In Vivo Positronium Lifetime Measurements with a Long Axial Field-of-View PET/CT
Authors: Mercolli Lorenzo , Steinberger William M. , Sari Hasan , Afshar-Oromieh Ali , Caobelli Federico , Conti Maurizio , Felgosa Cardoso Ângelo R. , Mingels Clemens , Moskal Paweł , Pyka Thomas , Rathod Narendra , Schepers Robin , Seifert Robert , Shi Kuangyu , Stępień Ewa Ł. , Viscione Marco , Rominger Axel O. 
Published: October 2024

AbstractPurposeThe lifetime of orthopositronium (oPs), a spin triplet of an electron and positron, depends on the molecular structure of the surrounding tissue. Therefore, measuring 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-617 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 from the list mode data based on energy, time and spatial selection criteria using a prototype software. The spatial location of the annihilation events is reconstructed using the annihilation photons’ time-of-flight. 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 lifetime’s 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 form 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). Through arterial and venous blood sampling, we were unable to confirm such a difference 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 (especially for68Ga-based measurements) and the interpretation of oPs lifetimes in human tissue remain major challenges that need to be addressed in future studies.