Roman Y. Shopa

Objective . Positronium-based imaging, including positronium lifetime imaging (PLI) and multi-photon positron emission tomography (PET), requires realistic modelling of positronium (Ps) decay in matter. Existing Monte Carlo (MC) implementations in Geant4 Application for Tomographic Emission (GATE) are limited to simplified single- or two-channel descriptions, preventing accurate representation of the multi-component lifetime structure observed in biological and material systems. The objective of this work is to develop and validate a flexible MC Ps decay source model supporting multiple annihilation channels within the GATE framework. Approach . We introduce a modular Ps decay model implemented in GATE 9.4 and GATE 10, enabling the definition of an arbitrary number of decay channels characterised by lifetime, branching fraction, annihilation multiplicity ( 2 γ / 3 γ ), and optional prompt photon emission. The model is validated through analytical and numerical benchmarks, including lifetime distributions, branching fraction consistency, photon kinematics, and prompt photon emission. Its practical applicability is demonstrated using simulations of mixed annihilation scenarios and the NEMA IEC phantom with a large field-of-view PET system. Results . The proposed model accurately reproduces input lifetime distributions as weighted sums of exponential components and correctly samples decay channel fractions. Simulated two- and three-photon annihilation kinematics are consistent with theoretical expectations. Complex mixtures of decay channels, including varying 3 γ -to- 2 γ ratios and multi-component ortho-positronium (o-Ps) lifetimes, are correctly modelled, with observable signatures reflected in both temporal and energy distributions. Phantom simulations demonstrate the capability to generate realistic positronium-sensitive datasets. Significance . This work provides the first general-purpose, multi-channel positronium decay model integrated into GATE, enabling realistic simulations of positronium behaviour in complex media. The model supports the development and optimisation of positronium-based imaging techniques, including PLI and multi-photon PET, and applies to medical imaging, industrial tomography, and fundamental physics studies. Its public availability and compatibility with standard GATE workflows make it a valuable tool for the broader research community.

Positronium is abundantly produced within the molecular voids of a patient’s body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo.

Positronium, an unstable atom consisting of an electron and a positron, is abundantly produced within the molecular voids of a patient’s body during positron emission tomography (PET) diagnosis. Its properties, such as its average lifetime between formation and annihilation into photons, dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen molecules. However, the diagnostic information that positronium may deliver about early molecular alterations remains unavailable in clinics with state-of-the-art PET scanners. This study presents the first in vivo images of positronium lifetime in humans. We developed a dedicated J-PET system with multiphoton detection capability for imaging. The measurements of positronium lifetime were performed on a patient with a glioblastoma tumor in the brain. The patient was injected intratumorally with the ⁶⁸ Ga radionuclide attached to Substance-P, which accumulates in glioma cells, and intravenously with ⁶⁸ Ga attached to the PSMA-11 ligand, which is selective to glioma cells and salivary glands. The ⁶⁸ Ga radionuclide is routinely used in PET for detecting radiopharmaceutical accumulation and was applied for positronium imaging because it can emit an additional prompt gamma. The prompt gamma enables the determination of the time of positronium formation, while the photons from positronium annihilation were used to reconstruct the place and time of its decay. The determined positronium mean lifetime in glioblastoma cells is shorter than in salivary glands, which in turn is shorter than in healthy brain tissues, demonstrating for the first time that positronium imaging can be used to diagnose disease in vivo . This study also demonstrates that if current total-body PET systems were equipped with multiphoton detection capability and the ⁴⁴ Sc radionuclide was applied, it would be possible to perform positronium imaging at 6500 times greater sensitivity than achieved in this research. Therefore, it is anticipated that positronium imaging has the potential to bring a new quality of cancer diagnosis in clinics.

Positron emission tomography (PET) is a widely utilized medical imaging modality that uses positron-emitting radiotracers to visualize biochemical processes in a living body. The spatiotemporal distribution of a radiotracer is estimated by detecting the coincidence photon pairs generated through positron annihilations. In human tissue, about 40% of the positrons form positroniums prior to the annihilation. The lifetime of these positroniums is influenced by the microenvironment in the tissue and could provide valuable information for better understanding of disease progression and treatment response. Currently, there are few methods available for reconstructing high-resolution lifetime images in practical applications. This paper presents an efficient statistical image reconstruction method for positronium lifetime imaging (PLI). We also analyze the random triple-coincidence events in PLI and propose a correction method for random events, which is essential for real applications. Both simulation and experimental studies demonstrate that the proposed method can produce lifetime images with high numerical accuracy, low variance, and resolution comparable to that of the activity images generated by a PET scanner with currently available time-of-flight resolution.

Positronium imaging is a new technique complementary to positron emission tomography (PET) based on the histogramming of time delay between the emission of a de-excitation photon, and a consequent electron-positron annihilation, to estimate the mean lifetime of orthopositronium (o-Ps), which depends on the local size of the voids, concentration of oxygen and bioactive molecules. We improve the resolution and reduce noise in positronium imaging by building time-delay spectra from the PET activity reconstructed by a 3-photon time-of-flight maximum likelihood expectation maximisation. The method was tested on the data measured for four human-tissue samples injected by 22Na and put in the Jagiellonian PET “Big barrel” scanner. Due to an ill-posed problem of fitting time-delay histograms, a multistage optimisation procedure was explored along with inferential analysis of the solution space. Run in parallel for multiple sets of initial guesses, we compared the second-order Levenberg- Marquardt algorithm (LMA) and the direct search Nelder-Mead simplex (NMS) method. The LMA proved to be faster and more precise, but the NMS was more stable with a higher convergence rate. The estimated mean o-Ps lifetimes in the 1.9 ns – 2.6 ns range were consistent with the reference results, while other fitting parameters allowed differentiation between the two patients who provided the tissue samples.

Objective. The Jagiellonian positron emission tomography (J-PET) technology, based on plastic scintillators, has been proposed as a cost effective tool for detecting range deviations during proton therapy. This study investigates the feasibility of using J-PET for range monitoring by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Approach. Discrepancies between prescribed and delivered treatments were artificially introduced in the simulations by means of shifts in patient positioning and in the Hounsfield unit to the relative proton stopping power calibration curve. A dual-layer, cylindrical J-PET geometry was simulated in an in-room monitoring scenario and a triple-layer, dual-head geometry in an in-beam protocol. The distribution of range shifts in reconstructed PET activity was visualized in the beam’s eye view. Linear prediction models were constructed from all patients in the cohort, using the mean shift in reconstructed PET activity as a predictor of the mean proton range deviation. Main results. Maps of deviations in the range of reconstructed PET distributions showed agreement with those of deviations in dose range in most patients. The linear prediction model showed a good fit, with coefficient of determination r ² = 0.84 (in-room) and 0.75 (in-beam). Residual standard error was below 1 mm: 0.33 mm (in-room) and 0.23 mm (in-beam). Significance. The precision of the proposed prediction models shows the sensitivity of the proposed J-PET scanners to shifts in proton range for a wide range of clinical treatment plans. Furthermore, it motivates the use of such models as a tool for predicting proton range deviations and opens up new prospects for investigations into the use of intra-treatment PET images for predicting clinical metrics that aid in the assessment of the quality of delivered treatment.