Regional CSF volume quantification using deep learning for comparative analysis of brain atrophy in frontotemporal dementia subtypes

Introduction Frontotemporal dementia (FTD) encompasses heterogeneous clinical syndromes, and distinguishing its subtypes using imaging remains challenging. Methods We developed a deep learning model to quantify brain atrophy by measuring cerebrospinal fluid (CSF) volumes in key regions of interest (RoIs) on standard MRI scans. In a retrospective study, we analyzed 3D T1-weighted MRI data from 1,854 individuals, including cognitively unimpaired (CU) controls, patients with dementia of the Alzheimer type (DAT), and FTD subtypes: behavioral variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). The model quantified CSF volumes in 14 clinically relevant RoIs and generated age- and sex-adjusted W-scores to express regional atrophy. Results Each FTD subtype exhibited a distinct, lateralized atrophy pattern: bvFTD showed widespread bilateral frontal and right-predominant parietal and temporal atrophy; nfvPPA showed left-predominant frontal and parietal atrophy; and svPPA exhibited marked left-lateralized temporal and hippocampal atrophy. All FTD subtypes demonstrated significantly greater CSF expansion in these characteristic regions compared to DAT and CU. Discussion This deep learning approach provides a simple, interpretable measure of brain atrophy that differentiates FTD subtypes, requiring only standard MRI with minimal preprocessing, and offers clinical utility.