Purpose: The objective of this study is to investigate the hippocampal neurodegeneration and its associated aberrant functions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients using simultaneous PET/MRI.
Methods: Forty-two cognitively normal controls (NC), 38 MCI, and 22 AD patients were enrolled in this study. All subjects underwent 18F-FDG PET/functional MRI (fMRI) and high-resolution T1-weighted MRI scans on a hybrid GE Signa PET/MRI scanner. Neurodegeneration in hippocampus and its subregions was quantified by regional gray matter volume and 18F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on 18F-FDG PET images. Regional gray matter volume was estimated from voxel-based morphometric analysis with MRI. fMRI data were analyzed after slice time correction and head motion correction using statistical parametric mapping (SPM12) with DPARSF toolbox. The regions of interest including hippocampus, cornu ammonis (CA1), CA2/3/dentate gyrus (DG), and subiculum were defined in the standard MNI space.
Results: Patient groups had reduced SUVR, gray matter volume, and functional connectivity compared to NC in CA1, CA2/3/DG, and subiculum (AD < MCI < NC). There was a linear correlation between the left CA2/3DG gray matter volume and 18F-FDG SUVR in AD patients (P < 0.001, r = 0.737). Significant correlation was also found between left CA2/3/DG-superior medial frontal gyrus functional connectivity and left CA2/3/DG hypometabolism in patients with AD. The functional connectivity of right CA1-precuneus in patients with MCI and right subiculum-superior frontal gyrus in patients with AD was positively correlated with mini mental status examination scores (P < 0.05).
Conclusion: Our findings demonstrate that the associations existed at subregional hippocampal level between the functional connectivity measured by fMRI and neurodegeneration measured by structural MRI and 18F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD.
Keywords: Alzheimer’s disease; Hippocampal subregions; Hybrid PET/MRI; Neurodegeneration; Voxel-based morphometric analysis.