Tractography algorithms leverage diffusion MRI to reconstruct the fibrous architecture of the brain's white matter. Among machine learning approaches, reinforcement learning (RL) has emerged as a promising framework for tractography, outperforming traditional methods in several key aspects. TractOracle-RL, a recent RL-based approach, reduces false positives by incorporating anatomical priors into the training process via a reward-based mechanism. In this paper, we investigate four extensions of the original TractOracle-RL framework by integrating recent advances in RL, and we evaluate their performance across five diverse diffusion MRI datasets. Results demonstrate that combining an oracle with the RL framework consistently leads to robust and reliable tractography, regardless of the specific method or dataset used. We also introduce a novel RL training scheme called Iterative Reward Training (IRT), inspired by the Reinforcement Learning from Human Feedback (RLHF) paradigm. Instead of relying on human input, IRT leverages bundle filtering methods to iteratively refine the oracle's guidance throughout training. Experimental results show that RL methods trained with oracle feedback significantly outperform widely used tractography techniques in terms of accuracy and anatomical validity.
The segmentation of cranial nerves (CNs) tract provides a valuable quantitative tool for the analysis of the morphology and trajectory of individual CNs. Multimodal CNs tract segmentation networks, e.g., CNTSeg, which combine structural Magnetic Resonance Imaging (MRI) and diffusion MRI, have achieved promising segmentation performance. However, it is laborious or even infeasible to collect complete multimodal data in clinical practice due to limitations in equipment, user privacy, and working conditions. In this work, we propose a novel arbitrary-modal fusion network for volumetric CNs tract segmentation, called CNTSeg-v2, which trains one model to handle different combinations of available modalities. Instead of directly combining all the modalities, we select T1-weighted (T1w) images as the primary modality due to its simplicity in data acquisition and contribution most to the results, which supervises the information selection of other auxiliary modalities. Our model encompasses an Arbitrary-Modal Collaboration Module (ACM) designed to effectively extract informative features from other auxiliary modalities, guided by the supervision of T1w images. Meanwhile, we construct a Deep Distance-guided Multi-stage (DDM) decoder to correct small errors and discontinuities through signed distance maps to improve segmentation accuracy. We evaluate our CNTSeg-v2 on the Human Connectome Project (HCP) dataset and the clinical Multi-shell Diffusion MRI (MDM) dataset. Extensive experimental results show that our CNTSeg-v2 achieves state-of-the-art segmentation performance, outperforming all competing methods.
Early and accurate assessment of brain microstructure using diffusion Magnetic Resonance Imaging (dMRI) is crucial for identifying neurodevelopmental disorders in neonates, but remains challenging due to low signal-to-noise ratio (SNR), motion artifacts, and ongoing myelination. In this study, we propose a rotationally equivariant Spherical Convolutional Neural Network (sCNN) framework tailored for neonatal dMRI. We predict the Fiber Orientation Distribution (FOD) from multi-shell dMRI signals acquired with a reduced set of gradient directions (30% of the full protocol), enabling faster and more cost-effective acquisitions. We train and evaluate the performance of our sCNN using real data from 43 neonatal dMRI datasets provided by the Developing Human Connectome Project (dHCP). Our results demonstrate that the sCNN achieves significantly lower mean squared error (MSE) and higher angular correlation coefficient (ACC) compared to a Multi-Layer Perceptron (MLP) baseline, indicating improved accuracy in FOD estimation. Furthermore, tractography results based on the sCNN-predicted FODs show improved anatomical plausibility, coverage, and coherence compared to those from the MLP. These findings highlight that sCNNs, with their inherent rotational equivariance, offer a promising approach for accurate and clinically efficient dMRI analysis, paving the way for improved diagnostic capabilities and characterization of early brain development.
Diffusion MRI (dMRI) plays a crucial role in studying brain white matter connectivity. Cortical surface reconstruction (CSR), including the inner whiter matter (WM) and outer pial surfaces, is one of the key tasks in dMRI analyses such as fiber tractography and multimodal MRI analysis. Existing CSR methods rely on anatomical T1-weighted data and map them into the dMRI space through inter-modality registration. However, due to the low resolution and image distortions of dMRI data, inter-modality registration faces significant challenges. This work proposes a novel end-to-end learning framework, DDCSR, which for the first time enables CSR directly from dMRI data. DDCSR consists of two major components, including: (1) an implicit learning module to predict a voxel-wise intermediate surface representation, and (2) an explicit learning module to predict the 3D mesh surfaces. Compared to several baseline and advanced CSR methods, we show that the proposed DDCSR can largely increase both accuracy and efficiency. Furthermore, we demonstrate a high generalization ability of DDCSR to data from different sources, despite the differences in dMRI acquisitions and populations.
Brain nuclei are clusters of anatomically distinct neurons that serve as important hubs for processing and relaying information in various neural circuits. Fine-scale parcellation of the brain nuclei is vital for a comprehensive understanding of its anatomico-functional correlations. Diffusion MRI tractography is an advanced imaging technique that can estimate the brain's white matter structural connectivity to potentially reveal the topography of the nuclei of interest for studying its subdivisions. In this work, we present a deep clustering pipeline, namely DeepNuParc, to perform automated, fine-scale parcellation of brain nuclei using diffusion MRI tractography. First, we incorporate a newly proposed deep learning approach to enable accurate segmentation of the nuclei of interest directly on the dMRI data. Next, we design a novel streamline clustering-based structural connectivity feature for a robust representation of voxels within the nuclei. Finally, we improve the popular joint dimensionality reduction and k-means clustering approach to enable nuclei parcellation at a finer scale. We demonstrate DeepNuParc on two important brain structures, i.e. the amygdala and the thalamus, that are known to have multiple anatomically and functionally distinct nuclei subdivisions. Experimental results show that DeepNuParc enables consistent parcellation of the nuclei into multiple parcels across multiple subjects and achieves good correspondence with the widely used coarse-scale atlases. Our codes are available at https://github.com/HarlandZZC/deep_nuclei_parcellation.
Diffusion MRI (dMRI) provides unique insights into fetal brain microstructure in utero. Longitudinal and cross-sectional fetal dMRI studies can reveal crucial neurodevelopmental changes but require precise spatial alignment across scans and subjects. This is challenging due to low data quality, rapid brain development, and limited anatomical landmarks. Existing registration methods, designed for high-quality adult data, struggle with these complexities. To address this, we introduce FetDTIAlign, a deep learning approach for fetal brain dMRI registration, enabling accurate affine and deformable alignment. FetDTIAlign features a dual-encoder architecture and iterative feature-based inference, reducing the impact of noise and low resolution. It optimizes network configurations and domain-specific features at each registration stage, enhancing both robustness and accuracy. We validated FetDTIAlign on data from 23 to 36 weeks gestation, covering 60 white matter tracts. It consistently outperformed two classical optimization-based methods and a deep learning pipeline, achieving superior anatomical correspondence. Further validation on external data from the Developing Human Connectome Project confirmed its generalizability across acquisition protocols. Our results demonstrate the feasibility of deep learning for fetal brain dMRI registration, providing a more accurate and reliable alternative to classical techniques. By enabling precise cross-subject and tract-specific analyses, FetDTIAlign supports new discoveries in early brain development.
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.
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.
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.
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.
Deformable image registration is crucial for aligning medical images in a nonlinear fashion across different modalities, allowing for precise spatial correspondence between varying anatomical structures. This paper presents NestedMorph, a novel network utilizing a Nested Attention Fusion approach to improve intra-subject deformable registration between T1-weighted (T1w) MRI and diffusion MRI (dMRI) data. NestedMorph integrates high-resolution spatial details from an encoder with semantic information from a decoder using a multi-scale framework, enhancing both local and global feature extraction. Our model notably outperforms existing methods, including CNN-based approaches like VoxelMorph, MIDIR, and CycleMorph, as well as Transformer-based models such as TransMorph and ViT-V-Net, and traditional techniques like NiftyReg and SyN. Evaluations using the HCP dataset demonstrate that NestedMorph achieves superior performance across key metrics, including SSIM, HD95, and SDlogJ, with the highest SSIM of 0.89, the lowest HD95 of 2.5 and SDlogJ of 0.22. These results highlight NestedMorph's ability to capture both local and global image features effectively, leading to superior registration performance. The promising outcomes of this study underscore NestedMorph's potential to significantly advance deformable medical image registration, providing a robust framework for future research and clinical applications. The source code and our implementation are available at: https://github.com/AS-Lab/Marthi-et-al-2024-NestedMorph-Deformable-Medical-Image-Registration
The Orientation Distribution Function (ODF) characterizes key brain microstructural properties and plays an important role in understanding brain structural connectivity. Recent works introduced Implicit Neural Representation (INR) based approaches to form a spatially aware continuous estimate of the ODF field and demonstrated promising results in key tasks of interest when compared to conventional discrete approaches. However, traditional INR methods face difficulties when scaling to large-scale images, such as modern ultra-high-resolution MRI scans, posing challenges in learning fine structures as well as inefficiencies in training and inference speed. In this work, we propose HashEnc, a grid-hash-encoding-based estimation of the ODF field and demonstrate its effectiveness in retaining structural and textural features. We show that HashEnc achieves a 10% enhancement in image quality while requiring 3x less computational resources than current methods. Our code can be found at https://github.com/MunzerDw/NODF-HashEnc.
Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain in-utero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain's cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.
In this study, we developed an Evidence-based Ensemble Neural Network, namely EVENet, for anatomical brain parcellation using diffusion MRI. The key innovation of EVENet is the design of an evidential deep learning framework to quantify predictive uncertainty at each voxel during a single inference. To do so, we design an evidence-based ensemble learning framework for uncertainty-aware parcellation to leverage the multiple dMRI parameters derived from diffusion MRI. Using EVENet, we obtained accurate parcellation and uncertainty estimates across different datasets from healthy and clinical populations and with different imaging acquisitions. The overall network includes five parallel subnetworks, where each is dedicated to learning the FreeSurfer parcellation for a certain diffusion MRI parameter. An evidence-based ensemble methodology is then proposed to fuse the individual outputs. We perform experimental evaluations on large-scale datasets from multiple imaging sources, including high-quality diffusion MRI data from healthy adults and clinically diffusion MRI data from participants with various brain diseases (schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, Parkinson's disease, cerebral small vessel disease, and neurosurgical patients with brain tumors). Compared to several state-of-the-art methods, our experimental results demonstrate highly improved parcellation accuracy across the multiple testing datasets despite the differences in dMRI acquisition protocols and health conditions. Furthermore, thanks to the uncertainty estimation, our EVENet approach demonstrates a good ability to detect abnormal brain regions in patients with lesions, enhancing the interpretability and reliability of the segmentation results.
Modern diffusion MRI sequences commonly acquire a large number of volumes with diffusion sensitization gradients of differing strengths or directions. Such sequences rely on echo-planar imaging (EPI) to achieve reasonable scan duration. However, EPI is vulnerable to off-resonance effects, leading to tissue susceptibility and eddy-current induced distortions. The latter is particularly problematic because it causes misalignment between volumes, disrupting downstream modelling and analysis. The essential correction of eddy distortions is typically done post-acquisition, with image registration. However, this is non-trivial because correspondence between volumes can be severely disrupted due to volume-specific signal attenuations induced by varying directions and strengths of the applied gradients. This challenge has been successfully addressed by the popular FSL~Eddy tool but at considerable computational cost. We propose an alternative approach, leveraging recent advances in image processing enabled by deep learning (DL). It consists of two convolutional neural networks: 1) An image translator to restore correspondence between images; 2) A registration model to align the translated images. Results demonstrate comparable distortion estimates to FSL~Eddy, while requiring only modest training sample sizes. This work, to the best of our knowledge, is the first to tackle this problem with deep learning. Together with recently developed DL-based susceptibility correction techniques, they pave the way for real-time preprocessing of diffusion MRI, facilitating its wider uptake in the clinic.
We provide a framework for solving inverse problems with diffusion models learned from linearly corrupted data. Our method, Ambient Diffusion Posterior Sampling (A-DPS), leverages a generative model pre-trained on one type of corruption (e.g. image inpainting) to perform posterior sampling conditioned on measurements from a potentially different forward process (e.g. image blurring). We test the efficacy of our approach on standard natural image datasets (CelebA, FFHQ, and AFHQ) and we show that A-DPS can sometimes outperform models trained on clean data for several image restoration tasks in both speed and performance. We further extend the Ambient Diffusion framework to train MRI models with access only to Fourier subsampled multi-coil MRI measurements at various acceleration factors (R=2, 4, 6, 8). We again observe that models trained on highly subsampled data are better priors for solving inverse problems in the high acceleration regime than models trained on fully sampled data. We open-source our code and the trained Ambient Diffusion MRI models: https://github.com/utcsilab/ambient-diffusion-mri .
Purpose: Demonstrating and assessing self-supervised machine learning fitting of the VERDICT (Vascular, Extracellular and Restricted DIffusion for Cytometry in Tumours) model for prostate. Methods: We derive a self-supervised neural network for fitting VERDICT (ssVERDICT) that estimates parameter maps without training data. We compare the performance of ssVERDICT to two established baseline methods for fitting diffusion MRI models: conventional nonlinear least squares (NLLS) and supervised deep learning. We do this quantitatively on simulated data, by comparing the Pearson's correlation coefficient, mean-squared error (MSE), bias, and variance with respect to the simulated ground truth. We also calculate in vivo parameter maps on a cohort of 20 prostate cancer patients and compare the methods' performance in discriminating benign from cancerous tissue via Wilcoxon's signed-rank test. Results: In simulations, ssVERDICT outperforms the baseline methods (NLLS and supervised DL) in estimating all the parameters from the VERDICT prostate model in terms of Pearson's correlation coefficient, bias, and MSE. In vivo, ssVERDICT shows stronger lesion conspicuity across all parameter maps, and improves discrimination between benign and cancerous tissue over the baseline methods. Conclusion: ssVERDICT significantly outperforms state-of-the-art methods for VERDICT model fitting, and shows for the first time, fitting of a complex three-compartment biophysical model with machine learning without the requirement of explicit training labels.