High-resolution MRI Guided Whole Mouse Brain Cell Type Atlas using Deep Learning

Cell types represent groupings of cells defined by shared anatomical and functional properties. Traditional mouse brain cell atlases rely heavily on single-cell sequencing, which provides valuable molecular detail but lacks whole-brain, isotropic resolution. Diffusion MRI (dMRI) offers a complementary approach for probing cytoarchitecture and myeloarchitecture, with quantitative metrics increasingly used as biomarkers of brain development and neurodegenerative disorders. Although prior work has linked dMRI metrics with gene expression, the capacity of dMRI to directly predict cell types remains unclear. Here, we present a deep learning framework that integrates high-resolution dMRI with three-dimensional light-sheet microscopy (LSM) registered to the Allen Mouse Brain Common Coordinate Framework (CCFv3). We investigated correlations between dMRI and spatial transcriptomics-derived cell types and generated a whole-brain cell type atlas at 10 micrometer isotropic resolution. Together, these results establish an efficient, high-resolution strategy for brain cell atlas generation and underscore the potential of advanced imaging to illuminate cellular mechanisms of the brain.