Multiparametric imaging hippocampal neurodegeneration and functional connectivity with simultaneous PET/MRI in Alzheimer’s disease

Abstract

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 18 F-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 18 F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on 18 F-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 18 F-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 18 F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD.

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

“…New experimental approaches including genome-wide association studies (GWAS) [ 188 , 191 , 192 ], CRISPR-Cas9 technology [ 193 , 194 , 195 ], high throughput screening (HTS) [ 196 ], organ-on-chip technologies [ 197 , 198 ], functional MRI (fMRI) techniques [ 199 , 200 ], and positron emission tomography (PET) [ 201 ] may lead to new drug targets for NDs, which can feed into future CADD projects.…”

Evaluating the association between brain atrophy, hypometabolism, and cognitive decline in Alzheimer’s disease: a PET/MRI study

“…In presenile-onset AD, the reduction in glucose metabolism is often centered in the parietotemporal association cortex, which is consistent with our study sample, whereas in senile-onset AD, glucose metabolism tends to be reduced in the limbic system and in the frontal lobe, which would be in line with studies reporting reduced hippocampal metabolism [ 30 , 31 ]. The other possible explanation is the heterogeneity of hippocampal subregion metabolism in AD patients, which showed lower glucose metabolism in specified subregions [ 22 ]. Due to selection bias, our selected coordinates may be located in subregions that had preserved hippocampal metabolism.…”

“…Therefore, PET/MR scanners are the ideal tool to investigate the relationship between multiple imaging features and cognitive performance in AD. To date, published studies on hybrid PET/MR of AD have mainly focused on the relationship between different modalities (e.g., metabolic activity, intrinsic network connectivity and brain volume) [ 22 – 25 ] as well as the relationship between functional image features and cognitive performance [ 22 , 25 ]. In the present study, by using hybrid PET/MRI, we hypothesized that the combination of atrophy and metabolic changes in the hippocampus and the DMN could be used to comprehensively explore the neural mechanisms underlying cognitive impairment in AD.…”

Zero Echo Time MRAC on FDG-PET/MR Maintains Diagnostic Accuracy for Alzheimer’s Disease; A Simulation Study Combining ADNI-Data

“…Positron emission tomography (PET)/magnetic resonance (MR) has been distributed worldwide and started to be used for the evaluation of dementia both in the clinical and research setting (Drzezga et al, 2014;Barthel et al, 2015;Fendler et al, 2016;Henriksen et al, 2016;Mainta et al, 2017;Zhang et al, 2017;Hope et al, 2019;Prato et al, 2019;Yan et al, 2020). The multimodal evaluation combining functional images such as PET and morphological images such as MR imaging (MRI) is optimal because each of them provides complementary information (Teipel et al, 2015;Kaltoft et al, 2019).…”

“…The multimodal evaluation combining functional images such as PET and morphological images such as MR imaging (MRI) is optimal because each of them provides complementary information (Teipel et al, 2015;Kaltoft et al, 2019). In addition, the motion artifact or partial volume effect on PET images can be minimized by utilizing simultaneous acquisition of MRI (Chen et al, 2018;Yan et al, 2020).…”