Hippocampus shape characterization with 3D Zernike transformation in clinical Alzheimer's disease progression

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia among older adults. Mild cognitive impairment (MCI) is considered a transitional phase between healthy cognitive aging and dementia. Progressive brain volume reduction/atrophy, particularly of the hippocampus, is associated with the transition from normal to MCI, and then to AD. We aimed to develop methods to characterize the shape of hippocampus and explore its potential as an imaging marker to monitor clinical AD progression. We implemented a 3D Zernike transformation to characterize the shape changes of hippocampus in 428 older subjects with high-quality T₁-weighted volumetric brain scans from the Alzheimer's Disease Neuroimaging Initiative data set (151 normal, 258 MCI, and 19 AD). Over 2 years, 15 cognitively normal subjects converted to MCI, and 42 subjects with MCI converted to AD. We found a significant correlation between hippocampal volume changes and Zernike shape metrics. Before a clinical diagnosis of AD, the shapes of the left and right hippocampi changed slowly. After AD diagnosis, both volume and shape changed rapidly but were uncorrelated to each other. During the transition from a clinical diagnosis of MCI to AD, the shape of the left and right hippocampi changed in a correlated manner but became uncorrelated after AD diagnosis. Finally, the pace of hippocampus shape change was associated with its shape and the subject's age and disease condition. In conclusion, the hippocampus shape features characterized with 3D Zernike transformation, in complement to volume measures, may serve as a novel imaging marker to monitor clinical AD progression.