Nikos Makris

Tengfei Xue, Fan Zhang, Chaoyi Zhang et al.

Diffusion MRI tractography is an advanced imaging technique that enables in vivo mapping of the brain's white matter connections. White matter parcellation classifies tractography streamlines into clusters or anatomically meaningful tracts. It enables quantification and visualization of whole-brain tractography. Currently, most parcellation methods focus on the deep white matter (DWM), whereas fewer methods address the superficial white matter (SWM) due to its complexity. We propose a novel two-stage deep-learning-based framework, Superficial White Matter Analysis (SupWMA), that performs an efficient and consistent parcellation of 198 SWM clusters from whole-brain tractography. A point-cloud-based network is adapted to our SWM parcellation task, and supervised contrastive learning enables more discriminative representations between plausible streamlines and outliers for SWM. We train our model on a large-scale tractography dataset including streamline samples from labeled long- and medium-range (over 40 mm) SWM clusters and anatomically implausible streamline samples, and we perform testing on six independently acquired datasets of different ages and health conditions (including neonates and patients with space-occupying brain tumors). Compared to several state-of-the-art methods, SupWMA obtains highly consistent and accurate SWM parcellation results on all datasets, showing good generalization across the lifespan in health and disease. In addition, the computational speed of SupWMA is much faster than other methods.

Yuqian Chen, Chaoyi Zhang, Tengfei Xue et al.

White matter fiber clustering is an important strategy for white matter parcellation, which enables quantitative analysis of brain connections in health and disease. In combination with expert neuroanatomical labeling, data-driven white matter fiber clustering is a powerful tool for creating atlases that can model white matter anatomy across individuals. While widely used fiber clustering approaches have shown good performance using classical unsupervised machine learning techniques, recent advances in deep learning reveal a promising direction toward fast and effective fiber clustering. In this work, we propose a novel deep learning framework for white matter fiber clustering, Deep Fiber Clustering (DFC), which solves the unsupervised clustering problem as a self-supervised learning task with a domain-specific pretext task to predict pairwise fiber distances. This process learns a high-dimensional embedding feature representation for each fiber, regardless of the order of fiber points reconstructed during tractography. We design a novel network architecture that represents input fibers as point clouds and allows the incorporation of additional sources of input information from gray matter parcellation to improve anatomical coherence of clusters. In addition, DFC conducts outlier removal naturally by rejecting fibers with low cluster assignment probability. We evaluate DFC on three independently acquired cohorts, including data from 220 individuals across genders, ages (young and elderly adults), and different health conditions (healthy control and multiple neuropsychiatric disorders). We compare DFC to several state-of-the-art white matter fiber clustering algorithms. Experimental results demonstrate superior performance of DFC in terms of cluster compactness, generalization ability, anatomical coherence, and computational efficiency.

Jianzhong He, Fan Zhang, Yiang Pan et al.

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.

Yuqian Chen, Fan Zhang, Chaoyi Zhang et al.

White matter tract microstructure has been shown to influence neuropsychological scores of cognitive performance. However, prediction of these scores from white matter tract data has not been attempted. In this paper, we propose a deep-learning-based framework for neuropsychological score prediction using microstructure measurements estimated from diffusion magnetic resonance imaging (dMRI) tractography, focusing on predicting performance on a receptive vocabulary assessment task based on a critical fiber tract for language, the arcuate fasciculus (AF). We directly utilize information from all points in a fiber tract, without the need to average data along the fiber as is traditionally required by diffusion MRI tractometry methods. Specifically, we represent the AF as a point cloud with microstructure measurements at each point, enabling adoption of point-based neural networks. We improve prediction performance with the proposed Paired-Siamese Loss that utilizes information about differences between continuous neuropsychological scores. Finally, we propose a Critical Region Localization (CRL) algorithm to localize informative anatomical regions containing points with strong contributions to the prediction results. Our method is evaluated on data from 806 subjects from the Human Connectome Project dataset. Results demonstrate superior neuropsychological score prediction performance compared to baseline methods. We discover that critical regions in the AF are strikingly consistent across subjects, with the highest number of strongly contributing points located in frontal cortical regions (i.e., the rostral middle frontal, pars opercularis, and pars triangularis), which are strongly implicated as critical areas for language processes.

Yuqian Chen, Fan Zhang, Leo R. Zekelman et al.

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.

Yuqian Chen, Leo R. Zekelman, Chaoyi Zhang et al.

We propose a geometric deep-learning-based framework, TractGeoNet, for performing regression using diffusion magnetic resonance imaging (dMRI) tractography and associated pointwise tissue microstructure measurements. By employing a point cloud representation, TractGeoNet can directly utilize pointwise tissue microstructure and positional information from all points within a fiber tract. To improve regression performance, we propose a novel loss function, the Paired-Siamese Regression loss, which encourages the model to focus on accurately predicting the relative differences between regression label scores rather than just their absolute values. In addition, we propose a Critical Region Localization algorithm to identify highly predictive anatomical regions within the white matter fiber tracts for the regression task. We evaluate the effectiveness of the proposed method by predicting individual performance on two neuropsychological assessments of language using a dataset of 20 association white matter fiber tracts from 806 subjects from the Human Connectome Project. The results demonstrate superior prediction performance of TractGeoNet compared to several popular regression models. Of the twenty tracts studied, we find that the left arcuate fasciculus tract is the most highly predictive of the two studied language performance assessments. The localized critical regions are widespread and distributed across both hemispheres and all cerebral lobes, including areas of the brain considered important for language function such as superior and anterior temporal regions, pars opercularis, and precentral gyrus. Overall, TractGeoNet demonstrates the potential of geometric deep learning to enhance the study of the brain's white matter fiber tracts and to relate their structure to human traits such as language performance.

Tengfei Xue, Yuqian Chen, Chaoyi Zhang et al.

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/.

Tengfei Xue, Fan Zhang, Leo R. Zekelman et al.

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.

Wan Liu, Yuqian Chen, Chuyang Ye et al.

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.

Sipei Li, Jianzhong He, Tengfei Xue et al.

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.

Yuxiang Wei, Tengfei Xue, Yogesh Rathi et al.

The brain's white matter (WM) undergoes developmental and degenerative processes during the human lifespan. To investigate the relationship between WM anatomical regions and age, we study diffusion magnetic resonance imaging tractography that is finely parcellated into fiber clusters in the deep, superficial, and cerebellar WM. We propose a deep-learning-based age prediction model that leverages large convolutional kernels and inverted bottlenecks. We improve performance using novel discrete multi-faceted mix data augmentation and a novel prior-knowledge-based loss function that encourages age predictions in the expected range. We study a dataset of 965 healthy young adults (22-37 years) derived from the Human Connectome Project (HCP). Experimental results demonstrate that the proposed model achieves a mean absolute error of 2.59 years and outperforms compared methods. We find that the deep WM is the most informative for age prediction in this cohort, while the superficial WM is the least informative. Overall, the most predictive WM tracts are the thalamo-frontal tract from the deep WM and the intracerebellar input and Purkinje tract from the cerebellar WM.

Yuqian Chen, Fan Zhang, Meng Wang et al.

The relationship between brain connections and non-imaging phenotypes is increasingly studied using deep neural networks. However, the local and global properties of brain white matter networks are often overlooked in convolutional network design. We introduce TractGraphFormer, a hybrid Graph CNN-Transformer deep learning framework tailored for diffusion MRI tractography. This model leverages local anatomical characteristics and global feature dependencies of white matter structures. The Graph CNN module captures white matter geometry and grey matter connectivity to aggregate local features from anatomically similar white matter connections, while the Transformer module uses self-attention to enhance global information learning. Additionally, TractGraphFormer includes an attention module for interpreting predictive white matter connections. We apply TractGraphFormer to tasks of sex and age prediction. TractGraphFormer shows strong performance in large datasets of children (n=9345) and young adults (n=1065). Overall, our approach suggests that widespread connections in the WM are predictive of the sex and age of an individual. For each prediction task, consistent predictive anatomical tracts are identified across the two datasets. The proposed approach highlights the potential of integrating local anatomical information and global feature dependencies to improve prediction performance in machine learning with diffusion MRI tractography.

Yuxiang Wei, Yuqian Chen, Tengfei Xue et al.

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.

Yui Lo, Yuqian Chen, Dongnan Liu et al.

Shape plays an important role in computer graphics, offering informative features to convey an object's morphology and functionality. Shape analysis in brain imaging can help interpret structural and functionality correlations of the human brain. In this work, we investigate the shape of the brain's 3D white matter connections and its potential predictive relationship to human cognitive function. We reconstruct brain connections as sequences of 3D points using diffusion magnetic resonance imaging (dMRI) tractography. To describe each connection, we extract 12 shape descriptors in addition to traditional dMRI connectivity and tissue microstructure features. We introduce a novel framework, Shape--fused Fiber Cluster Transformer (SFFormer), that leverages a multi-head cross-attention feature fusion module to predict subject-specific language performance based on dMRI tractography. We assess the performance of the method on a large dataset including 1065 healthy young adults. The results demonstrate that both the transformer-based SFFormer model and its inter/intra feature fusion with shape, microstructure, and connectivity are informative, and together, they improve the prediction of subject-specific language performance scores. Overall, our results indicate that the shape of the brain's connections is predictive of human language function.

Jin Wang, Bocheng Guo, Yijie Li et al.

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.

Hao He, Fan Zhang, Steve Pieper et al.

The human brain's white matter (WM) structure is of immense interest to the scientific community. Diffusion MRI gives a powerful tool to describe the brain WM structure noninvasively. To potentially enable monitoring of age-related changes and investigation of sex-related brain structure differences on the mapping between the brain connectome and healthy subjects' age and sex, we extract fiber-cluster-based diffusion features and predict sex and age with a novel ensembled neural network classifier. We conduct experiments on the Human Connectome Project (HCP) young adult dataset and show that our model achieves 94.82% accuracy in sex prediction and 2.51 years MAE in age prediction. We also show that the fractional anisotropy (FA) is the most predictive of sex, while the number of fibers is the most predictive of age and the combination of different features can improve the model performance.

Tengfei Xue, Fan Zhang, Chaoyi Zhang et al.

White matter parcellation classifies tractography streamlines into clusters or anatomically meaningful tracts to enable quantification and visualization. Most parcellation methods focus on the deep white matter (DWM), while fewer methods address the superficial white matter (SWM) due to its complexity. We propose a deep-learning-based framework, Superficial White Matter Analysis (SupWMA), that performs an efficient and consistent parcellation of 198 SWM clusters from whole-brain tractography. A point-cloud-based network is modified for our SWM parcellation task, and supervised contrastive learning enables more discriminative representations between plausible streamlines and outliers. We perform evaluation on a large tractography dataset with ground truth labels and on three independently acquired testing datasets from individuals across ages and health conditions. Compared to several state-of-the-art methods, SupWMA obtains a highly consistent and accurate SWM parcellation result. In addition, the computational speed of SupWMA is much faster than other methods.

Yuqian Chen, Chaoyi Zhang, Yang Song et al.

White matter fiber clustering (WMFC) enables parcellation of white matter tractography for applications such as disease classification and anatomical tract segmentation. However, the lack of ground truth and the ambiguity of fiber data (the points along a fiber can equivalently be represented in forward or reverse order) pose challenges to this task. We propose a novel WMFC framework based on unsupervised deep learning. We solve the unsupervised clustering problem as a self-supervised learning task. Specifically, we use a convolutional neural network to learn embeddings of input fibers, using pairwise fiber distances as pseudo annotations. This enables WMFC that is insensitive to fiber point ordering. In addition, anatomical coherence of fiber clusters is improved by incorporating brain anatomical segmentation data. The proposed framework enables outlier removal in a natural way by rejecting fibers with low cluster assignment probability. We train and evaluate our method using 200 datasets from the Human Connectome Project. Results demonstrate superior performance and efficiency of the proposed approach.