Assessment of dual time point protocols to produce parametric K_i images in FDG PET/CT: A virtual clinical study

Purpose: This simulation study investigated the feasibility of generating Patlak K_i images using a dual time point (DTP-K_i) scan protocol involving two 3-min/bed routine static PET scans and, subsequently, assessed DTP-K_i performance for an optimal DTP scan time frame combination, against conventional Patlak K_i estimated from complete 0–93 min dynamic PET data. Methods: Six realistic heterogeneous tumors of different characteristic spatiotemporal [¹⁸F]FDG uptake distributions for three noise levels commonly found in clinical studies and 20 noise realizations (N = 360 samples) were produced by analytic simulations of the XCAT phantom. Subsequently, DTP-K_i images were generated by performing standard linear indirect Patlak analysis with t* (Formula presented.) -min (Patlak_{t* = 12}) using a scaled population-based input function (sPBIF) model on 66 combinations of early and late 3-min/bed static whole-body PET reconstructed images. All DTP-K_i images were evaluated against respective DTP-K_i images estimated with Patlak_{t* = 12} and 0–93 min individual input functions (iIFs) and against gold standard K_i images estimated with Patlak_{t* = 12}, 0–93 min iIFs and tissue time activity curves from all reconstructed WB passes 12–93 min post injection. The optimal combination of early and late frames, in terms of attaining the highest correlation between DTP-K_i with sPBIF and gold standard K_i was also determined from a set of 66 different combinations of 2-min early and late frames. Moreover, the performance of DTP-K_i with sPBIF was compared against that of the retention index (RI) in terms of their correlation to the gold standard K_i. Finally, the feasibility and practicality of DTP protocol in the clinic were assessed through the analysis of nine patients. Results: High correlations (>0.9) were observed between DTP-K_i values from sPBIF and those from iIFs for all evaluated DTP protocols while the mean AUC difference between sPBIF and iIFs was less than 10%. The percentage difference of mean values between DTP-K_i from sPBIF and from iIFs was less than 1%. DTP K_i from sPBIF exhibited significantly higher correlation with gold standard K_i, in contrast to RI, across all 66 DTP protocols (p < 0.05 using the two-tailed t-test by Williams) with the highest correlation attained for the 50-53-min early + 90-93-min late scan time frames (optimal DTP protocol). Conclusion: Feasibility of generating Patlak K_i [¹⁸F] FDG images from an early and a late post injection 3-min/bed routine static scan using a population-based input function model was demonstrated and an optimal DTP scan protocol was determined. The results indicated high correlations between DTP-K_i and gold-standard K_i images that are significantly larger than those between RI and gold-standard K_i.