Pet parametric imaging of acetylcholine esterase activity without arterial blood sampling in normal subjects and patients with neurovegetative disease

The development of a method for a reliable quantification of 11C-MP4A PET images without arterial input function at pixel level in order to study acetylcholine esterase activity (AChE) is of clinical interest for the diagnosis of dementia and memory disorders. Two groups of subjects, normal control group (4 subjects - NC group) and Alzheimer disease group (7 subjects - AD group) participated for the study. AChE activity can be quantify by using a reference input function derived from region having a very high metabolism by AChE and a three-rate constant compartmental model. In order to obtain, at pixel level, accurate and precise estimates of model parameters in both low and moderate enzymatic expression regions, a novel method based on the use of the maximum a posteriori probability (MAP) Bayesian estimator has been developed. This method was compared to other approaches already published for quantification of AChE activity: 1) the method based on the use of a linear least squares (RLS) analysis; 2) the RRE method based on a simplification of the model structure; 3) the RRE_BF method which consider a basis function approach for RRE procedure; 4) the method R_NLLS based on a non linear least squares estimator. AChE activity was measured in terms of the rate constant for hydrolysis of 11C-MP4A, k3. Striatum (basal ganglia) was used as reference region based on its very high AChE activity. Parametric images of k3 obtained with MAP from areas with different levels of AChE activity were compared between groups and respect to the k3 estimates obtained with the other mathematical approaches. Despite the small group of subjects, the methods (RLS; RRE, RRE_BF, R_NLLS, MAP,) used to generate k3 parametric image were able to detect a reduction on AChE activity in neocortex of AD patients respect to NC. However, only MAP allows to quantify k3 in region with moderate enzyme expression like thalamus and brainstem. The different performance of the five estimation methods has an impact in the statistical significance of k3 differences. In fact, only the MAP method shows significant differences in thalamus and brainstem that are in good agreement with published study