A simulation-driven supervised learning framework to estimate brain microstructure using diffusion MRI.

We propose a framework to train supervised learning models on synthetic data to estimate brain microstructure parameters using diffusion magnetic resonance imaging (dMRI). Although further validation is necessary, the proposed framework aims to seamlessly incorporate realistic simulations into dMRI microstructure estimation. Synthetic data were generated from over 1,000 neuron meshes converted from digital neuronal reconstructions and linked to their neuroanatomical parameters (such as soma volume and neurite length) using an optimized diffusion MRI simulator that produces intracellular dMRI signals from the solution of the Bloch-Torrey partial differential equation. By combining random subsets of simulated neuron signals with a free diffusion compartment signal, we constructed a synthetic dataset containing dMRI signals and 40 tissue microstructure parameters of 1.45 million artificial brain voxels. To implement supervised learning models we chose multilayer perceptrons (MLPs) and trained them on a subset of the synthetic dataset to estimate some microstructure parameters, namely, the volume fractions of soma, neurites, and the free diffusion compartment, as well as the area fractions of soma and neurites. The trained MLPs perform satisfactorily on the synthetic test sets and give promising in-vivo parameter maps on the MGH Connectome Diffusion Microstructure Dataset (CDMD). Most importantly, the estimated volume fractions showed low dependence on the diffusion time, the diffusion time independence of the estimated parameters being a desired property of quantitative microstructure imaging. The synthetic dataset we generated will be valuable for the validation of models that map between the dMRI signals and microstructure parameters. The surface meshes and microstructures parameters of the aforementioned neurons have been made publicly available.

Scalable Query Answering Under Uncertainty to Neuroscientific Ontological Knowledge: The NeuroLang Approach.

Researchers in neuroscience have a growing number of datasets available to study the brain, which is made possible by recent technological advances. Given the extent to which the brain has been studied, there is also available ontological knowledge encoding the current state of the art regarding its different areas, activation patterns, keywords associated with studies, etc. Furthermore, there is inherent uncertainty associated with brain scans arising from the mapping between voxels-3D pixels-and actual points in different individual brains. Unfortunately, there is currently no unifying framework for accessing such collections of rich heterogeneous data under uncertainty, making it necessary for researchers to rely on ad hoc tools. In particular, one major weakness of current tools that attempt to address this task is that only very limited propositional query languages have been developed. In this paper we present NeuroLang, a probabilistic language based on first-order logic with existential rules, probabilistic uncertainty, ontologies integration under the open world assumption, and built-in mechanisms to guarantee tractable query answering over very large datasets. NeuroLang's primary objective is to provide a unified framework to seamlessly integrate heterogeneous data, such as ontologies, and map fine-grained cognitive domains to brain regions through a set of formal criteria, promoting shareable and highly reproducible research. After presenting the language and its general query answering architecture, we discuss real-world use cases showing how NeuroLang can be applied to practical scenarios.

Meta-analysis of the functional neuroimaging literature with probabilistic logic programming.

Inferring reliable brain-behavior associations requires synthesizing evidence from thousands of functional neuroimaging studies through meta-analysis. However, existing meta-analysis tools are limited to investigating simple neuroscience concepts and expressing a restricted range of questions. Here, we expand the scope of neuroimaging meta-analysis by designing NeuroLang: a domain-specific language to express and test hypotheses using probabilistic first-order logic programming. By leveraging formalisms found at the crossroads of artificial intelligence and knowledge representation, NeuroLang provides the expressivity to address a larger repertoire of hypotheses in a meta-analysis, while seamlessly modeling the uncertainty inherent to neuroimaging data. We demonstrate the language's capabilities in conducting comprehensive neuroimaging meta-analysis through use-case examples that address questions of structure-function associations. Specifically, we infer the specific functional roles of three canonical brain networks, support the role of the visual word-form area in visuospatial attention, and investigate the heterogeneous organization of the frontoparietal control network.

Functional gradients in the human lateral prefrontal cortex revealed by a comprehensive coordinate-based meta-analysis.

The lateral prefrontal cortex (LPFC) of humans enables flexible goal-directed behavior. However, its functional organization remains actively debated after decades of research. Moreover, recent efforts aiming to map the LPFC through meta-analysis are limited, either in scope or in the inferred specificity of structure-function associations. These limitations are in part due to the limited expressiveness of commonly-used data analysis tools, which restricts the breadth and complexity of questions that can be expressed in a meta-analysis. Here, we adopt NeuroLang, a novel approach to more expressive meta-analysis based on probabilistic first-order logic programming, to infer the organizing principles of the LPFC from 14,371 neuroimaging studies. Our findings reveal a rostrocaudal and a dorsoventral gradient, respectively explaining the most and second most variance in meta-analytic connectivity across the LPFC. Moreover, we identify a unimodal-to-transmodal spectrum of coactivation patterns along with a concrete-to-abstract axis of structure-function associations extending from caudal to rostral regions of the LPFC. Finally, we infer inter-hemispheric asymmetries along the principal rostrocaudal gradient, identifying hemisphere-specific associations with topics of language, memory, response inhibition, and sensory processing. Overall, this study provides a comprehensive meta-analytic mapping of the LPFC, grounding future hypothesis generation on a quantitative overview of past findings.

Foundational Number Sense Training Gains Are Predicted by Hippocampal-Parietal Circuits.

The development of mathematical skills in early childhood relies on number sense, the foundational ability to discriminate among quantities. Number sense in early childhood is predictive of academic and professional success, and deficits in number sense are thought to underlie lifelong impairments in mathematical abilities. Despite its importance, the brain circuit mechanisms that support number sense learning remain poorly understood. Here, we designed a theoretically motivated training program to determine brain circuit mechanisms underlying foundational number sense learning in female and male elementary school-age children (7-10 years). Our 4 week integrative number sense training program gradually strengthened the understanding of the relations between symbolic (Arabic numerals) and nonsymbolic (sets of items) representations of quantity. We found that our number sense training program improved symbolic quantity discrimination ability in children across a wide range of math abilities including children with learning difficulties. Crucially, the strength of pretraining functional connectivity between the hippocampus and intraparietal sulcus, brain regions implicated in associative learning and quantity discrimination, respectively, predicted individual differences in number sense learning across typically developing children and children with learning difficulties. Reverse meta-analysis of interregional coactivations across 14,371 fMRI studies and 89 cognitive functions confirmed a reliable role for hippocampal-intraparietal sulcus circuits in learning. Our study identifies a canonical hippocampal-parietal circuit for learning that plays a foundational role in children's cognitive skill acquisition. Findings provide important insights into neurobiological circuit markers of individual differences in children's learning and delineate a robust target for effective cognitive interventions.SIGNIFICANCE STATEMENT Mathematical skill development relies on number sense, the ability to discriminate among quantities. Here, we develop a theoretically motivated training program and investigate brain circuits that predict number sense learning in children during a period important for acquisition of foundational cognitive skills. Our integrated number sense training program was effective in children across a wide a range of math abilities, including children with learning difficulties. We identify hippocampal-parietal circuits that predict individual differences in learning gains. Our study identifies a brain circuit critical for the acquisition of foundational cognitive skills, which will be useful for developing effective interventions to remediate learning disabilities.

Clinical Characteristics, Care Trajectories and Mortality Rate of SARS-CoV-2 Infected Cancer Patients: A Multicenter Cohort Study.

BACKGROUND: COVID-19 may be more frequent and more severe in cancer patients than in other individuals. Our aims were to assess the rate of COVID-19 in hospitalized cancer patients, to describe their demographic characteristics, clinical features and care trajectories, and to assess the mortality rate. METHODS: This multicenter cohort study was based on the Electronic Health Records of the Assistance Publique-Hôpitaux de Paris (AP-HP). Cancer patients with a diagnosis of COVID-19 between 3 March and 19 May 2020 were included. Main outcome was all-cause mortality within 30 days of COVID-19 diagnosis. RESULTS: A total of 29,141 cancer patients were identified and 7791 (27%) were tested for SARS-CoV-2. Of these, 1359 (17%) were COVID-19-positive and 1148 (84%) were hospitalized; 217 (19%) were admitted to an intensive care unit. The mortality rate was 33% (383 deaths). In multivariate analysis, mortality-related factors were male sex (aHR = 1.39 [95% CI: 1.07-1.81]), advanced age (78-86 y: aHR = 2.83 [95% CI: 1.78-4.51] vs. <66 y; 86-103 y: aHR = 2.61 [95% CI: 1.56-4.35] vs. <66 y), more than two comorbidities (aHR = 2.32 [95% CI: 1.41-3.83]) and C-reactive protein >20 ng/mL (aHR = 2.20 [95% CI: 1.70-2.86]). Primary brains tumors (aHR = 2.19 [95% CI: 1.08-4.44]) and lung cancer (aHR = 1.66 [95% CI: 1.02-2.70]) were associated with higher mortality. Risk of dying was lower among patients with metabolic comorbidities (aHR = 0.65 [95% CI: 0.50-0.84]). CONCLUSIONS: In a hospital-based setting, cancer patients with COVID-19 had a high mortality rate. This mortality was mainly driven by age, sex, number of comorbidities and presence of inflammation. This is the first cohort of cancer patients in which metabolic comorbidities were associated with a better outcome.

Machine learning based white matter models with permeability: An experimental study in cuprizone treated in-vivo mouse model of axonal demyelination.

The intra-axonal water exchange time (τi), a parameter associated with axonal permeability, could be an important biomarker for understanding and treating demyelinating pathologies such as Multiple Sclerosis. Diffusion-Weighted MRI (DW-MRI) is sensitive to changes in permeability; however, the parameter has so far remained elusive due to the lack of general biophysical models that incorporate it. Machine learning based computational models can potentially be used to estimate such parameters. Recently, for the first time, a theoretical framework using a random forest (RF) regressor suggests that this is a promising new approach for permeability estimation. In this study, we adopt such an approach and for the first time experimentally investigate it for demyelinating pathologies through direct comparison with histology. We construct a computational model using Monte Carlo simulations and an RF regressor in order to learn a mapping between features derived from DW-MRI signals and ground truth microstructure parameters. We test our model in simulations, and find strong correlations between the predicted and ground truth parameters (intra-axonal volume fraction f: R2 =0.99, τi: R2 =0.84, intrinsic diffusivity d: R2 =0.99). We then apply the model in-vivo, on a controlled cuprizone (CPZ) mouse model of demyelination, comparing the results from two cohorts of mice, CPZ (N=8) and healthy age-matched wild-type (WT, N=8). We find that the RF model estimates sensible microstructure parameters for both groups, matching values found in literature. Furthermore, we perform histology for both groups using electron microscopy (EM), measuring the thickness of the myelin sheath as a surrogate for exchange time. Histology results show that our RF model estimates are very strongly correlated with the EM measurements (ρ = 0.98 for f, ρ = 0.82 for τi). Finally, we find a statistically significant decrease in τi in all three regions of the corpus callosum (splenium/genu/body) of the CPZ cohort (<τi>=310ms/330ms/350ms) compared to the WT group (<τi>=370ms/370ms/380ms). This is in line with our expectations that τi is lower in regions where the myelin sheath is damaged, as axonal membranes become more permeable. Overall, these results demonstrate, for the first time experimentally and in vivo, that a computational model learned from simulations can reliably estimate microstructure parameters, including the axonal permeability .

Towards linking diffusion MRI based macro- and microstructure measures with cortico-cortical transmission in brain tumor patients.

We aimed to link macro- and microstructure measures of brain white matter obtained from diffusion MRI with effective connectivity measures based on a propagation of cortico-cortical evoked potentials induced with intrasurgical direct electrical stimulation. For this, we compared streamline lengths and log-transformed ratios of streamlines computed from presurgical diffusion-weighted images, and the delays and amplitudes of N1 peaks recorded intrasurgically with electrocorticography electrodes in a pilot study of 9 brain tumor patients. Our results showed positive correlation between these two modalities in the vicinity of the stimulation sites (Pearson coefficient 0.54±0.13 for N1 delays, and 0.47±0.23 for N1 amplitudes), which could correspond to the neural propagation via U-fibers. In addition, we reached high sensitivities (0.78±0.07) and very high specificities (0.93±0.03) in a binary variant of our comparison. Finally, we used the structural connectivity measures to predict the effective connectivity using a multiple linear regression model, and showed a significant role of brain microstructure-related indices in this relation.

Fine-grain atlases of functional modes for fMRI analysis.

Population imaging markedly increased the size of functional-imaging datasets, shedding new light on the neural basis of inter-individual differences. Analyzing these large data entails new scalability challenges, computational and statistical. For this reason, brain images are typically summarized in a few signals, for instance reducing voxel-level measures with brain atlases or functional modes. A good choice of the corresponding brain networks is important, as most data analyses start from these reduced signals. We contribute finely-resolved atlases of functional modes, comprising from 64 to 1024 networks. These dictionaries of functional modes (DiFuMo) are trained on millions of fMRI functional brain volumes of total size 2.4 â€‹TB, spanned over 27 studies and many research groups. We demonstrate the benefits of extracting reduced signals on our fine-grain atlases for many classic functional data analysis pipelines: stimuli decoding from 12,334 brain responses, standard GLM analysis of fMRI across sessions and individuals, extraction of resting-state functional-connectomes biomarkers for 2500 individuals, data compression and meta-analysis over more than 15,000 statistical maps. In each of these analysis scenarii, we compare the performance of our functional atlases with that of other popular references, and to a simple voxel-level analysis. Results highlight the importance of using high-dimensional "soft" functional atlases, to represent and analyze brain activity while capturing its functional gradients. Analyses on high-dimensional modes achieve similar statistical performance as at the voxel level, but with much reduced computational cost and higher interpretability. In addition to making them available, we provide meaningful names for these modes, based on their anatomical location. It will facilitate reporting of results.

Diffusion MRI simulation of realistic neurons with SpinDoctor and the Neuron Module.

The diffusion MRI signal arising from neurons can be numerically simulated by solving the Bloch-Torrey partial differential equation. In this paper we present the Neuron Module that we implemented within the Matlab-based diffusion MRI simulation toolbox SpinDoctor. SpinDoctor uses finite element discretization and adaptive time integration to solve the Bloch-Torrey partial differential equation for general diffusion-encoding sequences, at multiple b-values and in multiple diffusion directions. In order to facilitate the diffusion MRI simulation of realistic neurons by the research community, we constructed finite element meshes for a group of 36 pyramidal neurons and a group of 29 spindle neurons whose morphological descriptions were found in the publicly available neuron repository NeuroMorpho.Org. These finite elements meshes range from having 15,163 nodes to 622,553 nodes. We also broke the neurons into the soma and dendrite branches and created finite elements meshes for these cell components. Through the Neuron Module, these neuron and cell components finite element meshes can be seamlessly coupled with the functionalities of SpinDoctor to provide the diffusion MRI signal attributable to spins inside neurons. We make these meshes and the source code of the Neuron Module available to the public as an open-source package. To illustrate some potential uses of the Neuron Module, we show numerical examples of the simulated diffusion MRI signals in multiple diffusion directions from whole neurons as well as from the soma and dendrite branches, and include a comparison of the high b-value behavior between dendrite branches and whole neurons. In addition, we demonstrate that the neuron meshes can be used to perform Monte-Carlo diffusion MRI simulations as well. We show that at equivalent accuracy, if only one gradient direction needs to be simulated, SpinDoctor is faster than a GPU implementation of Monte-Carlo, but if many gradient directions need to be simulated, there is a break-even point when the GPU implementation of Monte-Carlo becomes faster than SpinDoctor. Furthermore, we numerically compute the eigenfunctions and the eigenvalues of the Bloch-Torrey and the Laplace operators on the neuron geometries using a finite elements discretization, in order to give guidance in the choice of the space and time discretization parameters for both finite elements and Monte-Carlo approaches. Finally, we perform a statistical study on the set of 65 neurons to test some candidate biomakers that can potentially indicate the soma size. This preliminary study exemplifies the possible research that can be conducted using the Neuron Module.

Microstructural organization of human insula is linked to its macrofunctional circuitry and predicts cognitive control.

The human insular cortex is a heterogeneous brain structure which plays an integrative role in guiding behavior. The cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. Quantitative modeling of multi-shell diffusion MRI data from 413 participants revealed that human insula microstructure differs significantly across subdivisions that serve distinct cognitive and affective functions. Insular microstructural organization was mirrored in its functionally interconnected circuits with the anterior cingulate cortex that anchors the salience network, a system important for adaptive switching of cognitive control systems. Furthermore, insular microstructural features, confirmed in Macaca mulatta, were linked to behavior and predicted individual differences in cognitive control ability. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular cortex dysfunction, including autism, schizophrenia, and fronto-temporal dementia.

New insights into the neural foundations mediating movement/language interactions gained from intrasurgical direct electrostimulations.

Interactions between language and motricity have been a topic of interest in brain development as well as in pathological models. The role of the motor system in language has been investigated through neuroimaging and non-invasive brain stimulation methods. However, little is known about the neural basis that might be involved in such interactions. Meanwhile, brain direct electrostimulations (DES) have provided essential knowledges about the connectomic organization of both motor and language systems. We propose here to review the literature about DES from the outlook of interactions between language and motricity and to investigate common cortico-subcortical structures shared by both networks. Then we will report an experimental study about the spatial distribution of DES eliciting simultaneous speech and contralateral upper limb negative motor response in a series of 100 patients operated on under awake condition for a low-grade glioma. From the probabilistic map obtained, a structural connectivity analysis was performed to reveal the cortico-subcortical networks involved in language and motricity interactions. The embodiment suggested by these results takes place in parallel and distributed bilateral fronto-temporo-parietal networks rather than in a single and somatopically well defined organization as previously suggested.

SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization.

PURPOSE: We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health-supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors. PATIENTS AND METHODS: In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI. RESULTS: We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each. CONCLUSION: SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.

PEP: Parameter Ensembling by Perturbation.

Ensembling is now recognized as an effective approach for increasing the predictive performance and calibration of deep networks. We introduce a new approach, Parameter Ensembling by Perturbation (PEP), that constructs an ensemble of parameter values as random perturbations of the optimal parameter set from training by a Gaussian with a single variance parameter. The variance is chosen to maximize the log-likelihood of the ensemble average ( L ) on the validation data set. Empirically, and perhaps surprisingly, L has a well-defined maximum as the variance grows from zero (which corresponds to the baseline model). Conveniently, calibration level of predictions also tends to grow favorably until the peak of L is reached. In most experiments, PEP provides a small improvement in performance, and, in some cases, a substantial improvement in empirical calibration. We show that this "PEP effect" (the gain in log-likelihood) is related to the mean curvature of the likelihood function and the empirical Fisher information. Experiments on ImageNet pre-trained networks including ResNet, DenseNet, and Inception showed improved calibration and likelihood. We further observed a mild improvement in classification accuracy on these networks. Experiments on classification benchmarks such as MNIST and CIFAR-10 showed improved calibration and likelihood, as well as the relationship between the PEP effect and overfitting; this demonstrates that PEP can be used to probe the level of overfitting that occurred during training. In general, no special training procedure or network architecture is needed, and in the case of pre-trained networks, no additional training is needed.

The visual word form area (VWFA) is part of both language and attention circuitry.

While predominant models of visual word form area (VWFA) function argue for its specific role in decoding written language, other accounts propose a more general role of VWFA in complex visual processing. However, a comprehensive examination of structural and functional VWFA circuits and their relationship to behavior has been missing. Here, using high-resolution multimodal imaging data from a large Human Connectome Project cohort (N = 313), we demonstrate robust patterns of VWFA connectivity with both canonical language and attentional networks. Brain-behavior relationships revealed a striking pattern of double dissociation: structural connectivity of VWFA with lateral temporal language network predicted language, but not visuo-spatial attention abilities, while VWFA connectivity with dorsal fronto-parietal attention network predicted visuo-spatial attention, but not language abilities. Our findings support a multiplex model of VWFA function characterized by distinct circuits for integrating language and attention, and point to connectivity-constrained cognition as a key principle of human brain organization.

The Dmipy Toolbox: Diffusion MRI Multi-Compartment Modeling and Microstructure Recovery Made Easy.

Non-invasive estimation of brain microstructure features using diffusion MRI (dMRI)-known as Microstructure Imaging-has become an increasingly diverse and complicated field over the last decades. Multi-compartment (MC)-models, representing the measured diffusion signal as a linear combination of signal models of distinct tissue types, have been developed in many forms to estimate these features. However, a generalized implementation of MC-modeling as a whole, providing deeper insights in its capabilities, remains missing. To address this fact, we present Diffusion Microstructure Imaging in Python (Dmipy), an open-source toolbox implementing PGSE-based MC-modeling in its most general form. Dmipy allows on-the-fly implementation, signal modeling, and optimization of any user-defined MC-model, for any PGSE acquisition scheme. Dmipy follows a "building block"-based philosophy to Microstructure Imaging, meaning MC-models are modularly constructed to include any number and type of tissue models, allowing simultaneous representation of a tissue's diffusivity, orientation, volume fractions, axon orientation dispersion, and axon diameter distribution. In particular, Dmipy is geared toward facilitating reproducible, reliable MC-modeling pipelines, often allowing the whole process from model construction to parameter map recovery in fewer than 10 lines of code. To demonstrate Dmipy's ease of use and potential, we implement a wide range of well-known MC-models, including IVIM, AxCaliber, NODDI(x), Bingham-NODDI, the spherical mean-based SMT and MC-MDI, and spherical convolution-based single- and multi-tissue CSD. By allowing parameter cascading between MC-models, Dmipy also facilitates implementation of advanced approaches like CSD with voxel-varying kernels and single-shell 3-tissue CSD. By providing a well-tested, user-friendly toolbox that simplifies the interaction with the otherwise complicated field of dMRI-based Microstructure Imaging, Dmipy contributes to more reproducible, high-quality research.

Portable simulation framework for diffusion MRI.

The numerical simulation of the diffusion MRI signal arising from complex tissue micro-structures is helpful for understanding and interpreting imaging data as well as for designing and optimizing MRI sequences. The discretization of the Bloch-Torrey equation by finite elements is a more recently developed approach for this purpose, in contrast to random walk simulations, which has a longer history. While finite element discretization is more difficult to implement than random walk simulations, the approach benefits from a long history of theoretical and numerical developments by the mathematical and engineering communities. In particular, software packages for the automated solutions of partial differential equations using finite element discretization, such as FEniCS, are undergoing active support and development. However, because diffusion MRI simulation is a relatively new application area, there is still a gap between the simulation needs of the MRI community and the available tools provided by finite element software packages. In this paper, we address two potential difficulties in using FEniCS for diffusion MRI simulation. First, we simplified software installation by the use of FEniCS containers that are completely portable across multiple platforms. Second, we provide a portable simulation framework based on Python and whose code is open source. This simulation framework can be seamlessly integrated with cloud computing resources such as Google Colaboratory notebooks working on a web browser or with Google Cloud Platform with MPI parallelization. We show examples illustrating the accuracy, the computational times, and parallel computing capabilities. The framework contributes to reproducible science and open-source software in computational diffusion MRI with the hope that it will help to speed up method developments and stimulate research collaborations.

Advances in computational and statistical diffusion MRI.

Computational methods are crucial for the analysis of diffusion magnetic resonance imaging (MRI) of the brain. Computational diffusion MRI can provide rich information at many size scales, including local microstructure measures such as diffusion anisotropies or apparent axon diameters, whole-brain connectivity information that describes the brain's wiring diagram and population-based studies in health and disease. Many of the diffusion MRI analyses performed today were not possible five, ten or twenty years ago, due to the requirements for large amounts of computer memory or processor time. In addition, mathematical frameworks had to be developed or adapted from other fields to create new ways to analyze diffusion MRI data. The purpose of this review is to highlight recent computational and statistical advances in diffusion MRI and to put these advances into context by comparison with the more traditional computational methods that are in popular clinical and scientific use. We aim to provide a high-level overview of interest to diffusion MRI researchers, with a more in-depth treatment to illustrate selected computational advances.

Reducing the number of samples in spatiotemporal dMRI acquisition design.

PURPOSE: Acquisition time is a major limitation in recovering brain white matter microstructure with diffusion magnetic resonance imaging. The aim of this paper is to bridge the gap between growing demands on spatiotemporal resolution of diffusion signal and the real-world time limitations. The authors introduce an acquisition scheme that reduces the number of samples under adjustable quality loss. METHODS: Finding a sampling scheme that maximizes signal quality and satisfies given time constraints is NP-hard. Therefore, a heuristic method based on genetic algorithm is proposed in order to find suboptimal solutions in acceptable time. The analyzed diffusion signal representation is defined in the qτ space, so that it captures both spacial and temporal phenomena. RESULTS: The experiments on synthetic data and in vivo diffusion images of the C57Bl6 wild-type mouse corpus callosum reveal superiority of the proposed approach over random sampling and even distribution in the qτ space. CONCLUSIONS: The use of genetic algorithm allows to find acquisition parameters that guarantee high signal reconstruction accuracy under given time constraints. In practice, the proposed approach helps to accelerate the acquisition for the use of qτ-dMRI signal representation.

Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.