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In this work, we propose and test a new approach for non-linear kinetic parameters' estimation from dynamic PET data. A technique is discussed, to derive an analytical closed-form expression of the compartmental model used for kinetic parameters' evaluation, using an auxiliary parameter set, with the aim of reducing the computational burden and speeding up the fitting of these complex mathematical expressions to noisy TACs. Two alternative algorithms based on numeric calculations are considered and compared to the new proposal. We perform a simulation study aimed at (i) assessing agreement between the proposed method and other conventional ways of implementing compartmental model fitting, and (ii) quantifying the reduction in computational time required for convergence. It results in a speed-up factor of ∼120 when compared to a fully numeric version, or ∼38, with respect to a more conventional implementation, while converging to very similar values for the estimated model parameters. The proposed method is also tested on dynamic 3D PET clinical data of four control subjects. The results obtained supported those of the simulation study, and provided input and promising perspectives for the application of the proposed technique in clinical practice.

We propose and test a novel approach for direct parametric image reconstruction of dynamic PET data. We present a theoretical description of the problem of PET direct parametric maps estimation as an inference problem, from a probabilistic point of view, and we derive a simple iterative algorithm, based on the Iterated Conditional Mode (ICM) framework, which exploits the simplicity of a two-step optimization and the efficiency of an analytic method for estimating kinetic parameters from a nonlinear compartmental model. The resulting method is general enough to be flexible to an arbitrary choice of the kinetic model, and unlike many other solutions, it is capable to deal with nonlinear compartmental models without the need for linearization. We tested its performance on a two-tissue compartment model, including an analytical solution to the kinetic parameters evaluation, based on an auxiliary parameter set, with the aim of reducing computation errors and approximations. The new method is tested on simulated and clinical data. Simulation analysis led to the conclusion that the proposed algorithm gives a good estimation of the kinetic parameters in any noise condition. Furthermore, the application of the proposed method to clinical data gave promising results for further studies.

The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([The synthetic procedure and the quality control of the selected lead compound, [In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [The suitable pharmacokinetics and the specificity tested in the pre-treated animals have indicated the potentiality of this AEPH derivative to act as Pgp ligand, providing new opportunities for further studies on expression and function of this important efflux transporter in the fields of neurology and oncology.