Topology-Aware Training and Spatial Diagnostics for Fiber Bundle Segmentation in Tracer Histology

Diffusion MRI (dMRI) tractography enables non-invasive reconstruction of white-matter pathways, but its accuracy is fundamentally limited by indirect, low-resolution measurements of axonal organization. Tracer injection studies in non-human primates provide a gold standard for validating dMRI tractography. This, however, requires time-consuming manual annotation of fiber bundles in histology sections. We propose a synthetic-data augmented framework for automated fiber bundle segmentation in macaque tracer histology. Our approach uses ex vivo dMRI tractography as a generative prior to synthesize 2D image patches for training. This provides us with sufficiently realistic foreground texture, which we compose with backgrounds from blockface photos and diversify via domain randomization. A 2D U-Net is trained on mixed real and synthetic patches. Experiments on held-out brains demonstrate improved generalization across brains and fiber bundle densities compared to training with real data only. Training with synthetic data only leads to poor performance, underscoring the need for real supervision. Overall, our approach achieves performance comparable to the state-of-the-art while requiring 3x less manually annotated data.

The growing number of medical vision foundation models highlights the need for effective model selection. However, mainstream selection methods rely on exhaustive fine-tuning, which is computationally expensive. Most of the existing Transferability Estimation (TE) metrics are primarily designed for image-level classification. They fail to preserve spatial relationships and fine-grained boundary details, which are crucial for the segmentation task. Additionally, while image-level tasks typically process a single feature vector per input, dense prediction tasks in 3D medical imaging require voxel-wise evaluation against dense annotations. To bridge these gaps, we propose a non-parametric, topology-driven framework that estimates transferability directly from the alignment between the sparse 1-skeleton graph of dense features and semantic labels via Minimum Spanning Trees (MST). We decouple the alignment into two complementary geometric scales: Local Boundary-Aware Topological Consistency (LBTC) to assess boundary separability, where we prove that the MST leakage rate serves as a finite-sample lower bound on the Bayes error; and Global Representation Topology Divergence (GRTD) to evaluate the overall anatomical layout. Crucially, we formally justify a counterintuitive mechanism: Although without fine-tuning, the randomly initialized segmentation decoder acts as a topology-preserving spatial projector, reducing the variance of pairwise distance estimates and stabilizing global alignment evaluation. Fused via a task-adaptive gating mechanism, these dual metrics adapt to diverse clinical complexities. Evaluated on a large-scale benchmark of 114,000 3D medical volumes across diverse anatomical tasks, our topological framework achieves state-of-the-art transferability estimation with an average weighted Kendall (outperforming by 0.36) while accelerating evaluation by 56 times.

Vision language models have transformed 2D medical imaging, yet extending them to 3D white matter tractography remains challenging due to the complex topology of fiber bundles. We introduce TractoGraphVLM, a unified framework for four tasks, bundle classification, text-to-tract retrieval, anatomical captioning, and visual question answering, built on a shared GPS architecture, training procedure, and read-out design. Fiber bundles are represented as streamline graphs whose nodes encode 3D position and tangent orientation. A General, Powerful, Scalable (GPS) graph transformer produces bundle embeddings aligned with a frozen BiomedBERT text encoder via contrastive learning, while a BioGPT decoder with visual prefix tokens generates captions and answers. A single shared encoder and decoder is trained jointly across all four tasks and evaluated from one checkpoint. Trained on HCP Young Adult subjects, TractoGraphVLM achieves 91.8% bundle classification accuracy, 84.7% retrieval R@1, BLEU-4=20.1, ROUGE-L=66.8, and 66.4% VQA accuracy on a held-out test set. The same checkpoints transfer zero-shot to HCP Aging subjects, with a modest drop on discriminative tasks and a larger drop on generative tasks, showing robustness to age and acquisition shift. Language supervision yields richer representations than label-only training, recovering structure like hemisphere and fiber family, carried by captions but never given as a label. Swapping only the visual encoder, graphs preserving fiber orientation outperform volumetric baselines, with GPS giving the best balance. Generative metrics measure consistency with a structured knowledge base rather than independent clinical text; even so, TractoGraphVLM shows that classifying, retrieving, describing, and answering questions about a white matter bundle can be served by one jointly trained model that learns transferable neuroanatomy from language alone.