MR‐based spatiotemporal anisotropic atrophy evaluation of hippocampus in Alzheimer's disease progression by multiscale skeletal representation

Increasing evidence has shown a higher sensitivity of Alzheimer's disease (AD) progression by local hippocampal atrophy rather than the whole volume. However, existing morphological methods based on subfield‐volume or surface in imaging studies are not capable to describe the comprehensive process of hippocampal atrophy as sensitive as histological findings. To map histological distinctive measurements onto medical magnetic resonance (MR) images, we propose a multiscale skeletal representation (m‐s‐rep) to quantify focal hippocampal atrophy during AD progression in longitudinal cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The m‐s‐rep captures large‐to‐small‐scale hippocampal morphology by spoke interpolation over label projection on skeletal models. To enhance morphological correspondence within subjects, we align the longitudinal m‐s‐reps by surface‐based transformations from baseline to subsequent timepoints. Cross‐sectional and longitudinal measurements derived from m‐s‐rep are statistically analyzed to comprehensively evaluate the bilateral hippocampal atrophy. Our findings reveal that during the early AD progression, atrophy primarily affects the lateral‐medial extent of the hippocampus, with a difference of 1.8 mm in lateral‐medial width in 2 years preceding conversion (p < .001), and the medial head exhibits a maximum difference of 3.05%/year in local atrophy rate (p = .011) compared to controls. Moreover, progressive mild cognitive impairment (pMCI) exhibits more severe and widespread atrophy in the head and body compared to stable mild cognitive impairment (sMCI), with a maximum difference of 1.21 mm in thickness in the medial head 1 year preceding conversion (p = .012). In summary, our proposed method can quantitatively measure the hippocampal morphological changes on 3T MR images, potentially assisting the pre‐diagnosis and prognosis of AD.