 10.1002/hbm.26046
View details for Web of Science ID 000841648400001
View details for PubMedID 35980015
View details for PubMedCentralID PMC9842898
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Long-Term Effects of Repeated Blast Exposure in United States Special Operations Forces Personnel: A Pilot Study Protocol
JOURNAL OF NEUROTRAUMA
2022; 39 (19-20): 1391-1407
Abstract
Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.
View details for DOI 10.1089/neu.2022.0030
View details for Web of Science ID 000818401200001
View details for PubMedID 35620901
View details for PubMedCentralID PMC9529318
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Oxygen extraction efficiency and white matter lesion burden in older adults exhibiting radiological evidence of capillary shunting
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
2022; 42 (10): 1933-1943
Abstract
White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer's disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60-80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEFmax) with dynamic susceptibility contrast, and WML volume with T1-weighted MRI. We found a significant interaction between OEFmax and VHS presence on WML volume (p = 0.02), where lower OEFmax was associated with higher WML volume in participants with VHS, and higher OEFmax was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.
View details for DOI 10.1177/0271678X221105986
View details for Web of Science ID 000810120200001
View details for PubMedID 35673981
View details for PubMedCentralID PMC9536117
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Static and dynamic BOLD fMRI components along white matter fibre tracts and their dependence on the orientation of the local diffusion tensor axis relative to the B<sub>0</sub>-field
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
2022; 42 (10): 1905-1919
Abstract
Recent studies have reported functional MRI (fMRI) activation within cerebral white matter (WM) using blood-oxygenation-level-dependent (BOLD) contrast. Many blood vessels in WM run parallel to the fibre bundles, and other studies observed dependence of susceptibility contrast-based measures of blood volume on the local orientation of the fibre bundles relative to the magnetic field or B0 axis. Motivated by this, we characterized the dependence of gradient-echo BOLD fMRI on fibre orientation (estimated by the local diffusion tensor) relative to the B0 axis to test whether the alignment between bundles and vessels imparts an orientation dependence on resting-state BOLD fluctuations in the WM. We found that the baseline signal level of the T2*-weighted data is 11% higher in voxels containing fibres parallel to B0 than those containing perpendicular fibres, consistent with a static influence of either fibre or vessel orientation on local T2* values. We also found that BOLD fluctuations in most bundles exhibit orientation effects expected from oxygenation changes, with larger amplitudes from voxels containing perpendicular fibres. Different magnitudes of this orientation effect were observed across the major WM bundles, with inferior fasciculus, corpus callosum and optic radiation exhibiting 14-19% higher fluctuations in voxels containing perpendicular compared to parallel fibres.
View details for DOI 10.1177/0271678X221106277
View details for Web of Science ID 000806325700001
View details for PubMedID 35650710
View details for PubMedCentralID PMC9536127
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In vivo irreversible and reversible transverse relaxation rates in human cerebral cortex via line scans at 7 T with 250 micron resolution perpendicular to the cortical surface
MAGNETIC RESONANCE IMAGING
2022; 90: 44-52
Abstract
Understanding how and why MR signals and their associated relaxation rates vary with cortical depth could ultimately enable the noninvasive investigation of the laminar architecture of cerebral cortex in the living human brain. However, cortical gray matter is typically only a few millimeters thick, making it challenging to sample many cortical depths with the voxel sizes commonly used in MRI studies. Line-scan techniques provide a way to overcome this challenge and here we implemented a novel line-scan GESSE pulse sequence that allowed us to measure irreversible and reversible transverse relaxation rates-R2 and R2´, respectively-with extremely high resolution (250 μm) in the radial direction, perpendicular to the cortical surface. Eight healthy human subjects were scanned at 7 T using this sequence, with primary visual cortex (V1) targeted in three subjects and primary motor (M1) and somatosensory cortex (S1) targeted in the other five. In all three cortical areas, a peak in R2 values near the central depths was seen consistently across subjects-an observation that has not been made before, to our knowledge. On the other hand, no consistent pattern was apparent for R2´ values as a function of cortical depth. The intracortical R2 peak reported here is unlikely to be explained by myelin content or by deoxyhemoglobin in the microvasculature; however, this peak is in accord with the laminar distribution of non-heme iron in these cortical areas, known from prior histology studies. Obtaining information about tissue microstructure via measurements of transverse relaxation (and other quantitative MR contrast mechanisms) at the extremely high radial resolutions achievable through the use of line-scan techniques could therefore bring us closer to being able to perform "in vivo histology" of the cerebral cortex.
View details for DOI 10.1016/j.mri.2022.04.001
View details for Web of Science ID 000797331400002
View details for PubMedID 35398027
View details for PubMedCentralID PMC9930184
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Critical factors in achieving fine-scale functional MRI: Removing sources of inadvertent spatial smoothing
HUMAN BRAIN MAPPING
2022; 43 (11): 3311-3331
Abstract
Ultra-high Field (≥7T) functional magnetic resonance imaging (UHF-fMRI) provides opportunities to resolve fine-scale features of functional architecture such as cerebral cortical columns and layers, in vivo. While the nominal resolution of modern fMRI acquisitions may appear to be sufficient to resolve these features, several common data preprocessing steps can introduce unwanted spatial blurring, especially those that require interpolation of the data. These resolution losses can impede the detection of the fine-scale features of interest. To examine quantitatively and systematically the sources of spatial resolution losses occurring during preprocessing, we used synthetic fMRI data and real fMRI data from the human visual cortex-the spatially interdigitated human V2 "thin" and "thick" stripes. The pattern of these cortical columns lies along the cortical surface and thus can be best appreciated using surface-based fMRI analysis. We used this as a testbed for evaluating strategies that can reduce spatial blurring of fMRI data. Our results show that resolution losses can be mitigated at multiple points in preprocessing pathway. We show that unwanted blur is introduced at each step of volume transformation and surface projection, and can be ameliorated by replacing multi-step transformations with equivalent single-step transformations. Surprisingly, the simple approaches of volume upsampling and of cortical mesh refinement also helped to reduce resolution losses caused by interpolation. Volume upsampling also serves to improve motion estimation accuracy, which helps to reduce blur. Moreover, we demonstrate that the level of spatial blurring is nonuniform over the brain-knowledge which is critical for interpreting data in high-resolution fMRI studies. Importantly, our study provides recommendations for reducing unwanted blurring during preprocessing as well as methods that enable quantitative comparisons between preprocessing strategies. These findings highlight several underappreciated sources of a spatial blur. Individually, the factors that contribute to spatial blur may appear to be minor, but in combination, the cumulative effects can hinder the interpretation of fine-scale fMRI and the detectability of these fine-scale features of functional architecture.
View details for DOI 10.1002/hbm.25867
View details for Web of Science ID 000782038300001
View details for PubMedID 35417073
View details for PubMedCentralID PMC9248309
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SDnDTI: Self-supervised deep learning-based denoising for diffusion tensor MRI
NEUROIMAGE
2022; 253: 119033
Abstract
Diffusion tensor magnetic resonance imaging (DTI) is a widely adopted neuroimaging method for the in vivo mapping of brain tissue microstructure and white matter tracts. Nonetheless, the noise in the diffusion-weighted images (DWIs) decreases the accuracy and precision of DTI derived microstructural parameters and leads to prolonged acquisition time for achieving improved signal-to-noise ratio (SNR). Deep learning-based image denoising using convolutional neural networks (CNNs) has superior performance but often requires additional high-SNR data for supervising the training of CNNs, which reduces the feasibility of supervised learning-based denoising in practice. In this work, we develop a self-supervised deep learning-based method entitled "SDnDTI" for denoising DTI data, which does not require additional high-SNR data for training. Specifically, SDnDTI divides multi-directional DTI data into many subsets of six DWI volumes and transforms DWIs from each subset to along the same diffusion-encoding directions through the diffusion tensor model, generating multiple repetitions of DWIs with identical image contrasts but different noise observations. SDnDTI removes noise by first denoising each repetition of DWIs using a deep 3-dimensional CNN with the average of all repetitions with higher SNR as the training target, following the same approach as normal supervised learning based denoising methods, and then averaging CNN-denoised images for achieving higher SNR. The denoising efficacy of SDnDTI is demonstrated in terms of the similarity of output images and resultant DTI metrics compared to the ground truth generated using substantially more DWI volumes on two datasets with different spatial resolutions, b-values and numbers of input DWI volumes provided by the Human Connectome Project (HCP) and the Lifespan HCP in Aging. The SDnDTI results preserve image sharpness and textural details and substantially improve upon those from the raw data. The results of SDnDTI are comparable to those from supervised learning-based denoising and outperform those from state-of-the-art conventional denoising algorithms including BM4D, AONLM and MPPCA. By leveraging domain knowledge of diffusion MRI physics, SDnDTI makes it easier to use CNN-based denoising methods in practice and has the potential to benefit a wider range of research and clinical applications that require accelerated DTI acquisition and high-quality DTI data for mapping of tissue microstructure, fiber tracts and structural connectivity in the living human brain.
View details for DOI 10.1016/j.neuroimage.2022.119033
View details for Web of Science ID 000788154700001
View details for PubMedID 35240299
View details for PubMedCentralID PMC9511973
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Effect of vascular amyloid on white matter disease is mediated by vascular dysfunction in cerebral amyloid angiopathy
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
2022; 42 (7): 1272-1281
Abstract
We postulated that vascular dysfunction mediates the relationship between amyloid load and white matter hyperintensities (WMH) in cerebral amyloid angiopathy (CAA). Thirty-eight cognitively healthy patients with CAA (mean age 70 ± 7.1) were evaluated. WMH was quantified and expressed as percent of total intracranial volume (pWMH) using structural MRI. Mean global cortical Distribution Volume Ratio representing Pittsburgh Compound B (PiB) uptake (PiB-DVR) was calculated from PET scans. Time-to-peak [TTP] of blood oxygen level-dependent response to visual stimulation was used as an fMRI measure of vascular dysfunction. Higher PiB-DVR correlated with prolonged TTP (r = 0.373, p = 0.021) and higher pWMH (r = 0.337, p = 0.039). Prolonged TTP also correlated with higher pWMH (r = 0.485, p = 0.002). In a multivariate linear regression model, TTP remained independently associated with pWMH (p = 0.006) while PiB-DVR did not (p = 0.225). In a bootstrapping model, TTP had a significant indirect effect (ab = 0.97, 95% CI: 0.137-2.461), supporting that the association between PiB-DVR and pWMH is mediated by TTP response. There was no longer a direct effect independent of the hypothesized pathway. Our study suggests that the effect of vascular amyloid load on white matter disease is mediated by vascular dysfunction in CAA. Amyloid lowering strategies might prevent pathophysiological processes leading to vascular dysfunction, therefore limiting ischemic brain injury.
View details for DOI 10.1177/0271678X221076571
View details for Web of Science ID 000751172200001
View details for PubMedID 35086372
View details for PubMedCentralID PMC9207495
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Comprehensive diffusion MRI dataset for in vivo human brain microstructure mapping using 300 mT/m gradients.
Scientific data
1800; 9 (1): 7
Abstract
Strong gradient systems can improve the signal-to-noise ratio of diffusion MRI measurements and enable a wider range of acquisition parameters that are beneficial for microstructural imaging. We present a comprehensive diffusion MRI dataset of 26 healthy participants acquired on the MGH-USC 3T Connectome scanner equipped with 300 mT/m maximum gradient strength and a custom-built 64-channel head coil. For each participant, the one-hour long acquisition systematically sampled the accessible diffusion measurement space, including two diffusion times (19 and 49ms), eight gradient strengths linearly spaced between 30 mT/m and 290 mT/m for each diffusion time, and 32 or 64 uniformly distributed directions. The diffusion MRI data were preprocessed to correct for gradient nonlinearity, eddy currents, and susceptibility induced distortions. In addition, scan/rescan data from a subset of seven individuals were also acquired and provided. The MGH Connectome Diffusion Microstructure Dataset (CDMD) may serve as a test bed for the development of new data analysis methods, such as fiber orientation estimation, tractography and microstructural modelling.
View details for DOI 10.1038/s41597-021-01092-6
View details for PubMedID 35042861
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Imaging faster neural dynamics with fast fMRI: A need for updated models of the hemodynamic response
PROGRESS IN NEUROBIOLOGY
2021; 207: 102174
Abstract
Fast fMRI enables the detection of neural dynamics over timescales of hundreds of milliseconds, suggesting it may provide a new avenue for studying subsecond neural processes in the human brain. The magnitudes of these fast fMRI dynamics are far greater than predicted by canonical models of the hemodynamic response. Several studies have established nonlinear properties of the hemodynamic response that have significant implications for fast fMRI. We first review nonlinear properties of the hemodynamic response function that may underlie fast fMRI signals. We then illustrate the breakdown of canonical hemodynamic response models in the context of fast neural dynamics. We will then argue that the canonical hemodynamic response function is not likely to reflect the BOLD response to neuronal activity driven by sparse or naturalistic stimuli or perhaps to spontaneous neuronal fluctuations in the resting state. These properties suggest that fast fMRI is capable of tracking surprisingly fast neuronal dynamics, and we discuss the neuroscientific questions that could be addressed using this approach.
View details for DOI 10.1016/j.pneurobio.2021.102174
View details for Web of Science ID 000753820800003
View details for PubMedID 34525404
View details for PubMedCentralID PMC8688322
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The Global Configuration of Visual Stimuli Alters Co-Fluctuations of Cross-Hemispheric Human Brain Activity
JOURNAL OF NEUROSCIENCE
2021; 41 (47): 9756-9766
Abstract
We tested how a stimulus gestalt, defined by the neuronal interaction between local and global features of a stimulus, is represented within human primary visual cortex (V1). We used high-resolution fMRI, which serves as a surrogate of neuronal activation, to measure co-fluctuations within subregions of V1 as (male and female) subjects were presented with peripheral stimuli, each with different global configurations. We found stronger cross-hemisphere correlations when fine-scale V1 cortical subregions represented parts of the same object compared with different objects. This result was consistent with the vertical bias in global processing and, critically, was independent of the task and local discontinuities within objects. Thus, despite the relatively small receptive fields of neurons within V1, global stimulus configuration affects neuronal processing via correlated fluctuations between regions that represent different sectors of the visual field.SIGNIFICANCE STATEMENT We provide the first evidence for the impact of global stimulus configuration on cross-hemispheric fMRI fluctuations, measured in human primary visual cortex. Our results are consistent with changes in the level of γ-band synchrony, which has been shown to be affected by global stimulus configuration, being reflected in the level fMRI co-fluctuations. These data help narrow the gap between knowledge of global stimulus configuration encoding at the single-neuron level versus at the behavioral level.
View details for DOI 10.1523/JNEUROSCI.3214-20.2021
View details for Web of Science ID 000744255700007
View details for PubMedID 34663628
View details for PubMedCentralID PMC8612647
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Investigating mechanisms of fast BOLD responses: the effects of stimulus intensity and of spatial heterogeneity of hemodynamics.
NeuroImage
2021: 118658
Abstract
Recent studies have demonstrated that fast fMRI can track neural activity well above the temporal limit predicted by the canonical hemodynamic response model. While these findings are promising, the biophysical mechanisms underlying these fast fMRI phenomena remain underexplored. In this study, we discuss two aspects of the hemodynamic response, complementary to several existing hypotheses, that can accommodate faster fMRI dynamics beyond those predicted by the canonical model. First, we demonstrate, using both visual and somatosensory paradigms, that the timing and shape of hemodynamic response functions (HRFs) vary across graded levels of stimulus intensity-with lower-intensity stimulation eliciting faster and narrower HRFs. Second, we show that as the spatial resolution of fMRI increases, voxel-wise HRFs begin to deviate from the canonical model, with a considerable portion of voxels exhibiting faster temporal dynamics than predicted by the canonical HRF. Collectively, both stimulus/task intensity and image resolution can affect the sensitivity of fMRI to fast brain activity, which may partly explain recent observations of fast fMRI signals. It is further noteworthy that, while the present investigations focus on fast neural responses, our findings suggest that a revised hemodynamic model may benefit the many fMRI studies using paradigms with wide ranges of contrast levels (e.g., resting or naturalistic conditions) or with modern, high-resolution MR acquisitions.
View details for DOI 10.1016/j.neuroimage.2021.118658
View details for PubMedID 34656783
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Simultaneous pure T2 and varying T2'-weighted BOLD fMRI using Echo Planar Time-resolved Imaging for mapping cortical-depth dependent responses.
NeuroImage
2021; 245: 118641
Abstract
Spin-echo (SE) BOLD fMRI has high microvascular specificity, and thus provides a more reliable means to localize neural activity compared to conventional gradient-echo BOLD fMRI. However, the most common SE BOLD acquisition method, SE-EPI, is known to suffer from T2' contrast contamination with undesirable draining vein bias. To address this, in this study, we extended a recently developed distortion/blurring-free multi-shot EPI technique, Echo-Planar Time-resolved Imaging (EPTI), to cortical-depth dependent SE-fMRI at 7T to test whether it could provide purer SE BOLD contrast with minimal T2' contamination for improved neuronal specificity. From the same acquisition, the time-resolved feature of EPTI also provides a series of asymmetric SE (ASE) images with varying T2' weightings, and enables extraction of data equivalent to conventional SE EPI with different echo train lengths (ETLs). This allows us to systematically examine how T2'-contribution affects different SE acquisition strategies using a single dataset. A low-rank spatiotemporal subspace reconstruction was implemented for the SE-EPTI acquisition, which incorporates corrections for both shot-to-shot phase variations and dynamic B0 drifts. SE-EPTI was used in a visual task fMRI experiment to demonstrate that i) the pure SE image provided by EPTI results in the highest microvascular specificity; ii) the ASE EPTI series, with a graded introduction of T2' weightings at time points farther away from the pure SE, show a gradual sensitivity increase along with increasing draining vein bias; iii) the longer ETL seen in conventional SE EPI acquisitions will induce more draining vein bias. Consistent results were observed across multiple subjects, demonstrating the robustness of the proposed technique for SE-BOLD fMRI with high specificity.
View details for DOI 10.1016/j.neuroimage.2021.118641
View details for PubMedID 34655771
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Altered Blood Flow in the Ophthalmic and Internal Carotid Arteries in Patients with Age-Related Macular Degeneration Measured Using Noncontrast MR Angiography at 7T
AMERICAN JOURNAL OF NEURORADIOLOGY
2021; 42 (9): 1653-1660
Abstract
Age-related macular degeneration is associated with reduced perfusion of the eye; however, the role of altered blood flow in the upstream ophthalmic or internal carotid arteries is unclear. We used ultra-high-field MR imaging to investigate whether the diameter of and blood flow in the ophthalmic artery and/or the ICA are altered in age-related macular degeneration and whether any blood flow changes are associated with disease progression.Twenty-four patients with age-related macular degeneration and 13 similarly-aged healthy controls participated. TOF and high-resolution dynamic 2D phase-contrast MRA (0.26 × 0.26 × 2mm3, 100-ms effective sampling rate) was acquired at 7T. Vessel diameters were calculated from cross-sectional areas in phase-contrast acquisitions. Blood flow time-series were measured across the cardiac cycle.The ophthalmic artery vessel diameter was found to be significantly smaller in patients with age-related macular degeneration than in controls. Volumetric flow through the ophthalmic artery was significantly lower in patients with late age-related macular degeneration, with a significant trend of decreasing volumetric ophthalmic artery flow rates with increasing disease severity. The resistance index was significantly greater in patients with age-related macular degeneration than in controls in the ophthalmic artery. Flow velocity through the ophthalmic artery and ICA was significantly higher in patients with age-related macular degeneration. Ophthalmic artery blood flow as a percentage of ipsilateral ICA blood flow was nearly double in controls than in patients with age-related macular degeneration.These findings support the hypothesis that vascular changes upstream to the eye are associated with the severity of age-related macular degeneration. Additional investigation into the potential causality of this relationship and whether treatments that improve ocular circulation slow disease progression is warranted.
View details for DOI 10.3174/ajnr.A7187
View details for Web of Science ID 000670402700001
View details for PubMedID 34210664
View details for PubMedCentralID PMC8423057
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Improved cortical surface reconstruction using sub-millimeter resolution MPRAGE by image denoising
NEUROIMAGE
2021; 233: 117946
Abstract
Automatic cerebral cortical surface reconstruction is a useful tool for cortical anatomy quantification, analysis and visualization. Recently, the Human Connectome Project and several studies have shown the advantages of using T1-weighted magnetic resonance (MR) images with sub-millimeter isotropic spatial resolution instead of the standard 1-mm isotropic resolution for improved accuracy of cortical surface positioning and thickness estimation. Nonetheless, sub-millimeter resolution images are noisy by nature and require averaging multiple repetitions to increase the signal-to-noise ratio for precisely delineating the cortical boundary. The prolonged acquisition time and potential motion artifacts pose significant barriers to the wide adoption of cortical surface reconstruction at sub-millimeter resolution for a broad range of neuroscientific and clinical applications. We address this challenge by evaluating the cortical surface reconstruction resulting from denoised single-repetition sub-millimeter T1-weighted images. We systematically characterized the effects of image denoising on empirical data acquired at 0.6 mm isotropic resolution using three classical denoising methods, including denoising convolutional neural network (DnCNN), block-matching and 4-dimensional filtering (BM4D) and adaptive optimized non-local means (AONLM). The denoised single-repetition images were found to be highly similar to 6-repetition averaged images, with a low whole-brain averaged mean absolute difference of ~0.016, high whole-brain averaged peak signal-to-noise ratio of ~33.5 dB and structural similarity index of ~0.92, and minimal gray matter-white matter contrast loss (2% to 9%). The whole-brain mean absolute discrepancies in gray matter-white matter surface placement, gray matter-cerebrospinal fluid surface placement and cortical thickness estimation were lower than 165 μm, 155 μm and 145 μm-sufficiently accurate for most applications. These discrepancies were approximately one third to half of those from 1-mm isotropic resolution data. The denoising performance was equivalent to averaging ~2.5 repetitions of the data in terms of image similarity, and 1.6-2.2 repetitions in terms of the cortical surface placement accuracy. The scan-rescan variability of the cortical surface positioning and thickness estimation was lower than 170 μm. Our unique dataset and systematic characterization support the use of denoising methods for improved cortical surface reconstruction at sub-millimeter resolution.
View details for DOI 10.1016/j.neuroimage.2021.117946
View details for Web of Science ID 000647591400005
View details for PubMedID 33711484
View details for PubMedCentralID PMC8421085
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Lacunes, Microinfarcts, and Vascular Dysfunction in Cerebral Amyloid Angiopathy
NEUROLOGY
2021; 96 (12): E1646-E1654
Abstract
To analyze the relationship of lacunes with cortical cerebral microinfarcts (CMIs), to assess their association with vascular dysfunction, and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA).The count and topography of lacunes (deep/lobar), CMIs, and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time to peak (TTP) of blood oxygen level-dependent signal, an established measure of vascular dysfunction, was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH.The cohort consisted of 122 patients with probable CAA without dementia (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%); all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume (p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox regression models (p = 0.048 and p = 0.026, respectively).Our findings show a high prevalence of lobar lacunes, frequently coexisting with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism.
View details for DOI 10.1212/WNL.0000000000011631
View details for Web of Science ID 000656633700019
View details for PubMedID 33536272
View details for PubMedCentralID PMC8032369
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Efficient whole-brain tract-specific T<sub>1</sub> mapping at 3T with slice-shuffled inversion-recovery diffusion-weighted imaging
MAGNETIC RESONANCE IN MEDICINE
2021; 86 (2): 738-753
Abstract
Most voxels in white matter contain multiple fiber populations with different orientations and levels of myelination. Conventional T1 mapping measures 1 T1 value per voxel, representing a weighted average of the multiple tract T1 times. Inversion-recovery diffusion-weighted imaging (IR-DWI) allows the T1 times of multiple tracts in a voxel to be disentangled, but the scan time is prohibitively long. Recently, slice-shuffled IR-DWI implementations have been proposed to significantly reduce scan time. In this work, we demonstrate that we can measure tract-specific T1 values in the whole brain using simultaneous multi-slice slice-shuffled IR-DWI at 3T.We perform simulations to evaluate the accuracy and precision of our crossing fiber IR-DWI signal model for various fiber parameters. The proposed sequence and signal model are tested in a phantom consisting of crossing asparagus pieces doped with gadolinium to vary T1 , and in 2 human subjects.Our simulations show that tract-specific T1 times can be estimated within 5% of the nominal fiber T1 values. Tract-specific T1 values were resolved in subvoxel 2 fiber crossings in the asparagus phantom. Tract-specific T1 times were resolved in 2 different tract crossings in the human brain where myelination differences have previously been reported; the crossing of the cingulum and genu of the corpus callosum and the crossing of the corticospinal tract and pontine fibers.Whole-brain tract-specific T1 mapping is feasible using slice-shuffled IR-DWI at 3T. This technique has the potential to improve the microstructural characterization of specific tracts implicated in neurodevelopment, aging, and demyelinating disorders.
View details for DOI 10.1002/mrm.28734
View details for Web of Science ID 000630959100001
View details for PubMedID 33749017
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High-resolution fMRI at 7 Tesla: challenges, promises and recent developments for individual-focused fMRI studies
CURRENT OPINION IN BEHAVIORAL SCIENCES
2021; 40: 96-104
Abstract
Limited detection power has been a bottleneck for subject-specific functional MRI (fMRI) studies, however the higher signal-to-noise ratio afforded by ultra-high magnetic fields (≥ 7 Tesla) provides levels of sensitivity and resolution needed to study individual subjects. What may be surprising is that higher imaging resolution may provide both higher specificity and sensitivity due to reductions in partial volume effects and reduced physiological noise. However, challenges remain to ensure high data quality and to reduce variability in ultra-high field fMRI. We discuss session-specific biases including those caused by factors related to instrumentation, anatomy, and physiology-which can translate into variability across sessions-and how to minimize these to help ultra-high field fMRI reach its full potential for individual-focused studies.
View details for DOI 10.1016/j.cobeha.2021.01.011
View details for Web of Science ID 000709388900015
View details for PubMedID 33816717
View details for PubMedCentralID PMC8018601
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A suite of neurophotonic tools to underpin the contribution of internal brain states in fMRI
CURRENT OPINION IN BIOMEDICAL ENGINEERING
2021; 18
Abstract
Recent developments in optical microscopy, applicable for large-scale and longitudinal imaging of cortical activity in behaving animals, open unprecedented opportunities to gain a deeper understanding of neurovascular and neurometabolic coupling during different brain states. Future studies will leverage these tools to deliver foundational knowledge about brain state-dependent regulation of cerebral blood flow and metabolism as well as regulation as a function of brain maturation and aging. This knowledge is of critical importance to interpret hemodynamic signals observed with functional magnetic resonance imaging (fMRI).
View details for DOI 10.1016/j.cobme.2021.100273
View details for Web of Science ID 000663381500005
View details for PubMedID 33959688
View details for PubMedCentralID PMC8095678
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7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice
NEUROLOGY
2021; 96 (7): 327-341
Abstract
Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.
View details for DOI 10.1212/WNL.0000000000011413
View details for Web of Science ID 000656635000006
View details for PubMedID 33361257
View details for PubMedCentralID PMC8055334
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Ground-truth "resting-state" signal provides data-driven estimation and correction for scanner distortion of fMRI time-series dynamics
NEUROIMAGE
2021; 227: 117584
Abstract
The fMRI community has made great strides in decoupling neuronal activity from other physiologically induced T2* changes, using sensors that provide a ground-truth with respect to cardiac, respiratory, and head movement dynamics. However, blood oxygenation level-dependent (BOLD) time-series dynamics are also confounded by scanner artifacts, in complex ways that can vary not only between scanners but even, for the same scanner, between sessions. Unfortunately, the lack of an equivalent ground truth for BOLD time-series has thus far stymied the development of reliable methods for identification and removal of scanner-induced noise, a problem that we have previously shown to severely impact detection sensitivity of resting-state brain networks. To address this problem, we first designed and built a phantom capable of providing dynamic signals equivalent to that of the resting-state brain. Using the dynamic phantom, we then compared the ground-truth time-series with its measured fMRI data. Using these, we introduce data-quality metrics: Standardized Signal-to-Noise Ratio (ST-SNR) and Dynamic Fidelity that, unlike currently used measures such as temporal SNR (tSNR), can be directly compared across scanners. Dynamic phantom data acquired from four "best-case" scenarios: high-performance scanners with MR-physicist-optimized acquisition protocols, still showed scanner instability/multiplicative noise contributions of about 6-18% of the total noise. We further measured strong non-linearity in the fMRI response for all scanners, ranging between 8-19% of total voxels. To correct scanner distortion of fMRI time-series dynamics at a single-subject level, we trained a convolutional neural network (CNN) on paired sets of measured vs. ground-truth data. The CNN learned the unique features of each session's noise, providing a customized temporal filter. Tests on dynamic phantom time-series showed a 4- to 7-fold increase in ST-SNR and about 40-70% increase in Dynamic Fidelity after denoising, with CNN denoising outperforming both the temporal bandpass filtering and denoising using Marchenko-Pastur principal component analysis. Critically, we observed that the CNN temporal denoising pushes ST-SNR to a regime where signal power is higher than that of noise (ST-SNR > 1). Denoising human-data with ground-truth-trained CNN, in turn, showed markedly increased detection sensitivity of resting-state networks. These were visible even at the level of the single-subject, as required for clinical applications of fMRI.
View details for DOI 10.1016/j.neuroimage.2020.117584
View details for Web of Science ID 000617281900004
View details for PubMedID 33285328
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In vivo human whole-brain Connectom diffusion MRI dataset at 760 µm isotropic resolution.
Scientific data
2021; 8 (1): 122
Abstract
We present a whole-brain in vivo diffusion MRI (dMRI) dataset acquired at 760 μm isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy participant. The creation of this benchmark dataset is possible through the synergistic use of advanced acquisition hardware and software including the high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition method, and parallel imaging reconstruction with advanced ghost reduction algorithm. With its unprecedented resolution, SNR and image quality, we envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance the understanding of human brain structures and connectivity. This comprehensive dataset can also be used as a test bed for new modeling, sub-sampling strategies, denoising and processing algorithms, potentially providing a common testing platform for further development of in vivo high resolution dMRI techniques. Whole brain anatomical T1-weighted and T2-weighted images at submillimeter scale along with field maps are also made available.
View details for DOI 10.1038/s41597-021-00904-z
View details for PubMedID 33927203
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A 31-channel integrated "AC/DC" B0 shim and radiofrequency receive array coil for improved 7T MRI.
Magnetic resonance in medicine
2021
Abstract
To test an integrated "AC/DC" array approach at 7T, where B0 inhomogeneity poses an obstacle for functional imaging, diffusion-weighted MRI, MR spectroscopy, and other applications.A close-fitting 7T 31-channel (31-ch) brain array was constructed and tested using combined Rx and ΔB0 shim channels driven by a set of rapidly switchable current amplifiers. The coil was compared to a shape-matched 31-ch reference receive-only array for RF safety, signal-to-noise ratio (SNR), and inter-element noise correlation. We characterize the coil array's ability to provide global and dynamic (slice-optimized) shimming using ΔB0 field maps and echo planar imaging (EPI) acquisitions.The SNR and average noise correlation were similar to the 31-ch reference array. Global and slice-optimized shimming provide 11% and 40% improvements respectively compared to baseline second-order spherical harmonic shimming. Birdcage transmit coil efficiency was similar for the reference and AC/DC array setups.Adding ΔB0 shim capability to a 31-ch 7T receive array can significantly boost 7T brain B0 homogeneity without sacrificing the array's rdiofrequency performance, potentially improving ultra-high field neuroimaging applications that are vulnerable to off-resonance effects.
View details for DOI 10.1002/mrm.29022
View details for PubMedID 34632626
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Eye-selective fMRI activity in human primary visual cortex: Comparison between 3 T and 9.4 T, and effects across cortical depth
NEUROIMAGE
2020; 220: 117078
Abstract
The primary visual cortex of humans contains patches of neurons responding preferentially to stimulation of one eye (the ocular dominance columns). Multiple previous studies attempted to detect their activity using fMRI. The majority of these fMRI studies used magnetic field strengths of 4 T and higher. However, there have been reports of reliable eye-selective activations at 3 T as well. In this study we investigated the possibility of detecting eye-selective V1 activity using high-resolution GE-EPI fMRI at 3 T and sub-millimeter resolution fMRI at ultrahigh 9.4 T magnetic field strengths with acquisition parameters optimized for each field strength. High-resolution fMRI at 9.4 T also allowed us to examine the eye-selectivity responses across the cortical depth, which are expected to be strongest in the middle layers. We observed a substantial increase in the percentage of eye-selective voxels, as well as a doubling in run-to-run consistency of eye preference at ultrahigh field compared to 3 T. We also found that across cortical depth, eye selectivity increased towards the superficial layers, and that signal contrast increased while noise remained nearly constant towards the surface. The depth-resolved results are consistent with a distortion of spatial specificity of the GE-EPI signal by ascending venules and large draining veins on the cortical surface. The effects of larger vessels cause increasing signal amplitude, but also displacement of the maximum BOLD signal relative to neural activity. In summary, our results show that increase in spatial resolution, reduced partial volume effects, and improved sensitivity at 9.4 T allow for better detection of eye-selective signals related to ocular dominance columns. However, although ultrahigh field yields higher sensitivity to the ocular dominance signal, GE-EPI still suffers from specificity issues, with a prominent signal contribution at shallow depths from larger cortical vessels.
View details for DOI 10.1016/j.neuroimage.2020.117078
View details for Web of Science ID 000579184700035
View details for PubMedID 32585340
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Dynamic distortion correction for functional MRI using FID navigators
MAGNETIC RESONANCE IN MEDICINE
2021; 85 (3): 1294-1307
Abstract
To develop a method for slice-wise dynamic distortion correction for EPI using rapid spatiotemporal B0 field measurements from FID navigators (FIDnavs) and to evaluate the efficacy of this new approach relative to an established data-driven technique.A low-resolution reference image was used to create a forward model of FIDnav signal changes to enable estimation of spatiotemporal B0 inhomogeneity variations up to second order from measured FIDnavs. Five volunteers were scanned at 3 T using a 64-channel coil with FID-navigated EPI. The accuracy of voxel shift measurements and geometric distortion correction was assessed for experimentally induced magnetic field perturbations. The temporal SNR was evaluated in EPI time-series acquired at rest and with a continuous nose-touching action, before and after image realignment.Field inhomogeneity coefficients and voxel shift maps measured using FIDnavs were in excellent agreement with multi-echo EPI measurements. The FID-navigated distortion correction accurately corrected image geometry in the presence of induced magnetic field perturbations, outperforming the data-driven approach in regions with large field offsets. In functional MRI scans with nose touching, FIDnav-based correction yielded temporal SNR gains of 30% in gray matter. Following image realignment, which accounted for global image shifts, temporal SNR gains of 3% were achieved.Our proposed application of FIDnavs enables slice-wise dynamic distortion correction with high temporal efficiency. We achieved improved signal stability by leveraging the encoding information from multichannel coils. This approach can be easily adapted to other EPI-based sequences to improve temporal SNR for a variety of clinical and research applications.
View details for DOI 10.1002/mrm.28505
View details for Web of Science ID 000572250900001
View details for PubMedID 32970869
View details for PubMedCentralID PMC7718422
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Improving in vivo human cerebral cortical surface reconstruction using data-driven super-resolution.
Cerebral cortex (New York, N.Y. : 1991)
2020
Abstract
Accurate and automated reconstruction of the in vivo human cerebral cortical surface from anatomical magnetic resonance (MR) images facilitates the quantitative analysis of cortical structure. Anatomical MR images with sub-millimeter isotropic spatial resolution improve the accuracy of cortical surface and thickness estimation compared to the standard 1-millimeter isotropic resolution. Nonetheless, sub-millimeter resolution acquisitions require averaging multiple repetitions to achieve sufficient signal-to-noise ratio and are therefore long and potentially vulnerable to subject motion. We address this challenge by synthesizing sub-millimeter resolution images from standard 1-millimeter isotropic resolution images using a data-driven supervised machine learning-based super-resolution approach achieved via a deep convolutional neural network. We systematically characterize our approach using a large-scale simulated dataset and demonstrate its efficacy in empirical data. The super-resolution data provide improved cortical surfaces similar to those obtained from native sub-millimeter resolution data. The whole-brain mean absolute discrepancy in cortical surface positioning and thickness estimation is below 100mum at the single-subject level and below 50mum at the group level for the simulated data, and below 200mum at the single-subject level and below 100mum at the group level for the empirical data, making the accuracy of cortical surfaces derived from super-resolution sufficient for most applications.
View details for DOI 10.1093/cercor/bhaa237
View details for PubMedID 32887984
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DeepDTI: High-fidelity six-direction diffusion tensor imaging using deep learning.
NeuroImage
2020: 117017
Abstract
Diffusion tensor magnetic resonance imaging (DTI) is unsurpassed in its ability to map tissue microstructure and structural connectivity in the living human brain. Nonetheless, the angular sampling requirement for DTI leads to long scan times and poses a critical barrier to performing high-quality DTI in routine clinical practice and large-scale research studies. In this work we present a new processing framework for DTI entitled DeepDTI that minimizes the data requirement of DTI to six diffusion-weighted images (DWIs) required by conventional voxel-wise fitting methods for deriving the six unique unknowns in a diffusion tensor using data-driven supervised deep learning. DeepDTI maps the input b=0 image and six DWI volumes sampled along optimized diffusion-encoding directions, along with T1-weighted and T2-weighted image volumes, to the residuals between the input and high-quality output image volumes using a 10-layer three-dimensional convolutional neural network (CNN). The inputs and outputs of DeepDTI are uniquely formulated, which not only enables residual learning to boost CNN performance but also enables tensor fitting of resultant high-quality DWIs to generate orientational DTI metrics for tractography. The very deep CNN used by DeepDTI leverages the redundancy in local and non-local spatial information and across diffusion-encoding directions and image contrasts in the data. The performance of DeepDTI was systematically quantified in terms of the quality of the output images, DTI metrics, DTI-based tractography and tract-specific analysis results. We demonstrate rotationally-invariant and robust estimation of DTI metrics from DeepDTI that are comparable to those obtained with two b=0 images and 21 DWIs for the primary eigenvector derived from DTI and two b=0 images and 26-30 DWIs for various scalar metrics derived from DTI, achieving 3.3-4.6* acceleration, and twice as good as those of a state-of-the-art denoising algorithm at the group level. The twenty major white-matter tracts can be accurately identified from the tractography of DeepDTI results. The mean distance between the core of the major white-matter tracts identified from DeepDTI results and those from the ground-truth results using 18 b=0 images and 90 DWIs measures around 1-1.5 mm. DeepDTI leverages domain knowledge of diffusion MRI physics and power of deep learning to render DTI, DTI-based tractography, major white-matter tracts identification and tract-specific analysis more feasible for a wider range of neuroscientific and clinical studies.
View details for DOI 10.1016/j.neuroimage.2020.117017
View details for PubMedID 32504817
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Resting-state "physiological networks"
NEUROIMAGE
2020; 213: 116707
Abstract
Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations between distant brain regions. Here, we investigated whether such "physiological networks"-sets of segregated brain regions that exhibit similar responses following slow changes in systemic physiology-resemble patterns associated with large-scale networks typically attributed to remotely synchronized neuronal activity. By analyzing a large group of subjects from the 3T Human Connectome Project (HCP) database, we demonstrate brain-wide and noticeably heterogenous dynamics tightly coupled to either respiratory variation or heart rate changes. We show, using synthesized data generated from physiological recordings across subjects, that these physiologically-coupled fluctuations alone can produce networks that strongly resemble previously reported resting-state networks, suggesting that, in some cases, the "physiological networks" seem to mimic the neuronal networks. Further, we show that such physiologically-relevant connectivity estimates appear to dominate the overall connectivity observations in multiple HCP subjects, and that this apparent "physiological connectivity" cannot be removed by the use of a single nuisance regressor for the entire brain (such as global signal regression) due to the clear regional heterogeneity of the physiologically-coupled responses. Our results challenge previous notions that physiological confounds are either localized to large veins or globally coherent across the cortex, therefore emphasizing the necessity to consider potential physiological contributions in fMRI-based functional connectivity studies. The rich spatiotemporal patterns carried by such "physiological" dynamics also suggest great potential for clinical biomarkers that are complementary to large-scale neuronal networks.
View details for DOI 10.1016/j.neuroimage.2020.116707
View details for Web of Science ID 000525321000029
View details for PubMedID 32145437
View details for PubMedCentralID PMC7165049
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<i>In vivo</i> functional localization of the temporal monocular crescent representation in human primary visual cortex
NEUROIMAGE
2020; 209: 116516
Abstract
The temporal monocular crescent (TMC) is the most peripheral portion of the visual field whose perception relies solely on input from the ipsilateral eye. According to a handful of post-mortem histological studies in humans and non-human primates, the TMC is represented visuotopically within the most anterior portion of the primary visual cortical area (V1). However, functional evidence of the TMC visuotopic representation in human visual cortex is rare, mostly due to the small size of the TMC representation (~6% of V1) and due to the technical challenges of stimulating the most peripheral portion of the visual field inside the MRI scanner. In this study, by taking advantage of custom-built MRI-compatible visual stimulation goggles with curved displays, we successfully stimulated the TMC region of the visual field in eight human subjects, half of them right-eye dominant, inside a 3 T MRI scanner. This enabled us to localize the representation of TMC, along with the blind spot representation (another visuotopic landmark in V1), in all volunteers, which match the expected spatial pattern based on prior anatomical studies. In all hemispheres, the TMC visuotopic representation was localized along the peripheral border of V1, within the most anterior portion of the calcarine sulcus, without any apparent extension into the second visual area (V2). We further demonstrate the reliability of this localization within/across experimental sessions, and consistency in the spatial location of TMC across individuals after accounting for inter-subject structural differences.
View details for DOI 10.1016/j.neuroimage.2020.116516
View details for Web of Science ID 000517885100021
View details for PubMedID 31904490
View details for PubMedCentralID PMC7056564
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Two-photon microscopic imaging of capillary red blood cell flux in mouse brain reveals vulnerability of cerebral white matter to hypoperfusion
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
2020; 40 (3): 501-512
Abstract
Despite the importance of understanding the regulation of microvascular blood flow in white matter, no data on subcortical capillary blood flow parameters are available, largely due to the lack of appropriate imaging methods. To address this knowledge gap, we employed two-photon microscopy using a far-red fluorophore Alexa680 and photon-counting detection to measure capillary red blood cell (RBC) flux in both cerebral gray and white matter, in isoflurane-anesthetized mice. We have found that in control animals, baseline capillary RBC flux in the white matter was significantly higher than in the adjacent cerebral gray matter. In response to mild hypercapnia, RBC flux in the white matter exhibited significantly smaller fractional increase than in the gray matter. Finally, during global cerebral hypoperfusion, RBC flux in the white matter was reduced significantly in comparison to the controls, while RBC flux in the gray matter was preserved. Our results suggest that blood flow in the white matter may be less efficiently regulated when challenged by physiological perturbations as compared to the gray matter. Importantly, the blood flow in the white matter may be more susceptible to hypoperfusion than in the gray matter, potentially exacerbating the white matter deterioration in brain conditions involving global cerebral hypoperfusion.
View details for DOI 10.1177/0271678X19831016
View details for Web of Science ID 000513378300004
View details for PubMedID 30829101
View details for PubMedCentralID PMC7026840
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Impact of prospective motion correction, distortion correction methods and large vein bias on the spatial accuracy of cortical laminar fMRI at 9.4 Tesla
NEUROIMAGE
2020; 208: 116434
Abstract
Functional imaging with sub-millimeter spatial resolution is a basic requirement for assessing functional MRI (fMRI) responses across different cortical depths and is used extensively in the emerging field of laminar fMRI. Such studies seek to investigate the detailed functional organization of the brain and may develop to a new powerful tool for human neuroscience. However, several studies have shown that measurement of laminar fMRI responses can be biased by the image acquisition and data processing strategies. In this work, measurements with three different gradient-echo EPI BOLD fMRI protocols with a voxel size down to 650 μm isotropic were performed at 9.4 T. We estimated how prospective motion correction can help to improve spatial accuracy by reducing the number of spatial resampling steps in postprocessing. In addition, we demonstrate key requirements for accurate geometric distortion correction to ensure that distortion correction maps are properly aligned to the functional data and that strong variations of distortions near large veins can lead to signal overlays which cannot be corrected for during postprocessing. Furthermore, this study illustrates the spatial extent of bias induced by pial and other larger veins in laminar BOLD experiments. Since these issues under investigation affect studies performed with more conventional spatial resolutions, the methods applied in this work may also help to improve the understanding of the BOLD signal more broadly.
View details for DOI 10.1016/j.neuroimage.2019.116434
View details for Web of Science ID 000509981500018
View details for PubMedID 31812715
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Advanced Neuroimaging to Unravel Mechanisms of Cerebral Small Vessel Diseases
STROKE
2020; 51 (1): 29-37
View details for DOI 10.1161/STROKEAHA.119.024149
View details for Web of Science ID 000504225600020
View details for PubMedID 31752614
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Accelerated spin-echo functional MRI using multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider) simultaneous multislice echo-planar imaging
MAGNETIC RESONANCE IN MEDICINE
2020; 84 (1): 206–20
Abstract
Spin-echo functional MRI (SE-fMRI) has the potential to improve spatial specificity when compared with gradient-echo fMRI. However, high spatiotemporal resolution SE-fMRI with large slice-coverage is challenging as SE-fMRI requires a long echo time to generate blood oxygenation level-dependent (BOLD) contrast, leading to long repetition times. The aim of this work is to develop an acquisition method that enhances the slice-coverage of SE-fMRI at high spatiotemporal resolution.An acquisition scheme was developed entitled multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider). MESSI uses the dead-time during the long echo time by interleaving the excitation and readout of 2 slices to enable 2× slice-acceleration, while cgSlider uses the stable temporal background phase in SE-fMRI to encode/decode 2 adjacent slices simultaneously with a "phase-constrained" reconstruction method. The proposed cgSlider-MESSI was also combined with simultaneous multislice (SMS) to achieve further slice-acceleration. This combined approach was used to achieve 1.5-mm isotropic whole-brain SE-fMRI with a temporal resolution of 1.5 s and was evaluated using sensory stimulation and breath-hold tasks at 3T.Compared with conventional SE-SMS, cgSlider-MESSI-SMS provides 4-fold increase in slice-coverage for the same repetition time, with comparable temporal signal-to-noise ratio. Corresponding fMRI activation from cgSlider-MESSI-SMS for both fMRI tasks were consistent with those from conventional SE-SMS. Overall, cgSlider-MESSI-SMS achieved a 32× encoding-acceleration by combining Rinplane × MB × cgSlider × MESSI = 4 × 2 × 2 × 2.High-quality, high-resolution whole-brain SE-fMRI was acquired at a short repetition time using cgSlider-MESSI-SMS. This method should be beneficial for high spatiotemporal resolution SE-fMRI studies requiring whole-brain coverage.
View details for DOI 10.1002/mrm.28108
View details for Web of Science ID 000502704900001
View details for PubMedID 31840295
View details for PubMedCentralID PMC7083698
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Image processing and analysis methods for the Adolescent Brain Cognitive Development Study
NEUROIMAGE
2019; 202: 116091
Abstract
The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.
View details for DOI 10.1016/j.neuroimage.2019.116091
View details for Web of Science ID 000491861000051
View details for PubMedID 31415884
View details for PubMedCentralID PMC6981278
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Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep
SCIENCE
2019; 366 (6465): 628-+
Abstract
Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non-rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.
View details for DOI 10.1126/science.aax5440
View details for Web of Science ID 000494465700047
View details for PubMedID 31672896
View details for PubMedCentralID PMC7309589
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<SUP>7</SUP> Tesla MRI of the <i>ex vivo</i> human brain at 100 micron resolution
SCIENTIFIC DATA
2019; 6: 244
Abstract
We present an ultra-high resolution MRI dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 µm isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of scan time (25 hours per flip angle), allowing derivation of synthesized FLASH volumes. This dataset provides an unprecedented view of the three-dimensional neuroanatomy of the human brain. To optimize the utility of this resource, we warped the dataset into standard stereotactic space. We now distribute the dataset in both native space and stereotactic space to the academic community via multiple platforms. We envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance understanding of human brain anatomy in health and disease.
View details for DOI 10.1038/s41597-019-0254-8
View details for Web of Science ID 000494478200002
View details for PubMedID 31666530
View details for PubMedCentralID PMC6821740
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Highly accelerated multishot echo planar imaging through synergistic machine learning and joint reconstruction
MAGNETIC RESONANCE IN MEDICINE
2019; 82 (4): 1343–58
Abstract
To introduce a combined machine learning (ML)- and physics-based image reconstruction framework that enables navigator-free, highly accelerated multishot echo planar imaging (msEPI) and demonstrate its application in high-resolution structural and diffusion imaging.Single-shot EPI is an efficient encoding technique, but does not lend itself well to high-resolution imaging because of severe distortion artifacts and blurring. Although msEPI can mitigate these artifacts, high-quality msEPI has been elusive because of phase mismatch arising from shot-to-shot variations which preclude the combination of the multiple-shot data into a single image. We utilize deep learning to obtain an interim image with minimal artifacts, which permits estimation of image phase variations attributed to shot-to-shot changes. These variations are then included in a joint virtual coil sensitivity encoding (JVC-SENSE) reconstruction to utilize data from all shots and improve upon the ML solution.Our combined ML + physics approach enabled Rinplane × multiband (MB) = 8- × 2-fold acceleration using 2 EPI shots for multiecho imaging, so that whole-brain T2 and T2 * parameter maps could be derived from an 8.3-second acquisition at 1 × 1 × 3-mm3 resolution. This has also allowed high-resolution diffusion imaging with high geometrical fidelity using 5 shots at Rinplane × MB = 9- × 2-fold acceleration. To make these possible, we extended the state-of-the-art MUSSELS reconstruction technique to simultaneous multislice encoding and used it as an input to our ML network.Combination of ML and JVC-SENSE enabled navigator-free msEPI at higher accelerations than previously possible while using fewer shots, with reduced vulnerability to poor generalizability and poor acceptance of end-to-end ML approaches.
View details for DOI 10.1002/mrm.27813
View details for Web of Science ID 000483917000010
View details for PubMedID 31106902
View details for PubMedCentralID PMC6626584
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Dependence of resting-state fMRI fluctuation amplitudes on cerebral cortical orientation relative to the direction of B0 and anatomical axes
NEUROIMAGE
2019; 196: 337-350
Abstract
Functional magnetic resonance imaging (fMRI) is now capable of sub-millimetre scale measurements over the entire human brain, however with such high resolutions each voxel is influenced by the local fine-scale details of the cerebral cortical vascular anatomy. The cortical vasculature is structured with the pial vessels lying tangentially along the grey matter surface, intracortical diving arterioles and ascending venules running perpendicularly to the surface, and a randomly oriented capillary network within the parenchyma. It is well-known that the amplitude of the blood-oxygenation level dependent (BOLD) signal emanating from a vessel depends on its orientation relative to the B0-field. Thus the vascular geometric hierarchy will impart an orientation dependence to the BOLD signal amplitudes and amplitude differences due to orientation differences constitute a bias for interpreting neuronal activity. Here, we demonstrate a clear effect of cortical orientation to B0 in the resting-state BOLD-fMRI amplitude (quantified as the coefficient of temporal signal variation) for 1.1 mm isotropic data at 7T and 2 mm isotropic at 3T. The maximum bias, i.e. the fluctuation amplitude difference between regions where cortex is perpendicular to vs. parallel to B0, is about +70% at the pial surface at 7T and +11% at 3T. The B0 orientation bias declines with cortical depth, becomes progressively smaller closer to the white matter surface, but then increases again to a local maximum within the white matter just beneath the cortical grey matter, suggesting a distinct tangential network of white matter vessels that also generate a BOLD orientation effect. We further found significant (negative) biases with the cortex orientation to the anterior-posterior anatomical axis of the head: a maximum negative bias of about -30% at the pial surface at 7T and about -13% at 3T. The amount of signal variance explained by the low frequency drift, motion and the respiratory cycle also showed a cortical orientation dependence; only the cardiac cycle induced signal variance was independent of cortical orientation, suggesting that the cardiac induced component of the image time-series fluctuations is not related to a significant change in susceptibility. Although these orientation effects represent a signal bias, and are likely to be a nuisance in high-resolution analyses, they may help characterize the vascular influences on candidate fMRI acquisitions and, thereby, may be exploited to improve the neuronal specificity of fMRI.
View details for DOI 10.1016/j.neuroimage.2019.04.036
View details for Web of Science ID 000470833800032
View details for PubMedID 31002965
View details for PubMedCentralID PMC6559854
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<i>In vivo</i> measurements of irreversible and reversible transverse relaxation rates in human basal ganglia at 7 T: making inferences about the microscopic and mesoscopic structure of iron and calcification deposits
NMR IN BIOMEDICINE
2019; 32 (11): e4140
Abstract
The goal of this study was to measure irreversible and reversible transverse relaxation rates in the globus pallidus and putamen at 7 T, and to use these rates to make inferences about the sub-voxel structure of iron and calcification deposits. Gradient Echo Sampling of a Spin Echo (GESSE) data were acquired at 7 T on eighteen volunteers spanning a large range of ages (23-85 years), with calcifications in the globus pallidus incidentally observed in one volunteer. Maps of transverse relaxation rates were derived from the GESSE data, and the mean value of these rates in globus pallidus and putamen was estimated for each volunteer. Both irreversible and reversible transverse relaxation rates increased with the expected age-dependent iron content in these structures, except for the individual with calcifications for whom extremely large reversible relaxation rates but normal irreversible relaxation rates were found in the globus pallidus. Given the sensitivity of irreversible and reversible transverse relaxation rates to microscopic and mesoscopic field variations, respectively, our findings suggest that joint consideration of these rates may yield information not only about the amount of iron and calcification deposited in the brain, but also about the sub-voxel structure of these deposits, perhaps revealing certain aspects of their geometry and cellular distribution.
View details for DOI 10.1002/nbm.4140
View details for Web of Science ID 000478122600001
View details for PubMedID 31322331
View details for PubMedCentralID PMC6817385
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The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: A multimodal ultrahigh-field (7T) fMRI study
BRAIN STIMULATION
2019; 12 (4): 911-921
Abstract
Brainstem-focused mechanisms supporting transcutaneous auricular VNS (taVNS) effects are not well understood, particularly in humans. We employed ultrahigh field (7T) fMRI and evaluated the influence of respiratory phase for optimal targeting, applying our respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) technique.We proposed that targeting of nucleus tractus solitarii (NTS) and cardiovagal modulation in response to taVNS stimuli would be enhanced when stimulation is delivered during a more receptive state, i.e. exhalation.Brainstem fMRI response to auricular taVNS (cymba conchae) was assessed for stimulation delivered during exhalation (eRAVANS) or inhalation (iRAVANS), while exhalation-gated stimulation over the greater auricular nerve (GANctrl, i.e. earlobe) was included as control. Furthermore, we evaluated cardiovagal response to stimulation by calculating instantaneous HF-HRV from cardiac data recorded during fMRI.Our findings demonstrated that eRAVANS evoked fMRI signal increase in ipsilateral pontomedullary junction in a cluster including purported NTS. Brainstem response to GANctrl localized a partially-overlapping cluster, more ventrolateral, consistent with spinal trigeminal nucleus. A region-of-interest analysis also found eRAVANS activation in monoaminergic source nuclei including locus coeruleus (LC, noradrenergic) and both dorsal and median raphe (serotonergic) nuclei. Response to eRAVANS was significantly greater than iRAVANS for all nuclei, and greater than GANctrl in LC and raphe nuclei. Furthermore, eRAVANS, but not iRAVANS, enhanced cardiovagal modulation, confirming enhanced eRAVANS response on both central and peripheral neurophysiological levels.7T fMRI localized brainstem response to taVNS, linked such response with autonomic outflow, and demonstrated that taVNS applied during exhalation enhanced NTS targeting.
View details for DOI 10.1016/j.brs.2019.02.003
View details for Web of Science ID 000472482500010
View details for PubMedID 30803865
View details for PubMedCentralID PMC6592731
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Dependence of the MR signal on the magnetic susceptibility of blood studied with models based on real microvascular networks
MAGNETIC RESONANCE IN MEDICINE
2019; 81 (6): 3865-3874
Abstract
The primary goal of this study was to estimate the value of β , the exponent in the power law relating changes of the transverse relaxation rate and intra-extravascular local magnetic susceptibility differences as ΔR2∗∝(Δχ)β . The secondary objective was to evaluate any differences that might exist in the value of β obtained using a deoxyhemoglobin-weighted Δχ distribution versus a constant Δχ distribution assumed in earlier computations. The third objective was to estimate the value of β that is relevant for methods based on susceptibility contrast agents with a concentration of Δχ higher than that used for BOLD fMRI calculations.Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte-Carlo simulations to compute β from the first principles.Our results show that β=1 for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of β=1 .5 using uniform Δχ distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for Δχ , β=1 for B0≤ 9.4 T, whereas at 14 T β can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of Δχ is desired for experiments at high B0 .These results improve our understanding of the relationship between R2* and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively.
View details for DOI 10.1002/mrm.27660
View details for Web of Science ID 000481978700034
View details for PubMedID 30659643
View details for PubMedCentralID PMC6435380
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Echo planar time-resolved imaging (EPTI)
MAGNETIC RESONANCE IN MEDICINE
2019; 81 (6): 3599–3615
Abstract
To develop an efficient distortion- and blurring-free multi-shot EPI technique for time-resolved multiple-contrast and/or quantitative imaging.EPI is a commonly used sequence but suffers from geometric distortions and blurring. Here, we introduce a new multi-shot EPI technique termed echo planar time-resolved imaging (EPTI), which has the ability to rapidly acquire distortion- and blurring-free multi-contrast data set. The EPTI approach performs encoding in ky -t space and uses a new highly accelerated spatio-temporal CAIPI sampling trajectory to take advantage of signal correlation along these dimensions. Through this acquisition and a B0 -informed parallel imaging reconstruction, hundreds of "time-resolved" distortion- and blurring-free images at different TEs across the EPI readout window can be created at sub-millisecond temporal increments using a small number of EPTI shots. Moreover, a method for self-estimation and correction of shot-to-shot B0 variations was developed. Simultaneous multi-slice acquisition was also incorporated to further improve the acquisition efficiency.We evaluated EPTI under varying simulated acceleration factors, B0 -inhomogeneity, and shot-to-shot B0 variations to demonstrate its ability to provide distortion- and blurring-free images at multiple TEs. Two variants of EPTI were demonstrated in vivo at 3T: (1) a combined gradient- and spin-echo EPTI for quantitative mapping of T2 , T2* , proton density, and susceptibility at 1.1 × 1.1 × 3 mm3 whole-brain in 28 s (0.8 s/slice), and (2) a gradient-echo EPTI, for multi-echo and quantitative T2* fMRI at 2 × 2 × 3 mm3 whole-brain at a 3.3 s temporal resolution.EPTI is a new approach for multi-contrast and/or quantitative imaging that can provide fast acquisition of distortion- and blurring-free images at multiple TEs.
View details for DOI 10.1002/mrm.27673
View details for Web of Science ID 000481978700015
View details for PubMedID 30714198
View details for PubMedCentralID PMC6435385
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Teaching NeuroImages: In vivo visualization of Edinger comb and Wilson pencils
NEUROLOGY
2019; 92 (14): E1663-E1664
View details for DOI 10.1212/WNL.0000000000007252
View details for Web of Science ID 000480758600013
View details for PubMedID 30936236
View details for PubMedCentralID PMC6448452
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Parallel distributed networks resolved at high resolution reveal close juxtaposition of distinct regions
JOURNAL OF NEUROPHYSIOLOGY
2019; 121 (4): 1513–34
Abstract
Examination of large-scale distributed networks within the individual reveals details of cortical network organization that are absent in group-averaged studies. One recent discovery is that a distributed transmodal network, often referred to as the "default network," comprises two closely interdigitated networks, only one of which is coupled to posterior parahippocampal cortex. Not all studies of individuals have identified the same networks, and questions remain about the degree to which the two networks are separate, particularly within regions hypothesized to be interconnected hubs. In this study we replicate the observation of network separation across analytical (seed-based connectivity and parcellation) and data projection (volume and surface) methods in two individuals each scanned 31 times. Additionally, three individuals were examined with high-resolution (7T; 1.35 mm) functional magnetic resonance imaging to gain further insight into the anatomical details. The two networks were identified with separate regions localized to adjacent portions of the cortical ribbon, sometimes inside the same sulcus. Midline regions previously implicated as hubs revealed near complete spatial separation of the two networks, displaying a complex spatial topography in the posterior cingulate and precuneus. The network coupled to parahippocampal cortex also revealed a separate region directly within the hippocampus, at or near the subiculum. These collective results support that the default network is composed of at least two spatially juxtaposed networks. Fine spatial details and juxtapositions of the two networks can be identified within individuals at high resolution, providing insight into the network organization of association cortex and placing further constraints on interpretation of group-averaged neuroimaging data. NEW & NOTEWORTHY Recent evidence has emerged that canonical large-scale networks such as the "default network" fractionate into parallel distributed networks when defined within individuals. This research uses high-resolution imaging to show that the networks possess juxtapositions sometimes evident inside the same sulcus and within regions that have been previously hypothesized to be network hubs. Distinct circumscribed regions of one network were also resolved in the hippocampal formation, at or near the parahippocampal cortex and subiculum.
View details for DOI 10.1152/jn.00808.2018
View details for Web of Science ID 000465083500034
View details for PubMedID 30785825
View details for PubMedCentralID PMC6485740
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Intracortical smoothing of small-voxel fMRI data can provide increased detection power without spatial resolution losses compared to conventional large-voxel fMRI data
NEUROIMAGE
2019; 189: 601-614
Abstract
Continued improvement in MRI acquisition technology has made functional MRI (fMRI) with small isotropic voxel sizes down to 1 mm and below more commonly available. Although many conventional fMRI studies seek to investigate regional patterns of cortical activation for which conventional voxel sizes of 3 mm and larger provide sufficient spatial resolution, smaller voxels can help avoid contamination from adjacent white matter (WM) and cerebrospinal fluid (CSF), and thereby increase the specificity of fMRI to signal changes within the gray matter. Unfortunately, temporal signal-to-noise ratio (tSNR), a metric of fMRI sensitivity, is reduced in high-resolution acquisitions, which offsets the benefits of small voxels. Here we introduce a framework that combines small, isotropic fMRI voxels acquired at 7 T field strength with a novel anatomically-informed, surface mesh-navigated spatial smoothing that can provide both higher detection power and higher resolution than conventional voxel sizes. Our smoothing approach uses a family of intracortical surface meshes and allows for kernels of various shapes and sizes, including curved 3D kernels that adapt to and track the cortical folding pattern. Our goal is to restrict smoothing to the cortical gray matter ribbon and avoid noise contamination from CSF and signal dilution from WM via partial volume effects. We found that the intracortical kernel that maximizes tSNR does not maximize percent signal change (ΔS/S), and therefore the kernel configuration that optimizes detection power cannot be determined from tSNR considerations alone. However, several kernel configurations provided a favorable balance between boosting tSNR and ΔS/S, and allowed a 1.1-mm isotropic fMRI acquisition to have higher performance after smoothing (in terms of both detection power and spatial resolution) compared to an unsmoothed 3.0-mm isotropic fMRI acquisition. Overall, the results of this study support the strategy of acquiring voxels smaller than the cortical thickness, even for studies not requiring high spatial resolution, and smoothing them down within the cortical ribbon with a kernel of an appropriate shape to achieve the best performance-thus decoupling the choice of fMRI voxel size from the spatial resolution requirements of the particular study. The improvement of this new intracortical smoothing approach over conventional surface-based smoothing is expected to be modest for conventional resolutions, however the improvement is expected to increase with higher resolutions. This framework can also be applied to anatomically-informed intracortical smoothing of higher-resolution data (e.g. along columns and layers) in studies with prior information about the spatial structure of activation.
View details for DOI 10.1016/j.neuroimage.2019.01.054
View details for Web of Science ID 000461166900052
View details for PubMedID 30690157
View details for PubMedCentralID PMC6668026
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Immunotherapy with ponezumab for probable cerebral amyloid angiopathy
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
2019; 6 (4): 795-806
Abstract
Cerebral amyloid angiopathy (CAA) is caused by cerebrovascular deposition of β-amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double-blind trial in patients with probable CAA assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against Aβ 1-40.Thirty-six participants aged 55-80 years with probable CAA received intravenous placebo (n = 12) or ponezumab (n = 24). The change from baseline to Days 2 and 90 in cerebrovascular reactivity (CVR) was measured in the visual cortex as the natural log of the rising slope of the BOLD fMRI response to a visual stimulus. Safety and tolerability were also assessed.The mean change from baseline to Day 90 was 0.817 (ponezumab) and 0.958 (placebo): a mean ratio of 0.852 (90% CI 0.735-0.989) representing a trend towards reduced CVR in the ponezumab group. This trend was not present at Day 2. There was one asymptomatic occurrence of amyloid-related imaging abnormality-edema in the ponezumab group. The total number of new cerebral microbleeds from baseline to day 90 did not differ between groups. The ponezumab group had a participant with nonfatal new cerebral hemorrhage with aphasia and a participant with subdural hemorrhage that site investigators deemed to be nondrug related. In the placebo group one participant had a fatal intracerebral hemorrhage and one participant had migraine with aura.Ponezumab was safe and well-tolerated. The ponezumab group showed a trend towards treatment effect at Day 90 that was opposite to the hypothesized direction. The prespecified efficacy criteria were thus not met.
View details for DOI 10.1002/acn3.761
View details for Web of Science ID 000465023500018
View details for PubMedID 31020004
View details for PubMedCentralID PMC6469253
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On the analysis of rapidly sampled fMRI data
NEUROIMAGE
2019; 188: 807–20
View details for DOI 10.1016/j.neuroimage.2019.02.008
View details for Web of Science ID 000460064700068
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Stimulus-dependent hemodynamic response timing across the human subcortical-cortical visual pathway identified through high spatiotemporal resolution 7T fMRI
NEUROIMAGE
2018; 181: 279–91
Abstract
Recent developments in fMRI acquisition techniques now enable fast sampling with whole-brain coverage, suggesting fMRI can be used to track changes in neural activity at increasingly rapid timescales. When images are acquired at fast rates, the limiting factor for fMRI temporal resolution is the speed of the hemodynamic response. Given that HRFs may vary substantially in subcortical structures, characterizing the speed of subcortical hemodynamic responses, and how the hemodynamic response shape changes with stimulus duration (i.e. the hemodynamic nonlinearity), is needed for designing and interpreting fast fMRI studies of these regions. We studied the temporal properties and nonlinearities of the hemodynamic response function (HRF) across the human subcortical visual system, imaging superior colliculus (SC), lateral geniculate nucleus of the thalamus (LGN) and primary visual cortex (V1) with high spatiotemporal resolution 7 Tesla fMRI. By presenting stimuli of varying durations, we mapped the timing and nonlinearity of hemodynamic responses in these structures at high spatiotemporal resolution. We found that the hemodynamic response is consistently faster and narrower in subcortical structures than in cortex. However, the nonlinearity in LGN is similar to that in cortex, with shorter duration stimuli eliciting larger and faster responses than would have been predicted by a linear model. Using oscillatory visual stimuli, we tested the frequency response in LGN and found that its BOLD response tracked high-frequency (0.5 Hz) oscillations. The LGN response magnitudes were comparable to V1, allowing oscillatory BOLD signals to be detected in LGN despite the small size of this structure. These results suggest that the increase in the speed and amplitude of the hemodynamic response when neural activity is brief may be the key physiological driver of fast fMRI signals, enabling detection of high-frequency oscillations with fMRI. We conclude that subcortical visual structures exhibit fast and nonlinear hemodynamic responses, and that these dynamics enable detection of fast BOLD signals even within small deep brain structures when imaging is performed at ultra-high field.
View details for DOI 10.1016/j.neuroimage.2018.06.056
View details for Web of Science ID 000445165600024
View details for PubMedID 29935223
View details for PubMedCentralID PMC6245599
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Dual-polarity slice-GRAPPA for concurrent ghost correction and slice separation in simultaneous multi-slice EPI
MAGNETIC RESONANCE IN MEDICINE
2018; 80 (4): 1364–75
Abstract
A ghost correction strategy for Simultaneous Multi-Slice (SMS) EPI methods that provides improved ghosting artifact reduction compared to conventional methods is presented. Conventional Nyquist ghost correction methods for SMS-EPI rely on navigator data that contain phase errors from all slices in the simultaneously acquired slice-group. These navigator data may contain spatially nonlinear phase differences near regions of B0 inhomogeneity, which violates the linear model employed by most EPI ghost correction algorithms, resulting in poor reconstructions.Dual-Polarity GRAPPA (DPG) was previously shown to accurately model and correct both spatially nonlinear and 2D phase errors in conventional single-slice EPI data. Here, an extension we call Dual-Polarity slice-GRAPPA (DPsG) is adapted to the slice-GRAPPA method and applied to SMS-EPI data for slice separation and ghost correction concurrently-eliminating the need for a separate ghost correction step while also providing improved slice-specific EPI phase error correction.Images from in vivo SMS-EPI data reconstructed using DPsG in place of conventional Nyquist ghost correction and slice-GRAPPA are presented. DPsG is shown to reduce ghosting artifacts and provide improved temporal SNR compared to the conventional reconstruction.The proposed use of DPsG for SMS-EPI reconstruction can provide images with lower artifact levels, higher image fidelity, and improved time-series stability compared to conventional reconstruction methods.
View details for DOI 10.1002/mrm.27113
View details for Web of Science ID 000448869800009
View details for PubMedID 29424460
View details for PubMedCentralID PMC6085171
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The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites
DEVELOPMENTAL COGNITIVE NEUROSCIENCE
2018; 32: 43-54
Abstract
The ABCD study is recruiting and following the brain development and health of over 10,000 9-10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature.
View details for DOI 10.1016/j.dcn.2018.03.001
View details for Web of Science ID 000434985300007
View details for PubMedID 29567376
View details for PubMedCentralID PMC5999559
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Magnetic Resonance Imaging technology - bridging the gap between noninvasive human imaging and optical microscopy
CURRENT OPINION IN NEUROBIOLOGY
2018; 50: 250-260
Abstract
Technological advances in Magnetic Resonance Imaging (MRI) have provided substantial gains in the sensitivity and specificity of functional neuroimaging. Mounting evidence demonstrates that the hemodynamic changes utilized in functional MRI can be far more spatially and thus neuronally specific than previously believed. This has motivated a push toward novel, high-resolution MR imaging strategies that can match this biological resolution limit while recording from the entire human brain. Although sensitivity increases are a necessary component, new MR encoding technologies are required to convert improved sensitivity into higher resolution. These new sampling strategies improve image acquisition efficiency and enable increased image encoding in the time-frame needed to follow hemodynamic changes associated with brain activation.
View details for DOI 10.1016/j.conb.2018.04.026
View details for Web of Science ID 000436225100030
View details for PubMedID 29753942
View details for PubMedCentralID PMC6015259
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Characterizing Signals Within Lesions and Mapping Brain Network Connectivity After Traumatic Axonal Injury: A 7 Tesla Resting-State FMRI Study
BRAIN CONNECTIVITY
2018; 8 (5): 288–98
View details for DOI 10.1089/brain.2017.0499
View details for Web of Science ID 000440872000004
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Characterizing Signals within Lesions and Mapping Brain Network Connectivity After Traumatic Axonal Injury: A 7 Tesla Resting-State FMRI Study.
Brain connectivity
2018
Abstract
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
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Optimized inversion-time schedules for quantitative T<sub>1</sub> measurements based on high-resolution multi-inversion EPI
MAGNETIC RESONANCE IN MEDICINE
2018; 79 (4): 2101-2112
Abstract
Demonstrate an optimized multi-inversion echo-planar imaging technique to accelerate quantitative T1 mapping by judicious selection of inversion times for each slice.Slice ordering is optimized to maximize discrimination between tissues with different T1 values. The optimized slice orderings are tested in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom and compared with an unoptimized 21-measurement acquisition. The utility of the method is demonstrated in a healthy subject in vivo at 3 T and validated with a gold-standard inversion-recovery sequence. The in vivo precision of our technique was tested by repeated scans of the same subject within a scan session and across scan sessions, occurring 28 days apart.Phantom measurements yielded good agreement (R2 = 0.99) between the T1 estimates from the proposed optimized protocol, reference values from the National Institute of Standards and Technology phantom and gold-standard inversion-recovery values, as well as a negligible estimation bias that was slightly lower than that from the unoptimized 21-measurement protocol (0.74 versus 19 ms). The range of values for the scan-rescan coefficient of variation was 0.86 to 0.93 (within session) and 0.83 to 0.92 (across sessions) across all scan durations tested.Optimized slice orderings allow faster quantitative T1 mapping. The optimized sequence yielded accurate and precise T1 maps. Magn Reson Med 79:2101-2112, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
View details for DOI 10.1002/mrm.26889
View details for Web of Science ID 000425026800026
View details for PubMedID 28845547
View details for PubMedCentralID PMC5811323
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Analysis strategies for high-resolution UHF-fMRI data
NEUROIMAGE
2018; 168: 296-320
Abstract
Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential.
View details for DOI 10.1016/j.neuroimage.2017.04.053
View details for Web of Science ID 000427634500021
View details for PubMedID 28461062
View details for PubMedCentralID PMC5664177
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Neuroimaging with ultra-high field MRI: Present and future
NEUROIMAGE
2018; 168: 1-6
View details for DOI 10.1016/j.neuroimage.2018.01.072
View details for Web of Science ID 000427634500001
View details for PubMedID 29410013
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Challenges and opportunities for brainstem neuroimaging with ultrahigh field MRI
NEUROIMAGE
2018; 168: 412-426
Abstract
The human brainstem plays a central role in connecting the cerebrum, the cerebellum and the spinal cord to one another, hosting relay nuclei for afferent and efferent signaling, and providing source nuclei for several neuromodulatory systems that impact central nervous system function. While the investigation of the brainstem with functional or structural magnetic resonance imaging has been hampered for years due to this brain structure's physiological and anatomical characteristics, the field has seen significant advances in recent years thanks to the broader adoption of ultrahigh-field (UHF) MRI scanning. In the present review, we focus on the advantages offered by UHF in the context of brainstem imaging, as well as the challenges posed by the investigation of this complex brain structure in terms of data acquisition and analysis. We also illustrate how UHF MRI can shed new light on the neuroanatomy and neurophysiology underlying different brainstem-based circuitries, such as the central autonomic network and neurotransmitter/neuromodulator systems, discuss existing and foreseeable clinical applications to better understand diseases such as chronic pain and Parkinson's disease, and explore promising future directions for further improvements in brainstem imaging using UHF MRI techniques.
View details for DOI 10.1016/j.neuroimage.2017.02.052
View details for Web of Science ID 000427634500030
View details for PubMedID 28232189
View details for PubMedCentralID PMC5777900
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Ultra-Slow Single-Vessel BOLD and CBV-Based fMRI Spatiotemporal Dynamics and Their Correlation with Neuronal Intracellular Calcium Signals
NEURON
2018; 97 (4): 925-+
Abstract
Functional MRI has been used to map brain activity and functional connectivity based on the strength and temporal coherence of neurovascular-coupled hemodynamic signals. Here, single-vessel fMRI reveals vessel-specific correlation patterns in both rodents and humans. In anesthetized rats, fluctuations in the vessel-specific fMRI signal are correlated with the intracellular calcium signal measured in neighboring neurons. Further, the blood-oxygen-level-dependent (BOLD) signal from individual venules and the cerebral-blood-volume signal from individual arterioles show correlations at ultra-slow (<0.1 Hz), anesthetic-modulated rhythms. These data support a model that links neuronal activity to intrinsic oscillations in the cerebral vasculature, with a spatial correlation length of ∼2 mm for arterioles. In complementary data from awake human subjects, the BOLD signal is spatially correlated among sulcus veins and specified intracortical veins of the visual cortex at similar ultra-slow rhythms. These data support the use of fMRI to resolve functional connectivity at the level of single vessels.
View details for DOI 10.1016/j.neuron.2018.01.025
View details for Web of Science ID 000425713200018
View details for PubMedID 29398359
View details for PubMedCentralID PMC5845844
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Advantages of cortical surface reconstruction using submillimeter 7 T MEMPRAGE
NEUROIMAGE
2018; 165: 11-26
Abstract
Recent advances in MR technology have enabled increased spatial resolution for routine functional and anatomical imaging, which has created demand for software tools that are able to process these data. The availability of high-resolution data also raises the question of whether higher resolution leads to substantial gains in accuracy of quantitative morphometric neuroimaging procedures, in particular the cortical surface reconstruction and cortical thickness estimation. In this study we adapted the FreeSurfer cortical surface reconstruction pipeline to process structural data at native submillimeter resolution. We then quantified the differences in surface placement between meshes generated from (0.75 mm)3 isotropic resolution data acquired in 39 volunteers and the same data downsampled to the conventional 1 mm3 voxel size. We find that when processed at native resolution, cortex is estimated to be thinner in most areas, but thicker around the Cingulate and the Calcarine sulci as well as in the posterior bank of the Central sulcus. Thickness differences are driven by two kinds of effects. First, the gray-white surface is found closer to the white matter, especially in cortical areas with high myelin content, and thus low contrast, such as the Calcarine and the Central sulci, causing local increases in thickness estimates. Second, the gray-CSF surface is placed more interiorly, especially in the deep sulci, contributing to local decreases in thickness estimates. We suggest that both effects are due to reduced partial volume effects at higher spatial resolution. Submillimeter voxel sizes can therefore provide improved accuracy for measuring cortical thickness.
View details for DOI 10.1016/j.neuroimage.2017.09.060
View details for Web of Science ID 000417635900002
View details for PubMedID 28970143
View details for PubMedCentralID PMC6383677
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Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex
NEUROIMAGE
2018; 164: 194-201
Abstract
The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.
View details for DOI 10.1016/j.neuroimage.2017.01.041
View details for Web of Science ID 000417972000018
View details for PubMedID 28119135
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Functional density and edge maps: Characterizing functional architecture in individuals and improving cross-subject registration
NEUROIMAGE
2017; 158: 346-355
Abstract
Population-level inferences and individual-level analyses are two important aspects in functional magnetic resonance imaging (fMRI) studies. Extracting reliable and informative features from fMRI data that capture biologically meaningful inter-subject variation is critical for aligning and comparing functional networks across subjects, and connecting the properties of functional brain organization with variations in behavior, cognition and genetics. In this study, we derive two new measures, which we term functional density map and edge map, and demonstrate their usefulness in characterizing the function of individual brains. Specifically, using data from the Human Connectome Project (HCP), we show that (1) both functional maps capture intrinsic properties of the functional connectivity pattern in individuals while exhibiting large variation across subjects; (2) functional maps derived from either resting-state or task-evoked fMRI can be used to accurately identify subjects from a population; and (3) cross-subject alignment using these functional maps considerably reduces functional variation and improves functional correspondence across subjects over state-of-the-art multimodal registration algorithms. Our results suggest that the proposed functional density and edge maps are promising features in characterizing the functional architecture in individuals and provide an alternative way to explore the functional variation across subjects.
View details for DOI 10.1016/j.neuroimage.2017.07.019
View details for Web of Science ID 000411450600031
View details for PubMedID 28716714
View details for PubMedCentralID PMC5813497
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Impacting the effect of fMRI noise through hardware and acquisition choices - Implications for controlling false positive rates
NEUROIMAGE
2017; 154: 15-22
Abstract
We review the components of time-series noise in fMRI experiments and the effect of image acquisition parameters on the noise. In addition to helping determine the total amount of signal and noise (and thus temporal SNR), the acquisition parameters have been shown to be critical in determining the ratio of thermal to physiological induced noise components in the time series. Although limited attention has been given to this latter metric, we show that it determines the degree of spatial correlations seen in the time-series noise. The spatially correlations of the physiological noise component are well known, but recent studies have shown that they can lead to a higher than expected false-positive rate in cluster-wise inference based on parametric statistical methods used by many researchers. Based on understanding the effect of acquisition parameters on the noise mixture, we propose several acquisition strategies that might be helpful reducing this elevated false-positive rate, such as moving to high spatial resolution or using highly-accelerated acquisitions where thermal sources dominate. We suggest that the spatial noise correlations at the root of the inflated false-positive rate problem can be limited with these strategies, and the well-behaved spatial auto-correlation functions (ACFs) assumed by the conventional statistical methods are retained if the high resolution data is smoothed to conventional resolutions.
View details for DOI 10.1016/j.neuroimage.2016.12.057
View details for Web of Science ID 000405055900003
View details for PubMedID 28039092
View details for PubMedCentralID PMC5483395
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Reduction of across-run variability of temporal SNR in accelerated EPI time-series data through FLEET-based robust autocalibration
NEUROIMAGE
2017; 152: 348-359
Abstract
Temporal signal-to-noise ratio (tSNR) is a key metric for assessing the ability to detect brain activation in fMRI data. A recent study has shown substantial variation of tSNR between multiple runs of accelerated EPI acquisitions reconstructed with the GRAPPA method using protocols commonly used for fMRI experiments. Across-run changes in the location of high-tSNR regions could lead to misinterpretation of the observed brain activation patterns, reduced sensitivity of the fMRI studies, and biased results. We compared conventional EPI autocalibration (ACS) methods with the recently-introduced FLEET ACS method, measuring their tSNR variability, as well as spatial overlap and displacement of high-tSNR clusters across runs in datasets acquired from human subjects at 7T and 3T. FLEET ACS reconstructed data had higher tSNR levels, as previously reported, as well as better temporal consistency and larger overlap of the high-tSNR clusters across runs compared with reconstructions using conventional multi-shot (ms) EPI ACS data. tSNR variability across two different runs of the same protocol using ms-EPI ACS data was about two times larger than for the protocol using FLEET ACS for acceleration factors (R) 2 and 3, and one and half times larger for R=4. The level of across-run tSNR consistency for data reconstructed with FLEET ACS was similar to within-run tSNR consistency. The displacement of high-tSNR clusters across two runs (inter-cluster distance) decreased from ∼8mm in the time-series reconstructed using conventional ms-EPI ACS data to ∼4mm for images reconstructed using FLEET ACS. However, the performance gap between conventional ms-EPI ACS and FLEET ACS narrowed with increasing parallel imaging acceleration factor. Overall, the FLEET ACS method provides a simple solution to the problem of varying tSNR across runs, and therefore helps ensure that an assumption of fMRI analysis-that tSNR is largely consistent across runs-is met for accelerated acquisitions.
View details for DOI 10.1016/j.neuroimage.2017.02.029
View details for Web of Science ID 000402584500029
View details for PubMedID 28223186
View details for PubMedCentralID PMC5432429
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HIgh <i>b</i>-value and high Resolution Integrated Diffusion (HIBRID) imaging
NEUROIMAGE
2017; 150: 162-176
Abstract
The parameter selection for diffusion MRI experiments is dominated by the "k-q tradeoff" whereby the Signal to Noise Ratio (SNR) of the images is traded for either high spatial resolution (determined by the maximum k-value collected) or high diffusion sensitivity (effected by b-value or the q vector) but usually not both. Furthermore, different brain regions (such as gray matter and white matter) likely require different tradeoffs between these parameters due to the size of the structures to be visualized or the length-scale of the microstructure being probed. In this case, it might be advantageous to combine information from two scans - a scan with high q but low k (high angular resolution in diffusion but low spatial resolution in the image domain) to provide maximal information about white matter fiber crossing, and one low q but high k (low angular resolution but high spatial resolution) for probing the cortex. In this study, we propose a method, termed HIgh b-value and high Resolution Integrated Diffusion (HIBRID) imaging, for acquiring and combining the information from these two complementary types of scan with the goal of studying diffusion in the cortex without compromising white matter fiber information. The white-gray boundary and pial surface obtained from anatomical scans are incorporated as prior information to guide the fusion. We study the complementary advantages of the fused datasets, and assess the quality of the HIBRID data compared to either alone.
View details for DOI 10.1016/j.neuroimage.2017.02.002
View details for Web of Science ID 000399855800014
View details for PubMedID 28188913
View details for PubMedCentralID PMC5501959
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Intracortical depth analyses of frequency-sensitive regions of human auditory cortex using 7T fMRI
NEUROIMAGE
2016; 143: 116-127
Abstract
Despite recent advances in auditory neuroscience, the exact functional organization of human auditory cortex (AC) has been difficult to investigate. Here, using reversals of tonotopic gradients as the test case, we examined whether human ACs can be more precisely mapped by avoiding signals caused by large draining vessels near the pial surface, which bias blood-oxygen level dependent (BOLD) signals away from the actual sites of neuronal activity. Using ultra-high field (7T) fMRI and cortical depth analysis techniques previously applied in visual cortices, we sampled 1mm isotropic voxels from different depths of AC during narrow-band sound stimulation with biologically relevant temporal patterns. At the group level, analyses that considered voxels from all cortical depths, but excluded those intersecting the pial surface, showed (a) the greatest statistical sensitivity in contrasts between activations to high vs. low frequency sounds and (b) the highest inter-subject consistency of phase-encoded continuous tonotopy mapping. Analyses based solely on voxels intersecting the pial surface produced the least consistent group results, even when compared to analyses based solely on voxels intersecting the white-matter surface where both signal strength and within-subject statistical power are weakest. However, no evidence was found for reduced within-subject reliability in analyses considering the pial voxels only. Our group results could, thus, reflect improved inter-subject correspondence of high and low frequency gradients after the signals from voxels near the pial surface are excluded. Using tonotopy analyses as the test case, our results demonstrate that when the major physiological and anatomical biases imparted by the vasculature are controlled, functional mapping of human ACs becomes more consistent from subject to subject than previously thought.
View details for DOI 10.1016/j.neuroimage.2016.09.010
View details for Web of Science ID 000389683000011
View details for PubMedID 27608603
View details for PubMedCentralID PMC5124525
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Coil-to-Coil Physiological Noise Correlations and Their Impact on Functional MRI Time-Series Signal-to-Noise Ratio
MAGNETIC RESONANCE IN MEDICINE
2016; 76 (6): 1708-1719
Abstract
Physiological nuisance fluctuations ("physiological noise") are a major contribution to the time-series signal-to-noise ratio (tSNR) of functional imaging. While thermal noise correlations between array coil elements have a well-characterized effect on the image Signal to Noise Ratio (SNR0 ), the element-to-element covariance matrix of the time-series fluctuations has not yet been analyzed. We examine this effect with a goal of ultimately improving the combination of multichannel array data.We extend the theoretical relationship between tSNR and SNR0 to include a time-series noise covariance matrix Ψt , distinct from the thermal noise covariance matrix Ψ0 , and compare its structure to Ψ0 and the signal coupling matrix SSH formed from the signal intensity vectors S.Inclusion of the measured time-series noise covariance matrix into the model relating tSNR and SNR0 improves the fit of experimental multichannel data and is shown to be distinct from Ψ0 or SSH .Time-series noise covariances in array coils are found to differ from Ψ0 and more surprisingly, from the signal coupling matrix SSH . Correct characterization of the time-series noise has implications for the analysis of time-series data and for improving the coil element combination process. Magn Reson Med 76:1708-1719, 2016. © 2016 International Society for Magnetic Resonance in Medicine.
View details for DOI 10.1002/mrm.26041
View details for Web of Science ID 000389127200007
View details for PubMedID 26756964
View details for PubMedCentralID PMC5565210
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Anatomically Realistic Temperature Phantom for Radiofrequency Heating Measurements (vol 73, pg 442, 2015)
MAGNETIC RESONANCE IN MEDICINE
2016; 76 (5): 1642
View details for DOI 10.1002/mrm.26363
View details for Web of Science ID 000389127100032
View details for PubMedID 27747939
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Fast fMRI can detect oscillatory neural activity in humans
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2016; 113 (43): E6679–E6685
Abstract
Oscillatory neural dynamics play an important role in the coordination of large-scale brain networks. High-level cognitive processes depend on dynamics evolving over hundreds of milliseconds, so measuring neural activity in this frequency range is important for cognitive neuroscience. However, current noninvasive neuroimaging methods are not able to precisely localize oscillatory neural activity above 0.2 Hz. Electroencephalography and magnetoencephalography have limited spatial resolution, whereas fMRI has limited temporal resolution because it measures vascular responses rather than directly recording neural activity. We hypothesized that the recent development of fast fMRI techniques, combined with the extra sensitivity afforded by ultra-high-field systems, could enable precise localization of neural oscillations. We tested whether fMRI can detect neural oscillations using human visual cortex as a model system. We detected small oscillatory fMRI signals in response to stimuli oscillating at up to 0.75 Hz within single scan sessions, and these responses were an order of magnitude larger than predicted by canonical linear models. Simultaneous EEG-fMRI and simulations based on a biophysical model of the hemodynamic response to neuronal activity suggested that the blood oxygen level-dependent response becomes faster for rapidly varying stimuli, enabling the detection of higher frequencies than expected. Accounting for phase delays across voxels further improved detection, demonstrating that identifying vascular delays will be of increasing importance with higher-frequency activity. These results challenge the assumption that the hemodynamic response is slow, and demonstrate that fMRI has the potential to map neural oscillations directly throughout the brain.
View details for DOI 10.1073/pnas.1608117113
View details for Web of Science ID 000386087100018
View details for PubMedID 27729529
View details for PubMedCentralID PMC5087037
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Rapid brain MRI acquisition techniques at ultra-high fields
NMR IN BIOMEDICINE
2016; 29 (9): 1198–1221
Abstract
Ultra-high-field MRI provides large increases in signal-to-noise ratio (SNR) as well as enhancement of several contrast mechanisms in both structural and functional imaging. Combined, these gains result in a substantial boost in contrast-to-noise ratio that can be exploited for higher-spatial-resolution imaging to extract finer-scale information about the brain. With increased spatial resolution, however, there is a concurrent increased image-encoding burden that can cause unacceptably long scan times for structural imaging and slow temporal sampling of the hemodynamic response in functional MRI - particularly when whole-brain imaging is desired. To address this issue, new directions of imaging technology development - such as the move from conventional 2D slice-by-slice imaging to more efficient simultaneous multislice (SMS) or multiband imaging (which can be viewed as "pseudo-3D" encoding) as well as full 3D imaging - have provided dramatic improvements in acquisition speed. Such imaging paradigms provide higher SNR efficiency as well as improved encoding efficiency. Moreover, SMS and 3D imaging can make better use of coil sensitivity information in multichannel receiver arrays used for parallel imaging acquisitions through controlled aliasing in multiple spatial directions. This has enabled unprecedented acceleration factors of an order of magnitude or higher in these imaging acquisition schemes, with low image artifact levels and high SNR. Here we review the latest developments of SMS and 3D imaging methods and related technologies at ultra-high field for rapid high-resolution functional and structural imaging of the brain. Copyright © 2016 John Wiley & Sons, Ltd.
View details for DOI 10.1002/nbm.3478
View details for Web of Science ID 000383271800007
View details for PubMedID 26835884
View details for PubMedCentralID PMC5245168
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Dual-Polarity GRAPPA for Simultaneous Reconstruction and Ghost Correction of Echo Planar Imaging Data
MAGNETIC RESONANCE IN MEDICINE
2016; 76 (1): 32-44
Abstract
The purpose of this study was to seek improved image quality from accelerated echo planar imaging (EPI) data, particularly at ultrahigh fields. Certain artifacts in EPI reconstructions can be attributed to nonlinear phase differences between data acquired using frequency-encoding gradients of alternating polarity. These errors appear near regions of local susceptibility gradients and typically cannot be corrected with conventional Nyquist ghost correction (NGC) methods.We propose a new reconstruction method that integrates ghost correction into the parallel imaging data recovery process. This is achieved through a pair of generalized autocalibrating partially parallel acquisitions (GRAPPA) kernels that operate directly on the measured EPI data. The proposed dual-polarity GRAPPA (DPG) method estimates missing k-space data while simultaneously correcting inherent EPI phase errors.Simulation results showed that standard NGC is incapable of correcting higher-order phase errors, whereas the DPG kernel approach successfully removed these errors. The presence of higher-order phase errors near regions of local susceptibility gradients was demonstrated with in vivo data. DPG reconstructions of in vivo 3T and 7T EPI data acquired near these regions showed a marked improvement over conventional methods.This new parallel imaging method for reconstructing accelerated EPI data shows better resilience to inherent EPI phase errors, resulting in higher image quality in regions where higher-order EPI phase errors commonly occur. Magn Reson Med 76:32-44, 2016. © 2015 Wiley Periodicals, Inc.
View details for DOI 10.1002/mrm.25839
View details for Web of Science ID 000384996900003
View details for PubMedID 26208304
View details for PubMedCentralID PMC4758917
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Cortical atrophy in patients with cerebral amyloid angiopathy: a case-control study
LANCET NEUROLOGY
2016; 15 (8): 811-819
Abstract
Loss of cortical grey matter is a diagnostic marker of many neurodegenerative diseases, and is a key mediator of cognitive impairment. We postulated that cerebral amyloid angiopathy (CAA), characterised by cortical vascular amyloid deposits, is associated with cortical tissue loss independent of parenchymal Alzheimer's disease pathology. We tested this hypothesis in patients with hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease with minimal or no concomitant Alzheimer's disease pathology, as well as in patients with sporadic CAA and healthy and Alzheimer's disease controls.In this observational case-control study, we included six groups of participants: patients diagnosed with HCHWA-D using genetic testing; healthy controls age-matched to the HCHWA-D group; patients with probable sporadic CAA without dementia; two independent cohorts of healthy controls age-matched to the CAA group; and patients with Alzheimer's disease age-matched to the CAA group. De-identified (but unmasked) demographic, clinical, radiological, and genetic data were collected at Massachusetts General Hospital (Boston, MA, USA), at Leiden University (Leiden, Netherlands), and at sites contributing to Alzheimer's Disease Neuroimaging Initiative (ADNI). The primary outcome measure was cortical thickness. The correlations between cortical thickness and structural lesions, and blood-oxygen-level-dependent time-to-peak (BOLD-TTP; a physiological measure of vascular dysfunction) were analysed to understand the potential mechanistic link between vascular amyloid and cortical thickness. The radiological variables of interest were quantified using previously validated computer-assisted tools, and all results were visually reviewed to ensure their accuracy.Between March 15, 2006, and Dec 1, 2014, we recruited 369 individuals (26 patients with HCHWA-D and 28 age-matched, healthy controls; 63 patients with sporadic CAA without dementia; two healthy control cohorts with 63 and 126 individuals; and 63 patients with Alzheimer's disease). The 26 patients with HCHWA-D had thinner cortices (2·31 mm [SD 0·18]) than the 28 healthy controls (mean difference -0·112 mm, 95% CI -0·190 to -0·034, p=0·006). The 63 patients with sporadic CAA without dementia had thinner cortices (2·17 mm [SD 0·11]) than the two healthy control cohorts (n=63, mean difference -0·14 mm, 95% CI -0·17 to -0·10, p<0·0001; and n=126, -0·10, -0·13 to -0·06, p<0·0001). All differences remained independent in multivariable analyses. The 63 patients with Alzheimer's disease displayed more severe atrophy than the patients with sporadic CAA (2·1 mm [SD 0·14], difference 0·07 mm, 95% CI 0·11 to 0·02, p=0·005). We found strong associations between cortical thickness and vascular dysfunction in the patients with HCHWA-D (ρ=-0·58, p=0·003) or sporadic CAA (r=-0·4, p=0·015), but not in controls. Vascular dysfunction was identified as a mediator of the effect of hereditary CAA on cortical atrophy, accounting for 63% of the total effect.The appearance of cortical thinning in patients with HCHWA-D indicates that vascular amyloid is an independent contributor to cortical atrophy. These results were reproduced in patients with the more common sporadic CAA. Our findings also suggest that CAA-related cortical atrophy is at least partly mediated by vascular dysfunction. Our results also support the view that small vessel diseases such as CAA can cause cortical atrophy even in the absence of Alzheimer's disease, a conclusion that can help radiologists, neurologists, and other clinicians who diagnose these common geriatric conditions.National Institutes of Health.
View details for DOI 10.1016/S1474-4422(16)30030-8
View details for Web of Science ID 000377545800018
View details for PubMedID 27180034
View details for PubMedCentralID PMC5248657
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Automatic cortical surface reconstruction of high-resolution <i>T</i><sub>1</sub> echo planar imaging data
NEUROIMAGE
2016; 134: 338-354
Abstract
Echo planar imaging (EPI) is the method of choice for the majority of functional magnetic resonance imaging (fMRI), yet EPI is prone to geometric distortions and thus misaligns with conventional anatomical reference data. The poor geometric correspondence between functional and anatomical data can lead to severe misplacements and corruption of detected activation patterns. However, recent advances in imaging technology have provided EPI data with increasing quality and resolution. Here we present a framework for deriving cortical surface reconstructions directly from high-resolution EPI-based reference images that provide anatomical models exactly geometric distortion-matched to the functional data. Anatomical EPI data with 1mm isotropic voxel size were acquired using a fast multiple inversion recovery time EPI sequence (MI-EPI) at 7T, from which quantitative T1 maps were calculated. Using these T1 maps, volumetric data mimicking the tissue contrast of standard anatomical data were synthesized using the Bloch equations, and these T1-weighted data were automatically processed using FreeSurfer. The spatial alignment between T2(⁎)-weighted EPI data and the synthetic T1-weighted anatomical MI-EPI-based images was improved compared to the conventional anatomical reference. In particular, the alignment near the regions vulnerable to distortion due to magnetic susceptibility differences was improved, and sampling of the adjacent tissue classes outside of the cortex was reduced when using cortical surface reconstructions derived directly from the MI-EPI reference. The MI-EPI method therefore produces high-quality anatomical data that can be automatically segmented with standard software, providing cortical surface reconstructions that are geometrically matched to the BOLD fMRI data.
View details for DOI 10.1016/j.neuroimage.2016.04.004
View details for Web of Science ID 000378045900033
View details for PubMedID 27079529
View details for PubMedCentralID PMC5234090
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In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI
MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE
2016; 29 (3): 451–62
Abstract
Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data.We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s).The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work.Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.
View details for DOI 10.1007/s10334-016-0546-3
View details for Web of Science ID 000377457400013
View details for PubMedID 27126248
View details for PubMedCentralID PMC4892960
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Neuroimaging brainstem circuitry supporting cardiovagal response to pain: a combined heart rate variability/ultrahigh-field (7 T) functional magnetic resonance imaging study
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
2016; 374 (2067)
Abstract
Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2 min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain.
View details for DOI 10.1098/rsta.2015.0189
View details for Web of Science ID 000376159500014
View details for PubMedID 27044996
View details for PubMedCentralID PMC4822448
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The pulsatility volume index: an indicator of cerebrovascular compliance based on fast magnetic resonance imaging of cardiac and respiratory pulsatility
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
2016; 374 (2067)
Abstract
The influence of cardiac activity on the viscoelastic properties of intracranial tissue is one of the mechanisms through which brain-heart interactions take place, and is implicated in cerebrovascular disease. Cerebrovascular disease risk is not fully explained by current risk factors, including arterial compliance. Cerebrovascular compliance is currently estimated indirectly through Doppler sonography and magnetic resonance imaging (MRI) measures of blood velocity changes. In order to meet the need for novel cerebrovascular disease risk factors, we aimed to design and validate an MRI indicator of cerebrovascular compliance based on direct endogenous measures of blood volume changes. We implemented a fast non-gated two-dimensional MRI pulse sequence based on echo-planar imaging (EPI) with ultra-short repetition time (approx. 30-50 ms), which stepped through slices every approximately 20 s. We constrained the solution of the Bloch equations for spins moving faster than a critical speed to produce an endogenous contrast primarily dependent on spin volume changes, and an approximately sixfold signal gain compared with Ernst angle acquisitions achieved by the use of a 90° flip angle. Using cardiac and respiratory peaks detected on physiological recordings, average cardiac and respiratory MRI pulse waveforms in several brain compartments were obtained at 7 Tesla, and used to derive a compliance indicator, the pulsatility volume index (pVI). The pVI, evaluated in larger cerebral arteries, displayed significant variation within and across vessels. Multi-echo EPI showed the presence of significant pulsatility effects in both S0 and [Formula: see text] signals, compatible with blood volume changes. Lastly, the pVI dynamically varied during breath-holding compared with normal breathing, as expected for a compliance indicator. In summary, we characterized and performed an initial validation of a novel MRI indicator of cerebrovascular compliance, which might prove useful to investigate brain-heart interactions in cerebrovascular disease and other disorders.
View details for DOI 10.1098/rsta.2015.0184
View details for Web of Science ID 000376159500009
View details for PubMedID 27044992
View details for PubMedCentralID PMC4822444
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Interdigitated Color- and Disparity-Selective Columns within Human Visual Cortical Areas V2 and V3
JOURNAL OF NEUROSCIENCE
2016; 36 (6): 1841-1857
Abstract
In nonhuman primates (NHPs), secondary visual cortex (V2) is composed of repeating columnar stripes, which are evident in histological variations of cytochrome oxidase (CO) levels. Distinctive "thin" and "thick" stripes of dark CO staining reportedly respond selectively to stimulus variations in color and binocular disparity, respectively. Here, we first tested whether similar color-selective or disparity-selective stripes exist in human V2. If so, available evidence predicts that such stripes should (1) radiate "outward" from the V1-V2 border, (2) interdigitate, (3) differ from each other in both thickness and length, (4) be spaced ∼3.5-4 mm apart (center-to-center), and, perhaps, (5) have segregated functional connections. Second, we tested whether analogous segregated columns exist in a "next-higher" tier area, V3. To answer these questions, we used high-resolution fMRI (1 × 1 × 1 mm(3)) at high field (7 T), presenting color-selective or disparity-selective stimuli, plus extensive signal averaging across multiple scan sessions and cortical surface-based analysis. All hypotheses were confirmed. V2 stripes and V3 columns were reliably localized in all subjects. The two stripe/column types were largely interdigitated (e.g., nonoverlapping) in both V2 and V3. Color-selective stripes differed from disparity-selective stripes in both width (thickness) and length. Analysis of resting-state functional connections (eyes closed) showed a stronger correlation between functionally alike (compared with functionally unlike) stripes/columns in V2 and V3. These results revealed a fine-scale segregation of color-selective or disparity-selective streams within human areas V2 and V3. Together with prior evidence from NHPs, this suggests that two parallel processing streams extend from visual subcortical regions through V1, V2, and V3.In current textbooks and reviews, diagrams of cortical visual processing highlight two distinct neural-processing streams within the first and second cortical areas in monkeys. Two major streams consist of segregated cortical columns that are selectively activated by either color or ocular interactions. Because such cortical columns are so small, they were not revealed previously by conventional imaging techniques in humans. Here we demonstrate that such segregated columnar systems exist in humans. We find that, in humans, color versus binocular disparity columns extend one full area further, into the third visual area. Our approach can be extended to reveal and study additional types of columns in human cortex, perhaps including columns underlying more cognitive functions.
View details for DOI 10.1523/JNEUROSCI.3518-15.2016
View details for Web of Science ID 000369964500006
View details for PubMedID 26865609
View details for PubMedCentralID PMC4748071
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Reducing Sensitivity Losses Due to Respiration and Motion in Accelerated Echo Planar Imaging by Reordering the Autocalibration Data Acquisition
MAGNETIC RESONANCE IN MEDICINE
2016; 75 (2): 665-679
Abstract
To reduce the sensitivity of echo-planar imaging (EPI) auto-calibration signal (ACS) data to patient respiration and motion to improve the image quality and temporal signal-to-noise ratio (tSNR) of accelerated EPI time-series data.ACS data for accelerated EPI are generally acquired using segmented, multishot EPI to distortion-match the ACS and time-series data. The ACS data are, therefore, typically collected over multiple TR periods, leading to increased vulnerability to motion and dynamic B0 changes. The fast low-angle excitation echo-planar technique (FLEET) is adopted to reorder the ACS segments so that segments within any given slice are acquired consecutively in time, thereby acquiring ACS data for each slice as rapidly as possible.Subject breathhold and motion phantom experiments demonstrate that artifacts in the ACS data reduce tSNR and produce tSNR discontinuities across slices in the accelerated EPI time-series data. Accelerated EPI data reconstructed using FLEET-ACS exhibit improved tSNR and increased tSNR continuity across slices. Additionally, image quality is improved dramatically when bulk motion occurs during the ACS acquisition.FLEET-ACS provides reduced respiration and motion sensitivity in accelerated EPI, which yields higher tSNR and image quality. Benefits are demonstrated in both conventional-resolution 3T and high-resolution 7T EPI time-series data.
View details for DOI 10.1002/mrm.25628
View details for Web of Science ID 000370597000020
View details for PubMedID 25809559
View details for PubMedCentralID PMC4580494
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Rapid multi-orientation quantitative susceptibility mapping
NEUROIMAGE
2016; 125: 1131–41
Abstract
Three-dimensional gradient echo (GRE) is the main workhorse sequence used for susceptibility weighted imaging (SWI), quantitative susceptibility mapping (QSM), and susceptibility tensor imaging (STI). Achieving optimal phase signal-to-noise ratio requires late echo times, thus necessitating a long repetition time (TR). Combined with the large encoding burden of whole-brain coverage with high resolution, this leads to increased scan time. Further, the dipole kernel relating the tissue phase to the underlying susceptibility distribution undersamples the frequency content of the susceptibility map. Scans at multiple head orientations along with calculation of susceptibility through multi-orientation sampling (COSMOS) are one way to effectively mitigate this issue. Additionally, STI requires a minimum of 6 head orientations to solve for the independent tensor elements in each voxel. The requirements of high-resolution imaging with long TR at multiple orientations substantially lengthen the acquisition of COSMOS and STI. The goal of this work is to dramatically speed up susceptibility mapping at multiple head orientations. We demonstrate highly efficient acquisition using 3D-GRE with Wave-CAIPI and dramatically reduce the acquisition time of these protocols. Using R=15-fold acceleration with Wave-CAIPI permits acquisition per head orientation in 90s at 1.1mm isotropic resolution, and 5:35min at 0.5mm isotropic resolution. Since Wave-CAIPI fully harnesses the 3D spatial encoding capability of receive arrays, the maximum g-factor noise amplification remains below 1.30 at 3T and 1.12 at 7T. This allows a 30-min exam for STI with 12 orientations, thus paving the way to its clinical application.
View details for DOI 10.1016/j.neuroimage.2015.08.015
View details for Web of Science ID 000366647500105
View details for PubMedID 26277773
View details for PubMedCentralID PMC4691433
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MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.
NeuroImage
2016; 124 (Pt B): 1108-14
Abstract
The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography.
View details for DOI 10.1016/j.neuroimage.2015.08.075
View details for PubMedID 26364861
View details for PubMedCentralID PMC4651764
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A 32-Channel Combined RF and B-0 Shim Array for 3T Brain Imaging
MAGNETIC RESONANCE IN MEDICINE
2016; 75 (1): 441–51
Abstract
We add user-controllable direct currents (DC) to the individual elements of a 32-channel radio-frequency (RF) receive array to provide B0 shimming ability while preserving the array's reception sensitivity and parallel imaging performance.Shim performance using constrained DC current (± 2.5A) is simulated for brain arrays ranging from 8 to 128 elements. A 32-channel 3-tesla brain array is realized using inductive chokes to bridge the tuning capacitors on each RF loop. The RF and B0 shimming performance is assessed in bench and imaging measurements.The addition of DC currents to the 32-channel RF array is achieved with minimal disruption of the RF performance and/or negative side effects such as conductor heating or mechanical torques. The shimming results agree well with simulations and show performance superior to third-order spherical harmonic (SH) shimming. Imaging tests show the ability to reduce the standard frontal lobe susceptibility-induced fields and improve echo planar imaging geometric distortion. The simulation of 64- and 128-channel brain arrays suggest that even further shimming improvement is possible (equivalent to up to 6th-order SH shim coils).Including user-controlled shim currents on the loops of a conventional highly parallel brain array coil is feasible with modest current levels and produces improved B0 shimming performance over standard second-order SH shimming.
View details for DOI 10.1002/mrm.25587
View details for Web of Science ID 000367739200045
View details for PubMedID 25689977
View details for PubMedCentralID PMC4771493
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Toward an In Vivo Neuroimaging Template of Human Brainstem Nuclei of the Ascending Arousal, Autonomic, and Motor Systems
BRAIN CONNECTIVITY
2015; 5 (10): 597–607
Abstract
Brainstem nuclei (Bn) in humans play a crucial role in vital functions, such as arousal, autonomic homeostasis, sensory and motor relay, nociception, sleep, and cranial nerve function, and they have been implicated in a vast array of brain pathologies. However, an in vivo delineation of most human Bn has been elusive because of limited sensitivity and contrast for detecting these small regions using standard neuroimaging methods. To precisely identify several human Bn in vivo, we employed a 7 Tesla scanner equipped with multi-channel receive-coil array, which provided high magnetic resonance imaging sensitivity, and a multi-contrast (diffusion fractional anisotropy and T2-weighted) echo-planar-imaging approach, which provided complementary contrasts for Bn anatomy with matched geometric distortions and resolution. Through a combined examination of 1.3 mm(3) multi-contrast anatomical images acquired in healthy human adults, we semi-automatically generated in vivo probabilistic Bn labels of the ascending arousal (median and dorsal raphe), autonomic (raphe magnus, periaqueductal gray), and motor (inferior olivary nuclei, two subregions of the substantia nigra compatible with pars compacta and pars reticulata, two subregions of the red nucleus, and, in the diencephalon, two subregions of the subthalamic nucleus) systems. These labels constitute a first step toward the development of an in vivo neuroimaging template of Bn in standard space to facilitate future clinical and research investigations of human brainstem function and pathology. Proof-of-concept clinical use of this template is demonstrated in a minimally conscious patient with traumatic brainstem hemorrhages precisely localized to the raphe Bn involved in arousal.
View details for DOI 10.1089/brain.2015.0347
View details for Web of Science ID 000448191900001
View details for PubMedID 26066023
View details for PubMedCentralID PMC4684653
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Wave-CAIPI for highly accelerated 3D imaging
MAGNETIC RESONANCE IN MEDICINE
2015; 73 (6): 2152–62
Abstract
To introduce the wave-CAIPI (controlled aliasing in parallel imaging) acquisition and reconstruction technique for highly accelerated 3D imaging with negligible g-factor and artifact penalties.The wave-CAIPI 3D acquisition involves playing sinusoidal gy and gz gradients during the readout of each kx encoding line while modifying the 3D phase encoding strategy to incur interslice shifts as in 2D-CAIPI acquisitions. The resulting acquisition spreads the aliasing evenly in all spatial directions, thereby taking full advantage of 3D coil sensitivity distribution. By expressing the voxel spreading effect as a convolution in image space, an efficient reconstruction scheme that does not require data gridding is proposed. Rapid acquisition and high-quality image reconstruction with wave-CAIPI is demonstrated for high-resolution magnitude and phase imaging and quantitative susceptibility mapping.Wave-CAIPI enables full-brain gradient echo acquisition at 1 mm isotropic voxel size and R = 3 × 3 acceleration with maximum g-factors of 1.08 at 3T and 1.05 at 7T. Relative to the other advanced Cartesian encoding strategies (2D-CAIPI and bunched phase encoding) wave-CAIPI yields up to two-fold reduction in maximum g-factor for nine-fold acceleration at both field strengths.Wave-CAIPI allows highly accelerated 3D acquisitions with low artifact and negligible g-factor penalties, and may facilitate clinical application of high-resolution volumetric imaging.
View details for DOI 10.1002/mrm.25347
View details for Web of Science ID 000354729100013
View details for PubMedID 24986223
View details for PubMedCentralID PMC4281518
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Associations of Resting-State fMRI Functional Connectivity with Flow-BOLD Coupling and Regional Vasculature
BRAIN CONNECTIVITY
2015; 5 (3): 137-146
Abstract
There has been tremendous interest in applying functional magnetic resonance imaging-based resting-state functional connectivity (rs-fcMRI) measurements to the study of brain function. However, a lack of understanding of the physiological mechanisms of rs-fcMRI limits their ability to interpret rs-fcMRI findings. In this work, the authors examine the regional associations between rs-fcMRI estimates and dynamic coupling between the blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF), as well as resting macrovascular volume. Resting-state BOLD and CBF data were simultaneously acquired using a dual-echo pseudocontinuous arterial spin labeling (pCASL) technique, whereas macrovascular volume fraction was estimated using time-of-flight MR angiography. Functional connectivity within well-known functional networks—including the default mode, frontoparietal, and primary sensory-motor networks—was calculated using a conventional seed-based correlation approach. They found the functional connectivity strength to be significantly correlated with the regional increase in CBF-BOLD coupling strength and inversely proportional to macrovascular volume fraction. These relationships were consistently observed within all functional networks considered. Their findings suggest that highly connected networks observed using rs-fcMRI are not likely to be mediated by common vascular drainage linking distal cortical areas. Instead, high BOLD functional connectivity is more likely to reflect tighter neurovascular connections, attributable to neuronal pathways.
View details for DOI 10.1089/brain.2014.0299
View details for Web of Science ID 000448194700001
View details for PubMedID 25384681
View details for PubMedCentralID PMC4394176
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Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe
JOURNAL OF NEUROSCIENCE
2015; 35 (8): 3663-3675
Abstract
The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.
View details for DOI 10.1523/JNEUROSCI.3555-14.2015
View details for Web of Science ID 000350738800036
View details for PubMedID 25716864
View details for PubMedCentralID PMC4339366
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A DUAL-POLARITY GRAPPA KERNEL FOR THE ROBUST RECONSTRUCTION OF ACCELERATED EPI DATA
IEEE. 2015: 1244-1247
View details for Web of Science ID 000380546000298
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An Anatomically Realistic Temperature Phantom for Radiofrequency Heating Measurements
MAGNETIC RESONANCE IN MEDICINE
2015; 73 (1): 442-450
Abstract
An anthropomorphic phantom with realistic electrical properties allows for a more accurate reproduction of tissue current patterns during excitation. A temperature map can then probe the worst-case heating expected in the unperfused case. We describe an anatomically realistic human head phantom that allows rapid three-dimensional (3D) temperature mapping at 7T.The phantom was based on hand-labeled anatomical imaging data and consists of four compartments matching the corresponding human tissues in geometry and electrical properties. The increases in temperature resulting from radiofrequency excitation were measured with MR thermometry using a temperature-sensitive contrast agent (TmDOTMA(-)) validated by direct fiber optic temperature measurements.Acquisition of 3D temperature maps of the full phantom with a temperature accuracy better than 0.1°C was achieved with an isotropic resolution of 5 mm and acquisition times of 2-4 minutes.Our results demonstrate the feasibility of constructing anatomically realistic phantoms with complex geometries incorporating the ability to measure accurate temperature maps in the phantom. The anthropomorphic temperature phantom is expected to provide a useful tool for the evaluation of the heating effects of both conventional and parallel transmit pulses and help validate electromagnetic and temperature simulations.
View details for DOI 10.1002/mrm.25123
View details for Web of Science ID 000346908800042
View details for PubMedID 24549755
View details for PubMedCentralID PMC4136997
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Fast Quantitative Susceptibility Mapping with L1-Regularization and Automatic Parameter Selection
MAGNETIC RESONANCE IN MEDICINE
2014; 72 (5): 1444-1459
Abstract
To enable fast reconstruction of quantitative susceptibility maps with total variation penalty and automatic regularization parameter selection.ℓ(1) -Regularized susceptibility mapping is accelerated by variable splitting, which allows closed-form evaluation of each iteration of the algorithm by soft thresholding and fast Fourier transforms. This fast algorithm also renders automatic regularization parameter estimation practical. A weighting mask derived from the magnitude signal can be incorporated to allow edge-aware regularization.Compared with the nonlinear conjugate gradient (CG) solver, the proposed method is 20 times faster. A complete pipeline including Laplacian phase unwrapping, background phase removal with SHARP filtering, and ℓ(1) -regularized dipole inversion at 0.6 mm isotropic resolution is completed in 1.2 min using MATLAB on a standard workstation compared with 22 min using the CG solver. This fast reconstruction allows estimation of regularization parameters with the L-curve method in 13 min, which would have taken 4 h with the CG algorithm. The proposed method also permits magnitude-weighted regularization, which prevents smoothing across edges identified on the magnitude signal. This more complicated optimization problem is solved 5 times faster than the nonlinear CG approach. Utility of the proposed method is also demonstrated in functional blood oxygen level-dependent susceptibility mapping, where processing of the massive time series dataset would otherwise be prohibitive with the CG solver.Online reconstruction of regularized susceptibility maps may become feasible with the proposed dipole inversion.
View details for DOI 10.1002/mrm.25029
View details for Web of Science ID 000343873900026
View details for PubMedID 24259479
View details for PubMedCentralID PMC4111791
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Dynamic functional imaging of brain glucose utilization using fPET-FDG
NEUROIMAGE
2014; 100: 192-199
Abstract
Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[(18)F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.
View details for DOI 10.1016/j.neuroimage.2014.06.025
View details for Web of Science ID 000344235800016
View details for PubMedID 24936683
View details for PubMedCentralID PMC4224310
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A study-specific fMRI normalization approach that operates directly on high resolution functional EPI data at 7 Tesla
NEUROIMAGE
2014; 100: 710-714
Abstract
Due to the availability of ultra-high field scanners and novel imaging methods, high resolution, whole brain functional MR imaging (fMRI) has become increasingly feasible. However, it is common to use extensive spatial smoothing to account for inter-subject anatomical variation when pooling over subjects. This reduces the spatial details of group level functional activation considerably, even when the original data was acquired with high resolution. In our study we used an accelerated 3D EPI sequence at 7 Tesla to acquire whole brain fMRI data with an isotropic spatial resolution of 1.1mm which shows clear gray/white matter contrast due to the stronger T1 weighting of 3D EPI. To benefit from the high spatial resolution on the group level, we develop a study specific, high resolution anatomical template which is facilitated by the good anatomical contrast that is present in the average functional EPI images. Different template generations with increasing accuracy were created by using a hierarchical linear and stepwise non-linear registration approach. As the template is based on the functional data themselves no additional co-registration step with the usual T1-weighted anatomical data is necessary which eliminates a potential source of misalignment. To test the improvement of functional localization and spatial details we performed a group level analysis of a finger tapping experiment in eight subjects. The most accurate template shows better spatial localization--such as a separation of somatosensory and motor areas and of single digit activation--compared to the simple linear registration. The number of activated voxels is increased by a factor of 1.2, 2.5, and 3.1 for somatosensory, supplementary motor area, and dentate nucleus, respectively, for the functional contrast between left versus right hand. Similarly, the number of activated voxels is increased 1.4- and 2.4-fold for right little versus right index finger and left little versus left index finger, respectively. The Euclidian distance between the activation (center of gravity) of the respective fingers was found to be 13.90 mm using the most accurate template.
View details for DOI 10.1016/j.neuroimage.2014.06.045
View details for Web of Science ID 000344235800065
View details for PubMedID 24973602
View details for PubMedCentralID PMC4143421
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fMRI hemodynamics accurately reflects neuronal timing in the human brain measured by MEG (vol 78, pg 372, 2013)
NEUROIMAGE
2014; 95: 344
View details for DOI 10.1016/j.neuroimage.2014.03.070
View details for Web of Science ID 000337267900032
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Interslice Leakage Artifact Reduction Technique for Simultaneous Multislice Acquisitions
MAGNETIC RESONANCE IN MEDICINE
2014; 72 (1): 93–102
Abstract
Controlled aliasing techniques for simultaneously acquired echo-planar imaging slices have been shown to significantly increase the temporal efficiency for both diffusion-weighted imaging and functional magnetic resonance imaging studies. The "slice-GRAPPA" (SG) method has been widely used to reconstruct such data. We investigate robust optimization techniques for SG to ensure image reconstruction accuracy through a reduction of leakage artifacts.Split SG is proposed as an alternative kernel optimization method. The performance of Split SG is compared to standard SG using data collected on a spherical phantom and in vivo on two subjects at 3 T. Slice-accelerated and nonaccelerated data were collected for a spin-echo diffusion-weighted acquisition. Signal leakage metrics and time-series SNR were used to quantify the performance of the kernel fitting approaches.The Split SG optimization strategy significantly reduces leakage artifacts for both phantom and in vivo acquisitions. In addition, a significant boost in time-series SNR for in vivo diffusion-weighted acquisitions with in-plane 2× and slice 3× accelerations was observed with the Split SG approach.By minimizing the influence of leakage artifacts during the training of SG kernels, we have significantly improved reconstruction accuracy. Our robust kernel fitting strategy should enable better reconstruction accuracy and higher slice-acceleration across many applications.
View details for DOI 10.1002/mrm.24898
View details for Web of Science ID 000337624400012
View details for PubMedID 23963964
View details for PubMedCentralID PMC4364522
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Nineteen-Channel Receive Array and Four-Channel Transmit Array Coil for Cervical Spinal Cord Imaging at 7T
MAGNETIC RESONANCE IN MEDICINE
2014; 72 (1): 291–300
Abstract
To design and validate a radiofrequency (RF) array coil for cervical spinal cord imaging at 7T.A 19-channel receive array with a four-channel transmit array was developed on a close-fitting coil former at 7T. Transmit efficiency and specific absorption rate were evaluated in a B1 (+) mapping study and an electromagnetic model. Receive signal-to-noise ratio (SNR) and noise amplification for parallel imaging were evaluated and compared with a commercial 3T 19-channel head-neck array and a 7T four-channel spine array. The performance of the array was qualitatively demonstrated in human volunteers using high-resolution imaging (down to 300 μm in-plane).The transmit and receive arrays showed good bench performance. The SNR was approximately 4.2-fold higher in the 7T receive array at the location of the cord with respect to the 3T coil. The g-factor results showed an additional acceleration was possible with the 7T array. In vivo imaging was feasible and showed high SNR and tissue contrast.The highly parallel transmit and receive arrays were demonstrated to be fit for spinal cord imaging at 7T. The high sensitivity of the receive coil combined with ultra-high field will likely improve investigations of microstructure and tissue segmentation in the healthy and pathological spinal cord.
View details for DOI 10.1002/mrm.24911
View details for Web of Science ID 000337624400032
View details for PubMedID 23963998
View details for PubMedCentralID PMC4761437
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Quantitative comparison of cortical surface reconstructions from MP2RAGE and multi-echo MPRAGE data at 3 and 7 T
NEUROIMAGE
2014; 90: 60-73
Abstract
The Magnetization-Prepared 2 Rapid Acquisition Gradient Echo (MP2RAGE) method achieves spatially uniform contrast across the entire brain between gray matter and surrounding white matter tissue and cerebrospinal fluid by rapidly acquiring data at two points during an inversion recovery, and then combining the two volumes so as to cancel out sources of intensity and contrast bias, making it useful for neuroimaging studies at ultrahigh field strengths (≥7T). To quantify the effectiveness of the MP2RAGE method for quantitative morphometric neuroimaging, we performed tissue segmentation and cerebral cortical surface reconstruction of the MP2RAGE data and compared the results with those generated from conventional multi-echo MPRAGE (MEMPRAGE) data across a group of healthy subjects. To do so, we developed a preprocessing scheme for the MP2RAGE image data to allow for automatic cortical segmentation and surface reconstruction using FreeSurfer and analysis methods to compare the positioning of the surface meshes. Using image volumes with 1mm isotropic voxels we found a scan-rescan reproducibility of cortical thickness estimates to be 0.15 mm (or 6%) for the MEMPRAGE data and a slightly lower reproducibility of 0.19 mm (or 8%) for the MP2RAGE data. We also found that the thickness estimates were systematically smaller in the MP2RAGE data, and that both the interior and exterior cortical boundaries estimated from the MP2RAGE data were consistently positioned within the corresponding boundaries estimated from the MEMPRAGE data. Therefore several measureable differences exist in the appearance of cortical gray matter and its effect on automatic segmentation methods that must be considered when choosing an acquisition or segmentation method for studies requiring cortical surface reconstructions. We propose potential extensions to the MP2RAGE method that may help to reduce or eliminate these discrepancies.
View details for DOI 10.1016/j.neuroimage.2013.12.012
View details for Web of Science ID 000338909500007
View details for PubMedID 24345388
View details for PubMedCentralID PMC4035370
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Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal
NEUROIMAGE
2014; 84: 672-680
Abstract
Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.
View details for DOI 10.1016/j.neuroimage.2013.09.057
View details for Web of Science ID 000328868600061
View details for PubMedID 24099842
View details for PubMedCentralID PMC4323159
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The minimal preprocessing pipelines for the Human Connectome Project
NEUROIMAGE
2013; 80: 105-124
Abstract
The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinate spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCP's acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements to the pipelines.
View details for DOI 10.1016/j.neuroimage.2013.04.127
View details for Web of Science ID 000322416000011
View details for PubMedID 23668970
View details for PubMedCentralID PMC3720813
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Whole-head rapid fMRI acquisition using echo-shifted magnetic resonance inverse imaging
NEUROIMAGE
2013; 78: 325-338
Abstract
The acquisition time of BOLD contrast functional MRI (fMRI) data with whole-brain coverage typically requires a sampling rate of one volume in 1-3s. Although the volumetric sampling time of a few seconds is adequate for measuring the sluggish hemodynamic response (HDR) to neuronal activation, faster sampling of fMRI might allow for monitoring of rapid physiological fluctuations and detection of subtle neuronal activation timing information embedded in BOLD signals. Previous studies utilizing a highly accelerated volumetric MR inverse imaging (InI) technique have provided a sampling rate of one volume per 100 ms with 5mm spatial resolution. Here, we propose a novel modification of this technique, the echo-shifted InI, which allows TE to be longer than TR, to measure BOLD fMRI at an even faster sampling rate of one volume per 25 ms with whole-brain coverage. Compared with conventional EPI, echo-shifted InI provided an 80-fold speedup with similar spatial resolution and less than 2-fold temporal SNR loss. The capability of echo-shifted InI to detect HDR timing differences was tested empirically. At the group level (n=6), echo-spaced InI was able to detect statistically significant HDR timing differences of as low as 50 ms in visual stimulus presentation. At the level of individual subjects, significant differences in HDR timing were detected for 400 ms stimulus-onset differences. Our results also show that the temporal resolution of 25 ms is necessary for maintaining the temporal detecting capability at this level. With the capabilities of being able to distinguish the timing differences in the millisecond scale, echo-shifted InI could be a useful fMRI tool for obtaining temporal information at a time scale closer to that of neuronal dynamics.
View details for DOI 10.1016/j.neuroimage.2013.03.040
View details for Web of Science ID 000320488900032
View details for PubMedID 23563228
View details for PubMedCentralID PMC3672248
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fMRI hemodynamics accurately reflects neuronal timing in the human brain measured by MEG
NEUROIMAGE
2013; 78: 372-384
Abstract
Neuronal activation sequence information is essential for understanding brain functions. Extracting such timing information from blood oxygenation level dependent (BOLD) fMRI is confounded by interregional neurovascular differences and poorly understood relations between BOLD and electrophysiological response delays. Here, we recorded whole-head BOLD fMRI at 100 ms resolution and magnetoencephalography (MEG) during a visuomotor reaction-time task. Both methods detected the same activation sequence across five regions, from visual towards motor cortices, with linearly correlated interregional BOLD and MEG response delays. The smallest significant interregional BOLD delay was 100 ms; all delays ≥400 ms were significant. Switching the order of external events reversed the sequence of BOLD activations, indicating that interregional neurovascular differences did not confound the results. This may open new avenues for using fMRI to follow rapid activation sequences in the brain.
View details for DOI 10.1016/j.neuroimage.2013.04.017
View details for Web of Science ID 000320488900036
View details for PubMedID 23591071
View details for PubMedCentralID PMC3682657
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FOCUSR: Feature Oriented Correspondence Using Spectral Regularization-A Method for Precise Surface Matching
IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE
2013; 35 (9): 2143-2160
Abstract
Existing methods for surface matching are limited by the tradeoff between precision and computational efficiency. Here, we present an improved algorithm for dense vertex-to-vertex correspondence that uses direct matching of features defined on a surface and improves it by using spectral correspondence as a regularization. This algorithm has the speed of both feature matching and spectral matching while exhibiting greatly improved precision (distance errors of 1.4 percent). The method, FOCUSR, incorporates implicitly such additional features to calculate the correspondence and relies on the smoothness of the lowest-frequency harmonics of a graph Laplacian to spatially regularize the features. In its simplest form, FOCUSR is an improved spectral correspondence method that nonrigidly deforms spectral embeddings. We provide here a full realization of spectral correspondence where virtually any feature can be used as an additional information using weights on graph edges, but also on graph nodes and as extra embedded coordinates. As an example, the full power of FOCUSR is demonstrated in a real-case scenario with the challenging task of brain surface matching across several individuals. Our results show that combining features and regularizing them in a spectral embedding greatly improves the matching precision (to a submillimeter level) while performing at much greater speed than existing methods.
View details for DOI 10.1109/TPAMI.2012.276
View details for Web of Science ID 000322029000008
View details for PubMedID 23868776
View details for PubMedCentralID PMC3707975
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Sparsity-Promoting Calibration for GRAPPA Accelerated Parallel MRI Reconstruction
IEEE TRANSACTIONS ON MEDICAL IMAGING
2013; 32 (7): 1325-1335
Abstract
The amount of calibration data needed to produce images of adequate quality can prevent auto-calibrating parallel imaging reconstruction methods like generalized autocalibrating partially parallel acquisitions (GRAPPA) from achieving a high total acceleration factor. To improve the quality of calibration when the number of auto-calibration signal (ACS) lines is restricted, we propose a sparsity-promoting regularized calibration method that finds a GRAPPA kernel consistent with the ACS fit equations that yields jointly sparse reconstructed coil channel images. Several experiments evaluate the performance of the proposed method relative to unregularized and existing regularized calibration methods for both low-quality and underdetermined fits from the ACS lines. These experiments demonstrate that the proposed method, like other regularization methods, is capable of mitigating noise amplification, and in addition, the proposed method is particularly effective at minimizing coherent aliasing artifacts caused by poor kernel calibration in real data. Using the proposed method, we can increase the total achievable acceleration while reducing degradation of the reconstructed image better than existing regularized calibration methods.
View details for DOI 10.1109/TMI.2013.2256923
View details for Web of Science ID 000321220300014
View details for PubMedID 23584259
View details for PubMedCentralID PMC3696426
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Surface based analysis of diffusion orientation for identifying architectonic domains in the in vivo human cortex
NEUROIMAGE
2013; 69: 87-100
Abstract
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
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Denoising Sparse Images from GRAPPA Using the Nullspace Method (vol 68, pg 1176, 2012)
MAGNETIC RESONANCE IN MEDICINE
2013; 69 (4): 1200
View details for DOI 10.1002/mrm.24574
View details for Web of Science ID 000316629300033
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Physiological noise reduction using volumetric functional magnetic resonance inverse imaging
HUMAN BRAIN MAPPING
2012; 33 (12): 2815-2830
Abstract
Physiological noise arising from a variety of sources can significantly degrade the detection of task-related activity in BOLD-contrast fMRI experiments. If whole head spatial coverage is desired, effective suppression of oscillatory physiological noise from cardiac and respiratory fluctuations is quite difficult without external monitoring, since traditional EPI acquisition methods cannot sample the signal rapidly enough to satisfy the Nyquist sampling theorem, leading to temporal aliasing of noise. Using a combination of high speed magnetic resonance inverse imaging (InI) and digital filtering, we demonstrate that it is possible to suppress cardiac and respiratory noise without auxiliary monitoring, while achieving whole head spatial coverage and reasonable spatial resolution. Our systematic study of the effects of different moving average (MA) digital filters demonstrates that a MA filter with a 2 s window can effectively reduce the variance in the hemodynamic baseline signal, thereby achieving 57%-58% improvements in peak z-statistic values compared to unfiltered InI or spatially smoothed EPI data (FWHM = 8.6 mm). In conclusion, the high temporal sampling rates achievable with InI permit significant reductions in physiological noise using standard temporal filtering techniques that result in significant improvements in hemodynamic response estimation.
View details for DOI 10.1002/hbm.21403
View details for Web of Science ID 000310798800006
View details for PubMedID 21954026
View details for PubMedCentralID PMC3586826
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Denoising sparse images from GRAPPA using the nullspace method
MAGNETIC RESONANCE IN MEDICINE
2012; 68 (4): 1176-1189
Abstract
To accelerate magnetic resonance imaging using uniformly undersampled (nonrandom) parallel imaging beyond what is achievable with generalized autocalibrating partially parallel acquisitions (GRAPPA) alone, the DEnoising of Sparse Images from GRAPPA using the Nullspace method is developed. The trade-off between denoising and smoothing the GRAPPA solution is studied for different levels of acceleration. Several brain images reconstructed from uniformly undersampled k-space data using DEnoising of Sparse Images from GRAPPA using the Nullspace method are compared against reconstructions using existing methods in terms of difference images (a qualitative measure), peak-signal-to-noise ratio, and noise amplification (g-factors) as measured using the pseudo-multiple replica method. Effects of smoothing, including contrast loss, are studied in synthetic phantom data. In the experiments presented, the contrast loss and spatial resolution are competitive with existing methods. Results for several brain images demonstrate significant improvements over GRAPPA at high acceleration factors in denoising performance with limited blurring or smoothing artifacts. In addition, the measured g-factors suggest that DEnoising of Sparse Images from GRAPPA using the Nullspace method mitigates noise amplification better than both GRAPPA and L1 iterative self-consistent parallel imaging reconstruction (the latter limited here by uniform undersampling).
View details for DOI 10.1002/mrm.24116
View details for Web of Science ID 000309203500019
View details for PubMedID 22213069
View details for PubMedCentralID PMC3323741
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An implanted 8-channel array coil for high-resolution macaque MRI at 3 T
NEUROIMAGE
2012; 62 (3): 1529-1536
Abstract
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
View details for PubMedCentralID PMC3408578
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Functional Magnetic Resonance Imaging Detection of Vascular Reactivity in Cerebral Amyloid Angiopathy
ANNALS OF NEUROLOGY
2012; 72 (1): 76-81
Abstract
In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional magnetic resonance imaging (MRI) techniques to identify CAA-associated vascular dysfunction.Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age, 70.2 ± 7.8 years) and 12 healthy elderly controls (age, 75.3 ± 6.2 years). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling).CAA subjects demonstrated reduced response amplitude (percentage change in BOLD signal, 0.65 ± 0.28 vs 0.89 ± 0.14; p < 0.01), prolonged time to peak (11.1 ± 5.1 vs 6.4 ± 1.8 seconds; p < 0.001), and prolonged time to baseline (16.5 ± 6.7 vs 11.6 ± 3.1 seconds; p < 0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation, 0.53; p = 0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0 ± 12.6 vs 45.0 ± 10.0 ml/100 g/min, p = 0.8).Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.
View details for DOI 10.1002/ana.23566
View details for Web of Science ID 000307945700011
View details for PubMedID 22829269
View details for PubMedCentralID PMC3408630
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Blipped-controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g-factor penalty
MAGNETIC RESONANCE IN MEDICINE
2012; 67 (5): 1210–24
Abstract
Simultaneous multislice Echo Planar Imaging (EPI) acquisition using parallel imaging can decrease the acquisition time for diffusion imaging and allow full-brain, high-resolution functional MRI (fMRI) acquisitions at a reduced repetition time (TR). However, the unaliasing of simultaneously acquired, closely spaced slices can be difficult, leading to a high g-factor penalty. We introduce a method to create interslice image shifts in the phase encoding direction to increase the distance between aliasing pixels. The shift between the slices is induced using sign- and amplitude-modulated slice-select gradient blips simultaneous with the EPI phase encoding blips. This achieves the desired shifts but avoids an undesired "tilted voxel" blurring artifact associated with previous methods. We validate the method in 3× slice-accelerated spin-echo and gradient-echo EPI at 3 T and 7 T using 32-channel radio frequency (RF) coil brain arrays. The Monte-Carlo simulated average g-factor penalty of the 3-fold slice-accelerated acquisition with interslice shifts is <1% at 3 T (compared with 32% without slice shift). Combining 3× slice acceleration with 2× inplane acceleration, the g-factor penalty becomes 19% at 3 T and 10% at 7 T (compared with 41% and 23% without slice shift). We demonstrate the potential of the method for accelerating diffusion imaging by comparing the fiber orientation uncertainty, where the 3-fold faster acquisition showed no noticeable degradation.
View details for DOI 10.1002/mrm.23097
View details for Web of Science ID 000302619400003
View details for PubMedID 21858868
View details for PubMedCentralID PMC3323676
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T-2* mapping and B-o orientation-dependence at 7 T reveal cyto- and myeloarchitecture organization of the human cortex
NEUROIMAGE
2012; 60 (2): 1006-1014
Abstract
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
View details for PubMedCentralID PMC3442114
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ACCELERATED PARALLEL MAGNETIC RESONANCE IMAGING RECONSTRUCTION USING JOINT ESTIMATION WITH A SPARSE SIGNAL MODEL
IEEE. 2012: 221-224
View details for Web of Science ID 000309943200056
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32-Channel RF Coil Optimized for Brain and Cervical Spinal Cord at 3 T
MAGNETIC RESONANCE IN MEDICINE
2011; 66 (4): 1198-1208
Abstract
Diffusion and functional magnetic resonance imaging of the spinal cord remain challenging due to the small cross-sectional size of the cord and susceptibility-related distortions. Although partially addressable through parallel imaging, few highly parallel array coils have been implemented for the cervical cord. Here, we developed a 32-channel coil that fully covers the brain and c-spine and characterized its performance in comparison with a commercially available head/neck/spine array. Image and temporal signal-to-noise ratio were, respectively, increased by 2× and 1.8× in the cervical cord. Averaged g-factors at 4× acceleration were lowered by 22% in the brain and by 39% in the spinal cord, enabling 1-mm isotropic R = 4 multi-echo magnetization prepared gradient echo of the full brain and c-spine in 3:20 min. Diffusion imaging of the cord at 0.6 × 0.6 × 5 mm(3) resolution and tractography of the full brain and c-spine at 1.7-mm isotropic resolution were feasible without noticeable distortion. Improvements of this nature potentially enhance numerous basic and clinical research studies focused on spinal and supraspinal regions.
View details for DOI 10.1002/mrm.22906
View details for Web of Science ID 000295356500032
View details for PubMedID 21433068
View details for PubMedCentralID PMC3131444
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The organization of the human cerebral cortex estimated by intrinsic functional connectivity
JOURNAL OF NEUROPHYSIOLOGY
2011; 106 (3): 1125-1165
Abstract
Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.
View details for DOI 10.1152/jn.00338.2011
View details for Web of Science ID 000294775500007
View details for PubMedID 21653723
View details for PubMedCentralID PMC3174820
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Physiological noise and signal-to-noise ratio in fMRI with multi-channel array coils
NEUROIMAGE
2011; 55 (2): 597-606
Abstract
Sensitivity in BOLD fMRI is characterized by the signal to noise ratio (SNR) of the time-series (tSNR), which contains fluctuations from thermal and physiological noise sources. Alteration of an acquisition parameter can affect the tSNR differently depending on the relative magnitude of the physiological and thermal noise, therefore knowledge of this ratio is essential for optimizing fMRI acquisitions. In this study, we compare image and time-series SNR from array coils at 3T with and without parallel imaging (GRAPPA) as a function of image resolution and acceleration. We use the "absolute unit" SNR method of Kellman and McVeigh to calculate the image SNR (SNR(0)) in a way that renders it comparable to tSNR, allowing determination of the thermal to physiological noise ratio, and the pseudo-multiple replica method to quantify the image noise alterations due to the GRAPPA reconstruction. The Kruger and Glover noise model, in which the physiological noise standard deviation is proportional to signal strength, was found to hold for the accelerated and non-accelerated array coil data. Thermal noise dominated the EPI time-series for medium to large voxel sizes for single-channel and 12-channel head coil configurations, but physiological noise dominated the 32-channel array acquisition even at 1 mm × 1mm × 3 mm resolution. At higher acceleration factors, image SNR is reduced and the time-series becomes increasingly thermal noise dominant. However, the tSNR reduction is smaller than the reduction in image SNR due to the presence of physiological noise.
View details for DOI 10.1016/j.neuroimage.2010.11.084
View details for Web of Science ID 000287556200018
View details for PubMedID 21167946
View details for PubMedCentralID PMC3039683
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Regularizing GRAPPA using simultaneous sparsity to recover de-noised images
SPIE-INT SOC OPTICAL ENGINEERING. 2011
View details for DOI 10.1117/12.896655
View details for Web of Science ID 000297583100042
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Fast Brain Matching with Spectral Correspondence
SPRINGER-VERLAG BERLIN. 2011: 660-673
Abstract
Brain matching is an important problem in neuroimaging studies. Current surface-based methods for cortex matching and atlasing, although quite accurate, can require long computation times. Here we propose an approach based on spectral correspondence, where spectra of graphs derived from the surface model meshes are matched. Cerebral cortex matching problems can thus benefit from the tremendous speed advantage of spectral methods, which are able to calculate a cortex matching in seconds rather than hours. Moreover, spectral methods are extended in order to use additional information that can improve matching. Additional information, such as sulcal depth, surface curvature, and cortical thickness can be represented in a flexible way into graph node weights (rather than only into graph edge weights) and as extra embedded coordinates. In control experiments, cortex matching becomes almost perfect when using additional information. With real data from 12 subjects, the results of 288 correspondence maps are 88% equivalent to (and strongly correlated with) the correspondences computed with FreeSurfer, a leading computational tool used for cerebral cortex matching. Our fast and flexible spectral correspondence method could open new possibilities for brain studies that involve different types of information and that were previously limited by the computational burden.
View details for Web of Science ID 000305885000054
View details for PubMedID 21761694
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EVALUATING SPARSITY PENALTY FUNCTIONS FOR COMBINED COMPRESSED SENSING AND PARALLEL MRI
IEEE. 2011: 1589-1592
View details for Web of Science ID 000298849400363
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Atlas-based segmentation for globus pallidus internus targeting on low-resolution MRI
IEEE. 2011: 5706-5709
Abstract
In this paper we report a method to automatically segment the internal part of globus pallidus (GPi) on the pre-operative low-resolution magnetic resonance images (MRIs) of patients affected by Parkinson's disease. Herein we used an ultra-high resolution human brain dataset as electronic atlas of reference on which we segmented the GPi. First, we registered the ultra-high resolution dataset on the low-resolution dataset using a landmarks-based rigid registration. Then an affine and a non-rigid surface-based registration guided by the structures that surround the target was applied in order to propagate the labels of the GPi on the low-resolution un-segmented dataset and to accurately outline the target. The mapping of the atlas on the low-resolution MRI provided a highly accurate anatomical detail that can be useful for localizing the target.
View details for Web of Science ID 000298810004158
View details for PubMedID 22255635
View details for PubMedCentralID PMC3791323
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COMBINED COMPRESSED SENSING AND PARALLEL MRI COMPARED FOR UNIFORM AND RANDOM CARTESIAN UNDERSAMPLING OF K-SPACE
IEEE. 2011: 553-556
View details for Web of Science ID 000296062400139
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Laminar analysis of 7 T BOLD using an imposed spatial activation pattern in human V1
NEUROIMAGE
2010; 52 (4): 1334-1346
Abstract
With sufficient image encoding, high-resolution fMRI studies are limited by the biological point-spread of the hemodynamic signal. The extent of this spread is determined by the local vascular distribution and by the spatial specificity of blood flow regulation, as well as by measurement parameters that (i) alter the relative sensitivity of the acquisition to activation-induced hemodynamic changes and (ii) determine the image contrast as a function of vessel size. In particular, large draining vessels on the cortical surface are a major contributor to both the BOLD signal change and to the spatial bias of the BOLD activation away from the site of neuronal activity. In this work, we introduce a laminar surface-based analysis method and study the relationship between spatial localization and activation strength as a function of laminar depth by acquiring 1mm isotropic, single-shot EPI at 7 T and sampling the BOLD signal exclusively from the superficial, middle, or deep cortical laminae. We show that highly-accelerated EPI can limit image distortions to the point where a boundary-based registration algorithm accurately aligns the EPI data to the surface reconstruction. The spatial spread of the BOLD response tangential to the cortical surface was analyzed as a function of cortical depth using our surface-based analysis. Although sampling near the pial surface provided the highest signal strength, it also introduced the most spatial error. Thus, avoiding surface laminae improved spatial localization by about 40% at a cost of 36% in z-statistic, implying that optimal spatial resolution in functional imaging of the cortex can be achieved using anatomically-informed spatial sampling to avoid large pial vessels.
View details for DOI 10.1016/j.neuroimage.2010.05.005
View details for Web of Science ID 000280695200022
View details for PubMedID 20460157
View details for PubMedCentralID PMC3130346
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Near-isometric flattening of brain surfaces
NEUROIMAGE
2010; 51 (2): 694-703
Abstract
Flattened representations of brain surfaces are often used to visualize and analyze spatial patterns of structural organization and functional activity. Here, we present a set of rigorous criteria and accompanying test cases with which to evaluate flattening algorithms that attempt to preserve shortest-path distances on the original surface. We also introduce a novel flattening algorithm that is the first to satisfy all of these criteria and demonstrate its ability to produce accurate flat maps of human and macaque visual cortex. Using this algorithm, we have recently obtained results showing a remarkable, unexpected degree of consistency in the shape and topographic structure of visual cortical areas within humans and macaques, as well as between these two species.
View details for DOI 10.1016/j.neuroimage.2010.02.008
View details for Web of Science ID 000277141200020
View details for PubMedID 20149886
View details for PubMedCentralID PMC2856738
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<i>T</i><sub>2</sub>-Weighted 3D fMRI Using <i>S</i><sub>2</sub>-SSFP at 7 Tesla
MAGNETIC RESONANCE IN MEDICINE
2010; 63 (4): 1015-1020
Abstract
In this study, the sensitivity of the S(2)-steady-state free precession (SSFP) signal for functional MRI at 7 T was investigated. In order to achieve the necessary temporal resolution, a three-dimensional acquisition scheme with acceleration along two spatial axes was employed. Activation maps based on S(2)-steady-state free precession data showed similar spatial localization of activation and sensitivity as spin-echo echo-planar imaging (SE-EPI), but data can be acquired with substantially lower power deposition. The functional sensitivity estimated by the average z-values was not significantly different for SE-EPI compared to the S(2)-signal but was slightly lower for the S(2)-signal (6.74 +/- 0.32 for the TR = 15 ms protocol and 7.51 +/- 0.78 for the TR = 27 ms protocol) compared to SE-EPI (7.49 +/- 1.44 and 8.05 +/- 1.67) using the same activated voxels, respectively. The relative signal changes in these voxels upon activation were slightly lower for SE-EPI (2.37% +/- 0.18%) compared to the TR = 15 ms S(2)-SSFP protocol (2.75% +/- 0.53%) and significantly lower than the TR = 27 ms protocol (5.38% +/- 1.28%), in line with simulations results. The large relative signal change for the long TR SSFP protocol can be explained by contributions from multiple coherence pathways and the low intrinsic intensity of the S(2) signal. In conclusion, whole-brain T(2)-weighted functional MRI with negligible image distortion at 7 T is feasible using the S(2)-SSFP sequence and partially parallel imaging.
View details for DOI 10.1002/mrm.22283
View details for Web of Science ID 000276064300019
View details for PubMedID 20373402
View details for PubMedCentralID PMC2852274
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Performance evaluation of a 32-element head array with respect to the ultimate intrinsic SNR
NMR IN BIOMEDICINE
2010; 23 (2): 142-151
Abstract
The quality of an RF detector coil design is commonly judged on how it compares with other coil configurations. The aim of this article is to develop a tool for evaluating the absolute performance of RF coil arrays. An algorithm to calculate the ultimate intrinsic signal-to-noise ratio (SNR) was implemented for a spherical geometry. The same imaging tasks modeled in the calculations were reproduced experimentally using a 32-element head array. Coil performance maps were then generated based on the ratio of experimentally measured SNR to the ultimate intrinsic SNR, for different acceleration factors associated with different degrees of parallel imaging. The relative performance in all cases was highest near the center of the samples (where the absolute SNR was lowest). The highest performance was found in the unaccelerated case and a maximum of 85% was observed with a phantom whose electrical properties are consistent with values in the human brain. The performance remained almost constant for 2-fold acceleration, but deteriorated at higher acceleration factors, suggesting that larger arrays are needed for effective highly-accelerated parallel imaging. The method proposed here can serve as a tool for the evaluation of coil designs, as well as a tool to guide the development of original designs which may begin to approach the optimal performance.
View details for DOI 10.1002/nbm.1435
View details for Web of Science ID 000275706800004
View details for PubMedID 19904727
View details for PubMedCentralID PMC2830315
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96-Channel Receive-Only Head Coil for 3 Tesla: Design Optimization and Evaluation
MAGNETIC RESONANCE IN MEDICINE
2009; 62 (3): 754-762
Abstract
The benefits and challenges of highly parallel array coils for head imaging were investigated through the development of a 3T receive-only phased-array head coil with 96 receive elements constructed on a close-fitting helmet-shaped former. We evaluated several designs for the coil elements and matching circuitry, with particular attention to sources of signal-to-noise ratio (SNR) loss, including various sources of coil loading and coupling between the array elements. The SNR and noise amplification (g-factor) in accelerated imaging were quantitatively evaluated in phantom and human imaging and compared to a 32-channel array built on an identical helmet-shaped former and to a larger commercial 12-channel head coil. The 96-channel coil provided substantial SNR gains in the distal cortex compared to the 12- and 32-channel coils. The central SNR for the 96-channel coil was similar to the 32-channel coil for optimum SNR combination and 20% lower for root-sum-of-squares combination. There was a significant reduction in the maximum g-factor for 96 channels compared to 32; for example, the 96-channel maximum g-factor was 65% of the 32-channel value for acceleration rate 4. The performance of the array is demonstrated in highly accelerated brain images.
View details for DOI 10.1002/mrm.22028
View details for Web of Science ID 000269404900023
View details for PubMedID 19623621
View details for PubMedCentralID PMC2915832
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Predicting the location of entorhinal cortex from MRI
NEUROIMAGE
2009; 47 (1): 8-17
Abstract
Entorhinal cortex (EC) is a medial temporal lobe area critical to memory formation and spatial navigation that is among the earliest parts of the brain affected by Alzheimer's disease (AD). Accurate localization of EC would thus greatly facilitate early detection and diagnosis of AD. In this study, we used ultra-high resolution ex vivo MRI to directly visualize the architectonic features that define EC rostrocaudally and mediolaterally, then applied surface-based registration techniques to quantify the variability of EC with respect to cortical geometry, and made predictions of its location on in vivo scans. The results indicate that EC can be localized quite accurately based on cortical folding patterns, within 3 mm in vivo, a significant step forward in our ability to detect the earliest effects of AD when clinical intervention is most likely to be effective.
View details for DOI 10.1016/j.neuroimage.2009.04.033
View details for Web of Science ID 000266975300003
View details for PubMedID 19376238
View details for PubMedCentralID PMC2738987
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Locating the functional and anatomical boundaries of human primary visual cortex
NEUROIMAGE
2009; 46 (4): 915-922
Abstract
The primary visual cortex (V1) can be delineated both functionally by its topographic map of the visual field and anatomically by its distinct pattern of laminar myelination. Although it is commonly assumed that the specialized anatomy V1 exhibits corresponds in location with functionally defined V1, demonstrating this in human has not been possible thus far due to the difficulty of determining the location of V1 both functionally and anatomically in the same individual. In this study we use MRI to measure the anatomical and functional V1 boundaries in the same individual and demonstrate close agreement between them. Functional V1 location was measured by parcellating occipital cortex of 10 living humans into visual cortical areas based on the topographic map of the visual field measured using functional MRI. Anatomical V1 location was estimated for these same subjects using a surface-based probabilistic atlas derived from high-resolution structural MRI of the stria of Gennari in 10 intact ex vivo human hemispheres. To ensure that the atlas prediction was correct, it was validated against V1 location measured using an observer-independent cortical parcellation based on the laminar pattern of cell density in serial brain sections from 10 separate individuals. The close agreement between the independent anatomically and functionally derived V1 boundaries indicates that the whole extent of V1 can be accurately predicted based on cortical surface reconstructions computed from structural MRI scans, eliminating the need for functional localizers of V1. In addition, that the primary cortical folds predict the location of functional V1 suggests that the mechanism giving rise to V1 location is tied to the development of the cortical folds.
View details for DOI 10.1016/j.neuroimage.2009.03.036
View details for Web of Science ID 000266975600005
View details for PubMedID 19328238
View details for PubMedCentralID PMC2712139
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Exact Geodesics and Shortest Paths on Polyhedral Surfaces
IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE
2009; 31 (6): 1006-1016
Abstract
We present two algorithms for computing distances along convex and non-convex polyhedral surfaces. The first algorithm computes exact minimal-geodesic distances and the second algorithm combines these distances to compute exact shortest-path distances along the surface. Both algorithms have been extended to compute the exact minimal-geodesic paths and shortest paths. These algorithms have been implemented and validated on surfaces for which the correct solutions are known, in order to verify the accuracy and to measure the run-time performance, which is cubic or less for each algorithm. The exact-distance computations carried out by these algorithms are feasible for large-scale surfaces containing tens of thousands of vertices, and are a necessary component of near-isometric surface flattening methods that accurately transform curved manifolds into flat representations.
View details for DOI 10.1109/TPAMI.2008.213
View details for Web of Science ID 000265100000004
View details for PubMedID 19372606
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The Intrinsic Shape of Human and Macaque Primary Visual Cortex
CEREBRAL CORTEX
2008; 18 (11): 2586-2595
Abstract
Previous studies have reported considerable variability in primary visual cortex (V1) shape in both humans and macaques. Here, we demonstrate that much of this variability is due to the pattern of cortical folds particular to an individual and that V1 shape is similar among individual humans and macaques as well as between these 2 species. Human V1 was imaged ex vivo using high-resolution (200 microm) magnetic resonance imaging at 7 T. Macaque V1 was identified in published histological serial section data. Manual tracings of the stria of Gennari were used to construct a V1 surface, which was computationally flattened with minimal metric distortion of the cortical surface. Accurate flattening allowed investigation of intrinsic geometric features of cortex, which are largely independent of the highly variable cortical folds. The intrinsic shape of V1 was found to be similar across human subjects using both nonparametric boundary matching and a simple elliptical shape model fit to the data and is very close to that of the macaque monkey. This result agrees with predictions derived from current models of V1 topography. In addition, V1 shape similarity suggests that similar developmental mechanisms are responsible for establishing V1 shape in these 2 species.
View details for DOI 10.1093/cercor/bhn016
View details for Web of Science ID 000260135700011
View details for PubMedID 18308709
View details for PubMedCentralID PMC2733317
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Event-related single-shot volumetric functional magnetic resonance inverse imaging of visual processing
NEUROIMAGE
2008; 42 (1): 230-247
Abstract
Developments in multi-channel radio-frequency (RF) coil array technology have enabled functional magnetic resonance imaging (fMRI) with higher degrees of spatial and temporal resolution. While modest improvement in temporal acceleration has been achieved by increasing the number of RF coils, the maximum attainable acceleration in parallel MRI acquisition is intrinsically limited only by the amount of independent spatial information in the combined array channels. Since the geometric configuration of a large-n MRI head coil array is similar to that used in EEG electrode or MEG SQUID sensor arrays, the source localization algorithms used in MEG or EEG source imaging can be extended to also process MRI coil array data, resulting in greatly improved temporal resolution by minimizing k-space traversal during signal acquisition. Using a novel approach, we acquire multi-channel MRI head coil array data and then apply inverse reconstruction methods to obtain volumetric fMRI estimates of blood oxygenation level dependent (BOLD) contrast at unprecedented whole-brain acquisition rates of 100 ms. We call this combination of techniques magnetic resonance Inverse Imaging (InI), a method that provides estimates of dynamic spatially-resolved signal change that can be used to construct statistical maps of task-related brain activity. We demonstrate the sensitivity and inter-subject reliability of volumetric InI using an event-related design to probe the hemodynamic signal modulations in primary visual cortex. Robust results from both single subject and group analyses demonstrate the sensitivity and feasibility of using volumetric InI in high temporal resolution investigations of human brain function.
View details for DOI 10.1016/j.neuroimage.2008.04.179
View details for Web of Science ID 000258105000023
View details for PubMedID 18538587
View details for PubMedCentralID PMC2659356
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A 128-channel receive-only cardiac coil for highly accelerated cardiac MRI at 3 tesla
MAGNETIC RESONANCE IN MEDICINE
2008; 59 (6): 1431-1439
Abstract
A 128-channel receive-only array coil is described and tested for cardiac imaging at 3T. The coil is closely contoured to the body with a "clam-shell" geometry with 68 posterior and 60 anterior elements, each 75 mm in diameter, and arranged in a continuous overlapped array of hexagonal symmetry to minimize nearest neighbor coupling. Signal-to-noise ratio (SNR) and noise amplification for parallel imaging (G-factor) were evaluated in phantom and volunteer experiments. These results were compared to those of commercially available 24-channel and 32-channel coils in routine use for cardiac imaging. The in vivo measurements with the 128-channel coil resulted in SNR gains compared to the 24-channel coil (up to 2.2-fold in the apex). The 128- and 32-channel coils showed similar SNR in the heart, likely dominated by the similar element diameters of these coils. The maximum G-factor values were up to seven times better for a seven-fold acceleration factor (R=7) compared to the 24-channel coil and up to two-fold improved compared to the 32-channel coil. The ability of the 128-channel coil to facilitate highly accelerated cardiac imaging was demonstrated in four volunteers using acceleration factors up to seven-fold (R=7) in a single spatial dimension.
View details for DOI 10.1002/mrm.21598
View details for Web of Science ID 000256266400027
View details for PubMedID 18506789
View details for PubMedCentralID PMC2548273
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Accurate prediction of V1 location from cortical folds in a surface coordinate system
NEUROIMAGE
2008; 39 (4): 1585-1599
Abstract
Previous studies demonstrated substantial variability of the location of primary visual cortex (V1) in stereotaxic coordinates when linear volume-based registration is used to match volumetric image intensities [Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., and Zilles, K. (2000). Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? Neuroimage, 11(1):66-84]. However, other qualitative reports of V1 location [Smith, G. (1904). The morphology of the occipital region of the cerebral hemisphere in man and the apes. Anatomischer Anzeiger, 24:436-451; Stensaas, S.S., Eddington, D.K., and Dobelle, W.H. (1974). The topography and variability of the primary visual cortex in man. J Neurosurg, 40(6):747-755; Rademacher, J., Caviness, V.S., Steinmetz, H., and Galaburda, A.M. (1993). Topographical variation of the human primary cortices: implications for neuroimaging, brain mapping, and neurobiology. Cereb Cortex, 3(4):313-329] suggested a consistent relationship between V1 and the surrounding cortical folds. Here, the relationship between folds and the location of V1 is quantified using surface-based analysis to generate a probabilistic atlas of human V1. High-resolution (about 200 microm) magnetic resonance imaging (MRI) at 7 T of ex vivo human cerebral hemispheres allowed identification of the full area via the stria of Gennari: a myeloarchitectonic feature specific to V1. Separate, whole-brain scans were acquired using MRI at 1.5 T to allow segmentation and mesh reconstruction of the cortical gray matter. For each individual, V1 was manually identified in the high-resolution volume and projected onto the cortical surface. Surface-based intersubject registration [Fischl, B., Sereno, M.I., Tootell, R.B., and Dale, A.M. (1999b). High-resolution intersubject averaging and a coordinate system for the cortical surface. Hum Brain Mapp, 8(4):272-84] was performed to align the primary cortical folds of individual hemispheres to those of a reference template representing the average folding pattern. An atlas of V1 location was constructed by computing the probability of V1 inclusion for each cortical location in the template space. This probabilistic atlas of V1 exhibits low prediction error compared to previous V1 probabilistic atlases built in volumetric coordinates. The increased predictability observed under surface-based registration suggests that the location of V1 is more accurately predicted by the cortical folds than by the shape of the brain embedded in the volume of the skull. In addition, the high quality of this atlas provides direct evidence that surface-based intersubject registration methods are superior to volume-based methods at superimposing functional areas of cortex and therefore are better suited to support multisubject averaging for functional imaging experiments targeting the cerebral cortex.
View details for DOI 10.1016/j.neuroimage.2007.10.033
View details for Web of Science ID 000253241800010
View details for PubMedID 18055222
View details for PubMedCentralID PMC2258215
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Multi-area visuotopic map complexes in macaque striate and extra-striate cortex
VISION RESEARCH
2006; 46 (20): 3336-3359
Abstract
We propose that a simple, closed-form mathematical expression-the Wedge-Dipole mapping-provides a concise approximation to the full-field, two-dimensional topographic structure of macaque V1, V2, and V3. A single map function, which we term a map complex, acts as a simultaneous descriptor of all three areas. Quantitative estimation of the Wedge-Dipole parameters is provided via 2DG data of central-field V1 topography and a publicly available data set of full-field macaque V1 and V2 topography. Good quantitative agreement is obtained between the data and the model presented here. The increasing importance of fMRI-based brain imaging motivates the development of more sophisticated two-dimensional models of cortical visuotopy, in contrast to the one-dimensional approximations that have been in common use. One reason is that topography has traditionally supplied an important aspect of "ground truth," or validation, for brain imaging, suggesting that further development of high-resolution fMRI will be facilitated by this data analysis. In addition, several important insights into the nature of cortical topography follow from this work. The presence of anisotropy in cortical magnification factor is shown to follow mathematically from the shared boundary conditions at the V1-V2 and V2-V3 borders, and therefore may not causally follow from the existence of columnar systems in these areas, as is widely assumed. An application of the Wedge-Dipole model to localizing aspects of visual processing to specific cortical areas-extending previous work in correlating V1 cortical magnification factor to retinal anatomy or visual psychophysics data-is briefly discussed.
View details for DOI 10.1016/j.visres.2006.03.006
View details for Web of Science ID 000240786800006
View details for PubMedID 16831455
View details for PubMedCentralID PMC2248457
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Physical limits to spatial resolution of optical recording: Clarifying the spatial structure of cortical hypercolumns
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2005; 102 (11): 4158-4163
Abstract
Neurons in macaque primary visual cortex are spatially arranged by their global topographic position and in at least three overlapping local modular systems: ocular dominance columns, orientation pinwheels, and cytochrome oxidase (CO) blobs. Individual neurons in the blobs are not tuned to orientation, and populations of neurons in the pinwheel center regions show weak orientation tuning, suggesting a close relation between pinwheel centers and CO blobs. However, this hypothesis has been challenged by a series of optical recording experiments. In this report, we show that the statistical error associated with photon scatter and absorption in brain tissue combined with the blurring introduced by the optics of the imaging system has typically been in the range of 250 microm. These physical limitations cause a systematic error in the location of pinwheel centers because of the vectorial nature of these patterns, such that the apparent location of a pinwheel center measured by optical recording is never (on average) in the correct in vivo location. The systematic positional offset is approximately 116 microm, which is large enough to account for the claimed misalignment of CO blobs and pinwheel centers. Thus, optical recording, as it has been used to date, has insufficient spatial resolution to accurately locate pinwheel centers. The earlier hypothesis that CO blobs and pinwheel centers are coterminous remains the only hypothesis currently supported by reliable observation.
View details for DOI 10.1073/pnas.0500291102
View details for Web of Science ID 000227731000050
View details for PubMedID 15746240
View details for PubMedCentralID PMC554808
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The V1-V2-V3 complex: quasiconformal dipole maps in primate striate and extra-striate cortex
NEURAL NETWORKS
2002; 15 (10): 1157-1163
Abstract
The mapping function w = k log(z + a) is a widely accepted approximation to the topographic structure of primate V1 foveal and parafoveal regions. A better model, at the cost of an additional parameter, captures the full field topographic map in terms of the dipole map function w = k log[(z + a)/(z + b)]. However, neither model describes topographic shear since they are both explicitly complex-analytic or conformal. In this paper, we adopt a simple ansatz for topographic shear in V1, V2, and V3 that assumes that cortical topographic shear is rotational, i.e. a compression along iso-eccentricity contours. We model the constant rotational shear with a quasiconformal mapping, the wedge mapping. Composing this wedge mapping with the dipole mapping provides an approximation to V1, V2, and V3 topographic structure, effectively unifying all three areas into a single V1-V2-V3 complex using five independent parameters. This work represents the first full-field, multi-area, quasiconformal model of striate and extra-striate topographic map structure.
View details for DOI 10.1016/S0893-6080(02)00094-1
View details for Web of Science ID 000179011600001
View details for PubMedID 12425434
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Neural representation of sensory data
BEHAVIORAL AND BRAIN SCIENCES
2002; 25 (2): 207-+
View details for DOI 10.1017/S0140525X02470045
View details for Web of Science ID 000183686300027