Shape and diffusion tensor imaging based integrative analysis of the hippocampus and the amygdala in Alzheimer's disease

Abstract

We analyzed, in an integrative fashion, the morphometry and structural integrity of the bilateral hippocampi and amygdalas in Alzheimer's disease (AD) using T1-weighted images and diffusion tensor images (DTIs). We detected significant hippocampal and amygdalar volumetric atrophies in AD relative to healthy controls (HCs). Shape analysis revealed significant region-specific atrophies with the hippocampal atrophy mainly being concentrated on the CA1 and CA2 while the amygdalar atrophy was concentrated on the basolateral and basomedial. In all structures, the structural integrity displayed a significantly decreased mean fractional anisotropy (FA) value and an increased mean trace value in AD. In addition to the inter-group comparisons, we systematically evaluated the discriminative power of our three types of features (volume, shape, and DTI), both individually and in their possible combinations, when differentiating between AD and HCs. We found the volume features to be redundant when the more sophisticated shape features were available. A combination of the shape and DTI features of the right hippocampus, with classification automatically performed by support vector machine, yielded the strongest classification result (overall accuracy, 94.6%; sensitivity, 95.5%; specificity, 93.3%).

Keywords: Amygdala; Diffusion tensor imaging; Hippocampus; Linear discriminant analysis; Shape; Support vector machine.

Conflict of interest statement

Michael I. Miller owns an equal share in Anatomyworks LLC. The terms of this arrangement have been reviewed and approved by the Johns Hopkins University, in accordance with its conflict of interest policy.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Fig. 1. Classification workflow

Work flow of the classification experiments using various combinations of features in a leave-one-out fashion.

Fig. 2. Volumetric measurement of each subject for each structure

Scatterplots of the volumetric measurements (in mm3) for the bilateral hippocampi and amygdalas in HC (blue diamonds) and AD (red outlined circles) subjects. Bars denote the mean volumetric measurements of each group.

Fig. 3. Shape analysis results on the left hippocampus

Panel (a) and panel (b) show the statistically significant vertex-wise surface area differences of the left hippocampus after FWER-correction and FDR-correction respectively. The color bar denotes the proportion of atrophy in AD relative to HC. Panel (c) denotes the four-compartment subdivisions of the study-specific template surface of the left hippocampus.

Fig. 4. Shape analysis results on the right hippocampus

Panel (a) and panel (b) show the statistically significant vertex-wise surface area differences of the right hippocampus after FWER-correction and FDR-correction respectively. The color bar denotes the proportion of atrophy in AD relative to HC. Panel (c) denotes the four-compartment subdivisions of the study-specific template surface of the right hippocampus.

Fig. 5. Shape analysis results on the left amygdala

Panel (a) and panel (b) show the statistically significant vertex-wise surface area differences of the left amygdala after FWER-correction and FDR-correction respectively. The color bar denotes the proportion of atrophy in AD relative to HC. Panel (c) denotes the four-compartment subdivisions of the study-specific template surface of the left amygdala.

Fig. 6. Shape analysis results on the right amygdala

Panel (a) and panel (b) show the statistically significant vertex-wise surface area differences of the right amygdala after FWER-correction and FDR-correction respectively. The color bar denotes the proportion of atrophy in AD relative to HC. Panel (c) denotes the four-compartment subdivisions of the study-specific template surface of the right amygdala.

Fig. 7. Mean FA value of each subject within each structure

Scatterplots of the mean FA values within the left and right hippocampus and amygdala in HC (blue diamonds) and AD (red open circles) subjects. Bars denote the value of the mean FA averaged across each group.

Fig. 8. Mean trace value of each subject within each structure

Scatterplots of the mean trace values within the left and right hippocampus and amygdala in HC (blue diamonds) and AD (red open circles) subjects. Bars denote the value of the mean trace averaged across each group.