Whole-body direct 4D parametric PET imaging employing nested generalized Patlak expectation-maximization reconstruction

Whole-body (WB) dynamic PET has recently demonstrated its potential in translating the quantitative benefits of parametric imaging to the clinic. Post-reconstruction standard Patlak (sPatlak) WB graphical analysis utilizes multi-bed multi-pass PET acquisition to produce quantitative WB images of the tracer influx rate K-i as a complimentary metric to the semi-quantitative standardized uptake value (SUV). The resulting K-i images may suffer from high noise due to the need for short acquisition frames. Meanwhile, a generalized Patlak (gPatlak) WB post-reconstruction method had been suggested to limit K-i bias of sPatlak analysis at regions with non-negligible F-18-FDG uptake reversibility; however, gPatlak analysis is non-linear and thus can further amplify noise. In the present study, we implemented, within the open-source software for tomographic image reconstruction platform, a clinically adoptable 4D WB reconstruction framework enabling efficient estimation of sPatlak and gPatlak images directly from dynamic multi-bed PET raw data with substantial noise reduction. Furthermore, we employed the optimization transfer methodology to accelerate 4D expectation-maximization ( EM) convergence by nesting the fast image-based estimation of Patlak parameters within each iteration cycle of the slower projection-based estimation of dynamic PET images. The novel gPatlak 4D method was initialized from an optimized set of sPatlak ML-EM iterations to facilitate EM convergence. Initially, realistic simulations were conducted utilizing published F-18-FDG kinetic parameters coupled with the XCAT phantom. Quantitative analyses illustrated enhanced K-i target-to-background ratio ( TBR) and especially contrast-to-noise ratio ( CNR) performance for the 4D versus the indirect methods and static SUV. Furthermore, considerable convergence acceleration was observed for the nested algorithms involving 10-20 subiterations. Moreover, systematic reduction in K-i % bias and improved TBR were observed for gPatlak versus sPatlak. Finally, validation on clinical WB dynamic data demonstrated the clinical feasibility and superior Ki CNR performance for the proposed 4D framework compared to indirect Patlak and SUV imaging.