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The perirhinal cortex (PRC) is a site of early neurofibrillary tangle (NFT) pathology in Alzheimer's disease (AD). Subtle morphological changes in the PRC have been reported in MRI studies of early AD, which has significance for clinical trials targeting preclinical AD. However, the PRC exhibits considerable anatomical variability with multiple discrete variants described in the neuroanatomy literature. We hypothesize that different anatomical variants are associated with different patterns of AD-related effects in the PRC. Single-template approaches conventionally used for automated image-based brain morphometry are ill-equipped to test this hypothesis. This study uses graph-based groupwise registration and diffeomorphic landmark matching with geodesic shooting to build statistical shape models of discrete PRC variants and examine variant-specific effects of AD on PRC shape and thickness. Experimental results demonstrate that the statistical models recover the folding patterns of the known PRC variants and capture the expected shape variability within the population. By applying the proposed pipeline to a large dataset with subjects from different stages in the AD spectrum, we find 1) a pattern of cortical thinning consistent with the NFT pathology progression, 2) different patterns of the initial spatial distribution of cortical thinning between anatomical variants, and 3) an effect of AD on medial temporal lobe shape. As such, the proposed pipeline could have important utility in the early detection and monitoring of AD.

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Characterizing Anatomical Variability and Alzheimer’s Disease Related Cortical Thinning in the Medial Temporal Lobe Using Graph-Based Groupwise Registration and Point Set Geodesic Shooting