Direct Estimation of Voxel-Wise Neurotransmitter Response Maps From Dynamic PET Data

Computational methods, such as the linear parametric neurotransmitter PET (lp-ntPET) method, have been developed to characterize the transient changes in radiotracer kinetics in the target tissue during endogenous neurotransmitter release. In this paper, we describe and evaluate a parametric reconstruction algorithm that uses an expectation maximization framework, along with the lp-ntPET model, to estimate the endogenous neurotransmitter response to stimuli directly from the measured PET data. Computer simulations showed that the proposed direct reconstruction method offers improved accuracy and precision for the estimated timing parameters of the neurotransmitter response at the voxel level ( ${t}_{d}=1\pm 2 $ min, for activation onset bias and standard deviation) compared with conventional post reconstruction modeling ( ${t}_{d}=4\pm 7 $ min). In addition, we applied the proposed direct parameter estimation methodology to a [11C]raclopride displacement study of an awake rat and generated parametric maps illustrating the magnitude of ligand displacement from striatum. Although the estimated parametric maps of activation magnitude obtained from both direct and post reconstruction methodologies suffered from false positive activations, the proposed direct reconstruction framework offered more reliable parametric maps when the activation onset parameter was constrained.