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

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 used an implicit neural representation method to combine isotropic T1-weighted (T1w) and anisotropic T2w MRI to upsample an atlas set of expert-annotated MTL subregions, establishing a multi-modality, high-resolution training set of isotropic data for automatic segmentation with the nnU-Net framework. In an independent test set, the morphological measures extracted using this isotropic model showed stronger effect sizes than models trained on anisotropic in distinguishing participants with mild cognitive impairment (MCI) and cognitively unimpaired individuals. In test-retest analysis, morphological measures extracted using the isotropic model had greater stability. 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.