Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural...

Imaging biomarkers in magnetic resonance imaging (MRI) are important tools for diagnosing, tracking and treating Alzheimer's disease (AD). Neurofibrillary tau pathology in AD is closely linked to neurodegeneration and generally follows a pattern of spread in the brain, with early stages involving subregions of the medial temporal lobe (MTL). Accurate segmentation of MTL subregions is needed to extract granular biomarkers of AD progression. MTL subregions are often imaged using T2-weighted (T2w) MRI scans that are highly anisotropic due to constraints of MRI physics and image acquisition, making it difficult to reliably model MTL subregions geometrically and extract morphological measures, such as thickness. In this study, we propose a segmentation framework for MTL subregions in isotropic space, in which an implicit neural representation is used to construct the isotropic training atlas from the anisotropic low-resolution T2w data, with T1w MRI as an auxiliary modality to support the INR and segmentation. In an independent test set, the morphological measures extracted using this isotropic model showed stronger effect sizes than those from models trained on anisotropic data in distinguishing participants with mild cognitive impairment (MCI) from cognitively unimpaired individuals. In the test-retest analysis, the morphological measures extracted using the isotropic model showed greater stability than those from the anisotropic segmentation. This study demonstrates improved reliability of MRI-derived MTL subregion biomarkers without additional atlas annotation effort, which may more accurately quantify and track the relationship between AD pathology and brain atrophy for monitoring disease progression.