TractoRC: A Unified Probabilistic Learning Framework for Joint Tractography Registration and Clustering

Diffusion MRI (dMRI) tractography is the only noninvasive approach for mapping white-matter pathways in the living human brain. It represents each brain as a tractogram: a large, unordered set of three-dimensional streamlines that includes information about both local streamline geometry and whole-brain anatomical organization. This structure makes tractograms a natural but challenging target for representation learning. Existing methods treat streamline classification and subject-level prediction as separate problems: streamline classifiers focus on geometric patterns, whereas subject-level prediction often depends on hand-crafted features. As a result, current methods do not learn reusable representations that connect streamline anatomy with whole-brain inter-subject variation. Here we introduce TractFM, a tractogram foundation model that learns reusable representations directly from whole-brain streamline sets. TractFM combines a local streamline encoder with a permutation-equivariant tractogram encoder, allowing all streamlines from a subject to be contextualized jointly in a single forward pass. Pretraining on dense anatomical tract parcellation, i.e., assigning anatomical labels to individual streamlines, yields two complementary representations: contextualized streamline-level embeddings for tract parcellation and compact subject-level descriptors for downstream prediction of subject phenotypes. Across three tractography algorithms and five dMRI datasets, TractFM transfers to both streamline-level and subject-level tasks. Its frozen representations achieve accurate tract parcellation and predict age and sex across independent datasets. These results show that whole-brain geometric context, learned once, can generalize across tractography pipelines, datasets, and prediction tasks.

Cortical surface registration is often driven by local geometric descriptors (e.g., sulcal depth and curvature). While this approach achieves geometric correspondence, it neglects the long-range wiring constraints imposed by white-matter anatomy. Diffusion MRI tractography offers these crucial constraints; however, prior connectivity-informed pipelines typically align precomputed connectivity matrices, making the optimization highly sensitive to connectivity estimation and its resolution. In this paper, we introduce a novel connectivity-based surface registration method that aligns cortical surfaces by operating directly on white-matter fiber-tract endpoints. We model tract endpoints as a point cloud on the product manifold $Ω\times Ω$, where $Ω$ represents the spherical domain of the inflated cortical hemispheres. Our alignment method iteratively (i) computes a small diffeomorphic warp for $Ω$ by minimizing connectivity mismatch, and (ii) updates the endpoints based on this warp. The method relies on a geometric framework that ensures output warps are diffeomorphisms and has a final goal that optimizes the matching of well-known fiber bundles. Experiments on Human Connectome Project (HCP) data demonstrate improved tract-level correspondence, achieving higher connectivity-level overlap coefficients on major fiber bundles and stronger robustness across grid resolutions for $Ω$ compared to state-of-the-art methods such as ENCORE and MSMAll.

The superficial white matter (SWM), a critical brain region for cognition across the lifespan and brain disease, contains abundant short-range association fibers whose organization remains incompletely characterized, in part because the short trajectories and highly variable cortical folding make correspondence across individuals challenging. Anatomically corresponding connections may vary in spatial location across individuals and therefore may not be adequately defined by geometric proximity alone. We introduce FiberGeoText (FGT), a vision-language model (VLM) for organizing short-range superficial white matter (SWM) streamlines reconstructed from ultra-high-resolution diffusion MRI into population-level clusters. FGT jointly represents three complementary properties of each streamline: its three-dimensional trajectory, its cortical anatomical context, and its shape. Cortical endpoint information from multiple parcellation schemes is expressed as text and encoded using a pretrained large language model (LLM), enabling heterogeneous anatomical descriptions to contribute to a common continuous representation. We evaluated FGT on acquired submillimeter 0.76 mm diffusion MRI data. Compared with state-of-the-art (SOTA) methods, FGT produced substantially greater cortical parcel coherence, within-cluster shape consistency, cluster-size consistency, and cross-subject correspondence. The trained model also generalizes well to unseen subjects with an average of 96.7% of the 5,000 learned clusters recovered, and high consistency of cluster structure between training and testing data. Together, these findings demonstrate that integrating geometric, anatomical, and shape information by learning multimodal deep embeddings with a VLM model enables robust learning of population-consistent SWM organization despite interindividual anatomical variability.