Models and methods for derivation of in vivo neuroreceptor parameters withPET and SPECT reversible radiotracers

The science of quantitative analysis of PET and SPECT neuroreceptor imaging studies has grown considerably over the past decade. A number of methods h ave been proposed in which receptor parameter estimation results from fitti ng data to a model of the underlying kinetics of ligand uptake in the brain . These approaches have come to be collectively known as model-based method s and several have received widespread use. Here, we briefly review the mos t frequently used methods and examine their strengths and weaknesses. Kinet ic modeling is the most direct implementation of the compartment models, bu t with some tracers accurate input function measurement and good compartmen t configuration identification can be difficult to obtain. Other methods we re designed to overcome some particular vulnerability to error of classical kinetic modeling, but introduced new vulnerabilities in the process. Refer ence region methods obviate the need fur arterial plasma measurement, but a re not as robust to violations of the underlying modeling assumptions as me thods using the arterial input function. Graphical methods give estimates o f V-T without the requirement of compartment model specification. but provi de a biased estimator in the presence of statistical noise. True equilibriu m methods are quite robust, but their use is limited to experiments with tr acers that are suitable for constant infusion. In conclusion, there is no u niversally "best" method that is applicable to all neuroreceptor imaging st udies, and carefully evaluation of model-based methods is required for each radiotracer. (C) 2001 Elsevier Science Inc. All rights reserved.