Effective characterisation of the brain grey matter cytoarchitecture with quantitative sensitivity to soma density and volume remains an unsolved challenge in diffusion MRI (dMRI). Solving the problem of relating the dMRI signal with cytoarchitectural characteristics calls for the definition of a mathematical model that describes brain tissue via a handful of physiologically-relevant parameters and an algorithm for inverting the model. To address this issue, we propose a new forward model, specifically a new system of equations, requiring a few relatively sparse b-shells. We then apply modern tools from Bayesian analysis known as likelihood-free inference (LFI) to invert our proposed model. As opposed to other approaches from the literature, our algorithm yields not only an estimation of the parameter vector $\theta$ that best describes a given observed data point $x_0$, but also a full posterior distribution $p(\theta|x_0)$ over the parameter space. This enables a richer description of the model inversion, providing indicators such as credible intervals for the estimated parameters and a complete characterization of the parameter regions where the model may present indeterminacies. We approximate the posterior distribution using deep neural density estimators, known as normalizing flows, and fit them using a set of repeated simulations from the forward model. We validate our approach on simulations using dmipy and then apply the whole pipeline on two publicly available datasets.
Diffusion Magnetic Resonance Imaging (dMRI) is a promising method to analyze the subtle changes in the tissue structure. However, the lengthy acquisition time is a major limitation in the clinical application of dMRI. Different image acquisition techniques such as parallel imaging, compressed sensing, has shortened the prolonged acquisition time but creating high-resolution 3D dMRI slices still requires a significant amount of time. In this study, we have shown that high-resolution 3D dMRI can be reconstructed from the highly undersampled k-space and q-space data using a Kernel LowRank method. Our proposed method has outperformed the conventional CS methods in terms of both image quality and diffusion maps constructed from the diffusion-weighted images
Multiple sclerosis is an inflammatory disorder of the central nervous system. Quantitative MRI has huge potential to provide intrinsic and normative values of tissue properties useful for diagnosis, prognosis and ultimately clinical follow-up of this disease. However, there is a large discrepancy between the clinical observations and how the pathology is exhibited in MRI brain scans. Complementary to brain imaging, the study of multiple sclerosis lesions in the spinal cord has recently gained interest as a potential marker for early physical impairment. Therefore, investigating how the spinal cord is damaged using quantitative imaging, in particular, diffusion MRI, becomes an acute challenge. In this work, we extract average diffusion MRI metrics per vertebral level from spinal cord data acquired from multiple clinical sites. The diffusion-based metrics involved are extracted from the diffusion tensor imaging and Ball-and-Stick models and quantified for every cervical vertebral level using a collection of image processing methods and an atlas-based approach. Then, we perform a statistical analysis study to characterize the feasibility of these metrics to detect lesions. Specifically, we study the usefulness of combining different metrics to improve the accuracy prediction score associated with the presence of multiple sclerosis lesions. We demonstrate the grade of sensitivity to underlying microstructure changes in MS patients of each metric. Ball-and-Stick provides novel information about the MS damage to tissue microstructure. In addition, we show that choosing a subset of metrics: [FA, RD, MD] and [FWW, MD, Stick-AD, RD], which bring complementary information, has significantly increased the prediction score of the presence of the MS lesion in the cervical spinal cord.
Background: Magnetic field inhomogeneities generate important geometric distortions in reconstructed echo-planar images. Various procedures were proposed for correcting these distortions on brain images; yet, few neuroimaging studies tailored and incorporated the use of these techniques in spinal cord diffusion MRI. Purpose: We present a comparative evaluation of distortion correction methods that use the reversed gradient polarity technique on spinal cord. We propose novel geometric metrics to measure the alignment of the reconstructed diffusion model with the apparent centerline of the spinal cord. Subjects: 95 subjects, among which 29 healthy controls and 66 multiple sclerosis patients. Assessment: Geometric distortions were corrected using 4 state-of-the-art methods. We measured the alignment of the principal direction of diffusion with the apparent centerline of the spine after correction and the correlation with the reference anatomical image. Results are computed per vertebral level, to evaluate the impact on different portions of the spine. Besides, subjective evaluation of the quality of the correction of healthy subjects images was performed by three expert raters. Results: As a result of distortion correction, the diffusion directions are better aligned locally with the centerline, in particular at both ends of the acquisition window. The cross-correlation with anatomical image is also improved by Hyperelastic Susceptibility Artefact Correction (HySCO) and block-matching. The subjective evaluation for HySCO is significantly better (p < 0.05) than for Block-Matching; TOPUP performs significantly worse than the three other methods. Conclusion: Correction based on HySCO provide best results among the selected methods.
In Multiple Sclerosis (MS), there is a large discrepancy between the clinical observations and how the pathology is exhibited on brain images, this is known as the clinical-radiological paradox (CRP). One of the hypotheses is that the clinical deficit may be more related to the spinal cord damage than the number or location of lesions in the brain. Therefore, investigating how the spinal cord is damaged becomes an acute challenge to better understand and overcome the CRP. Diffusion MRI is known to provide quantitative figures of neuronal degeneration and axonal loss, in the brain as well as in the spinal cord. In this paper, we propose to investigate how diffusion MRI metrics vary in the different cervical regions with the progression of the disease. We first study the reproducibility of diffusion MRI on healthy volunteers with a test-retest procedure using both standard diffusion tensor imaging (DTI) and multi-compartment Ball-and-Stick models. Then, based on the test re-test quantitative calibration, we provide quantitative figures of pathology evolution between M0 and M12 in the cervical spine on a set of 31 MS patients, exhibiting how the pathology damage spans in the cervical spinal cord.
We propose a novel and efficient algorithm to model high-level topological structures of neuronal fibers. Tractography constructs complex neuronal fibers in three dimensions that exhibit the geometry of white matter pathways in the brain. However, most tractography analysis methods are time consuming and intractable. We develop a computational geometry-based tractography representation that aims to simplify the connectivity of white matter fibers. Given the trajectories of neuronal fiber pathways, we model the evolution of trajectories that encodes geometrically significant events and calculate their point correspondence in the 3D brain space. Trajectory inter-distance is used as a parameter to control the granularity of the model that allows local or global representation of the tractogram. Using diffusion MRI data from Alzheimer's patient study, we extract tractography features from our model for distinguishing the Alzheimer's subject from the normal control. Software implementation of our algorithm is available on GitHub.
We present Clinica (www.clinica.run), an open-source software platform designed to make clinical neuroscience studies easier and more reproducible. Clinica aims for researchers to i) spend less time on data management and processing, ii) perform reproducible evaluations of their methods, and iii) easily share data and results within their institution and with external collaborators. The core of Clinica is a set of automatic pipelines for processing and analysis of multimodal neuroimaging data (currently, T1-weighted MRI, diffusion MRI and PET data), as well as tools for statistics, machine learning and deep learning. It relies on the brain imaging data structure (BIDS) for the organization of raw neuroimaging datasets and on established tools written by the community to build its pipelines. It also provides converters of public neuroimaging datasets to BIDS (currently ADNI, AIBL, OASIS and NIFD). Processed data include image-valued scalar fields (e.g. tissue probability maps), meshes, surface-based scalar fields (e.g. cortical thickness maps) or scalar outputs (e.g. regional averages). These data follow the ClinicA Processed Structure (CAPS) format which shares the same philosophy as BIDS. Consistent organization of raw and processed neuroimaging files facilitates the execution of single pipelines and of sequences of pipelines, as well as the integration of processed data into statistics or machine learning frameworks. The target audience of Clinica is neuroscientists or clinicians conducting clinical neuroscience studies involving multimodal imaging, and researchers developing advanced machine learning algorithms applied to neuroimaging data.
Convolutional neural networks have been highly successful in image-based learning tasks due to their translation equivariance property. Recent work has generalized the traditional convolutional layer of a convolutional neural network to non-Euclidean spaces and shown group equivariance of the generalized convolution operation. In this paper, we present a novel higher order Volterra convolutional neural network (VolterraNet) for data defined as samples of functions on Riemannian homogeneous spaces. Analagous to the result for traditional convolutions, we prove that the Volterra functional convolutions are equivariant to the action of the isometry group admitted by the Riemannian homogeneous spaces, and under some restrictions, any non-linear equivariant function can be expressed as our homogeneous space Volterra convolution, generalizing the non-linear shift equivariant characterization of Volterra expansions in Euclidean space. We also prove that second order functional convolution operations can be represented as cascaded convolutions which leads to an efficient implementation. Beyond this, we also propose a dilated VolterraNet model. These advances lead to large parameter reductions relative to baseline non-Euclidean CNNs. To demonstrate the efficacy of the VolterraNet performance, we present several real data experiments involving classification tasks on spherical-MNIST, atomic energy, Shrec17 data sets, and group testing on diffusion MRI data. Performance comparisons to the state-of-the-art are also presented.
Current deep learning approaches for diffusion MRI modeling circumvent the need for densely-sampled diffusion-weighted images (DWIs) by directly predicting microstructural indices from sparsely-sampled DWIs. However, they implicitly make unrealistic assumptions of static $q$-space sampling during training and reconstruction. Further, such approaches can restrict downstream usage of variably sampled DWIs for usages including the estimation of microstructural indices or tractography. We propose a generative adversarial translation framework for high-quality DWI synthesis with arbitrary $q$-space sampling given commonly acquired structural images (e.g., B0, T1, T2). Our translation network linearly modulates its internal representations conditioned on continuous $q$-space information, thus removing the need for fixed sampling schemes. Moreover, this approach enables downstream estimation of high-quality microstructural maps from arbitrarily subsampled DWIs, which may be particularly important in cases with sparsely sampled DWIs. Across several recent methodologies, the proposed approach yields improved DWI synthesis accuracy and fidelity with enhanced downstream utility as quantified by the accuracy of scalar microstructure indices estimated from the synthesized images. Code is available at https://github.com/mengweiren/q-space-conditioned-dwi-synthesis.
Being complex-valued and low in signal-to-noise ratios, magnitude-based diffusion MRI is confounded by the noise-floor that falsely elevates signal magnitude and incurs bias to the commonly used diffusion indices, such as fractional anisotropy (FA). To avoid noise-floor, most existing phase correction methods explore improving filters to estimate the noise-free background phase. In this work, after diving into the phase correction procedures, we argue that even a perfect filter is insufficient for phase correction because the correction procedures are incapable of distinguishing sign-symbols of noise, resulting in artifacts (\textit{i.e.}, arbitrary signal loss). With this insight, we generalize the definition of noise-floor to a complex polar coordinate system and propose a calibration procedure that could conveniently distinguish noise sign symbols. The calibration procedure is conceptually simple and easy to implement without relying on any external technique while keeping distinctly effective.
Diffusion magnetic resonance imaging (dMRI) tractography is an advanced imaging technique that enables in vivo mapping of the brain's white matter connections at macro scale. Over the last two decades, the study of brain connectivity using dMRI tractography has played a prominent role in the neuroimaging research landscape. In this paper, we provide a high-level overview of how tractography is used to enable quantitative analysis of the brain's structural connectivity in health and disease. We first provide a review of methodology involved in three main processing steps that are common across most approaches for quantitative analysis of tractography, including methods for tractography correction, segmentation and quantification. For each step, we aim to describe methodological choices, their popularity, and potential pros and cons. We then review studies that have used quantitative tractography approaches to study the brain's white matter, focusing on applications in neurodevelopment, aging, neurological disorders, mental disorders, and neurosurgery. We conclude that, while there have been considerable advancements in methodological technologies and breadth of applications, there nevertheless remains no consensus about the "best" methodology in quantitative analysis of tractography, and researchers should remain cautious when interpreting results in research and clinical applications.
Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized by diffuse and focal areas of tissue loss. Conventional MRI techniques such as T1-weighted and T2-weighted scans are generally used in the diagnosis and prognosis of the disease. Yet, these methods are limited by the lack of specificity between lesions, their perilesional area and non-lesional tissue. Alternative MRI techniques exhibit a higher level of sensitivity to focal and diffuse MS pathology than conventional MRI acquisitions. However, they still suffer from limited specificity when considered alone. In this work, we have combined tissue microstructure information derived from multicompartment diffusion MRI and T2 relaxometry models to explore the voxel-based prediction power of a machine learning model in a cohort of MS patients and healthy controls. Our results show that the combination of multi-modal features, together with a boosting enhanced decision-tree based classifier, which combines a set of weak classifiers to form a strong classifier via a voting mechanism, is able to utilise the complementary information for the classification of abnormal tissue.
Multi-modal neuroimaging projects are advancing our understanding of human brain architecture, function, connectivity using high-quality non-invasive data from many subjects. However, ground truth validation of connectivity using invasive tracers is not feasible in humans. 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.
This paper proposes a novel topological learning framework that integrates networks of different sizes and topology through persistent homology. Such challenging task is made possible through the introduction of a computationally efficient topological loss. The use of the proposed loss bypasses the intrinsic computational bottleneck associated with matching networks. We validate the method in extensive statistical simulations to assess its effectiveness when discriminating networks with different topology. The method is further demonstrated in a twin brain imaging study where we determine if brain networks are genetically heritable. The challenge here is due to the difficulty of overlaying the topologically different functional brain networks obtained from resting-state functional MRI onto the template structural brain network obtained through diffusion MRI.
Alzheimer's disease (AD) is the most common age-related dementia. It remains a challenge to identify the individuals at risk of dementia for precise management. Brain MRI offers a noninvasive biomarker to detect brain aging. Previous evidence shows that the brain structural change detected by diffusion MRI is associated with dementia. Mounting studies has conceptualised the brain as a complex network, which has shown the utility of this approach in characterising various neurological and psychiatric disorders. Therefore, the structural connectivity shows promise in dementia classification. The proposed BrainNetGAN is a generative adversarial network variant to augment the brain structural connectivity matrices for binary dementia classification tasks. Structural connectivity matrices between separated brain regions are constructed using tractography on diffusion MRI data. The BrainNetGAN model is trained to generate fake brain connectivity matrices, which are expected to reflect latent distribution of the real brain network data. Finally, a convolutional neural network classifier is proposed for binary dementia classification. Numerical results show that the binary classification performance in the testing set was improved using the BrainNetGAN augmented dataset. The proposed methodology allows quick synthesis of an arbitrary number of augmented connectivity matrices and can be easily transferred to similar classification tasks.
Artifacts are a common occurrence in Diffusion MRI (dMRI) scans. Identifying and removing them is essential to ensure the accuracy and viability of any post processing carried out on these scans. This makes QC (quality control) a crucial first step prior to any analysis of dMRI data. Several QC methods for artifact detection exist, however they suffer from problems like requiring manual intervention and the inability to generalize across different artifacts and datasets. In this paper, we propose an automated deep learning (DL) pipeline that utilizes a 3D-Densenet architecture to train a model on diffusion volumes for automatic artifact detection. Our method is applied on a vast dataset consisting of 9000 volumes sourced from 7 large clinical datasets. These datasets comprise scans from multiple scanners with different gradient directions, high and low b values, single shell and multi shell acquisitions. Additionally, they represent diverse subject demographics like the presence or absence of pathologies. Our QC method is found to accurately generalize across this heterogenous data by correctly detecting 92% artifacts on average across our test set. This consistent performance over diverse datasets underlines the generalizability of our method, which currently is a significant barrier hindering the widespread adoption of automated QC techniques. For these reasons, we believe that 3D-QCNet can be integrated in diffusion pipelines to effectively automate the arduous and time-intensive process of artifact detection.
We present a rotation-equivariant unsupervised learning framework for the sparse deconvolution of non-negative scalar fields defined on the unit sphere. Spherical signals with multiple peaks naturally arise in Diffusion MRI (dMRI), where each voxel consists of one or more signal sources corresponding to anisotropic tissue structure such as white matter. Due to spatial and spectral partial voluming, clinically-feasible dMRI struggles to resolve crossing-fiber white matter configurations, leading to extensive development in spherical deconvolution methodology to recover underlying fiber directions. However, these methods are typically linear and struggle with small crossing-angles and partial volume fraction estimation. In this work, we improve on current methodologies by nonlinearly estimating fiber structures via unsupervised spherical convolutional networks with guaranteed equivariance to spherical rotation. Experimentally, we first validate our proposition via extensive single and multi-shell synthetic benchmarks demonstrating competitive performance against common baselines. We then show improved downstream performance on fiber tractography measures on the Tractometer benchmark dataset. Finally, we show downstream improvements in terms of tractography and partial volume estimation on a multi-shell dataset of human subjects.
Inter-scanner and inter-protocol discrepancy in MRI datasets are known to lead to significant quantification variability. Hence image-to-image or scanner-to-scanner translation is a crucial frontier in the area of medical image analysis with a lot of potential applications. Nonetheless, a significant percentage of existing algorithms cannot explicitly exploit and preserve texture details from target scanners and offers individual solutions towards specialized task-specific architectures. In this paper, we design a multi-scale texture transfer to enrich the reconstruction images with more details. Specifically, after calculating textural similarity, the multi-scale texture can adaptively transfer the texture information from target images or reference images to restored images. Different from the pixel-wise matching space as done by previous algorithms, we match texture features in a multi-scale scheme implemented in the neural space. The matching mechanism can exploit multi-scale neural transfer that encourages the model to grasp more semantic-related and lesion-related priors from the target or reference images. We evaluate our multi-scale texture GAN on three different tasks without any task-specific modifications: cross-protocol super-resolution of diffusion MRI, T1-Flair, and Flair-T2 modality translation. Our multi-texture GAN rehabilitates more high-resolution structures (i.e., edges and anatomy), texture (i.e., contrast and pixel intensities), and lesion information (i.e., tumor). The extensively quantitative and qualitative experiments demonstrate that our method achieves superior results in inter-protocol or inter-scanner translation over state-of-the-art methods.
Convolutional networks are successful, but they have recently been outperformed by new neural networks that are equivariant under rotations and translations. These new networks work better because they do not struggle with learning each possible orientation of each image feature separately. So far, they have been proposed for 2D and 3D data. Here we generalize them to 6D diffusion MRI data, ensuring joint equivariance under 3D roto-translations in image space and the matching 3D rotations in $q$-space, as dictated by the image formation. Such equivariant deep learning is appropriate for diffusion MRI, because microstructural and macrostructural features such as neural fibers can appear at many different orientations, and because even non-rotation-equivariant deep learning has so far been the best method for many diffusion MRI tasks. We validate our equivariant method on multiple-sclerosis lesion segmentation. Our proposed neural networks yield better results and require fewer scans for training compared to non-rotation-equivariant deep learning. They also inherit all the advantages of deep learning over classical diffusion MRI methods. Our implementation is available at https://github.com/philip-mueller/equivariant-deep-dmri and can be used off the shelf without understanding the mathematical background.
Neurite orientation dispersion and density imaging (NODDI) enables the assessment of intracellular, extracellular and free water signals from multi-shell diffusion MRI data. It is an insightful approach to characterize brain tissue microstructure. Single-shell reconstruction for NODDI parameters has been discouraged in previous studies caused by failure when fitting, especially for the neurite density index (NDI). Here, we investigated the possibility of creating robust NODDI parameter maps with single-shell data, using the isotropic volume fraction (fISO) as prior. Prior estimation was made independent of the NODDI model constraint using a dictionary learning approach. First, we used a stochastic sparse dictionary-based network (DictNet) in predicting fISO which is trained with data obtained from in vivo and simulated diffusion MRI data. In single-shell cases, the mean diffusivity (MD) and raw T2 signal with no diffusion weighting (S0) was incorporated in the dictionary for the fISO estimation. Then, the NODDI framework was used with the known fISO to estimate the NDI and orientation dispersion index (ODI). The fISO estimated by our model was compared with other fISO estimators in the simulation. Further, using both synthetic data simulation and human data collected on a 3T scanner, we compared the performance of our dictionary-based learning prior NODDI (DLpN) with the original NODDI for both single-shell and multi-shell data. Our results suggest that DLpN derived NDI and ODI parameters for single-shell protocols are comparable with original multi-shell NODDI, and protocol with b=2000 s/mm2 performs the best (error ~5% in white and grey matter). This may allow NODDI evaluation of studies on single-shell data by multi-shell scanning of two subjects for DictNet fISO training.