Spatial Feature-wise Linear Modulation (SpFiLM) for Contrast Agent-Aware Brain Parcellation

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.

Focal cortical dysplasia (FCD) is one of the leading structural causes of drug-resistant focal epilepsy, yet its subtle and heterogeneous imaging characteristics make accurate identification and delineation challenging on conventional magnetic resonance imaging (MRI). Although T1-weighted (T1w) and fluid-attenuated inversion recovery (FLAIR) images are routinely acquired for presurgical evaluation, the contribution of different MRI representations to deep learning-based FCD segmentation remains poorly understood. In this study, we present a systematic benchmark of MRI representations for automated FCD segmentation using the nnU-Net framework. A publicly available presurgical MRI dataset comprising 85 FCD subjects and 25 healthy controls was used to evaluate eight input configurations, including conventional MRI contrasts (T1w and FLAIR), ratio-derived representations, and their multimodal combinations. To isolate the effect of MRI representation, all experiments employed identical preprocessing, network architecture, optimization strategy, and five-fold cross-validation. Among the evaluated single-modality representations, FLAIR achieved the strongest overall performance, whereas ratio-derived representations alone were insufficient for reliable identification of subtle FCD. Incorporating ratio-derived representations with conventional T1w and FLAIR images consistently improved lesion delineation, with the four-channel multimodal configuration achieving the highest overall Dice score (0.376), representing a 5.0% relative improvement over the conventional T1w+FLAIR representation. These findings demonstrate that MRI representation design is an important yet underexplored component of deep learning-based FCD segmentation and should be optimized alongside network architecture.

Focal cortical dysplasia (FCD) type II is an important structural cause of drug-resistant focal epilepsy, but its small size, heterogeneous appearance, and subtle MRI characteristics make automated segmentation challenging. Conventional multimodal networks commonly concatenate T1-weighted (T1w) and fluid-attenuated inversion recovery (FLAIR) images, requiring subsequent layers to learn useful cross-modal relationships implicitly. We propose CRIL-U-Net, a 3D U-Net incorporating a Compact Ratio-Interaction Learning module that combines local spatial features, voxel-wise cross-modal mixing, and bidirectional ratio-inspired interactions. CRIL-U-Net was compared with a conventional 3D U-Net and an input self-attention U-Net using five-fold cross-validation on 85 FCD subjects and 25 healthy controls. Each architecture was trained independently using Dice-binary cross-entropy (Dice-BCE) and Focal Tversky-Focal (FTF) losses. With FTF, CRIL-U-Net achieved the highest mean Dice score (0.196 +/- 0.262), compared with 0.136 +/- 0.224 for the U-Net and 0.135 +/- 0.214 for the attention comparator. It produced nonzero lesion overlap in 44 of 85 cases, compared with 36 for the U-Net. Under FTF, CRIL-U-Net significantly outperformed both comparison architectures after false-discovery-rate correction. These findings suggest that compact cross-modal representation learning can improve FCD segmentation within a controlled U-Net setting when combined with an imbalance-aware objective, although the remaining zero-overlap rate of 48.2% highlights the need for further validation and methodological development.