Whither the hippocampus? FDG-PET hippocampal hypometabolism in Alzheimer disease revisited.

ABSTRACT:

Background and purpose

The hippocampus is a widely recognized area of early change in AD, yet voxelwise analyses of FDG-PET activity differences between AD and CN controls have consistently failed to identify hippocampal hypometabolism. In this article, we propose a high-dimensional PET-specific analysis framework to determine whether important hippocampal metabolic FDG-PET activity differences between patients with AD and CN subjects are embedded in the Jacobian information generated during spatial normalization.

Materials and methods

Resting FDG-PET data were obtained from 102 CN and 92 participants with AD from the ADNI data base. A PET-study-specific template was constructed using symmetric diffeomorphic registration. Spatially normalized raw FDG maps, Jacobian determinant maps, and modulated maps were generated for all subjects. Statistical parametric mapping and tensor-based morphometry were performed, comparing patients with AD with CN subjects.

Results

Whole-brain spatially normalized raw FDG maps demonstrated robust hypometabolism in cingulate gyrus and bilateral parietal areas. No hippocampal differences were present, except on ROI-based analyses with a hippocampal mask. Whole-brain modulated maps demonstrated robust bilateral hippocampal hypometabolism, and some hypometabolism in the posterior cingulate. Tensor-based morphometry demonstrated robust hippocampal differences only.

Conclusions

These results demonstrate that hippocampal metabolic differences are embedded in the Jacobian information from the spatial normalization procedure. We introduce a voxelwise PET-specific analysis framework based on the use of a PET-population-specific template, high-dimensional symmetric diffeomorphic normalization, and the use of Jacobian information, which can provide substantially increased statistical power and an order of magnitude decrease in imaging costs.

SUBMITTER: Maldjian JA 

PROVIDER: S-EPMC7964612 | biostudies-literature |

REPOSITORIES: biostudies-literature