Abstract

AbstractBackgroundLongitudinal measurement of medial temporal lobe (MTL) atrophy is shown to be effective in measuring Alzheimer’s disease (AD) progression and has been extensively studied on T1‐weighted MRI. However, there has been little work analyzing atrophy on high‐resolution T2‐weighted MRI of the hippocampal region, and it is unknown which MRI modality would yield a more effective biomarker of disease progression. We compare atrophy measurements derived from T1 and T2‐weighted MRI using a deep learning framework DeepAtrophy and a deformation‐based morphometry method ALOHA.MethodT2‐weighted MRI of 481 participants from ADNI2/3 are included in the study. DeepAtrophy was trained on 74 participants and evaluated on 407. During training, DeepAtrophy explicitly infers temporal information, such as the scan temporal order for a single scan pair and which image pair has a longer scan time interval for multiple scan pairs. During inference, DeepAtrophy predicts a “total progression score” for each scan pair. This score is expected to be higher (more progression) in individuals with more advanced AD. A similar experiment was conducted using T1‐weighted MRI from 481 ADNI2/GO participants (partially overlapping with T2‐weighted experiment). ALOHA pipelines tailored for T1‐weighted and hippocampal T2‐weighted MRI were evaluated on the same subjects and scan pairs as DeepAtrophy.ResultFor both T1 and T2‐weighted MRI, DeepAtrophy is more accurate, compared with ALOHA, in inferring the temporal order of a pair of longitudinal scans. In hypothetical one‐year and two‐years clinical trials scenarios simulated using ADNI data, DeepAtrophy has an improvement over ALOHA in detecting differences in progression between disease groups in both imaging modalities. The strongest effect for differentiating between Amyloid‐positive and Amyloid‐negative cognitively unimpaired group was obtained using DeepAtrophy progression measures on T2‐weighted MRI.ConclusionThis study supports the potential of high‐resolution focal T2‐weighted MRI of the hippocampus as a longitudinal biomarker of early AD progression suitable for future clinical trials.

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