In Vivo Positronium Lifetime Measurements with a Long Axial Field-of-View PET/CT

PurposeMeasuring orthopositronium (oPs) lifetime could in principle provide diagnostic information about the tissue microenvironment that goes beyond standard positron emission tomography (PET) imaging. This study demonstrates that in vivo oPs lifetime measurement is feasible with a commercial long axial field-of-view (LAFOV) PET/CT scanner. MethodsThree subjects received a dose of 148.8 MBq [68Ga]-Ga-DOTA-TOC, 159.7 MBq [68Ga]Ga-PSMA-11 and 420.7 MBq [82Rb]Cl. In addition to the standard protocol, the three subjects were scanned for 20, 40 and 10 minutes with a single-crystal interaction acquisition mode on a Biograph Vision Quadra (Siemens Healthineers) PET/CT. Three-photon events, that include two annihilation photons and a prompt photon from the decay of the radionuclide, are then selected and localized with time-of-flight using a prototype software. Through a Bayesian fit to the measured time difference between the annihilation and the prompt photons, we are able to determine the oPs lifetime for selected organs. The Bayesian fitting methodology is extended to a hierarchical model in order to investigate possible common oPs lifetime distributions of the heart chambers in the [82Rb]Cl scan. ResultsFrom the segmentation of the subjects histoimages of three-photon events, we present the highest density intervals (HDI) of the oPs lifetimes marginalized posterior distribution for selected organs. Interestingly, the mean values of the right heart chambers were higher than in the left heart chambers of the subject that received [82Rb]Cl: the 68% HDI of the atria are [1.15 ns, 1.72 ns] (left) and [1.46 ns, 1.99 ns] (right) with mean values 1.50 ns and 1.76 ns, respectively. For the ventricles we obtained [1.22 ns, 1.60 ns] (left) and [1.69 ns, 2.18 ns] (right) with mean values 1.44 ns and 1.96 ns. This might signal the different oxygenation levels of venous and arterial blood. Fitting a hierarchical model, we found that the oPs lifetime for volumes-of-interest with arterial blood can be sampled from a posterior distribution with a 68% HDI of [1.4 ns, 1.84 ns] (mean 1.62 ns) and while those containing venous blood have a HDI of [1.78 ns, 2.21 ns] (mean 2.0 ns). The 68Ga measurements showed significantly worse count statistics and therefore larger errors in the oPs lifetime. ConclusionIn vivo oPs lifetime measurements on a commercial LAFOV PET/CT system are feasible at the organ level with an unprecedented level of statistical power. Nevertheless, count statistics of three-photon events and the interpretation of oPs lifetimes in human tissue remain major challenges that need to be addressed in future studies.