Can target-to-pons ratio be used as a reliable method for the analysis of [ 11C]PIB brain scans?

Rationale: 11C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [ 11C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [ 11C]PIB binding. Methods: 12 sporadic AD subjects aged 65±4.5yrs with a mean MMSE 21.4±4 and 10 age-matched control subjects had [ 11C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [ 11C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V T) were generated with Logan analysis. Additionally, parametric maps of the 60-90min target-to-cerebellar ratio (RATIO CER) and the 60-90min target-to-pons ratio (RATIO PONS) were computed. Results: All three approaches were able to differentiate AD from controls (p<0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIO CER and RATIO PONS differences higher than V T with use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient>0.83); RATIO CER performed best closely followed by RATIO PONS. The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO CER, but the RATIO PONS approach revealed higher [ 11C]PIB binding in cortex and cerebellum. Conclusion: This study established 60-90min target-to-pons RATIOs as a reliable method of analysis in [ 11C]PIB PET studies where cerebellum is not an appropriate reference region. © 2012 Elsevier Inc.