Regional shape abnormalities in mild cognitive impairment and Alzheimer's disease

Abstract

Magnetic resonance (MR) based shape analysis provides an opportunity to detect regional specificity of volumetric changes that may distinguish mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy elderly controls (CON), and predict future conversion to AD. We assessed the surface deformation of seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, body and temporal horn of the lateral ventricles) in 383 MRI volumes, based on data shared through the publicly available Alzheimer's Disease Neuroimaging Initiative (ADNI), to identify regionally-specific shape abnormalities in MCI and AD. Large deformation diffeomorphic metric mapping (LDDMM) was used to generate the shapes of seven structures based on template shapes injected into segmented subcortical volumes. LDDMM then constructed the surface deformation maps encoding the local shape variation of each subject relative to the template. Hierarchical models were developed to detect differences in local shape in MCI and AD relative to CON. Our findings revealed that surface inward-deformation in MCI and AD is most prominent in the anterior hippocampal segment and the basolateral complex of the amygdala. Most pronounced surface outward-deformation in MCI and AD occurs in the lateral ventricles. Mild surface inward-deformation in MCI and AD occurs in the anterior-lateral and ventral-lateral aspects of the thalamus, with no evidence of regionally-specific deformation in the putamen or globus pallidus. Although the locations of the shape abnormalities in MCI and AD are primarily within the mesial temporal region, analyses support distinct components of correlated shape variation that may help predict future MCI conversion.

Fig. 1

Figure illustrates the schematic of a shape analysis pipeline, including FreeSurfer subcortical segmentation, template shape injection, surface deformation map generation, and statistical random field testing. Panels 2 and 3 as well as template panel show color coded seven structures in the surface representation. The fourth panel illustrates the deformation map of one subject relative to the template, which is used in a random field model to make statistical inference.

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 associated with group comparisons are listed in Table 2.

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 the former group. Cool color denotes regions where structures have surface outward-deformation in the latter group when compared with the former group. Key: Am — amygdala, Hp — hippocampus, V — ventricles, iLV — inferior lateral ventricles, Cd — caudate, Pu — putamen, Pa — globus pallidus, Th — thalamus.

Fig. 4

For visualization purpose, the deformation maps of the hippocampus, amygdala, and lateral ventricles shown in Fig. 3 are repeatedly illustrated in this figure. Panels (a–c) respectively show the deformation differences between CON and MCI, CON and AD, as well as MCI and AD. The superior and inferior views of the hippocampus and amygdala are shown in the first two columns and the medial view of the lateral ventricles is shown in the last column.

Fig. 5

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.

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 scale is used as in Figs. 3(a–c).