Early diagnosis and noninvasive monitoring of neurological disorders require sensitivity to elusive cellular-level alterations that occur much earlier than volumetric changes observable with the millimeter-resolution of medical imaging modalities. Morphological changes in axons, such as axonal varicosities or beadings, are observed in neurological disorders, as well as in development and aging. Here, we reveal the sensitivity of time-dependent diffusion MRI (dMRI) to axonal morphology at the micrometer scale. Scattering theory uncovers the two parameters that determine the diffusive dynamics of water in axons: the average reciprocal cross-section and the variance of long-range cross-sectional fluctuations. This theoretical development allowed us to predict dMRI metrics sensitive to axonal alterations across tens of thousands of axons in seconds rather than months of simulations in a rat model of traumatic brain injury. Our approach bridges the gap between micrometers and millimeters in resolution, offering quantitative, objective biomarkers applicable to a broad spectrum of neurological disorders.
Three-dimensional (3D) multi-slab acquisition is a technique frequently employed in high-resolution diffusion-weighted MRI in order to achieve the best signal-to-noise ratio (SNR) efficiency. However, this technique is limited by slab boundary artifacts that cause intensity fluctuations and aliasing between slabs which reduces the accuracy of anatomical imaging. Addressing this issue is crucial for advancing diffusion MRI quality and making high-resolution imaging more feasible for clinical and research applications. In this work, we propose a regularized slab profile encoding (PEN) method within a Plug-and-Play ADMM framework, incorporating multi-scale energy (MuSE) regularization to effectively improve the slab combined reconstruction. Experimental results demonstrate that the proposed method significantly improves image quality compared to non-regularized and TV-regularized PEN approaches. The regularized PEN framework provides a more robust and efficient solution for high-resolution 3D diffusion MRI, potentially enabling clearer, more reliable anatomical imaging across various applications.
Diffusion magnetic resonance imaging (dMRI) often suffers from low spatial and angular resolution due to inherent limitations in imaging hardware and system noise, adversely affecting the accurate estimation of microstructural parameters with fine anatomical details. Deep learning-based super-resolution techniques have shown promise in enhancing dMRI resolution without increasing acquisition time. However, most existing methods are confined to either spatial or angular super-resolution, limiting their effectiveness in capturing detailed microstructural features. Furthermore, traditional pixel-wise loss functions struggle to recover intricate image details essential for high-resolution reconstruction. To address these challenges, we propose SARL-dMRI, a novel Spatial-Angular Representation Learning framework for high-fidelity, continuous super-resolution in dMRI. SARL-dMRI explores implicit neural representations and spherical harmonics to model continuous spatial and angular representations, simultaneously enhancing both spatial and angular resolution while improving microstructural parameter estimation accuracy. To further preserve image fidelity, a data-fidelity module and wavelet-based frequency loss are introduced, ensuring the super-resolved images remain consistent with the original input and retain fine details. Extensive experiments demonstrate that, compared to five other state-of-the-art methods, our method significantly enhances dMRI data resolution, improves the accuracy of microstructural parameter estimation, and provides better generalization capabilities. It maintains stable performance even under a 45$\times$ downsampling factor.
Magnetic Resonance Imaging (MRI), including diffusion MRI (dMRI), serves as a ``microscope'' for anatomical structures and routinely mitigates the influence of low signal-to-noise ratio scans by compromising temporal or spatial resolution. However, these compromises fail to meet clinical demands for both efficiency and precision. Consequently, denoising is a vital preprocessing step, particularly for dMRI, where clean data is unavailable. In this paper, we introduce Di-Fusion, a fully self-supervised denoising method that leverages the latter diffusion steps and an adaptive sampling process. Unlike previous approaches, our single-stage framework achieves efficient and stable training without extra noise model training and offers adaptive and controllable results in the sampling process. Our thorough experiments on real and simulated data demonstrate that Di-Fusion achieves state-of-the-art performance in microstructure modeling, tractography tracking, and other downstream tasks. Code is available at https://github.com/FouierL/Di-Fusion.
Diffusion-weighted Magnetic Resonance Imaging (dMRI) is an essential tool in neuroimaging. It is arguably the sole noninvasive technique for examining the microstructural properties and structural connectivity of the brain. Recent years have seen the emergence of machine learning and data-driven approaches that enhance the speed, accuracy, and consistency of dMRI data analysis. However, traditional deep learning models often fell short, as they typically utilize pixel-level or volumetric patch-level embeddings similar to those used in structural MRI, and do not account for the unique distribution of various gradient encodings. In this paper, we propose a novel method called Polyhedra Encoding Transformer (PE-Transformer) for dMRI, designed specifically to handle spherical signals. Our approach involves projecting an icosahedral polygon onto a unit sphere to resample signals from predetermined directions. These resampled signals are then transformed into embeddings, which are processed by a transformer encoder that incorporates orientational information reflective of the icosahedral structure. Through experimental validation with various gradient encoding protocols, our method demonstrates superior accuracy in estimating multi-compartment models and Fiber Orientation Distributions (FOD), outperforming both conventional CNN architectures and standard transformers.
Modern brain imaging technologies have enabled the detailed reconstruction of human brain connectomes, capturing structural connectivity (SC) from diffusion MRI and functional connectivity (FC) from functional MRI. Understanding the intricate relationships between SC and FC is vital for gaining deeper insights into the brain's functional and organizational mechanisms. However, obtaining both SC and FC modalities simultaneously remains challenging, hindering comprehensive analyses. Existing deep generative models typically focus on synthesizing a single modality or unidirectional translation between FC and SC, thereby missing the potential benefits of bi-directional translation, especially in scenarios where only one connectome is available. Therefore, we propose Structural-Functional Connectivity GAN (SFC-GAN), a novel framework for bidirectional translation between SC and FC. This approach leverages the CycleGAN architecture, incorporating convolutional layers to effectively capture the spatial structures of brain connectomes. To preserve the topological integrity of these connectomes, we employ a structure-preserving loss that guides the model in capturing both global and local connectome patterns while maintaining symmetry. Our framework demonstrates superior performance in translating between SC and FC, outperforming baseline models in similarity and graph property evaluations compared to ground truth data, each translated modality can be effectively utilized for downstream classification.
Nonrigid registration is vital to medical image analysis but remains challenging for diffusion MRI (dMRI) due to its high-dimensional, orientation-dependent nature. While classical methods are accurate, they are computationally demanding, and deep neural networks, though efficient, have been underexplored for nonrigid dMRI registration compared to structural imaging. We present a novel, deep learning framework for model-free, nonrigid registration of raw diffusion MRI data that does not require explicit reorientation. Unlike previous methods relying on derived representations such as diffusion tensors or fiber orientation distribution functions, in our approach, we formulate the registration as an equivariant diffeomorphism of position-and-orientation space. Central to our method is an $\mathsf{SE}(3)$-equivariant UNet that generates velocity fields while preserving the geometric properties of a raw dMRI's domain. We introduce a new loss function based on the maximum mean discrepancy in Fourier space, implicitly matching ensemble average propagators across images. Experimental results on Human Connectome Project dMRI data demonstrate competitive performance compared to state-of-the-art approaches, with the added advantage of bypassing the overhead for estimating derived representations. This work establishes a foundation for data-driven, geometry-aware dMRI registration directly in the acquisition space.
Ex-vivo MRI offers invaluable insights into the complexity of the human brain, enabling high-resolution anatomical delineation and integration with histopathology, and thus, contributes to both basic and clinical studies on normal and pathological brains. However, ex-vivo MRI is challenging in sample preparation, acquisition, and data analysis, and existing ex-vivo MRI datasets are often single image modality and lack of ethnic diversity. In our study, we aimed to address these limitations by constructing a comprehensive multimodal MRI database acquired from six ex-vivo Chinese human brains. This database included structural MRI, high-angular resolution diffusion MRI, quantitative susceptibility mapping, and quantitative T1 and T2 maps, which enabled multifaceted depiction of brain microstructure and connectivity. Furthermore, we generated population-averaged multimodal templates and the segmentation labels to facilitate analysis of ex-vivo brain MRI. This public database offers a collection of high-resolution and multi-parametric ex-vivo human brain MRI and filled the gap of lacking Asian brain samples in existing databases.
Diffusion magnetic resonance imaging (dMRI) provides critical insights into the microstructural and connectional organization of the human brain. However, the availability of high-field, open-access datasets that include raw k-space data for advanced research remains limited. To address this gap, we introduce Diff5T, a first comprehensive 5.0 Tesla diffusion MRI dataset focusing on the human brain. This dataset includes raw k-space data and reconstructed diffusion images, acquired using a variety of imaging protocols. Diff5T is designed to support the development and benchmarking of innovative methods in artifact correction, image reconstruction, image preprocessing, diffusion modelling and tractography. The dataset features a wide range of diffusion parameters, including multiple b-values and gradient directions, allowing extensive research applications in studying human brain microstructure and connectivity. With its emphasis on open accessibility and detailed benchmarks, Diff5T serves as a valuable resource for advancing human brain mapping research using diffusion MRI, fostering reproducibility, and enabling collaboration across the neuroscience and medical imaging communities.
Human braingraphs or connectomes are widely studied in the last decade to understand the structural and functional properties of our brain. In the last several years our research group has computed and deposited thousands of human braingraphs to the braingraph.org site, by applying public structural (diffusion) MRI data from young and healthy subjects. Here we describe a recent addition to the {\tt braingraph.org} site, which contains connectomes from healthy and demented subjects between 42 and 95 years of age, based on the public release of the OASIS-3 dataset. The diffusion MRI data was processed with the Connectome Mapper Toolkit v.3.1. We believe that the new addition to the braingraph.org site will become a useful resource for enlightening the aging circuitry of the human brain in healthy and diseased subjects, including those with Alzheimer's disease in several stages.
Spatiotemporal magnetic field variations from B0-inhomogeneity and diffusion-encoding-induced eddy-currents can be detrimental to rapid image-encoding schemes such as spiral, EPI and 3D-cones, resulting in undesirable image artifacts. In this work, a data driven approach for automatic estimation of these field imperfections is developed by combining autofocus metrics with deep learning, and by leveraging a compact basis representation of the expected field imperfections. The method was applied to single-shot spiral diffusion MRI at high b-values where accurate estimation of B0 and eddy were obtained, resulting in high quality image reconstruction without need for additional external calibrations.
We introduce and demonstrate a new paradigm for quantitative parameter mapping in MRI. Parameter mapping techniques, such as diffusion MRI and quantitative MRI, have the potential to robustly and repeatably measure biologically-relevant tissue maps that strongly relate to underlying microstructure. Quantitative maps are calculated by fitting a model to multiple images, e.g. with least-squares or machine learning. However, the overwhelming majority of model fitting techniques assume that each voxel is independent, ignoring any co-dependencies in the data. This makes model fitting sensitive to voxelwise measurement noise, hampering reliability and repeatability. We propose a self-supervised deep variational approach that breaks the assumption of independent pixels, leveraging redundancies in the data to effectively perform data-driven regularisation of quantitative maps. We demonstrate that our approach outperforms current model fitting techniques in dMRI simulations and real data. Especially with a Gaussian mixture prior, our model enables sharper quantitative maps, revealing finer anatomical details that are not presented in the baselines. Our approach can hence support the clinical adoption of parameter mapping methods such as dMRI and qMRI.
Each voxel in a diffusion MRI (dMRI) image contains a spherical signal corresponding to the direction and strength of water diffusion in the brain. This paper advances the analysis of such spatio-spherical data by developing convolutional network layers that are equivariant to the $\mathbf{E(3) \times SO(3)}$ group and account for the physical symmetries of dMRI including rotations, translations, and reflections of space alongside voxel-wise rotations. Further, neuronal fibers are typically antipodally symmetric, a fact we leverage to construct highly efficient spatio-hemispherical graph convolutions to accelerate the analysis of high-dimensional dMRI data. In the context of sparse spherical fiber deconvolution to recover white matter microstructure, our proposed equivariant network layers yield substantial performance and efficiency gains, leading to better and more practical resolution of crossing neuronal fibers and fiber tractography. These gains are experimentally consistent across both simulation and in vivo human datasets.
White matter alterations are increasingly implicated in neurological diseases and their progression. International-scale studies use diffusion-weighted magnetic resonance imaging (DW-MRI) to qualitatively identify changes in white matter microstructure and connectivity. Yet, quantitative analysis of DW-MRI data is hindered by inconsistencies stemming from varying acquisition protocols. There is a pressing need to harmonize the preprocessing of DW-MRI datasets to ensure the derivation of robust quantitative diffusion metrics across acquisitions. In the MICCAI-CDMRI 2023 QuantConn challenge, participants were provided raw data from the same individuals collected on the same scanner but with two different acquisitions and tasked with preprocessing the DW-MRI to minimize acquisition differences while retaining biological variation. Submissions are evaluated on the reproducibility and comparability of cross-acquisition bundle-wise microstructure measures, bundle shape features, and connectomics. The key innovations of the QuantConn challenge are that (1) we assess bundles and tractography in the context of harmonization for the first time, (2) we assess connectomics in the context of harmonization for the first time, and (3) we have 10x additional subjects over prior harmonization challenge, MUSHAC and 100x over SuperMUDI. We find that bundle surface area, fractional anisotropy, connectome assortativity, betweenness centrality, edge count, modularity, nodal strength, and participation coefficient measures are most biased by acquisition and that machine learning voxel-wise correction, RISH mapping, and NeSH methods effectively reduce these biases. In addition, microstructure measures AD, MD, RD, bundle length, connectome density, efficiency, and path length are least biased by these acquisition differences.
Fiber tractography is a cornerstone of neuroimaging, enabling the detailed mapping of the brain's white matter pathways through diffusion MRI. This is crucial for understanding brain connectivity and function, making it a valuable tool in neurological applications. Despite its importance, tractography faces challenges due to its complexity and susceptibility to false positives, misrepresenting vital pathways. To address these issues, recent strategies have shifted towards deep learning, utilizing supervised learning, which depends on precise ground truth, or reinforcement learning, which operates without it. In this work, we propose Tract-RLFormer, a network utilizing both supervised and reinforcement learning, in a two-stage policy refinement process that markedly improves the accuracy and generalizability across various data-sets. By employing a tract-specific approach, our network directly delineates the tracts of interest, bypassing the traditional segmentation process. Through rigorous validation on datasets such as TractoInferno, HCP, and ISMRM-2015, our methodology demonstrates a leap forward in tractography, showcasing its ability to accurately map the brain's white matter tracts.
Tractography fiber clustering using diffusion MRI (dMRI) is a crucial strategy for white matter (WM) parcellation. Current methods primarily use the geometric information of fibers (i.e., the spatial trajectories) to group similar fibers into clusters, overlooking the important functional signals present along the fiber tracts. There is increasing evidence that neural activity in the WM can be measured using functional MRI (fMRI), offering potentially valuable multimodal information for fiber clustering. In this paper, we develop a novel deep learning fiber clustering framework, namely Deep Multi-view Fiber Clustering (DMVFC), that uses joint dMRI and fMRI data to enable functionally consistent WM parcellation. DMVFC can effectively integrate the geometric characteristics of the WM fibers with the fMRI BOLD signals along the fiber tracts. It includes two major components: 1) a multi-view pretraining module to compute embedding features from fiber geometric information and functional signals separately, and 2) a collaborative fine-tuning module to simultaneously refine the two kinds of embeddings. In the experiments, we compare DMVFC with two state-of-the-art fiber clustering methods and demonstrate superior performance in achieving functionally meaningful and consistent WM parcellation results.
Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI), a widely used modality for brain age estimation, presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that minimizes the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information minimized, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two state-of-the-art T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Approximately 4 years before MCI diagnosis, dMRI-based brain age yields better performance than T1w MRI-based brain ages in predicting transition from CN to MCI.
Brain imaging studies have demonstrated that diffusion MRI tractography geometric shape descriptors can inform the study of the brain's white matter pathways and their relationship to brain function. In this work, we investigate the possibility of utilizing a deep learning model to compute shape measures of the brain's white matter connections. We introduce a novel framework, TractShapeNet, that leverages a point cloud representation of tractography to compute five shape measures: length, span, volume, total surface area, and irregularity. We assess the performance of the method on a large dataset including 1065 healthy young adults. Experiments for shape measure computation demonstrate that our proposed TractShapeNet outperforms other point cloud-based neural network models in both the Pearson correlation coefficient and normalized error metrics. We compare the inference runtime results with the conventional shape computation tool DSI-Studio. Our results demonstrate that a deep learning approach enables faster and more efficient shape measure computation. We also conduct experiments on two downstream language cognition prediction tasks, showing that shape measures from TractShapeNet perform similarly to those computed by DSI-Studio. Our code will be available at: https://github.com/SlicerDMRI/TractShapeNet.
The shape of the brain's white matter connections is relatively unexplored in diffusion MRI tractography analysis. While it is known that tract shape varies in populations and across the human lifespan, it is unknown if the variability in dMRI tractography-derived shape may relate to the brain's functional variability across individuals. This work explores the potential of leveraging tractography fiber cluster shape measures to predict subject-specific cognitive performance. We implement machine learning models to predict individual cognitive performance scores. We study a large-scale database from the HCP-YA study. We apply an atlas-based fiber cluster parcellation to the dMRI tractography of each individual. We compute 15 shape, microstructure, and connectivity features for each fiber cluster. Using these features as input, we train a total of 210 models to predict 7 different NIH Toolbox cognitive performance assessments. We apply an explainable AI technique, SHAP, to assess the importance of each fiber cluster for prediction. Our results demonstrate that shape measures are predictive of individual cognitive performance. The studied shape measures, such as irregularity, diameter, total surface area, volume, and branch volume, are as effective for prediction as microstructure and connectivity measures. The overall best-performing feature is a shape feature, irregularity, which describes how different a cluster's shape is from an idealized cylinder. Further interpretation using SHAP values suggest that fiber clusters with features highly predictive of cognitive ability are widespread throughout the brain, including fiber clusters from the superficial association, deep association, cerebellar, striatal, and projection pathways. This study demonstrates the strong potential of shape descriptors to enhance the study of the brain's white matter and its relationship to cognitive function.
Divergent brain connectivity is thought to underlie the behavioral and cognitive symptoms observed in many neurodevelopmental disorders. Quantifying divergence from neurotypical connectivity patterns offers a promising pathway to inform diagnosis and therapeutic interventions. While advanced neuroimaging techniques, such as diffusion MRI (dMRI), have facilitated the mapping of brain's structural connectome, the challenge lies in accurately modeling developmental trajectories within these complex networked structures to create robust neurodivergence markers. In this work, we present the Brain Representation via Individualized Deep Generative Embedding (BRIDGE) framework, which integrates normative modeling with a bio-inspired deep generative model to create a reference trajectory of connectivity transformation as part of neurotypical development. This will enable the assessment of neurodivergence by comparing individuals to the established neurotypical trajectory. BRIDGE provides a global neurodivergence score based on the difference between connectivity-based brain age and chronological age, along with region-wise neurodivergence maps that highlight localized connectivity differences. Application of BRIDGE to a large cohort of children with autism spectrum disorder demonstrates that the global neurodivergence score correlates with clinical assessments in autism, and the regional map offers insights into the heterogeneity at the individual level in neurodevelopmental disorders. Together, the neurodivergence score and map form powerful tools for quantifying developmental divergence in connectivity patterns, advancing the development of imaging markers for personalized diagnosis and intervention in various clinical contexts.