Spatiotemporal Kernel Reconstruction for Linear Parametric Neurotransmitter PET Kinetic Modeling in Motion Correction Brain PET of Awake Rats

The linear parametric neurotransmitter positron emission tomography (lp-ntPET) kinetic model can be used to detect transient changes (activation) in endogenous neurotransmitter levels. Preclinical PET scans in awake animals can be performed to investigate neurotransmitter transient changes. Here we use the spatiotemporal kernel reconstruction (Kernel) for noise reduction in dynamic PET, and lp-ntPET kinetic modeling. Kernel is adapted for motion correction reconstruction, applied in awake rat PET scans. We performed 2D rat brain phantom simulation using the ntPET model at 3 different noise levels. Data was reconstructed with independent frame reconstruction (IFR), IFR with HYPR denoising, and Kernel, and lp-ntPET kinetic parameters (k(2a): efflux rate, γ: activation magnitude, t(d): activation onset time, and t(p): activation peak time) were calculated. Additionally, significant activation magnitude (γ) difference with respect to a region with no activation (rest) was calculated. Finally, [(11)C]raclopride experiments were performed in anesthetized and awake rats, injecting cold raclopride at 20 min after scan start to simulate endogenous neurotransmitter release. For simulated data at the regional level, IFR coefficient of variation (COV) of k(2a), γ, t(d) and t(p) was reduced with HYPR denoising, but Kernel showed the lowest COV (2 fold reduction compared with IFR). At the pixel level the same trend is observed for k(2a), γ, t(d) and t(p) COV, but reduction is larger with Kernel compared with IFR (10–14 fold). Bias in γ with respect with noise-free values was additionally reduced using Kernel (difference of 292, 72.4, and −6.92% for IFR, IFR+KYPR, and Kernel, respectively). Significant difference in activation between the rest and active region could be detected at a simulated activation of 160% for IFR and IFR+HYPR, and of 120% for Kernel. In rat experiments, lp-ntPET parameters have better confidence intervals using Kernel. In the γ, and t(d) parametric maps, the striatum structure can be identified with Kernel but not with IFR. Striatum voxel-wise γ, t(d) and t(p) values have lower variability using Kernel compared with IFR and IFR+HYPR. The spatiotemporal kernel reconstruction adapted for motion correction reconstruction allows to improve lp-ntPET kinetic modeling noise in awake rat studies, as well as detection of subtle neurotransmitter activations.