Not yet reviewed by Pith; the record is open.

Diffusion MRI tractography is an advanced imaging technique for quantitative mapping of the brain's structural connectivity. Whole brain tractography (WBT) data contains over hundreds of thousands of individual fiber streamlines (estimated brain connections), and this data is usually parcellated to create compact representations for data analysis applications such as disease classification. In this paper, we propose a novel parcellation-free WBT analysis framework, TractoFormer, that leverages tractography information at the level of individual fiber streamlines and provides a natural mechanism for interpretation of results using the attention mechanism of transformers. TractoFormer includes two main contributions. First, we propose a novel and simple 2D image representation of WBT, TractoEmbedding, to encode 3D fiber spatial relationships and any feature of interest that can be computed from individual fibers (such as FA or MD). Second, we design a network based on vision transformers (ViTs) that includes: 1) data augmentation to overcome model overfitting on small datasets, 2) identification of discriminative fibers for interpretation of results, and 3) ensemble learning to leverage fiber information from different brain regions. In a synthetic data experiment, TractoFormer successfully identifies discriminative fibers with simulated group differences. In a disease classification experiment comparing several methods, TractoFormer achieves the highest accuracy in classifying schizophrenia vs control. Discriminative fibers are identified in left hemispheric frontal and parietal superficial white matter regions, which have previously been shown to be affected in schizophrenia patients.