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


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.
Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA. maldjian@wakehealth.edu
J A
JA
Maldjian
C T
CT
Whitlow
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18