Metrics to track dopamine release magnitude using PET: Comparison of Residual Space Detection and linear parametric neurotransmitter PET

Residual Space Detection (RSD) has been previously shown to improve upon traditional methods for detecting low-magnitude dopamine (DA) release in the human brain by use of [11C]raclopride PET scanning. This work aims to extend this methodology, by examining RSD’s ability to track DA release-induced changes in synaptic DA levels, with the goal of identifying a suitable metric that can be related to behavioural and clinical measures of interest to various research studies. We compare RSD outputs with the traditional metric from linear parametric neurotransmitter PET (lp-ntPET) by means of simulation. Both methods track transient changes in synaptic DA concentration well, exhibiting near-linear scaling of their respective metric with simulated levels of DA release and achieving coefficients of variation between 20-40%. For simulated DA concentration increases from 50 to 275 pmol, RSD’s metric exhibited a 3 to 4x increase compared to lp-ntPET’s 1.5 to 2x increase, along with a y-intercept of close to zero, providing a more sensitive and interpretable measure to track single-task DA release.