High Resolution Diffusion MRI Research Articles

The nonhuman primate neuroimaging and neuroanatomy project

Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, ‘ground truth’ validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how “functional connectivity” from fMRI and “tractographic connectivity” from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.

A probabilistic atlas of locus coeruleus pathways to transentorhinal cortex for connectome imaging in Alzheimer's disease

According to the latest Braak staging of Alzheimer's disease (AD), tau pathology occurs earliest in the brain in the locus coeruleus (LC) of the brainstem, then propagates to the transentorhinal cortex (TEC), and later to other neocortical regions. Recent animal and in vivo human brain imaging research also support the trans-axonal propagation of tau pathology. In addition, neurochemical studies link norepinephrine to behavioral symptoms in AD. It is thus critical to examine the integrity of the LC-TEC pathway in studying the early development of the disease, but there has been limited work in this direction. By leveraging the high-resolution and multi-shell diffusion MRI data from the Human Connectome Project (HCP), in this work we develop a novel method for the reconstruction of the LC-TEC pathway in a cohort of 40 HCP subjects carefully selected based on rigorous quality control of the residual distortion artifacts in the brainstem. A probabilistic atlas of the LC-TEC pathway of both hemispheres is then developed in the MNI152 space and distributed publicly on the NITRC website. To apply our atlas on clinical imaging data, we develop an automated approach to calculate the medial core of the LC-TEC pathway for localized analysis of connectivity changes. In a cohort of 138 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we demonstrate the detection of the decreased fiber integrity in the LC-TEC pathways with increasing disease severity.

Spherical deconvolution with tissue-specific response functions and multi-shell diffusion MRI to estimate multiple fiber orientation distributions (mFODs)

In diffusion MRI, spherical deconvolution approaches can estimate local white matter (WM) fiber orientation distributions (FOD) which can be used to produce fiber tractography reconstructions. The applicability of spherical deconvolution to gray matter (GM), however, is still limited, despite its critical role as start/endpoint of WM fiber pathways. The advent of multi-shell diffusion MRI data offers additional contrast to model the GM signal but, to date, only isotropic models have been applied to GM. Evidence from both histology and high-resolution diffusion MRI studies suggests a marked anisotropic character of the diffusion process in GM, which could be exploited to improve the description of the cortical organization. In this study, we investigated whether performing spherical deconvolution with tissue specific models of both WM and GM can improve the characterization of the latter while retaining state-of-the-art performances in WM. To this end, we developed a framework able to simultaneously accommodate multiple anisotropic response functions to estimate multiple, tissue-specific, fiber orientation distributions (mFODs). As proof of principle, we used the diffusion kurtosis imaging model to represent the WM signal, and the neurite orientation dispersion and density imaging (NODDI) model to represent the GM signal. The feasibility of the proposed approach is shown with numerical simulations and with data from the Human Connectome Project (HCP). The performance of our method is compared to the current state of the art, multi-shell constrained spherical deconvolution (MSCSD). The simulations show that with our new method we can accurately estimate a mixture of two FODs at SNR≥50. With HCP data, the proposed method was able to reconstruct both tangentially and radially oriented FODs in GM, and performed comparably well to MSCSD in computing FODs in WM. When performing fiber tractography, the trajectories reconstructed with mFODs reached the cortex with more spatial continuity and for a longer distance as compared to MSCSD and allowed to reconstruct short trajectories tangential to the cortical folding. In conclusion, we demonstrated that our proposed method allows to perform spherical deconvolution of multiple anisotropic response functions, specifically improving the performances of spherical deconvolution in GM tissue.

Generalized Richardson-Lucy (GRL) for analyzing multi-shell diffusion MRI data

Spherical deconvolution is a widely used approach to quantify the fiber orientation distribution (FOD) from diffusion MRI data of the brain. The damped Richardson-Lucy (dRL) is an algorithm developed to perform robust spherical deconvolution on single-shell diffusion MRI data while suppressing spurious FOD peaks due to noise or partial volume effects. Due to recent progress in acquisition hardware and scanning protocols, it is becoming increasingly common to acquire multi-shell diffusion MRI data, which allows for the modelling of multiple tissue types beyond white matter. While the dRL algorithm could, in theory, be directly applied to multi-shell data, it is not optimised to exploit its information content to model the signal from multiple tissue types. In this work, we introduce a new framework based on dRL – dubbed generalized Richardson-Lucy (GRL) – that uses multi-shell data in combination with user-chosen tissue models to disentangle partial volume effects and increase the accuracy in FOD estimation. Further, GRL estimates signal fraction maps associated to each user-selected model, which can be used during fiber tractography to dissect and terminate the tracking without need for additional structural data. The optimal weighting of multi-shell data in the fit and the robustness to noise and to partial volume effects of GRL was studied with synthetic data. Subsequently, we investigated the performance of GRL in comparison to dRL and to multi-shell constrained spherical deconvolution (MSCSD) on a high-resolution diffusion MRI dataset from the Human Connectome Project and on an MRI dataset acquired at 3T on a clinical scanner. In line with previous studies, we described the signal of the cerebrospinal-fluid and of the grey matter with isotropic diffusion models, whereas four diffusion models were considered to describe the white matter. With a third dataset including small diffusion weightings, we studied the feasibility of including intra-voxel incoherent motion effects due to blood pseudo-diffusion in the modelling. Further, the reliability of GRL was demonstrated with a test-retest scan of a subject acquired at 3T. Results of simulations show that GRL can robustly disentangle different tissue types at SNR above 20 with respect to the non-weighted image, and that it improves the angular accuracy of the FOD estimation as compared to dRL. On real data, GRL provides signal fraction maps that are physiologically plausible and consistent with those obtained with MSCSD, with correlation coefficients between the two methods up to 0.96. When considering IVIM effects, a high blood pseudo-diffusion fraction is observed in the medial temporal lobe and in the sagittal sinus. In comparison to dRL and MSCSD, GRL provided sharper FODs and less spurious peaks in presence of partial volume effects, but the FOD reconstructions are also highly dependent on the chosen modelling of white matter. When performing fiber tractography, GRL allows to terminate fiber tractography using the signal fraction maps, which results in a better tract termination at the grey-white matter interface or at the outer cortical surface. In terms of inter-scan reliability, GRL performed similarly to or better than compared methods. In conclusion, GRL offers a new modular and flexible framework to perform spherical deconvolution of multi-shell data.

Fast submillimeter diffusion MRI using gSlider-SMS and SNR-enhancing joint reconstruction.

We evaluate a new approach for achieving diffusion MRI data with high spatial resolution, large volume coverage, and fast acquisition speed. A recent method called gSlider-SMS enables whole-brain submillimeter diffusion MRI with high signal-to-noise ratio (SNR) efficiency. However, despite the efficient acquisition, the resulting images can still suffer from low SNR due to the small size of the imaging voxels. This work proposes to mitigate the SNR problem by combining gSlider-SMS with a regularized SNR-enhancing reconstruction approach. Illustrative results show that, from gSlider-SMS data acquired over a span of only 25minutes on a 3T scanner, the proposed method is able to produce 71 MRI images (64 diffusion encoding orientations with b = 1500s/ , and 7 images without diffusion weighting) of the entire in vivo human brain with nominal 0.66mm spatial resolution. Using data acquired from 75minutes of acquisition as a gold standard reference, we demonstrate that the proposed SNR-enhancement procedure leads to substantial improvements in estimated diffusion parameters compared to conventional gSlider reconstruction. Results also demonstrate that the proposed method has advantages relative to denoising methods based on low-rank matrix modeling. A theoretical analysis of the trade-off between spatial resolution and SNR suggests that the proposed approach has high efficiency. The combination of gSlider-SMS with advanced regularized reconstruction enables high-resolution quantitative diffusion MRI from a relatively fast acquisition.

Unsupervised Deep Learning for Susceptibility Distortion Correction in Connectome Imaging.

To reduce the residual distortion in high resolution diffusion MRI (dMRI) data preprocessed by the HCP-Pipeline, we propose an unsupervised deep learning based method to correct the residual susceptibility induced distortion. Instead of using B0 images from two phase encoding (PE), fiber orientation distribution (FOD) images computed from dMRI data, which provide more reliable contrast information, are used in our method. Our deep learning framework named DistoRtion Correction Net (DrC-Net) uses an U-Net to capture the latent features from FOD images and estimates a deformation field along the phase encoding direction. With the help of a transformer network, we can propagate the deformation feature to the FOD images and back propagate the losses between the deformed images and true undistorted images. The proposed DrC-Net is trained on 60 subjects randomly selected from 100 subjects in the Human Connectome Project (HCP) dataset. We evaluated the DrC-Net on the rest 40 subjects and the results show a similar performance compared to the training dataset. Our evaluation method used mean squared difference (MSD) of fractional anisotropy (FA) and minimum angular difference between two PEs. We compared the DrC-Net to topup method used in the HCP-Pipeline, and the results show a significant improvement to correct the susceptibility induced distortions in both evaluation methods.

Improved MUSSELS reconstruction for high-resolution multi-shot diffusion weighted imaging.

MUSSELS is a one-step iterative reconstruction method for multishot diffusion weighted (msDW) imaging. The current work presents an efficient implementation, termed IRLS MUSSELS, that enables faster reconstruction to enhance its utility for high-resolution diffusion MRI studies. The recently proposed MUSSELS reconstruction belongs to a new class of parallel imaging-based methods that recover artifact-free DWIs from msDW data without needing phase compensation. The reconstruction is achieved via structured low-rank matrix completion algorithms, which are computationally demanding due to the large size of the Hankel matrices and their associated computations involving singular value decompositions. Because of this, computational demands of the MUSSELS reconstruction scales as the matrix size and the number of shots increases, which hinders its practical utility for high-resolution applications. In this work, we derive a computationally efficient MUSSELS formulation by modifying the iterative reweighted least squares (IRLS) method that were proposed earlier to solve such problems. Using whole-brain in vivo data, we show the utility of the IRLS MUSSELS for routine high-resolution studies with reduced computational burden. IRLS MUSSELS provides about five times faster reconstruction for matrix sizes 192 × 192 and 256 × 256 compared to the earlier MUSSELS implementation. The widely employed conjugate symmetry priors can also be incorporated into IRLS MUSSELS to reduce blurring of the partial Fourier acquisitions, without incurring much computational burden. The proposed method is observed to be computationally efficient to enable routine high-resolution studies. The computational complexity matches the traditional msDWI reconstruction methods and provides improved reconstruction results with the additional constraints.

XQ-SR: Joint x-q space super-resolution with application to infant diffusion MRI.

Diffusion MRI (DMRI) is a powerful tool for studying early brain development and disorders. However, the typically low spatio-angular resolution of DMRI diminishes structural details and limits quantitative analysis to simple diffusion models. This problem is aggravated for infant DMRI since (i) the infant brain is significantly smaller than that of an adult, demanding higher spatial resolution to capture subtle structures; and (ii) the typically limited scan time of unsedated infants poses significant challenges to DMRI acquisition with high spatio-angular resolution. Post-acquisition super-resolution (SR) is an important alternative for increasing the resolution of DMRI data without prolonging acquisition times. However, most existing methods focus on the SR of only either the spatial domain (x-space) or the diffusion wavevector domain (q-space). For more effective resolution enhancement, we propose a framework for joint SR in both spatial and wavevector domains. More specifically, we first establish the signal relationships in x-q space using a robust neighborhood matching technique. We then harness the signal relationships to regularize the ill-posed inverse problem associated with the recovery of high-resolution data from their low-resolution counterpart. Extensive experiments on synthetic, adult, and infant DMRI data demonstrate that our method is able to recover high-resolution DMRI data with remarkably improved quality.

A 3D k-space Fourier encoding and reconstruction framework for simultaneous multi-slab acquisition.

To propose a novel 3D k-space Fourier encoding and reconstruction framework for simultaneous multi-slab (SMSlab) acquisition and demonstrate its efficacy in high-resolution imaging. First, it is illustrated in theory how the inter-slab gap interferes with the formation of the SMSlab 3D k-space. Then, joint RF and gradient encoding are applied to remove the inter-slab gap interference and form a SMSlab 3D k-space. In vivo experiments are performed to validate the proposed theory. Acceleration in the proposed SMSlab 3D k-space is also evaluated. High-resolution (1.0 mm isotropic) images can be reconstructed using the proposed SMSlab 3D framework. Controlled aliasing in parallel imaging sampling and 2D GRAPPA reconstruction can also be applied in the SMSlab 3D k-space. Compared with conventional multi-slab acquisition, SMSlab exhibits better SNR maintainability (such as lower g-factors), especially at high acceleration factors. It is demonstrated that the joint application of RF and gradient encoding enables SMSlab within a 3D Fourier encoding framework. Images with high isotropic resolution can be reconstructed, and further acceleration is also applicable. The proposed SMSlab 3D k-space can be valuable for both high-resolution and high-efficiency diffusion and functional MRI.

Functionally defined white matter of the macaque monkey brain reveals a dorso-ventral attention network.

Classical studies of attention have identified areas of parietal and frontal cortex as sources of attentional control. Recently, a ventral region in the macaque temporal cortex, the posterior infero-temporal dorsal area PITd, has been suggested as a third attentional control area. This raises the question of whether and how spatially distant areas coordinate a joint focus of attention. Here we tested the hypothesis that parieto-frontal attention areas and PITd are directly interconnected. By combining functional MRI with ex-vivo high-resolution diffusion MRI, we found that PITd and dorsal attention areas are all directly connected through three specific fascicles. These results ascribe a new function, the communication of attention signals, to two known fiber-bundles, highlight the importance of vertical interactions across the two visual streams, and imply that the control of endogenous attention, hitherto thought to reside in macaque dorsal cortical areas, is exerted by a dorso-ventral network.

Dosimetric Predictors of Cognitive Decline in Attention and Processing Speed after Fractionated Brain Radiation Therapy

Neurocognitive decline, including changes in attention/processing speed, can be an unfortunate consequence of brain radiation therapy (RT). The corpus callosum (CC) and right-sided subcortical white matter (WM) are known to subserve this cognitive function. We aimed to determine dosimetric predictors of attention/processing decline at 6 months after fractionated RT in patients with primary brain tumors. Twenty-three patients with primary brain tumors were enrolled on a prospective cohort study. Patients had neurocognitive assessments and high-resolution diffusion and volumetric MRI imaging pre-RT and 6 months post RT. Subjects were tested on Delis-Kaplan Executive Function System trail making number and letter sequencing. Reliable change indices accounting for practice effects (RCI-PE) scores were calculated as a normalized measure of cognition change from pre-RT to post-RT. Practice effects accounts for expected improvements in tasks with repetition. Binary variables decline and substantial decline were defined as RCI-PE <0 and <-1, respectively. Brain WM regions were segmented using a validated probabilistic diffusion tensor WM atlas. Regions of interest (ROIs) were CC and total right-sided subcortical WM with and without CC. Tumor and edema were censored from ROIs. Data including Vx (structure volume receiving ≥ x Gy) in 5 Gy intervals, minimum, maximum, and mean doses to each ROI were extracted from RT plans. A general linear model on dosimetric/volumetric data was created to identify predictors of decline (significance defined as p<0.05). Most patients (n=15, 62%) had benign or low-grade tumors. Median age at RT was 51 years (range 20-75) and 48% of patients were male. Fifteen patients (65%) underwent resection pre-RT and 9 (39%) patients received concurrent chemotherapy. Between 60-69% of patients experienced a decline; substantial number and letter sequencing decline was seen in 5 (22%) and 2 (9%) patients, respectively. Minimum dose to CC predicted for substantial letter sequencing decline (p<0.001), but there were no significant predictors of number sequencing. In right sided subcortical WM excluding CC, V30 predicted for substantial number sequencing decline (p<0.001) while minimum dose (p<0.001) and V30-V40 (all p<0.001) predicted for substantial letter sequencing decline. Within right-sided subcortical WM including CC, V30 predicted for substantial number sequencing decline (p<0.001) while V30-V35 (p<0.001) predicted for substantial letter sequencing decline. In this prospective cohort study, increasing volume receiving 30-40Gy within the right-sided total subcortical WM predicted for decreased attention/processing speed at 6 months after RT. Minimum dose to CC also predicted for decline. This suggests that dose-dependent subcortical WM effects contribute to cognitive decline. Further complex modeling is needed to generate normal tissue parameters for WM structures to guide cognitive sparing brain RT.

Post mortem high resolution diffusion MRI for large specimen imaging at 11.7 T with 3D segmented echo-planar imaging

Background: Diffusion weighted imaging (DWI) is the only in vivo technique allowing for the mapping of tissue fiber architecture. Post mortem DWI is an increasingly popular method, since longer acquisition times (compared to in vivo) allow higher spatial and angular resolutions to be achieved. However, DWI protocols must be adapted to post mortem tissue (e.g., tuning acquisition parameters to account for changes in T1/T2).New method: In this work, we developed a framework to obtain high quality diffusion weighted images on post mortem large samples by using a combination of fast imaging with 3D diffusion-weighted segmented EPI (3D-DW seg-EPI), Gadolinium soaking and data denoising. Analyses including tractography were used to check the quality of the acquired data, including a comparison with 3D-DW SE acquisitions.Comparison with existing method: Effects on diffusion data of each of the components of the framework were tested: 3D-DW seg-EPI versus 3D-DW SE EPI; with and without data denoising; with and without Gd-soaking.Conclusions: Our study demonstrated the feasibility of analysing anatomical connectivity using diffusion imaging of a post mortem macaque brain with a 3D-DW seg-EPI sequence acquired at ultra-high field. The combination of high angular and spatial resolution DWI with Gd-soaking and denoising provided data allowing us to perform diffusion tractography with results very similar to those obtained with a 3D-DW SE acquisition (with shorter acquisition times: 222 h versus 37 h for 3D-DW seg-EPI).

Simultaneous and inherent correction of B0 and eddy-current induced distortions in high-resolution diffusion MRI using reversed polarity gradients and multiplexed sensitivity encoding (RPG-MUSE)

In diffusion MRI (dMRI), static magnetic field (B0) inhomogeneity and time varying gradient eddy currents induce spatial distortions in reconstructed images. These distortions are exacerbated when high spatial resolutions are used, and many field-mapping based correction techniques often only acquire maps of static B0 distortion, which are not adequate for correcting eddy current induced image distortions. This report presents a novel technique, termed RPG-MUSE, for achieving distortion-free high-resolution diffusion MRI by integrating reversed polarity gradients (RPG) into the multi-shot echo planar imaging acquisition scheme used in multiplexed sensitivity encoding (MUSE). By alternating the phase encoding direction between shots in both baseline and diffusion-weighted acquisitions, maps of both static B0 and eddy current induced field inhomogeneities can be inherently derived, without the need for additional data acquisition. Through both 2D and 3D encoded dMRI acquisitions, it is shown that an RPG-MUSE reconstruction can simultaneously achieve high spatial resolution, high spatial fidelity, and subsequently, high accuracy in diffusion metrics.

Structural network maturation of the preterm human brain

During the 3rd trimester, large-scale neural circuits are formed in the human brain, resulting in a highly efficient and segregated connectome at birth. Despite recent findings identifying important preterm human brain network properties such as rich-club organization, how the structural network develops differentially across brain regions and among different types of connections in this period is not yet known. Here, using high resolution diffusion MRI of 77 preterm-born and full-term neonates scanned at 31.9–41.7 postmenstrual weeks (PMW), we constructed structural connectivity matrices and performed graph-theory-based analyses. Faster increases of nodal efficiency were mainly located at the brain hubs distributed in primary sensorimotor regions, superior-middle frontal, and precuneus regions during 31.9–41.7PMW. Higher rates of edge strength increases were found in the rich-club and within-module connections, compared to other connections. The edge strength of short-range connections increased faster than that of long-range connections. Nodal efficiencies of the hubs predicted individual postmenstrual ages more accurately than those of non-hubs. Collectively, these findings revealed more rapid efficiency increases of the hub and rich-club connections as well as higher developmental rates of edge strength in short-range and within-module connections. These jointly underlie network segregation and differentiated emergence of brain functions.

High resolution and high field diffusion MRI in the visual system of primates (P3.086)

High resolution and high field diffusion MRI in the visual system of primates (P3.086)

FOD-based Registration for Susceptibility Distortion Correction in Connectome Imaging.

Multi-shell, high resolution diffusion MRI (dMRI) data from the Human Connectome Project (HCP) provides an unprecedented opportunity for the in vivo mapping of human brain pathways. It was recently noted, however, that significant distortions remain present in the data of most subjects preprocessed by the HCP-Pipeline, which have been widely distributed and used extensively in connectomics research. Fundamentally this is caused by the reliance of the HCP tools on the B0 images for registering data from different phase encodings (PEs). In this work, we develop an improved framework to remove the residual distortion in data generated by the HCP-Pipeline. Our method is based on more advanced registration of fiber orientation distribution (FOD) images, which represent information of dMRI scans from all gradient directions and thus provide more reliable contrast to align data from different PEs. In our experiments, we focus on the brainstem area and compare our method with the preprocessing steps in the HCP-Pipeline. We show that our method can provide much improved distortion correction and generate FOD images with more faithful representation of brain pathways.

Gray Matter Atrophy Is Primarily Related to Demyelination of Lesions in Multiple Sclerosis: A Diffusion Tensor Imaging MRI Study.

Objective: Cortical pathology, periventricular demyelination, and lesion formation in multiple sclerosis (MS) are related (Hypothesis 1). Factors in the cerebrospinal fluid close to these compartments could possibly drive the parallel processes. Alternatively, the cortical atrophy could be caused by remote axonal transection (Hypothesis 2). Since MRI can differentiate between demyelination and axon loss, we used this imaging modality to investigate the correlation between the pattern of diffusion parameter changes in the periventricular- and deep white matter and the gray matter atrophy.Methods: High-resolution T1-weighted, FLAIR, and diffusion MRI images were acquired in 52 RRMS patients and 50 healthy, age-matched controls. We used EDSS to estimate the clinical disability. We used Tract Based Spatial Statistics to compare diffusion parameters (fractional anisotropy, mean, axial, and radial diffusivity) between groups. We evaluated global brain, white, and gray matter atrophy with SIENAX. Averaged, standard diffusion parameters were calculated in four compartment: periventricular lesioned and normal appearing white matter, non-periventricular lesioned and normal appearing white matter. PLS regression was used to identify which diffusion parameter and in which compartment best predicts the brain atrophy and clinical disability.Results: In our diffusion tensor imaging study compared to controls we found extensive alterations of fractional anisotropy, mean and radial diffusivity and smaller changes of axial diffusivity (maximal p > 0.0002) in patients that suggested demyelination in the lesioned and in the normal appearing white matter. We found significant reduction in total brain, total white, and gray matter (patients: 718.764 ± 14.968, 323.237 ± 7.246, 395.527 ± 8.050 cm3, controls: 791.772 ± 22.692, 355.350 ± 10.929, 436.422 ± 12.011 cm3; mean ± SE), (p < 0.015; p < 0.0001; p < 0.009; respectively) of patients compared to controls. The PLS analysis revealed a combination of demyelination-like diffusion parameters (higher mean and radial diffusivity in patients) in the lesions and in the non-lesioned periventricular white matter, which best predicted the gray matter atrophy (p < 0.001). Similarly, EDSS was best predicted by the radial diffusivity of the lesions and the non-lesioned periventricular white matter, but axial diffusivity of the periventricular lesions also contributed significantly (p < 0.0001).Interpretation: Our investigation showed that gray matter atrophy and white matter demyelination are related in MS but white matter axonal loss does not significantly contribute to the gray matter pathology.

Automatic Segmentation of Human Cortical Layer-Complexes and Architectural Areas Using Ex vivo Diffusion MRI and Its Validation.

Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.

High-resolution diffusion MRI at 7T using a three-dimensional multi-slab acquisition

High-resolution diffusion MRI can provide the ability to resolve small brain structures, enabling investigations of detailed white matter architecture. A major challenge for in vivo high-resolution diffusion MRI is the low signal-to-noise ratio. In this work, we combine two highly compatible methods, ultra-high field and three-dimensional multi-slab acquisition to improve the SNR of high-resolution diffusion MRI. As each kz plane is encoded using a single-shot echo planar readout, scan speeds of the proposed technique are similar to the commonly used two-dimensional diffusion MRI. In-plane parallel acceleration is applied to reduce image distortions. To reduce the sensitivity of auto-calibration signal data to subject motion and respiration, several new adaptions of the fast low angle excitation echo-planar technique (FLEET) that are suitable for 3D multi-slab echo planar imaging are proposed and evaluated. A modified reconstruction scheme is proposed for auto-calibration with the most robust method, Slice-FLEET acquisition, to make it compatible with navigator correction of motion induced phase errors. Slab boundary artefacts are corrected using the nonlinear slab profile encoding method recently proposed by our group. In vivo results demonstrate that using 7T and three-dimensional multi-slab acquisition with improved auto-calibration signal acquisition and nonlinear slab boundary artefacts correction, high-quality diffusion MRI data with ~1mm isotropic resolution can be achieved.

Histological validation of high-resolution DTI in human post mortem tissue.

Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10°. The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects.