Title:Imaging Biomarkers for Neurodegenerative Diseases from Detailed Segmentation of Medial Temporal Lobe Subregions on in vivo Brain MRI Using Upsampling Strategy Guided by High-resolution ex vivo MRI

Abstract:The medial temporal lobe (MTL) is a region impacted extensively and non-uniformly in early stages of Alzheimer's disease (AD). Regional MTL morphometric measures extracted from magnetic resonance imaging (MRI) are supportive features for the diagnosis of AD and related disorders (ADRD). Different MRI modalities have distinct advantages for MTL morphometry. Anisotropic T2-weighted (T2w) MRI is preferred for hippocampal subfields due to its higher contrast between hippocampal layers. Isotropic T1-weighted (T1w) MRI is beneficial for thickness calculation of extra-hippocampal subregions due to its stable image quality and isotropic resolution. We propose a multi-modality MTL segmentation algorithm that bridges the T1w and T2w modalities by bringing both to a nearly isotropic voxel space. Guided by high-resolution ex vivo 9.4T MRI, an upsampling model was designed for the ground truth segmentations. Combined with non-local means upsampling, this model was used to construct a nearly iso-tropic T1w and T2w MTL subregion segmentation training set, which was used to train a nnUNet model. Morphometric biomarkers extracted by this model were compared to those extracted using conventional models operating in anisotropic spaces on downstream tasks. Biomarkers extracted using the proposed model had greater ability to discriminate between individuals with mild cognitive impairment and cognitively unimpaired; and had great-er longitudinal stability. These findings suggest that the biomarkers derived from T1w and T2w MRI unsampled to nearly isotropic resolution have sig-nificant potential for improving disease diagnosis and monitoring disease progression in ADRD.