The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.
Deep learning-based dMRI super-resolution methods can effectively enhance image resolution by leveraging the learning capabilities of neural networks on large datasets. However, these methods tend to learn a fixed scale mapping between low-resolution (LR) and high-resolution (HR) images, overlooking the need for radiologists to scale the images at arbitrary resolutions. Moreover, the pixel-wise loss in the image domain tends to generate over-smoothed results, losing fine textures and edge information. To address these issues, we propose a novel continuous super-resolution method for dMRI, called CSR-dMRI, which utilizes an anatomical structure-assisted implicit neural representation learning approach. Specifically, the CSR-dMRI model consists of two components. The first is the latent feature extractor, which primarily extracts latent space feature maps from LR dMRI and anatomical images while learning structural prior information from the anatomical images. The second is the implicit function network, which utilizes voxel coordinates and latent feature vectors to generate voxel intensities at corresponding positions. Additionally, a frequency-domain-based loss is introduced to preserve the structural and texture information, further enhancing the image quality. Extensive experiments on the publicly available HCP dataset validate the effectiveness of our approach. Furthermore, our method demonstrates superior generalization capability and can be applied to arbitrary-scale super-resolution, including non-integer scale factors, expanding its applicability beyond conventional approaches.
Diffusion MRI (dMRI) streamline tractography, the gold standard for in vivo estimation of brain white matter (WM) pathways, has long been considered indicative of macroscopic relationships with WM microstructure. However, recent advances in tractography demonstrated that convolutional recurrent neural networks (CoRNN) trained with a teacher-student framework have the ability to learn and propagate streamlines directly from T1 and anatomical contexts. Training for this network has previously relied on high-resolution dMRI. In this paper, we generalize the training mechanism to traditional clinical resolution data, which allows generalizability across sensitive and susceptible study populations. We train CoRNN on a small subset of the Baltimore Longitudinal Study of Aging (BLSA), which better resembles clinical protocols. Then, we define a metric, termed the epsilon ball seeding method, to compare T1 tractography and traditional diffusion tractography at the streamline level. Under this metric, T1 tractography generated by CoRNN reproduces diffusion tractography with approximately two millimeters of error.
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 .
Diffusion MRI tractography is an important tool for identifying and analyzing the intracranial course of cranial nerves (CNs). However, the complex environment of the skull base leads to ambiguous spatial correspondence between diffusion directions and fiber geometry, and existing diffusion tractography methods of CNs identification are prone to producing erroneous trajectories and missing true positive connections. To overcome the above challenge, we propose a novel CNs identification framework with anatomy-guided fiber trajectory distribution, which incorporates anatomical shape prior knowledge during the process of CNs tracing to build diffusion tensor vector fields. We introduce higher-order streamline differential equations for continuous flow field representations to directly characterize the fiber trajectory distribution of CNs from the tract-based level. The experimental results on the vivo HCP dataset and the clinical MDM dataset demonstrate that the proposed method reduces false-positive fiber production compared to competing methods and produces reconstructed CNs (i.e. CN II, CN III, CN V, and CN VII/VIII) that are judged to better correspond to the known anatomy.
\hspace{2mm} Diffusion-weighted magnetic resonance imaging (dMRI) of the brain offers unique capabilities including noninvasive probing of tissue microstructure and structural connectivity. It is widely used for clinical assessment of disease and injury, and for neuroscience research. Analyzing the dMRI data to extract useful information for medical and scientific purposes can be challenging. The dMRI measurements may suffer from strong noise and artifacts, and may exhibit high inter-session and inter-scanner variability in the data, as well as inter-subject heterogeneity in brain structure. Moreover, the relationship between measurements and the phenomena of interest can be highly complex. Recent years have witnessed increasing use of machine learning methods for dMRI analysis. This manuscript aims to assess these efforts, with a focus on methods that have addressed data preprocessing and harmonization, microstructure mapping, tractography, and white matter tract analysis. We study the main findings, strengths, and weaknesses of the existing methods and suggest topics for future research. We find that machine learning may be exceptionally suited to tackle some of the difficult tasks in dMRI analysis. However, for this to happen, several shortcomings of existing methods and critical unresolved issues need to be addressed. There is a pressing need to improve evaluation practices, to increase the availability of rich training datasets and validation benchmarks, as well as model generalizability, reliability, and explainability concerns.
Connectivity matrices derived from diffusion MRI (dMRI) provide an interpretable and generalizable way of understanding the human brain connectome. However, dMRI suffers from inter-site and between-scanner variation, which impedes analysis across datasets to improve robustness and reproducibility of results. To evaluate different harmonization approaches on connectivity matrices, we compared graph measures derived from these matrices before and after applying three harmonization techniques: mean shift, ComBat, and CycleGAN. The sample comprises 168 age-matched, sex-matched normal subjects from two studies: the Vanderbilt Memory and Aging Project (VMAP) and the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD). First, we plotted the graph measures and used coefficient of variation (CoV) and the Mann-Whitney U test to evaluate different methods' effectiveness in removing site effects on the matrices and the derived graph measures. ComBat effectively eliminated site effects for global efficiency and modularity and outperformed the other two methods. However, all methods exhibited poor performance when harmonizing average betweenness centrality. Second, we tested whether our harmonization methods preserved correlations between age and graph measures. All methods except for CycleGAN in one direction improved correlations between age and global efficiency and between age and modularity from insignificant to significant with p-values less than 0.05.
Large datasets often contain multiple distinct feature sets, or views, that offer complementary information that can be exploited by multi-view learning methods to improve results. We investigate anatomical multi-view data, where each brain anatomical structure is described with multiple feature sets. In particular, we focus on sets of white matter microstructure and connectivity features from diffusion MRI, as well as sets of gray matter area and thickness features from structural MRI. We investigate machine learning methodology that applies multi-view approaches to improve the prediction of non-imaging phenotypes, including demographics (age), motor (strength), and cognition (picture vocabulary). We present an explainable multi-view network (EMV-Net) that can use different anatomical views to improve prediction performance. In this network, each individual anatomical view is processed by a view-specific feature extractor and the extracted information from each view is fused using a learnable weight. This is followed by a wavelet transform-based module to obtain complementary information across views which is then applied to calibrate the view-specific information. Additionally, the calibrator produces an attention-based calibration score to indicate anatomical structures' importance for interpretation.
The amygdala plays a vital role in emotional processing and exhibits structural diversity that necessitates fine-scale parcellation 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 amygdala for studying its subdivisions. In this work, we present a deep clustering pipeline to perform automated, fine-scale parcellation of the amygdala using diffusion MRI tractography. First, we incorporate a newly proposed deep learning approach to enable accurate segmentation of the amygdala directly on the dMRI data. Next, we design a novel streamline clustering-based structural connectivity feature for a robust representation of voxels within the amygdala. Finally, we improve the popular joint dimensionality reduction and k-means clustering approach to enable amygdala parcellation at a finer scale. With the proposed method, we obtain nine unique amygdala parcels. Experiments show that these parcels can be consistently identified across subjects and have good correspondence to the widely used coarse-scale amygdala parcellation.
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.
Early brain development is characterized by the formation of a highly organized structural connectome. The interconnected nature of this connectome underlies the brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development and imaging difficulties. Combined with high inter-subject variability, these factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational framework, based on spatio-temporal averaging, for determining such baselines. We used this framework to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in perinatal stage. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. We observed increases in global and local efficiency, a decrease in characteristic path length, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. The new computational method and results are useful for assessing normal and abnormal development of the structural connectome early in life.
We present a novel way to model diffusion magnetic resonance imaging (dMRI) datasets, that benefits from the structural coherence of the human brain while only using data from a single subject. Current methods model the dMRI signal in individual voxels, disregarding the intervoxel coherence that is present. We use a neural network to parameterize a spherical harmonics series (NeSH) to represent the dMRI signal of a single subject from the Human Connectome Project dataset, continuous in both the angular and spatial domain. The reconstructed dMRI signal using this method shows a more structurally coherent representation of the data. Noise in gradient images is removed and the fiber orientation distribution functions show a smooth change in direction along a fiber tract. We showcase how the reconstruction can be used to calculate mean diffusivity, fractional anisotropy, and total apparent fiber density. These results can be achieved with a single model architecture, tuning only one hyperparameter. In this paper we also demonstrate how upsampling in both the angular and spatial domain yields reconstructions that are on par or better than existing methods.
Diffusion MRI is commonly performed using echo-planar imaging (EPI) due to its rapid acquisition time. However, the resolution of diffusion-weighted images is often limited by magnetic field inhomogeneity-related artifacts and blurring induced by T2- and T2*-relaxation effects. To address these limitations, multi-shot EPI (msEPI) combined with parallel imaging techniques is frequently employed. Nevertheless, reconstructing msEPI can be challenging due to phase variation between multiple shots. In this study, we introduce a novel msEPI reconstruction approach called zero-MIRID (zero-shot self-supervised learning of Multi-shot Image Reconstruction for Improved Diffusion MRI). This method jointly reconstructs msEPI data by incorporating deep learning-based image regularization techniques. The network incorporates CNN denoisers in both k- and image-spaces, while leveraging virtual coils to enhance image reconstruction conditioning. By employing a self-supervised learning technique and dividing sampled data into three groups, the proposed approach achieves superior results compared to the state-of-the-art parallel imaging method, as demonstrated in an in-vivo experiment.
Diffusion MRI tractography parcellation classifies streamlines into anatomical fiber tracts to enable quantification and visualization for clinical and scientific applications. Current tractography parcellation methods rely heavily on registration, but registration inaccuracies can affect parcellation and the computational cost of registration is high for large-scale datasets. Recently, deep-learning-based methods have been proposed for tractography parcellation using various types of representations for streamlines. However, these methods only focus on the information from a single streamline, ignoring geometric relationships between the streamlines in the brain. We propose TractCloud, a registration-free framework that performs whole-brain tractography parcellation directly in individual subject space. We propose a novel, learnable, local-global streamline representation that leverages information from neighboring and whole-brain streamlines to describe the local anatomy and global pose of the brain. We train our framework on a large-scale labeled tractography dataset, which we augment by applying synthetic transforms including rotation, scaling, and translations. We test our framework on five independently acquired datasets across populations and health conditions. TractCloud significantly outperforms several state-of-the-art methods on all testing datasets. TractCloud achieves efficient and consistent whole-brain white matter parcellation across the lifespan (from neonates to elderly subjects, including brain tumor patients) without the need for registration. The robustness and high inference speed of TractCloud make it suitable for large-scale tractography data analysis. Our project page is available at https://tractcloud.github.io/.
Inferring brain connectivity and structure \textit{in-vivo} requires accurate estimation of the orientation distribution function (ODF), which encodes key local tissue properties. However, estimating the ODF from diffusion MRI (dMRI) signals is a challenging inverse problem due to obstacles such as significant noise, high-dimensional parameter spaces, and sparse angular measurements. In this paper, we address these challenges by proposing a novel deep-learning based methodology for continuous estimation and uncertainty quantification of the spatially varying ODF field. We use a neural field (NF) to parameterize a random series representation of the latent ODFs, implicitly modeling the often ignored but valuable spatial correlation structures in the data, and thereby improving efficiency in sparse and noisy regimes. An analytic approximation to the posterior predictive distribution is derived which can be used to quantify the uncertainty in the ODF estimate at any spatial location, avoiding the need for expensive resampling-based approaches that are typically employed for this purpose. We present empirical evaluations on both synthetic and real in-vivo diffusion data, demonstrating the advantages of our method over existing approaches.
The brain white matter consists of a set of tracts that connect distinct regions of the brain. Segmentation of these tracts is often needed for clinical and research studies. Diffusion-weighted MRI offers unique contrast to delineate these tracts. However, existing segmentation methods rely on intermediate computations such as tractography or estimation of fiber orientation density. These intermediate computations, in turn, entail complex computations that can result in unnecessary errors. Moreover, these intermediate computations often require dense multi-shell measurements that are unavailable in many clinical and research applications. As a result, current methods suffer from low accuracy and poor generalizability. Here, we propose a new deep learning method that segments these tracts directly from the diffusion MRI data, thereby sidestepping the intermediate computation errors. Our experiments show that this method can achieve segmentation accuracy that is on par with the state of the art methods (mean Dice Similarity Coefficient of 0.826). Compared with the state of the art, our method offers far superior generalizability to undersampled data that are typical of clinical studies and to data obtained with different acquisition protocols. Moreover, we propose a new method for detecting inaccurate segmentations and show that it is more accurate than standard methods that are based on estimation uncertainty quantification. The new methods can serve many critically important clinical and scientific applications that require accurate and reliable non-invasive segmentation of white matter tracts.
The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. Diffusion MRI tractography is the only method that enables the study of the anatomy and variability of the CST pathway in human health. In this work, we explored the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. We perform experiments using diffusion MRI data from the Human Connectome Project. Four quantitative measurements including reconstruction rate, the WM-GM interface coverage, anatomical distribution of streamlines, and correlation with cortical volumes to assess the advantages and limitations of each method. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face area) and medial portions (leg area), remains an important challenge for diffusion MRI tractography.
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a critical imaging method for capturing and modeling tissue microarchitecture at a millimeter scale. A common practice to model the measured DW-MRI signal is via fiber orientation distribution function (fODF). This function is the essential first step for the downstream tractography and connectivity analyses. With recent advantages in data sharing, large-scale multi-site DW-MRI datasets are being made available for multi-site studies. However, measurement variabilities (e.g., inter- and intra-site variability, hardware performance, and sequence design) are inevitable during the acquisition of DW-MRI. Most existing model-based methods (e.g., constrained spherical deconvolution (CSD)) and learning based methods (e.g., deep learning (DL)) do not explicitly consider such variabilities in fODF modeling, which consequently leads to inferior performance on multi-site and/or longitudinal diffusion studies. In this paper, we propose a novel data-driven deep constrained spherical deconvolution method to explicitly constrain the scan-rescan variabilities for a more reproducible and robust estimation of brain microstructure from repeated DW-MRI scans. Specifically, the proposed method introduces a new 3D volumetric scanner-invariant regularization scheme during the fODF estimation. We study the Human Connectome Project (HCP) young adults test-retest group as well as the MASiVar dataset (with inter- and intra-site scan/rescan data). The Baltimore Longitudinal Study of Aging (BLSA) dataset is employed for external validation. From the experimental results, the proposed data-driven framework outperforms the existing benchmarks in repeated fODF estimation. The proposed method is assessing the downstream connectivity analysis and shows increased performance in distinguishing subjects with different biomarkers.
Diffusion MRI (dMRI) is a widely used imaging modality, but requires long scanning times to acquire high resolution datasets. By leveraging the unique geometry present within this domain, we present a novel approach to dMRI angular super-resolution that extends upon the parametric continuous convolution (PCConv) framework. We introduce several additions to the operation including a Fourier feature mapping, global coordinates, and domain specific context. Using this framework, we build a fully parametric continuous convolution network (PCCNN) and compare against existing models. We demonstrate the PCCNN performs competitively while using significantly less parameters. Moreover, we show that this formulation generalises well to clinically relevant downstream analyses such as fixel-based analysis, and neurite orientation dispersion and density imaging.
The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.