Assessment of motion and model bias on the detection of dopamine response to behavioral challenge

Compartmental modeling analysis of ¹¹C-raclopride (RAC) PET data can be used to measure the dopaminergic response to intra-scan behavioral tasks. Bias in estimates of binding potential (BP_ND) and its dynamic changes (ΔBP_ND) can arise both when head motion is present and when the compartmental model used for parameter estimation deviates from the underlying biology. The purpose of this study was to characterize the effects of motion and model bias within the context of a behavioral task challenge, examining the impacts of different mitigation strategies. Seventy healthy adults were administered bolus plus constant infusion RAC during a simultaneous PET/magnetic resonance (MR) scan with a reward task experiment. BP_ND and ΔBP_ND were estimated using an extension of the Multilinear Reference Tissue Model (E-MRTM2) and a new method (DE-MRTM2) was proposed to selectively discount the contribution of the initial uptake period. Motion was effectively corrected with a standard frame-based approach, which performed equivalently to a more complex reconstruction-based approach. DE-MRTM2 produced estimates of ΔBP_ND in putamen and nucleus accumbens that were significantly different from those estimated from E-MRTM2, while also decoupling ΔBP_ND values from first-pass k₂' estimation and removing skew in the spatial bias distribution of parametric ΔBP_ND estimates within the striatum.