Parametric visualisation and quantification of tau pathology in human brain using PET with [C-11]PBB3

Objectives Tau accumulation is a pathological hallmark in the brain of patients with Alzheimer's disease (AD) and other tauopathies such as progressive supranuclear palsy and corticobasal syndrome. Parametric visualizulization and quantification of tau accumulation should help physicians to diagnose and prognosticate tauopathies. We developed a method to generate parametric images reflecting tau accumulation in the brain using a reference tissue model (MRTMo) and [C-11]PBB3 dynamic data. The method was validated by modified graphical analyses to account for radioactive metabolites entering the brain.

Methods Seven PIB-positive AD patients and 7 PIB-negative healthy controls (HC) went a 70-min dynamic PET scan after an injection of [C-11]PBB3. Parametric images of binding potential (BP_ND) were generated with MRTMo. In the regions with high and low tau accumulation, the parametric BP_ND values were compared to those BP_P values estimated from ROI-based modified graphical analyses (J Nucl Med 1999,1902). To shorten the scan length, parametric images with initial 30-min data and standardized uptake value ratio images (SUVR-1) from 50-70 min data were also evaluated.

Results The parametric images showed clear contrasts of BP_ND values in the cortices between AD patients and HC except in the extra-axial venous sinus with high artifact BP_ND values. Parametric BP_ND values showed an excellent correlation with graphical BP_P values (r² = 0.87). BP_ND values with short-scan length and SUVR-1 values also showed good correlation, but they showed underestimation and overestimation of the BP_P values (r² = 0.81 and 0.73), respectively.

Conclusions Parametric imaging with MRTMo for [C-11]PBB3 PET appears an excellent way to visualize and quantify tau accumulation in the brain.