VesselBoost: A Python Toolbox for Small Blood Vessel Segmentation in Human Magnetic Resonance Angiography Data.

Magnetic resonance angiography (MRA) performed at ultra-high magnetic field provides a unique opportunity to study the arteries of the living human brain at the mesoscopic level. From this, we can gain new insights into the brain's blood supply and vascular disease affecting small vessels. However, for quantitative characterization and precise representation of human angioarchitecture to, for example, inform blood-flow simulations, detailed segmentations of the smallest vessels are required. Given the success of deep learning-based methods in many segmentation tasks, we here explore their application to high-resolution MRA data, and address the difficulty of obtaining large data sets of correctly and comprehensively labelled data. We introduce VesselBoost, a vessel segmentation package, which utilizes deep learning and imperfect training labels for accurate vasculature segmentation. Combined with an innovative data augmentation technique, which leverages the resemblance of vascular structures, VesselBoost enables detailed vascular segmentations.

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.

The temporal specificity of BOLD fMRI is systematically related to anatomical and vascular features of the human brain.

The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter smoothing out rapid changes. However, hemodynamic responses (their shape and timing) are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of fMRI signals, or the ability of fMRI to preserve fast information, should also vary substantially across the cortex. In this work we investigated how local differences in hemodynamic response timing impact the temporal specificity of fMRI. We conducted our research using ultra-high field (7T) fMRI at high spatiotemporal resolution, using the primary visual cortex (V1) as a model area for investigation. We used visual stimuli oscillating at slow and fast frequencies to probe the temporal specificity of individual voxels. As expected, we identified substantial variability in temporal specificity, with some voxels preserving their responses to fast neural activity more effectively than others. We investigated which voxels had the highest temporal specificity and related those to anatomical and vascular features of V1. We found that low temporal specificity is only weakly explained by the presence of large veins or cerebral cortical depth. Notably, however, temporal specificity depended strongly on a voxel's position along the anterior-posterior anatomical axis of V1, with voxels within the calcarine sulcus being capable of preserving close to 25% of their amplitude as the frequency of stimulation increased from 0.05-Hz to 0.20-Hz, and voxels nearest to the occipital pole preserving less than 18%. These results indicate that detection biases in high-resolution fMRI will depend on the anatomical and vascular features of the area being imaged, and that these biases will differ depending on the timing of the underlying neuronal activity. Importantly, this spatial heterogeneity of temporal specificity suggests that it could be exploited to achieve higher specificity in some locations, and that tailored data analysis strategies may help improve the detection and interpretation of fast fMRI responses.

Romer-EPTI: rotating-view motion-robust super-resolution EPTI for SNR-efficient distortion-free in-vivo mesoscale dMRI and microstructure imaging.

Purpose: To overcome the major challenges in dMRI acquisition, including low SNR, distortion/blurring, and motion vulnerability. Methods: A novel Romer-EPTI technique is developed to provide distortion-free dMRI with significant SNR gain, high motion-robustness, sharp spatial resolution, and simultaneous multi-TE imaging. It introduces a ROtating-view Motion-robust supEr-Resolution technique (Romer) combined with a distortion/blurring-free EPTI encoding. Romer enhances SNR by a simultaneous multi-thick-slice acquisition with rotating-view encoding, while providing high motion-robustness through a motion-aware super-resolution reconstruction, which also incorporates slice-profile and real-value diffusion, to resolve high-isotropic-resolution volumes. The in-plane encoding is performed using distortion/blurring-free EPTI, which further improves effective spatial resolution and motion robustness by preventing not only T2/T2*-blurring but also additional blurring resulting from combining encoded volumes with inconsistent geometries caused by dynamic distortions. Self-navigation was incorporated to enable efficient phase correction. Additional developments include strategies to address slab-boundary artifacts, achieve minimal TE for SNR gain at 7T, and achieve high robustness to strong phase variations at high b-values. Results: Using Romer-EPTI, we demonstrate distortion-free whole-brain mesoscale in-vivo dMRI at both 3T (500-µm-iso) and 7T (485-µm-iso) for the first time, with high SNR efficiency (e.g., 25×), and high image quality free from distortion and slab-boundary artifacts with minimal blurring. Motion experiments demonstrate Romer-EPTI's high motion-robustness and ability to recover sharp images in the presence of motion. Romer-EPTI also demonstrates significant SNR gain and robustness in high b-value (b=5000s/mm2) and time-dependent dMRI. Conclusion: Romer-EPTI significantly improves SNR, motion-robustness, and image quality, providing a highly efficient acquisition for high-resolution dMRI and microstructure imaging.

Single-shot Echo Planar Time-resolved Imaging for multi-echo functional MRI and distortion-free diffusion imaging.

Purpose: To develop EPTI, a multi-shot distortion-free multi-echo imaging technique, into a single-shot acquisition to achieve improved robustness to motion and physiological noise, increased temporal resolution, and high SNR efficiency for dynamic imaging applications. Methods: A new spatiotemporal encoding was developed to achieve single-shot EPTI by enhancing spatiotemporal correlation in k-t space. The proposed single-shot encoding improves reconstruction conditioning and sampling efficiency, with additional optimization under various accelerations to achieve optimized performance. To achieve high SNR efficiency, continuous readout with minimized deadtime was employed that begins immediately after excitation and extends for an SNR-optimized length. Moreover, k-t partial Fourier and simultaneous multi-slice acquisition were integrated to further accelerate the acquisition and achieve high spatial and temporal resolution. Results: We demonstrated that ss-EPTI achieves higher tSNR efficiency than multi-shot EPTI, and provides distortion-free imaging with densely-sampled multi-echo images at resolutions ~1.25-3 mm at 3T and 7T-with high SNR efficiency and with comparable temporal resolutions to ss-EPI. The ability of ss-EPTI to eliminate dynamic distortions common in EPI also further improves temporal stability. For fMRI, ss-EPTI also provides early-TE images (e.g., 2.9ms) to recover signal-intensity and functional-sensitivity dropout in challenging regions. The multi-echo images provide TE-dependent information about functional fluctuations, successfully distinguishing noise-components from BOLD signals and further improving tSNR. For diffusion MRI, ss-EPTI provides high-quality distortion-free diffusion images and multi-echo diffusion metrics. Conclusion: ss-EPTI provides distortion-free imaging with high image quality, rich multi-echo information, and enhanced efficiency within comparable temporal resolution to ss-EPI, offering a robust and efficient acquisition for dynamic imaging.

Predicting the macrovascular contribution to resting-state fMRI functional connectivity at 3 Tesla: A model-informed approach.

Macrovascular biases have been a long-standing challenge for fMRI, limiting its ability to detect spatially specific neural activity. Recent experimental studies, including our own (Huck et al., 2023; Zhong et al., 2023), found substantial resting-state macrovascular BOLD fMRI contributions from large veins and arteries, extending into the perivascular tissue at 3 T and 7 T. The objective of this study is to demonstrate the feasibility of predicting, using a biophysical model, the experimental resting-state BOLD fluctuation amplitude (RSFA) and associated functional connectivity (FC) values at 3 Tesla. We investigated the feasibility of both 2D and 3D infinite-cylinder models as well as macrovascular anatomical networks (mVANs) derived from angiograms. Our results demonstrate that: 1) with the availability of mVANs, it is feasible to model macrovascular BOLD FC using both the mVAN-based model and 3D infinite-cylinder models, though the former performed better; 2) biophysical modelling can accurately predict the BOLD pairwise correlation near to large veins (with R 2 ranging from 0.53 to 0.93 across different subjects), but not near to large arteries; 3) compared with FC, biophysical modelling provided less accurate predictions for RSFA; 4) modelling of perivascular BOLD connectivity was feasible at close distances from veins (with R 2 ranging from 0.08 to 0.57), but not arteries, with performance deteriorating with increasing distance. While our current study demonstrates the feasibility of simulating macrovascular BOLD in the resting state, our methodology may also apply to understanding task-based BOLD. Furthermore, these results suggest the possibility of correcting for macrovascular bias in resting-state fMRI and other types of fMRI using biophysical modelling based on vascular anatomy.

Multilayer Network Analysis across Cortical Depths in Resting-State 7T fMRI.

In graph theory, "multilayer networks" represent systems involving several interconnected topological levels. A neuroscience example is the hierarchy of connections between different cortical depths or "lamina". This hierarchy is becoming non-invasively accessible in humans using ultra-high-resolution functional MRI (fMRI). Here, we applied multilayer graph theory to examine functional connectivity across different cortical depths in humans, using 7T 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 then compared networks where the inter-regional connections were limited to a single cortical depth only ("layer-by-layer matrices") to those considering all possible connections between regions and cortical depths ("multilayer matrix"). We utilized global and local graph theory features that quantitatively characterize network attributes such as network composition, nodal centrality, path-based measures, and hub segregation. Detecting functional differences between cortical depths was improved using multilayer connectomics compared to the layer-by-layer versions. Superficial aspects of the cortex dominated information transfer and deeper aspects clustering. These differences were largest in frontotemporal and limbic brain regions. fMRI functional connectivity across different cortical depths may contain neurophysiologically relevant information. Multilayer connectomics could provide a methodological framework for studies on how information flows across this hierarchy.