Abstract
BackgroundMultimodal PET/MRI image data simultaneously obtained from patients with early-stage of Alzheimer’s disease (eAD) were assessed in order to observe pathophysiologic and functional changes, as well as alterations of morphology and connectivity in the brain. Fifty-eight patients with mild cognitive impairment and early dementia (29 males, 69 ± 12 years) underwent [11C]Pittsburgh compound-B (PiB) PET/MRI with 70-min PET and MRI scans. Sixteen age-matched healthy controls (CTL) (9 males, 68 ± 11 years) were also studied with the same scanning protocol. Cerebral blood flow (CBF) was calculated from the early phase PET images using the image-derived input function method. A standardized uptake value ratio (SUVr) was calculated from 50 to 70 min PET data with a reference region of the cerebellar cortex. MR images such as 3D-T1WI, resting-state functional MRI (RS-fMRI), diffusion tensor image (DTI), and perfusion MRI acquired during the dynamic PET scan were also analyzed to evaluate various brain functions on MRI.ResultsTwenty-seven of the 58 patients were determined as eAD based on the results of PiB-PET and clinical findings, and a total of 43 subjects’ data including CTL were analyzed in this study. PiB SUVr values in all cortical regions of eAD were significantly greater than those of CTL. The PiB accumulation intensity was negatively correlated with cognitive scores. The regional PET-CBF values of eAD were significantly lower in the bilateral parietal lobes and right temporal lobe compared with CTL, but not in MRI perfusion; however, SPM showed regional differences on both PET- and MRI-CBF. SPM analysis of RS-fMRI delineated regional differences between the groups in the anterior cingulate cortex and the left precuneus. VBM analysis showed atrophic changes in the AD group in a part of the bilateral hippocampus; however, analysis of fractional anisotropy calculated from DTI data did not show differences between the two groups.ConclusionMultimodal analysis conducted with various image data from PiB-PET/MRI scans showed differences in regional CBF, cortical volume, and neuronal networks in different regions, indicating that pathophysiologic and functional changes in the AD brain can be observed from various aspects of neurophysiologic parameters. Application of multimodal brain images using PET/MRI would be ideal for investigating pathophysiologic changes in patients with dementia and other neurodegenerative diseases.
Highlights
Multimodal positron emission tomography (PET)/magnetic resonance imaging (MRI) image data simultaneously obtained from patients with early-stage of Alzheimer’s disease were assessed in order to observe pathophysiologic and functional changes, as well as alterations of morphology and connectivity in the brain
To control for motion confounds in the resting-state functional MRI (RS-fMRI) data, we investigated the effects of head motion by computing the mean frame-to-frame root mean squared motion, and frame-wise displacement obtained during the realignment process [27, 28]
The hippocampus volumes in Alzheimer’s disease (AD) patients tended to decrease in the Z-score of VSRAD, the difference was not significant in comparison with CTL (P > 0.05)
Summary
Multimodal PET/MRI image data simultaneously obtained from patients with early-stage of Alzheimer’s disease (eAD) were assessed in order to observe pathophysiologic and functional changes, as well as alterations of morphology and connectivity in the brain. MR images such as 3D-T1WI, resting-state functional MRI (RS-fMRI), diffusion tensor image (DTI), and perfusion MRI acquired during the dynamic PET scan were analyzed to evaluate various brain functions on MRI Molecular imaging methods such as amyloid/tau PET are very important recently for appropriate diagnosis of patients with dementia, who have cognitive complaints induced by neurodegenerative changes. A new hybrid functional brain imaging system combining positron emission tomography (PET) and MRI, the PET/MRI scanner, is very beneficial in this regard, and seems to be ideal in the neuropsychiatric field to apply a molecular and functional imaging approach to the assessment of cerebral pathophysiologic changes [1, 2] This system has been applied to the studies of neurodegenerative diseases including Alzheimer’s disease (AD) as well as cerebrovascular diseases [3,4,5,6]. Several studies showed relationships between changes in metabolism or blood flow and functional or morphological MRI information; reports of integrated analysis using amyloid/tau imaging and functional MRI are very few
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