Impact of repeated blast exposure on active-duty United States Special Operations Forces.

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.

Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

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.

Role of articulatory motor networks in perceptual categorization of speech signals: a 7T fMRI study.

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.

Cortical depth profiles of auditory and visual 7 T functional MRI responses in human superior temporal areas.

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.

High-resolution motion- and phase-corrected functional MRI at 7 T using shuttered multishot echo-planar imaging.

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.

T1 relaxation time of ISMRM/NIST T1 phantom spheres at 7 T.

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.

The Global Configuration of Visual Stimuli Alters Co-Fluctuations of Cross-Hemispheric Human Brain Activity.

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.

SDnDTI: Self-supervised deep learning-based denoising for diffusion tensor MRI.

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.

Slice-direction geometric distortion evaluation and correction with reversed slice-select gradient acquisitions.

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.

Critical factors in achieving fine-scale functional MRI: Removing sources of inadvertent spatial smoothing.

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.

Real-time shimming with FID navigators.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A 31-channel integrated "AC/DC" B0 shim and radiofrequency receive array coil for improved 7T MRI.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cerebellar atrophy and its implications on gait in cerebral amyloid angiopathy.

OBJECTIVE: Recent data suggest that cerebral amyloid angiopathy (CAA) causes haemorrhagic lesions in cerebellar cortex as well as subcortical cerebral atrophy. However, the potential effect of CAA on cerebellar tissue loss and its clinical implications have not been investigated. METHODS: Our study included 70 non-demented patients with probable CAA, 70 age-matched healthy controls (HCs) and 70 age-matched patients with Alzheimer's disease (AD). The cerebellum was segmented into percent of cerebellar subcortical volume (pCbll-ScV) and percent of cerebellar cortical volume (pCbll-CV) represented as percent (p) of estimated total intracranial volume. We compared pCbll-ScV and pCbll-CV between patients with CAA, HCs and those with AD. Gait velocity (metres/second) was used to investigate gait function in patients with CAA. RESULTS: Patients with CAA had significantly lower pCbll-ScV compared with both HC (1.49±0.1 vs 1.73±0.2, p<0.001) and AD (1.49±0.1 vs 1.66±0.24, p<0.001) and lower pCbll-CV compared with HCs (6.03±0.5 vs 6.23±0.6, p=0.028). Diagnosis of CAA was independently associated with lower pCbll-ScV compared with HCs (p<0.001) and patients with AD (p<0.001) in separate linear regression models adjusted for age, sex and presence of hypertension. Lower pCbll-ScV was independently associated with worse gait velocity (ß=0.736, 95% CI 0.28 to 1.19, p=0.002) in a stepwise linear regression analysis including pCbll-CV along with other relevant variables. INTERPRETATION: Patients with CAA show more subcortical cerebellar atrophy than HC or patients with AD and more cortical cerebellar atrophy than HCs. Reduced pCbll-ScV correlated with lower gait velocity in regression models including other relevant variables. Overall, this study suggests that CAA causes cerebellar injury, which might contribute to gait disturbance.

Improving in vivo human cerebral cortical surface reconstruction using data-driven super-resolution.

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 100 µm at the single-subject level and below 50 µm at the group level for the simulated data, and below 200 µm at the single-subject level and below 100 µm at the group level for the empirical data, making the accuracy of cortical surfaces derived from super-resolution sufficient for most applications.

Simultaneous pure T2 and varying T2'-weighted BOLD fMRI using Echo Planar Time-resolved Imaging for mapping cortical-depth dependent responses.

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.

Improved cortical surface reconstruction using sub-millimeter resolution MPRAGE by image denoising.

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.

Investigating mechanisms of fast BOLD responses: The effects of stimulus intensity and of spatial heterogeneity of hemodynamics.

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.

Ground-truth "resting-state" signal provides data-driven estimation and correction for scanner distortion of fMRI time-series dynamics.

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.

Probing in vivo cortical myeloarchitecture in humans via line-scan diffusion acquisitions at 7 T with 250-500 micron radial resolution.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Ultra-high spatial resolution BOLD fMRI in humans using combined segmented-accelerated VFA-FLEET with a recursive RF pulse design.

PURPOSE: 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. THEORY AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.