Quantifying brain atrophy in Frontotemporal Dementia: a head-to-head comparison of neuroimaging techniques

Frontotemporal Dementia (FTD) is a neurodegenerative disorder characterized by extensive atrophy in the frontal and temporal lobes of the brain as well as high cerebrovascular burden. While anatomical Magnetic Resonance Imaging (MRI) is well established for quantifying brain atrophy in FTD, the variability in (pre-)processing methods limits the generalizability and comparability of findings. This study systematically compared the robustness and sensitivity of multiple widely used neuroimaging approaches, namely Deformation-Based Morphometry (DBM), Voxel-Based Morphometry (VBM), Cortical Thickness (CT), and segmentation-based Volumes, in detecting atrophy across FTD subtypes. We processed 732 T1-weighted MRI scans from 156 participants with FTD and 139 healthy controls from the Frontotemporal Lobar Degeneration Neuroimaging Initiative using our in-house pipeline PELICAN for volumetric measures and FreeSurfer for CT and segmentations. Visual quality control at each step of the pipelines revealed significantly higher failure rates for CT (38.52%) and segmentations (23.63%) relative to volumetric measures (2.04% DBM, 3.05% VBM). We then applied linear-mixed effects models to assess each metric’s sensitivity in detecting differences between FTD groups and controls as well as longitudinal anatomical changes. While CT yielded effect sizes comparable to VBM and DBM when analyzing the same subset of successfully processed scans, VBM and DBM demonstrated enhanced power to detect effects due to lower failure rates and higher participant retention in the full sample. Overall, we demonstrate that image processing methodology and pipeline selection profoundly influences effect sizes and statistical power to detect meaningful between-group differences or longitudinal changes. In the FTD cohort examined here, volumetric measures (DBM and VBM) yielded sufficiently robust results to maintain adequate statistical power for capturing atrophy patterns after quality control procedures.