A Preliminary Study Of¹¹C-PIB PET In Alzheimer’s Disease And Amnestic Mild Cognitive Impairment

Alzheimer’s disease (AD) is a neurodegenerative disease. It is difficult to make an early diagnosis because it is insidious onset and lack of specific biomarkers. One of the neuropathological hallmarks of AD is the formation of senile plaques, which is composed of fibril amyloid β-protein (Aβ). And amyloid deposition is an early event on the path to dementia.Objective "C-PIB can selectively bind to fibrillar amyloid-β deposits, and quantitatively monitor the Aβ plaque changes in vivo. In the present study, aMCI and AD patients were investigated with PET/CT using11C-PIB to study relationship between the plaque deposition and neuronal activity in comparison with18F-FDG PET. We further explore the pathogenesis of AD through the default network. We also combined the APOE ε4allele to explore the correlation between aMCI and AD. This is a preliminary study to test the ability of11C-PIB in screening the AD type MCI and to assess the role of PIB PET imaging in early diagnosis, early intervention and anti-amyloid therapy effect evaluation.Materials and methods Twenty three subjects including4normal contol (NC),10amnestic mild cognitive impairment (aMCI), and9AD were enrolled in this study.The expression of ApoE alleles were examined by PCR. The resting state of T1WIMRI,11C-PIB and18F-FDG PET were performed in the same day. The PIB PET scans were acquired during a90-min dynamic PET acquisition and the FDG PET scans were acquired with a10-min static PET acquisition. Subsequently, the PET results were evaluated by three different methods including visual analysis, the SPM (statistical parametric mapping) and the voxel-based automated quantitative analysis. Visual anlysis were performed independently by two nuclear medicine physicians blinded to final diagnosis with consensus. SPM was performed to determine the functional anatomy by co-registration, normalization, smoothing effect and statistical analysis on original dataset. The significance level was set as P<0.005. The voxel-based automated quantitative analysis was performed by SPM software. A grey matter imaging was firstly extracted from MR imaging and then fused with PET imaging. Eleven regions of interest (ROIs) was set on MFG, MPFC, IP, LTC, PCCPre, HF+, OL, STG, SMA, Striatum and Thalamus, both inside and outside the DMN. PET and their PIB and FDG uptake were measured with posterior lobe of the cerebellar cortex as reference region. Independent Student’s t-tests were used to assess the differences in PIB and FDG means between AD group and NC group. Pearson’s correlations were used to assess the relationships between PIB and FDG uptake of AD group. Pearson’s correlations were used to assess the relationships between PIB uptake of AD group and FDG uptake of NC group. ANOVA were used to compare differences in radiotracer uptake within different brain regions among aMCI PIB+group, aMCI PIB-group, AD group and NC group. P<0.05was considered to indicate a statistically significant difference.Rusults(1) Visual analysis showed there was very lower PIB uptake in cerebral cortex, subcortical structures and cerebellum in NC group. Little PIB uptake was detected in white matter area. In AD group, there is higher PIB uptake in frontal lobe, precuneus, lateral temporal lobe and striatum, mostly bilaterally. Little PIB uptake was detected in cerebellum.(2) Voxel-based automatic quantitative analysis shows that the mean PIB SUVR of all ROIs in NC group ranged from1.1to1.2. In AD group, the SUVR of IP, LTC, MFG, MPFC, PCCPRE,OL,SMA and Striatum ranged from1.8to2.1, which were1.6-1.9times more than that in NC group. These two groups showed significant difference (P<0.05). Although HF+in AD group showed relatively lower PIB uptake, it had significant difference (P<0.05) with that of NC group. Thalamus in AD group displays lower PIB uptake and has no significant difference (P>0.05) with that of NC group.(3) PIB binding levels in aMCI were bimodal. Using1.6as negative cutoff value of PIB, the aMCI group could be divided into PIB+aMCI subgroup and PIB-aMCI subgroup. There was no significant difference either between PIB+aMCI subgroup and AD group (P>0.05) or between PIB-aMCI subgroup and NC group in all ROIs (P>0.05).(4) The ApoE s4allele carriers account for75%in PIB+aMCI subgroup, and0%in PIB-aMCI subgroup. (5) There are3PIB+aMCI subjects showed bilateral parietal lobe, temporal lobe and precuneus hypometabolism and3PIB-aMCI subjects showed bilateral frontal lobe, anterior cingulated hypometabolism. The rest4subjects displayed normal in FDG PET. Two of them were PIB+aMCI and others were PIB-aMCI.(6) SPM analysis reveals that amyloid deposition and hypometabolism were in the same regions, but the most remarkable regions in amyloid deposition and hypometabolism are different. The ROIs of PIB and FDG SUVR in AD group showed no correlations. The correlation between the PIB uptake of AD group and FDG uptake of NC group is strong (r=0.63, P<0.05).Conclusions1. The A(3plaque depositoion level in AD is significant higher than in NC. PIB binding levels in aMCI are bimodal. PIB PET is a powerful tool to screen aMCI with AD pathology. And aMCI PIB+group take the ApoE s4allele are more than the aMCI PIB-group. PIB PET has the ability in screening the AD type MCI and can be used to make early diagnosis, early intervention and anti-amyloid therapy effect evaluation.2. High resting glucose metabolic activity, rather than glucose hypometabolism, is associated with the pattern of Aβ plaque deposition both inside and outside the DMN.