Christopher A. Brown

Yue Li, Pulkit Khandelwal, Long Xie et al.

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.

Xavier Beltran-Urbano, Yiran Li, Xinglin Zeng et al.

Arterial spin labeling (ASL) perfusion MRI allows direct quantification of regional cerebral blood flow (CBF) without exogenous contrast, enabling noninvasive measurements that can be repeated without constraints imposed by contrast injection. ASL is increasingly acquired in research studies and clinical MRI protocols. Building on successes in structural imaging, recent efforts have implemented deep learning based methods to improve image quality, enable automated quality control, and derive robust quantitative and predictive biomarkers with ASL derived CBF. However, progress has been limited by variable image quality, substantial inter-site, vendor and protocol differences, and limited availability of labeled datasets needed to train models that generalize across cohorts. To address these challenges, we introduce ICHOR, a self supervised pre-training approach for ASL CBF maps that learns transferable representations using 3D masked autoencoders. ICHOR is pretrained via masked image modeling using a Vision Transformer backbone and can be used as a general-purpose encoder for downstream ASL tasks. For pre-training, we curated one of the largest ASL datasets to date, comprising 11,405 ASL CBF scans from 14 studies spanning multiple sites and acquisition protocols. We evaluated the pre-trained ICHOR encoder on three downstream diagnostic classification tasks and one ASL CBF map quality prediction regression task. Across all evaluations, ICHOR outperformed existing neuroimaging self-supervised pre-training methods adapted to ASL. Pre-trained weights and code will be made publicly available.

Yue Li, Pulkit Khandelwal, Rohit Jena et al.

Imaging biomarkers in magnetic resonance imaging (MRI) are important tools for diagnosing and tracking Alzheimer's disease (AD). As medial temporal lobe (MTL) is the earliest region to show AD-related hallmarks, brain atrophy caused by AD can first be observed in the MTL. Accurate segmentation of MTL subregions and extraction of imaging biomarkers from them are important. However, due to imaging limitations, the resolution of T2-weighted (T2w) MRI is anisotropic, which makes it difficult to accurately extract the thickness of cortical subregions in the MTL. In this study, we used an implicit neural representation method to combine the resolution advantages of T1-weighted and T2w MRI to accurately upsample an MTL subregion atlas set from anisotropic space to isotropic space, establishing a multi-modality, high-resolution atlas set. Based on this atlas, we developed an isotropic MTL subregion segmentation model. In an independent test set, the cortical subregion thickness extracted using this isotropic model showed higher significance than an anisotropic method in distinguishing between participants with mild cognitive impairment and cognitively unimpaired (CU) participants. In longitudinal analysis, the biomarkers extracted using isotropic method showed greater stability in CU participants. This study improved the accuracy of AD imaging biomarkers without increasing the amount of atlas annotation work, which may help to more accurately quantify the relationship between AD and brain atrophy and provide more accurate measures for disease tracking.