We present Roto-Translation Equivariant Spherical Deconvolution (RT-ESD), an $E(3)\times SO(3)$ equivariant framework for sparse deconvolution of volumes where each voxel contains a spherical signal. Such 6D data naturally arises in diffusion MRI (dMRI), a medical imaging modality widely used to measure microstructure and structural connectivity. As each dMRI voxel is typically a mixture of various overlapping structures, there is a need for blind deconvolution to recover crossing anatomical structures such as white matter tracts. Existing dMRI work takes either an iterative or deep learning approach to sparse spherical deconvolution, yet it typically does not account for relationships between neighboring measurements. This work constructs equivariant deep learning layers which respect to symmetries of spatial rotations, reflections, and translations, alongside the symmetries of voxelwise spherical rotations. As a result, RT-ESD improves on previous work across several tasks including fiber recovery on the DiSCo dataset, deconvolution-derived partial volume estimation on real-world \textit{in vivo} human brain dMRI, and improved downstream reconstruction of fiber tractograms on the Tractometer dataset. Our implementation is available at https://github.com/AxelElaldi/e3so3_conv
Brain structural connectivity, capturing the white matter fiber tracts among brain regions inferred by diffusion MRI (dMRI), provides a unique characterization of brain anatomical organization. One fundamental question to address with structural connectivity is how to properly summarize and perform statistical inference for a group-level connectivity architecture, for instance, under different sex groups, or disease cohorts. Existing analyses commonly summarize group-level brain connectivity by a simple entry-wise sample mean or median across individual brain connectivity matrices. However, such a heuristic approach fully ignores the associations among structural connections and the topological properties of brain networks. In this project, we propose a latent space-based generative network model to estimate group-level brain connectivity. We name our method the attributes-informed brain connectivity (ABC) model, which compared with existing group-level connectivity estimations, (1) offers an interpretable latent space representation of the group-level connectivity, (2) incorporates the anatomical knowledge of nodes and tests its co-varying relationship with connectivity and (3) quantifies the uncertainty and evaluates the likelihood of the estimated group-level effects against chance. We devise a novel Bayesian MCMC algorithm to estimate the model. By applying the ABC model to study brain structural connectivity stratified by sex among Alzheimer's Disease (AD) subjects and healthy controls incorporating the anatomical attributes (volume, thickness and area) on nodes, our method shows superior predictive power on out-of-sample structural connectivity and identifies meaningful sex-specific network neuromarkers for AD.
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a non-invasive way of imaging white matter tracts in the human brain. DW-MRIs are usually acquired using echo-planar imaging (EPI) with high gradient fields, which could introduce severe geometric distortions that interfere with further analyses. Most tools for correcting distortion require two minimally weighted DW-MRI images (B0) acquired with different phase-encoding directions, and they can take hours to process per subject. Since a great amount of diffusion data are only acquired with a single phase-encoding direction, the application of existing approaches is limited. We propose a deep learning-based registration approach to correct distortion using only the B0 acquired from a single phase-encoding direction. Specifically, we register undistorted T1-weighted images and distorted B0 to remove the distortion through a deep learning model. We apply a differentiable mutual information loss during training to improve inter-modality alignment. Experiments on the Human Connectome Project dataset show the proposed method outperforms SyN and VoxelMorph on several metrics, and only takes a few seconds to process one subject.
Diffusion-weighted (DW) MRI measures the direction and scale of the local diffusion process in every voxel through its spectrum in q-space, typically acquired in one or more shells. Recent developments in micro-structure imaging and multi-tissue decomposition have sparked renewed attention to the radial b-value dependence of the signal. Applications in tissue classification and micro-architecture estimation, therefore, require a signal representation that extends over the radial as well as angular domain. Multiple approaches have been proposed that can model the non-linear relationship between the DW-MRI signal and biological microstructure. In the past few years, many deep learning-based methods have been developed towards faster inference speed and higher inter-scan consistency compared with traditional model-based methods (e.g., multi-shell multi-tissue constrained spherical deconvolution). However, a multi-stage learning strategy is typically required since the learning process relies on various middle representations, such as simple harmonic oscillator reconstruction (SHORE) representation. In this work, we present a unified dynamic network with a single-stage spherical convolutional neural network, which allows efficient fiber orientation distribution function (fODF) estimation through heterogeneous multi-shell diffusion MRI sequences. We study the Human Connectome Project (HCP) young adults with test-retest scans. From the experimental results, the proposed single-stage method outperforms prior multi-stage approaches in repeated fODF estimation with shell dropoff and single-shell DW-MRI sequences.
Purpose: Biophysical models of diffusion MRI have been developed to characterize microstructure in various tissues, but existing models are not suitable for tissue composed of permeable spherical cells. In this study we introduce Cellular Exchange Imaging (CEXI), a model tailored for permeable spherical cells, and compares its performance to a related Ball \& Sphere (BS) model that neglects permeability. Methods: We generated DW-MRI signals using Monte-Carlo simulations with a PGSE sequence in numerical substrates made of spherical cells and their extracellular space for a range of membrane permeability. From these signals, the properties of the substrates were inferred using both BS and CEXI models. Results: CEXI outperformed the impermeable model by providing more stable estimates cell size and intracellular volume fraction that were diffusion time-independent. Notably, CEXI accurately estimated the exchange time for low to moderate permeability levels previously reported in other studies ($\kappa<25\mu m/s$). However, in highly permeable substrates ($\kappa=50\mu m/s$), the estimated parameters were less stable, particularly the diffusion coefficients. Conclusion: This study highlights the importance of modeling the exchange time to accurately quantify microstructure properties in permeable cellular substrates. Future studies should evaluate CEXI in clinical applications such as lymph nodes, investigate exchange time as a potential biomarker of tumor severity, and develop more appropriate tissue models that account for anisotropic diffusion and highly permeable membranes.
Neuroimaging measures of the brain's white matter connections can enable the prediction of non-imaging phenotypes, such as demographic and cognitive measures. Existing works have investigated traditional microstructure and connectivity measures from diffusion MRI tractography, without considering the shape of the connections reconstructed by tractography. In this paper, we investigate the potential of fiber tract shape features for predicting non-imaging phenotypes, both individually and in combination with traditional features. We focus on three basic shape features: length, diameter, and elongation. Two different prediction methods are used, including a traditional regression method and a deep-learning-based prediction method. Experiments use an efficient two-stage fusion strategy for prediction using microstructure, connectivity, and shape measures. To reduce predictive bias due to brain size, normalized shape features are also investigated. Experimental results on the Human Connectome Project (HCP) young adult dataset (n=1065) demonstrate that individual shape features are predictive of non-imaging phenotypes. When combined with microstructure and connectivity features, shape features significantly improve performance for predicting the cognitive score TPVT (NIH Toolbox picture vocabulary test). Overall, this study demonstrates that the shape of fiber tracts contains useful information for the description and study of the living human brain using machine learning.
Diffusion MRI is a non-invasive, in-vivo biomedical imaging method for mapping tissue microstructure. Applications include structural connectivity imaging of the human brain and detecting microstructural neural changes. However, acquiring high signal-to-noise ratio dMRI datasets with high angular and spatial resolution requires prohibitively long scan times, limiting usage in many important clinical settings, especially for children, the elderly, and in acute neurological disorders that may require conscious sedation or general anesthesia. We employ a Swin UNEt Transformers model, trained on augmented Human Connectome Project data and conditioned on registered T1 scans, to perform generalized denoising of dMRI. We also qualitatively demonstrate super-resolution with artificially downsampled HCP data in normal adult volunteers. Remarkably, Swin UNETR can be fine-tuned for an out-of-domain dataset with a single example scan, as we demonstrate on dMRI of children with neurodevelopmental disorders and of adults with acute evolving traumatic brain injury, each cohort scanned on different models of scanners with different imaging protocols at different sites. We exceed current state-of-the-art denoising methods in accuracy and test-retest reliability of rapid diffusion tensor imaging requiring only 90 seconds of scan time. Applied to tissue microstructural modeling of dMRI, Swin UNETR denoising achieves dramatic improvements over the state-of-the-art for test-retest reliability of intracellular volume fraction and free water fraction measurements and can remove heavy-tail noise, improving biophysical modeling fidelity. Swin UNeTR enables rapid diffusion MRI with unprecedented accuracy and reliability, especially for probing biological tissues for scientific and clinical applications. The code and model are publicly available at https://github.com/ucsfncl/dmri-swin.
Quantitative MRI (qMRI) aims to map tissue properties non-invasively via models that relate these unknown quantities to measured MRI signals. Estimating these unknowns, which has traditionally required model fitting - an often iterative procedure, can now be done with one-shot machine learning (ML) approaches. Such parameter estimation may be complicated by intrinsic qMRI signal model degeneracy: different combinations of tissue properties produce the same signal. Despite their many advantages, it remains unclear whether ML approaches can resolve this issue. Growing empirical evidence appears to suggest ML approaches remain susceptible to model degeneracy. Here we demonstrate under the right circumstances ML can address this issue. Inspired by recent works on the impact of training data distributions on ML-based parameter estimation, we propose to resolve model degeneracy by designing training data distributions. We put forward a classification of model degeneracies and identify one particular kind of degeneracies amenable to the proposed attack. The strategy is demonstrated successfully using the Revised NODDI model with standard multi-shell diffusion MRI data as an exemplar. Our results illustrate the importance of training set design which has the potential to allow accurate estimation of tissue properties with ML.
Magnetic resonance imaging (MRI) is a common and life-saving medical imaging technique. However, acquiring high signal-to-noise ratio MRI scans requires long scan times, resulting in increased costs and patient discomfort, and decreased throughput. Thus, there is great interest in denoising MRI scans, especially for the subtype of diffusion MRI scans that are severely SNR-limited. While most prior MRI denoising methods are supervised in nature, acquiring supervised training datasets for the multitude of anatomies, MRI scanners, and scan parameters proves impractical. Here, we propose Denoising Diffusion Models for Denoising Diffusion MRI (DDM$^2$), a self-supervised denoising method for MRI denoising using diffusion denoising generative models. Our three-stage framework integrates statistic-based denoising theory into diffusion models and performs denoising through conditional generation. During inference, we represent input noisy measurements as a sample from an intermediate posterior distribution within the diffusion Markov chain. We conduct experiments on 4 real-world in-vivo diffusion MRI datasets and show that our DDM$^2$ demonstrates superior denoising performances ascertained with clinically-relevant visual qualitative and quantitative metrics.
The structure and variability of the brain's connections can be investigated via prediction of non-imaging phenotypes using neural networks. However, known neuroanatomical relationships between input features are generally ignored in network design. We propose TractGraphCNN, a novel, anatomically informed graph CNN framework for machine learning tasks using diffusion MRI tractography. An EdgeConv module aggregates features from anatomically similar white matter connections indicated by graph edges, and an attention module enables interpretation of predictive white matter tracts. Results in a sex prediction testbed task demonstrate strong performance of TractGraphCNN in two large datasets (HCP and ABCD). Graphs informed by white matter geometry demonstrate higher performance than graphs informed by gray matter connectivity. Overall, the bilateral cingulum and left middle longitudinal fasciculus are consistently highly predictive of sex. This work shows the potential of incorporating anatomical information, especially known anatomical similarities between input features, to guide convolutions in neural networks.
Mapping of human brain structural connectomes via diffusion MRI offers a unique opportunity to understand brain structural connectivity and relate it to various human traits, such as cognition. However, head displacement during image acquisition can compromise the accuracy of connectome reconstructions and subsequent inference results. We develop a generative model to learn low-dimensional representations of structural connectomes invariant to motion-induced artifacts, so that we can link brain networks and human traits more accurately, and generate motion-adjusted connectomes. We apply the proposed model to data from the Adolescent Brain Cognitive Development (ABCD) study and the Human Connectome Project (HCP) to investigate how our motion-invariant connectomes facilitate understanding of the brain network and its relationship with cognition. Empirical results demonstrate that the proposed motion-invariant variational auto-encoder (inv-VAE) outperforms its competitors in various aspects. In particular, motion-adjusted structural connectomes are more strongly associated with a wide array of cognition-related traits than other approaches without motion adjustment.
We consider the 1015-vertex human consensus connectome computed from the diffusion MRI data of 1064 subjects. We define seven different orders on these 1015 graph vertices, where the orders depend on parameters derived from the brain circuitry, that is, from the properties of the edges (or connections) incident to the vertices ordered. We order the vertices according to their degree, the sum, the maximum, and the average of the fiber counts on the incident edges, and the sum, the maximum and the average length of the fibers in the incident edges. We analyze the similarities of these seven orders by the Spearman correlation coefficient and by their inversion numbers and have found that all of these seven orders have great similarities. In other words, if we interpret the orders as scoring of the importance of the vertices in the consensus connectome, then the scores of the vertices will be similar in all seven orderings. That is, important vertices of the human connectome typically have many neighbors, connected with long and thick axonal fibers (where thickness is measured by fiber numbers), and their incident edges have high maximum and average values of length and fiber-number parameters, too. Therefore, these parameters may yield robust ways of deciding which vertices are more important in the anatomy of our brain circuitry than the others.
As the largest human cerebellar nucleus, the dentate nucleus (DN) functions significantly in the communication between the cerebellum and the rest of the brain. Structural connectivity-based parcellation has the potential to reveal the topography of the DN and enable the study of its subregions. In this paper, we investigate a deep nonnegative matrix factorization clustering method (DNMFC) for parcellation of the human DN based on its structural connectivity using diffusion MRI tractography. We propose to describe the connectivity of the DN using a set of curated tractography fiber clusters within the cerebellum. Experiments are conducted on the diffusion MRI data of 50 healthy adults from the Human Connectome Project. In comparison with state-of-the-art clustering methods, DN parcellations resulting from DNMFC show better quality and consistency of parcels across subjects.
Diffusion magnetic resonance imaging is sensitive to the microstructural properties of brain tissue. However, estimating clinically and scientifically relevant microstructural properties from the measured signals remains a highly challenging inverse problem that machine learning may help solve. This study investigated if recently developed rotationally invariant spherical convolutional neural networks can improve microstructural parameter estimation. We trained a spherical convolutional neural network to predict the ground-truth parameter values from efficiently simulated noisy data and applied the trained network to imaging data acquired in a clinical setting to generate microstructural parameter maps. Our network performed better than the spherical mean technique and multi-layer perceptron, achieving higher prediction accuracy than the spherical mean technique with less rotational variance than the multi-layer perceptron. Although we focused on a constrained two-compartment model of neuronal tissue, the network and training pipeline are generalizable and can be used to estimate the parameters of any Gaussian compartment model. To highlight this, we also trained the network to predict the parameters of a three-compartment model that enables the estimation of apparent neural soma density using tensor-valued diffusion encoding.
The retinogeniculate pathway (RGVP) is responsible for carrying visual information from the retina to the lateral geniculate nucleus. Identification and visualization of the RGVP are important in studying the anatomy of the visual system and can inform treatment of related brain diseases. Diffusion MRI (dMRI) tractography is an advanced imaging method that uniquely enables in vivo mapping of the 3D trajectory of the RGVP. Currently, identification of the RGVP from tractography data relies on expert (manual) selection of tractography streamlines, which is time-consuming, has high clinical and expert labor costs, and affected by inter-observer variability. In this paper, we present what we believe is the first deep learning framework, namely DeepRGVP, to enable fast and accurate identification of the RGVP from dMRI tractography data. We design a novel microstructure-informed supervised contrastive learning method that leverages both streamline label and tissue microstructure information to determine positive and negative pairs. We propose a simple and successful streamline-level data augmentation method to address highly imbalanced training data, where the number of RGVP streamlines is much lower than that of non-RGVP streamlines. We perform comparisons with several state-of-the-art deep learning methods that were designed for tractography parcellation, and we show superior RGVP identification results using DeepRGVP.
A major data pre-processing step for large, multi-site studies is to handle site effects by harmonizing data, generating a dataset that enables more powerful analyses and more robust algorithms. There is a wide variety of data harmonization techniques, but there are few tools that streamline the process of harmonizing data, comparing across techniques, and benchmarking new techniques. In this paper, we introduce HArmonization BEnchmarking Tool (HABET), an open source tool for generating harmonized images and evaluating the performance of different harmonization algorithms. To demonstrate the capabilities of HABET, we harmonize diffusion MRI images from the Adolescent Brain and Cognitive Development (ABCD) study using two different approaches, and we compare their performance.
Artificial Intelligence (Deep Learning(DL)/ Machine Learning(ML)) techniques are widely being used to address and overcome all kinds of ill-posed problems in medical imaging which was or in fact is seemingly impossible. Reducing gradient directions but harnessing high angular resolution(HAR) diffusion data in MR that retains clinical features is an important and challenging problem in the field. While the DL/ML approaches are promising, it is important to incorporate relevant context for the data to ensure that maximum prior information is provided for the AI model to infer the posterior. In this paper, we introduce HemiHex (HH) subsampling to suggestively address training data sampling on q-space geometry, followed by a nearest neighbor regression training on the HH-samples to finally upsample the dMRI data. Earlier studies has tried to use regression for up-sampling dMRI data but yields performance issues as it fails to provide structured geometrical measures for inference. Our proposed approach is a geometrically optimized regression technique which infers the unknown q-space thus addressing the limitations in the earlier studies.
Diffusion magnetic resonance imaging (MRI) is the only imaging modality for non-invasive movement detection of in vivo water molecules, with significant clinical and research applications. Diffusion weighted imaging (DWI) MRI acquired by multi-shot techniques can achieve higher resolution, better signal-to-noise ratio, and lower geometric distortion than single-shot, but suffers from inter-shot motion-induced artifacts. These artifacts cannot be removed prospectively, leading to the absence of artifact-free training labels. Thus, the potential of deep learning in multi-shot DWI reconstruction remains largely untapped. To break the training data bottleneck, here, we propose a Physics-Informed Deep DWI reconstruction method (PIDD) to synthesize high-quality paired training data by leveraging the physical diffusion model (magnitude synthesis) and inter-shot motion-induced phase model (motion phase synthesis). The network is trained only once with 100,000 synthetic samples, achieving encouraging results on multiple realistic in vivo data reconstructions. Advantages over conventional methods include: (a) Better motion artifact suppression and reconstruction stability; (b) Outstanding generalization to multi-scenario reconstructions, including multi-resolution, multi-b-value, multi-under-sampling, multi-vendor, and multi-center; (c) Excellent clinical adaptability to patients with verifications by seven experienced doctors (p<0.001). In conclusion, PIDD presents a novel deep learning framework by exploiting the power of MRI physics, providing a cost-effective and explainable way to break the data bottleneck in deep learning medical imaging.
Neuroimaging-based prediction of neurocognitive measures is valuable for studying how the brain's structure relates to cognitive function. However, the accuracy of prediction using popular linear regression models is relatively low. We propose a novel deep regression method, namely TractoSCR, that allows full supervision for contrastive learning in regression tasks using diffusion MRI tractography. TractoSCR performs supervised contrastive learning by using the absolute difference between continuous regression labels (i.e. neurocognitive scores) to determine positive and negative pairs. We apply TractoSCR to analyze a large-scale dataset including multi-site harmonized diffusion MRI and neurocognitive data from 8735 participants in the Adolescent Brain Cognitive Development (ABCD) Study. We extract white matter microstructural measures using a fine parcellation of white matter tractography into fiber clusters. Using these measures, we predict three scores related to domains of higher-order cognition (general cognitive ability, executive function, and learning/memory). To identify important fiber clusters for prediction of these neurocognitive scores, we propose a permutation feature importance method for high-dimensional data. We find that TractoSCR improves the accuracy of neurocognitive score prediction compared to other state-of-the-art methods. We find that the most predictive fiber clusters are predominantly located within the superficial white matter and projection tracts, particularly the superficial frontal white matter and striato-frontal connections. Overall, our results demonstrate the utility of contrastive representation learning methods for regression, and in particular for improving neuroimaging-based prediction of higher-order cognitive abilities.
Machine learning is a powerful approach for fitting microstructural models to diffusion MRI data. Early machine learning microstructure imaging implementations trained regressors to estimate model parameters in a supervised way, using synthetic training data with known ground truth. However, a drawback of this approach is that the choice of training data impacts fitted parameter values. Self-supervised learning is emerging as an attractive alternative to supervised learning in this context. Thus far, both supervised and self-supervised learning have typically been applied to isotropic models, such as intravoxel incoherent motion (IVIM), as opposed to models where the directionality of anisotropic structures is also estimated. In this paper, we demonstrate self-supervised machine learning model fitting for a directional microstructural model. In particular, we fit a combined T1-ball-stick model to the multidimensional diffusion (MUDI) challenge diffusion-relaxation dataset. Our self-supervised approach shows clear improvements in parameter estimation and computational time, for both simulated and in-vivo brain data, compared to standard non-linear least squares fitting. Code for the artificial neural net constructed for this study is available for public use from the following GitHub repository: https://github.com/jplte/deep-T1-ball-stick