We investigated shape abnormalities in MCI and AD through the surface deformation maps of the seven structures. Their deformation maps were characterized by total 120 LB basis functions using Eq. (1)
. PCA extracted 9 principal components that accounted for 85% of the variance in these LB-coefficients. Linear regression analysis revealed the 1st, 4th, and 7th PCs with significant effects of diagnosis at significance level of 0.005 (p
-values in the first column of after controlling for age, sex, and eTIV. illustrates the scatterplot of these PC-scores within each diagnostic group.
The first column lists the principal components (PCs) with significant diagnostic effects on the surface deformation, while the rest of the columns list the PCs associated with significant differences in the surface deformation between paired groups
Fig. 2 The 1st, 4th, and 7th PC-scores from each individual subject are shown. Asterisks, circles, and diamonds respectively represent the measurements from the groups of healthy controls, patients with MCI and AD. Red marks represent mean values. The p-values (more ...)
Post-hoc pairwise comparisons revealed that the 1st and 7th PCs show significant group difference between CON and MCI; the 1st, 4th, and 7th PCs for the comparison between CON and AD; and only the 4th PC for the comparison between MCI and AD (p-values in ). To visualize significant shape differences between any two groups, for instance, between CON and MCI, we back projected the 1st and 7th PCs to the LB-coefficient space then to the template coordinates. illustrates this result in terms of ratio of local structural volume in CON to one in MCI. Based on the color scale, suggests most pronounced surface inward-deformation in MCI in the anterior segment of the hippocampus, basolateral complex of the amygdala and mild surface inward-deformation in the anterior aspect of caudate nucleus, anterior-lateral and ventral-lateral aspects of the thalamus, and no regionally-specific effects on the putamen or globus pallidus. also suggests most pronounced surface outward-deformation in the lateral ventricles and mild outward-deformation in the posterior segment of the hippocampus and medial aspect of the thalamus. Similarly, show group shape differences between CON and AD constructed by PCs 1, 4, 7 and between MCI and AD constructed by the 4th PC, respectively. Interestingly, the atrophic regions of the amygdala and hippocampus are adjacent to the inferior lateral ventricle with the outward-deformation in the more severe disease group (). To emphasize the significant changes in this mesial temporal area, illustrates the significant group shape differences only in the hippocampus, amygdala and lateral ventricles.
Fig. 3 Panels (a–c) respectively show group differences in the surface deformation between CON and MCI, CON and AD, as well as MCI and AD. Warm color denotes regions where structures have surface inward-deformation in the latter group when compared with (more ...)
Fig. 4 For visualization purpose, the deformation maps of the hippocampus, amygdala, and lateral ventricles shown in are repeatedly illustrated in this figure. Panels (a–c) respectively show the deformation differences between CON and MCI, CON (more ...)
The 4th PC contributes to the group shape differences between AD and CON or AD and MCI but not between CON and MCI (). We thus hypothesized that effects of AD on the seven shapes can be separated into two stages. The earlier stage associated with preclinical AD may be demonstrated by the 1st and 7th PCs; the late stage associated with AD by the 4th PC. To test this hypothesis, we respectively constructed the group differences between CON and AD using the 1st and 7th PC () and using the 4th PC (). The pattern in is highly correlated to the group shape difference between CON and MCI in (correlation coefficient: r = 1), while it has relatively low correlation with the one between MCI and AD in (r = 0.45). In contrast, is highly correlated with one in (r = 1) but has low correlation with one in (r = 0.45).
Panel (a) illustrates the shape difference between CON and AD constructed by the 1st and 7th PCs. Panel (b) illustrates the shape difference between CON and AD constructed by the 4th PC.
To evaluate the reliability of the findings shown in , the statistical testing procedure was repeatedly applied to the subset of the population. The results from the first subset are shown on the top row of , while those from the second subset are on the bottom row of . We quantitatively evaluated the correlation of the statistical surface deformation findings from the entire population () with ones from the subsets () in the pairwise group comparisons. All correlation coefficients are greater than 0.90 (p-values less than 0.0001), which suggest that the patterns of the differences in surface deformation obtained from the two subsets are highly consistent with those using the entire dataset.
Fig. 6 Reliability of the statistical findings. Panels (a–c) show the group comparisons in shapes conducted from the first subset with 194 subjects, while panels (d–f) illustrate those using the second subset with 189 subjects. The same color (more ...)