Diffusion MRI Transformer with a Diffusion Space Rotary Positional Embedding (D-RoPE)

Diffusion Magnetic Resonance Imaging (dMRI) plays a critical role in studying microstructural changes in the brain. It is, therefore, widely used in clinical practice; yet progress in learning general-purpose representations from dMRI has been limited. A key challenge is that existing deep learning approaches are not well-suited to capture the unique properties of diffusion signals. Brain dMRI is normally composed of several brain volumes, each with different attenuation characteristics dependent on the direction and strength of the diffusion-sensitized gradients. Thus, there is a need to jointly model spatial, diffusion-weighting, and directional dependencies in dMRI. Furthermore, varying acquisition protocols (e.g., differing numbers of directions) further limit traditional models. To address these gaps, we introduce a diffusion space rotatory positional embedding (D-RoPE) plugged into our dMRI transformer to capture both the spatial structure and directional characteristics of diffusion data, enabling robust and transferable representations across diverse acquisition settings and an arbitrary number of diffusion directions. After self-supervised masked autoencoding pretraining, tests on several downstream tasks show that the learned representations and the pretrained model can provide competitive or superior performance compared to several baselines in these downstream tasks (even compared to a fully trained baseline); the finetuned features from our pretrained encoder resulted in a 6% higher accuracy in classifying mild cognitive impairment and a 0.05 increase in the correlation coefficient when predicting cognitive scores. Code is available at: github.com/gustavochau/D-RoPE.

Interpretable Cross-Network Attention for Resting-State fMRI Representation Learning

Understanding how large-scale functional brain networks reorganize during cognitive decline remains a central challenge in neuroimaging. While recent self-supervised models have shown promise for learning representations from resting-state fMRI, their internal mechanisms are difficult to interpret, limiting mechanistic insight. We propose BrainInterNet, a network-aware self-supervised framework based on masked reconstruction with cross-attention that explicitly models inter-network dependencies in rs-fMRI. By selectively masking predefined functional networks and reconstructing them from remaining context, our approach enables direct quantification of network predictability and interpretable analysis of cross-network interactions. We train BrainInterNet on multi-cohort fMRI data (from the ABCD, HCP Development, HCP Young Adults, and HCP Aging datasets) and evaluate on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, in total comprising 5,582 recordings. Our method reveals systematic alterations in the brain's network interactions under AD, including in the default mode, limbic, and attention networks. In parallel, the learned representations support accurate Alzheimer's-spectrum classification and yield a compact summary marker that tracks disease severity longitudinally. Together, these results demonstrate that network-guided masked modeling with cross-attention provides an interpretable and effective framework for characterizing functional reorganization in neurodegeneration.

Generating Novel Brain Morphology by Deforming Learned Templates

Designing generative models for 3D structural brain MRI that synthesize morphologically-plausible and attribute-specific (e.g., age, sex, disease state) samples is an active area of research. Existing approaches based on frameworks like GANs or diffusion models synthesize the image directly, which may limit their ability to capture intricate morphological details. In this work, we propose a 3D brain MRI generation method based on state-of-the-art latent diffusion models (LDMs), called MorphLDM, that generates novel images by applying synthesized deformation fields to a learned template. Instead of using a reconstruction-based autoencoder (as in a typical LDM), our encoder outputs a latent embedding derived from both an image and a learned template that is itself the output of a template decoder; this latent is passed to a deformation field decoder, whose output is applied to the learned template. A registration loss is minimized between the original image and the deformed template with respect to the encoder and both decoders. Empirically, our approach outperforms generative baselines on metrics spanning image diversity, adherence with respect to input conditions, and voxel-based morphometry. Our code is available at https://github.com/alanqrwang/morphldm.