Positron Emission Tomographic Measurement of Brain Acetylcholinesterase Activity Using N-[11C] methylpiperidin-4-yl Acetate Without Arterial Blood Sampling:Methodology of Shape Analysis and its Diagnostic Power for Alzheimer\u27s Disease

N-[11C] methylpiperidin-4-yl acetate([11C]MP4A) is a radiotracer that has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET) using a standard compartment model analysis and a metabolitecorrected arterial input function. In the current study, the authors evaluated the applicability of a simple kinetic analysis without blood sampling, namely shape analysis.First,the authors used computer simulations to analyze factors that affect the precision and bias of shape analysis, then optimized the shape analysis procedure for [11C]MP4A. Befor shape analysis execution, the later part of dynamic PET data except for the initial 3 minutes were smoothed by fitting to a bi-exponential function followed by linear interpolation of 8 data points between each of adjacen scan frames. Simulations showed that shape analysis yielded estimates of regional metabolic rates of [11C]MP4A by AChE(K3) with acceptable precision and bias in brain regions with low K3 values such as neocotex. Estimates in regions with higher K3 values became progressively more inaccurate. The authors then applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients with Alzheimer s disease(AD). There was a highly significant linear correlation in regional K3 estimates between shape and compartment analyses(300 neocortical regions,[shape K3]=0.93x[NLS K3], r=0.89,P<0.001). Significant reductions in K3 estimates of frontal, temporal,parietal,occipital,and sensorimotor cerebral cortices in patients with AD as compared with controls were observed when using shape analysis (P