The use of PIB-PET as a dual pathological and functional biomarker in AD

Abstract

Amyloid imaging with positron emission tomography (PET) is presently used in Alzheimer's disease (AD) research. In this study we investigated the possibility to use early frames (ePIB) of the PIB scans as a rough index of CBF by comparing normalised early PIB values with cerebral glucose metabolism (rCMRglc). PIB-PET and FDG-PET were performed in 37 AD patients, 21 subjects with mild cognitive impairment (MCI) and 6 healthy controls (HC). The patients were divided based on their PIB retention (amyloid load) as either PIB positive (PIB+) or PIB negative (PIB-). Data of the unidirectional influx K(1) from a subset of the subjects including 7 AD patients and 3 HC was used for correlative analysis. Data was analysed using regions of interest (ROI) analysis. A strong, positive correlation was observed across brain regions between K(1) and ePIB (r=0.70; p≤0.001). The ePIB values were significantly lower in the posterior cingulate (p≤0.001) and the parietal cortices (p=0.002) in PIB+ subjects compared to PIB-, although the group difference were stronger for rCMRglc in cortical areas (p≤0.001). Strong positive correlations between ePIB and rCMRglc were observed in all cortical regions analysed, especially in the posterior cingulate and parietal cortices (p≤0.001). A single dynamic PIB-PET scan may provide information about pathological and functional changes (amyloidosis and impaired blood flow). This might be important for diagnosis of AD, enrichment of patients in clinical trials and evaluation of treatment effects. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

“…A time frame for early PiB uptake (1e8 minutes) exhibited a high correlation with FDG uptake and resulted in a comparable diagnostic value for discriminating between AD and frontotemporal lobe dementia. Furthermore, a strong correlation between FDG-PET and early PiB signal using the first 6 minutes of a dynamic PiB-PET scan was shown (Forsberg et al, 2012). When AD, MCI, and HCS were pooled and stratified into PiB-positive and -negative subjects, PiB-positive (i.e., high cortical amyloid load) subjects exhibited lower cerebral glucose metabolism and reduced early uptake of PiB (ePiB) indicating reduced CBF.…”

“…Regions analyzed for ePiB were single VOIs of the Hammers N30R83: left and right IFG, PCC, hipp, parahippocampal gyrus (parahipp) (including ambient gyrus), SPG, and a volume-weighted averaged group consisting of posterior temporal lobe and inferolateral remainder of parietal lobe henceforth referred to as the TR. Frames 0e6 minutes were selected as they have been shown to correlate with K1 and cerebral glucose metabolism (Forsberg et al, 2012).…”

Tracer Kinetic Analysis of (S)-18F-THK5117 as a PET Tracer for Assessing Tau Pathology

“…When combined with the relatively poor correlation and agreement between SUVr 70-90 -1 and BP ND and the fact that SRTM BP ND and reference Logan DVR-1 values are relatively stable over time for scan durations of 60 min or more whereas SUVr-1 values are not, this would suggest that a 60-min dynamic scan can be highly recommended over a single-time-point scan for the quantitative assessment of (S)-18 F-THK5117 binding to tau. Moreover, a dynamic scan can not only result in a parametric image of tau binding but also give a relative cerebral blood flow (R 1 ) image, which may be used for the assessment of overall brain function (24,25).…”

Dual-phase amyloid PET: hitting two birds with one stone

“…The data available so far show that early phase images have strong similarities with FDG PET images in AD and frontotemporal lobar degeneration [10,[12][13][14], can distinguish MCI from healthy controls [15], and recent evidence suggests a potential diagnostic advantage also in patients with cerebral amyloid angiopathy [16].…”