Faculty of Physics, Astronomy
and Applied Computer Science

Annihilation photons are quantum-entangled in polarization, a phenomenon that has not been exploited in medical diagnostics so far. We present the first in vivo imaging of the degree of quantum entanglement of photons originating from positron-electron annihilation within a human subject. This study utilized the Jagiellonian Positron Emission Tomography (J-PET) scanner, constructed from plastic scintillators. In plastics, annihilation photons interact primarily via the Compton effect, which provides simultaneous information regarding the photon interaction position and time, as well as the photon polarization plane. The patient was injected with a DOTA-TATE radiopharmaceutical labeled with the 68Ga radionuclide. Using the J-PET scanner, we determined the image of the radiopharmaceutical uptake and, simultaneously, the image of the degree of quantum entanglement. The latter was determined from the relative angle between the polarization planes of the annihilation photons. The values of the degree of quantum entanglement extracted for the liver and the spleen are smaller than those predicted for maximally entangled two-photon states, yet larger than expected for separable photons. This demonstration opens new perspectives for the application of quantum entanglement in clinical diagnostics.

Annihilation photons are quantum entangled in their polarization, a property that is not accessible in state-of-the-art clinical Positron Emission Tomography (PET). This roadmap describes the current status of research in the emerging field of quantum entanglement applications involving these photons for medical diagnosis. It outlines the underlying physics phenomena and the development of detector systems that can serve as a foundation for future Quantum Entanglement PET (QE-PET) scanners. These scanners will be capable of utilizing the entanglement between annihilation photons by measuring their Compton scattering on electrons. This roadmap comprises up-to-date experimental results on the study of quantum entanglement and the ecoherence of annihilation photons, alongside the current theoretical understanding of these phenomena. The methods and detector technologies described herein are being developed (i) in order to enhance standard PET imaging by suppressing random coincidences in the reconstruction of annihilation site density distributions, (ii) in order to establish the degree of quantum entanglement as a diagnostic biomarker for tissue pathology and oxygenation, and (iii) in order to elaborate a method for pH imaging. Whether entanglement-based imaging and pH mapping can be successfully translated into clinical practice remains an open question and a subject of exciting ongoing research. This roadmap serves as an invitation to the scientific community to join this burgeoning field.

This manuscript introduces a novel method to assess tissue oxygen concentration via the quantum entanglement (QE) of photons originating from positronium which is produced within the patient's body during positron emission tomography. We also investigate the possibility of assessing hypoxia by simultaneously detecting positronium lifetime and the positronium decay rate ratio. We introduce two distinct quantum sensing approaches. Method 1 utilizes the correlation between oxygen concentration and ortho-positronium (o-Ps) decay rates, relying on the simultaneous measurement of the mean o-Ps lifetime ( ) and the -to- annihilation rate ratio of o-Ps ( ). Method 2 introduces a novel hypothesis: that the degree of QE is sensitive to the relative contribution of annihilation mechanisms (pick-off vs. conversion), which in turn depends on oxygen concentration. We derive a formula for partial pressure of oxygen ( ) as a function of and and estimate the measurement accuracy required for these parameters - and for the degree of QE - to sense in-vivo oxygen pressure in the range between hypoxic and physoxic conditions. Theoretical models and quantitative estimates for , and for the degree of QE ( ) as a function of are provided for water, isopropanol, cyclohexane, isooctane, and adipose tissue. In particular, applying the formulas derived under the working hypothesis that in pick-off process the photons are not entangled, we estimated that for , the degree of quantum entanglement is equal to 0.890 for adipose, 0.886 for isopropanol, 0.867 for water, 0.818 for cyclohexane, and 0.784 for isooctane.

Objective: The goal of the work is to develop a set of methods for calibrating the positron emission tomography system built from plastic scintillators, and to present the results of the modular J-PET scanner time of flight (TOF) and time over threshold (TOT) synchronisation. Methods: Measurements with radionuclide 22Na and 44Sc (used as a point-like source and enclosed in a collimator) were performed using the modular J-PET scanner, which detects signals from annihilation photons and prompt gamma. The data were gathered with a trigger-less data acquisition system and analysed with a dedicated software framework. The detection modules were synchronised with the procedures, correcting time offsets and normalising TOT measurements. Results: The application of the time calibration methods yields a fully synchronised detector that is capable of producing the image of the source. TOF resolution for modular J-PET is determined to be about 490 ps (FWHM). Conclusions: The J-PET scanner, built from plastic scintillators, can be calibrated using betta+gamma emitters and taking advantage of the fact that the direction of propagation of annihilation and prompt photons are not correlated.

Positronium Lifetime Imaging (PLI), an emerging extension of conventional positron emission tomography (PET) imaging, offers a novel window for probing the submolecular properties of biological tissues by imaging the mean lifetime of the positronium atom. Currently, the method is under rapid development in terms of reconstruction and detection systems. Recently, the first in vivo PLI of the human brain was performed using the J-PET scanner utilizing the 68Ga isotope. However, this isotope has limitations due to its comparatively low prompt gamma yields, which is crucial for positronium lifetime measurement. Among alternative radionuclides, 44Sc stands out as a promising isotope for PLI, characterized by a clinically suitable half-life (4.04 hours) emitting 1157 keV prompt gamma in 100% cases after the emission of the positron. This study reports the first experimental demonstration of PLI with 44Sc, carried out on a NEMA-Image Quality (IQ) phantom using the Modular J-PET tomograph?the first plastic scintillators-based PET scanner.

This study demonstrates applicability of 52Mn and 55Co radionuclides for positronium imaging. Positronium Lifetime Imaging (PLI) extends positron emission tomography by using the lifetime of positronium atoms as a probe of tissue molecular architecture. However, its practical use requires ?+ emitters that also provide an additional prompt ? ray to mark the positron creation time. In this work, we report the first PLI measurements performed with 52Mn and 55Co using the modular J-PET. Four samples were studied in each experiment: two Certified Reference Materials (polycarbonate and fused silica) and two human tissues (cardiac myxoma and adipose). The selection of PLI events was based on the registration of two 511 keV annihilation photons and one prompt gamma in triple coincidence. From the resulting lifetime spectra we extracted the mean ortho-positronium lifetime ?oPs and the mean positron lifetime ?Tmean for each sample. The measured values of ?oPs in polycarbonate using both isotopes matches well with the certified reference values. Furthermore, 55Co reproduced identical results for fused-silica measurements at their respective uncertainty levels. In contrast, measurements with 52Mn in fused silica show a minor deviation, which could be caused by the Parafilm spacer. In myxoma and adipose tissue, the reduced ?oPs values are mainly linked to the long storage history of the samples rather than to the choice of isotope. Comparing peak-to-background ratios and spectral purity, 55Co provides cleaner PLI data under the same experimental conditions. Although 52Mn offers a longer half-life and a multi gamma cascade enhancing ?+ + ? coincidences, but at the expense of higher background. In this study, we demonstrate that the applied selection criteria on the data measured with the modular J-PET can be used for PLI studies even with radionuclides with complex decay patterns.

This study presents the first ex-vivo positronium imaging of human tissues using the modular J-PET scanner with the 44Sc radionuclide. The 44Sc isotope was produced via the 44Ca(p, n)44Sc nuclear reaction and used to perform positronium imaging of phantom composed of human adipose tissue, cardiac myxoma tissue, thrombi blood clot, and also porous polymer XAD4, and a certified reference material (CRM) made from fused silica. The experiment demonstrates the suitability of 44Sc as a positron source for positronium imaging. The performance of J-PET for positronium imaging with 44Sc was validated by proper reconstruction of the mean orthopositronium lifetime for CRM material and XAD-4 polymer. The mean ortho-positronium (oPs) lifetimes determined for adipose tissue, cardiac myxoma tissues and thrombi were consistent with results of previous experiments. The study highlights the potential Sc radionuclide for positronium lifetime imaging (PLI).

A direct test of the CPT symmetry is performed for the electromagnetic decays of ortho-positronium using the Jagiellonian positron emission tomograph (J-PET). We present the precise measurement of the CPT-sensitive angular correlation entailing the positronium spin and the momenta of its annihilation photons, surpassing previous studies utilizing the same detection system. Positrons originating from a 22Na source are emitted from the detector?s center and subsequently form positronium atoms within the spherical chamber covered with porous material. Reconstruction of annihilation locations using the 192-strip J-PET detector makes it possible to determine the positronium emission direction, which defines the quantization axis along which positronium is polarized, without the application of external magnetic fields. The measurements were performed in total for 356 days resulting in an identification of 47.8×10^6 events with ortho-positronium decays into three photons. The results are consistent with the exactness of CPT symmetry with measured asymmetry amplitude -0.00029+-0.00022 (stat.) and with statistical error four times smaller than the previous best measurement.

Positron Annihilation Lifetime Spectroscopy (PALS) is a well-established non-destructive technique used for nanostructural characterization of porous materials. It is based on the annihilation of a positron and an electron. Mean positron lifetime in the material depends on the free voids size and molecular environment, allowing the study of porosity and structural transitions in the nanometer scale. We have developed a novel method enabling spatially resolved PALS, thus providing tomography of nanostructural characterization of an extended object. Correlating space (position) and structural (lifetime) information brings new insight in materials studies, especially in the characterization of the purity and pore distribution. For the first time, a porosity image using stationary positron sources for the simultaneous measurement of the porous polymers XAD4, silica aerogel powder IC3100, and polyvinyl toluene scintillator PVT by the J-PET (Jagiellonian Positron Emission Tomography) system is demonstrated.

Modern data acquisition systems in physics experiments of various scales rely heavily on precise time synchronization of electronic components used for digitizing analog signals generated by detectors. Scientific collaborations often develop custom, in-house solutions designed for particular use cases that form ecosystems of compatible hardware platforms, protocols, and standards. In this work, we present and evaluate a set of gateware and software components that enable the implementation of complete data acquisition systems with synchronization, data transport, and control functionalities over multi-gigabit transceivers. The components can be organized to form a logical system structure, including the master, data concentrators, and endpoint modules, on virtually any hardware platform equipped with a Field-Programmable Gate Array with an exposed transceiver. The system allows for a rapid deployment of complete measurement systems with facilitated integration of new elements on both commercially available and custom-designed platforms.

The development of PET and positronium imaging techniques is strictly related to the availability of suitable radionuclides and robust radiochemistry platforms. Among the emerging candidates, 44Sc has attracted significant interest due to its favourable physical properties, including a half-life of 4 hours, a pure emission profile, and the additional prompt -emission that enables advanced triple-photon detection schemes. These characteristics make 44Sc particularly promising for highresolution imaging and novel quantitative methodologies. However, routine clinical and preclinical implementation requires a practical, sustainable, and cost-efficient production route. In this context, we propose a titanium-scandium radionuclide generator as an optimal solution. This study focuses on optimising the synthesis of the long-lived parent isotope, 44Ti (T1/2 = 59.1 years), from which 44Sc can be selectively eluted in a chemically pure form when needed. An analysis of various production pathways was conducted, including proton and deuteron reactions on scandium, as well as alpha-particle and lithium-induced reactions on calcium, to determine the most efficient reaction parameters, target design, and expected yield. Furthermore, we identify some existing cyclotron facilities suitable for implementing this technology. Results indicate that efficient Ti production is achievable using proton beams in the 20-30 MeV range under extended irradiation conditions. The proposed generator system would enable routine and decentralised 44Sc supply. Its integration with the novel J-PET scanner may significantly reduce diagnostic costs and improve access to advanced PET imaging in regions with limited medical imaging infrastructure.

The Jagiellonian positron emission tomograph (J-PET) is a novel technology employed to detect multiple photons from positronium annihilation. It employs plastic scintillator strips optimized for the detection of photons in the sub-MeV energy range. The experimental setup consists of a positron-emitting source surrounded by chambers coated with porous materials to facilitate positronium formation. Owing to its large geometrical acceptance and high angular resolution, J-PET enables the reconstruction of various kinematic configurations of positronium annihilations, allowing for precise measurements of angular correlations in ortho-positronium decays. The detector has already demonstrated high sensitivity in charge?parity and charge?parity?time symmetry tests based on such correlations. In the present work, we report a systematic study of the effects of non-uniformity in porous materials used for positronium production in the J-PET setup, performed in the context of a charge?parity?time symmetry test. The systematic uncertainty obtained from this study is 0.59 x 10-5, and contributes negligibly to the total uncertainty of the charge?parity?time symmetry test.

Understanding the entangled polarization of photons produced in positron?electron annihilation remains experimentally challenging. Recently, it has been proposed to utilize this correlation in positron emission tomography imaging to suppress the random background and as a diagnostic parameter. Conventional positron emission tomographs rely on the registration of the two annihilation photons from positron annihilation. However, measuring polarization correlations requires scattering of annihilation photons in the detector volume and the registration of their corresponding scatters. Such a 4-hit event topology inherently suffers from low efficiency and high background. Therefore, translating this quantum information into medical imaging requires a method to overcome the inherent limitations of conventional geometric cuts. We present a machine learning classification framework trained on simulated detector events. This approach enables a high-purity separation of polarization-correlated signal from background and simultaneously achieves a significant improvement in computational efficiency.

The main aim of this research is to test the charge?parity discrete symmetry in the ortho-positronium (o-Ps) atom decay using the modular Jagiellonian positron emission tomography (J-PET) detector. The J-PET is distinguished by its ability to determine the polarization plane of photons emitted during positronium annihilation. The J-PET detector can investigate discrete symmetry by examining the non-zero expectation values of the symmetry-odd operators constructed from the momentum and direction of polarization plane of gamma (?) quanta coming from o-Ps annihilation. In positronium decay, the photon?photon interactions in the final state due to vacuum polarization may mimic a charge?parity symmetry violation at the level of 10-9, according to the Standard Model prediction. Currently, with the help of the 192-strip J-PET detector, the experimental limits on charge?parity symmetry violation in o-Ps decay are set at a precision value of 0.0005 ? 0.0007. Using the modular J-PET detector, we aim to improve this value by at least an order of magnitude. This article focuses on developing analysis criteria towards improving the sensitivity level for charge?parity-discrete symmetry studies in o-Ps decay using the modular J-PET detector.

Objective: Positron Emission Tomography enables non-invasive imaging of metabolic processes. Standard PET reconstructs radiotracer distribution using two back-to-back photons from electron-positron annihilation. However, about 1% of annihilations results in creation of three photons. Three photons may be created in direct annihilation and in annihilation via formation of metastable ortho-positronium carrying additional information not used by conventional PET. The Jagiellonian-PET detector allows us to use this information by applying positronium imaging based on ortho-positronium lifetime or the 3gamma/2gamma decay ratio. Accurate tomographic images require attenuation correction. This study investigates photon absorption in phantom models to form a basis for future attenuation maps for three-gamma decays. Methods: Monte Carlo simulations in ROOT and GATE were performed for water sphere, cylinder, a simplified head model, and the mesh50_XCAT phantom. Both p-Ps and o-Ps decays were simulated as uniformly distributed sources. Absorption probabilities were calculated by checking whether any photon in a multiplet interacted within the phantom. Emission-point-specific absorption maps were generated for all models. Toy Monte Carlo and GATE simulations showed good overall agreement. Results: Photon triplets from o-Ps decays experienced higher absorption than photon pairs from p-Ps due to lower individual energies and higher attenuation. Absorption maps showed dependence of photon survival probability on the decay location. In the mesh50_XCAT phantom, 24.9% of p-Ps pairs and 10.3% of o-Ps triplets escaped without interaction. Conclusions: Gamma absorption depends strongly on positronium decay mode and location, with o-Ps events experiencing higher attenuation. The generated absorption maps provide the first step toward dedicated attenuation correction for three-gamma positronium imaging, enabling accurate reconstruction in novel 3?/2? positronium imaging technique. A Study presented indicates that the absorption of 3gamma in the head is only about 2.5 times higher than for the 2gamma, which is encouraging for further development of the 3gamma/2gamma rate ratio imaging.

Objective: To quantitatively assess how different preparation methods alter the nanoscale free-volume architecture of human plasma blood clots using positron annihilation lifetime spectroscopy (PALS), and to establish the relevance of PALS for fibrin network characterisation in biomedical research. Materials: Human plasma blood clots prepared in four distinct physical states: fresh, glutaraldehyde-fixed, desiccator-dried and critical-point-dried (CPD). Methods: High-resolution fast-coincidence PALS measurements were performed at 37°C. Ortho-positronium (o-Ps) lifetimes and intensities were extracted using PALS Avalanche and independently verified by fitting in the Origin software package. Reported values represent mean ? SD from n = 3 independent plasma clots prepared and measured under identical conditions. Comparative analysis across preparation states was conducted to assess preparation-dependent variations in o-Ps parameters. Results: Distinct o-Ps lifetime (??) and intensity (I?) values were observed across clot states: fresh (1.95 ? 0.01 ns; 11 ? 0.07%), fixed (2.11 ? 0.02 ns; 16 ? 0.16%), desiccator-dried (2.15 ? 0.04 ns; 6 ? 0.11%), and CPD (1.95 ? 0.01 ns; 9 ? 0.07%). These differences indicate that preparation protocols substantially affect positronium (Ps) lifetime characteristics and formation probability within plasma clots. Conclusions: Sample preparation has a pronounced effect on PALS-derived o-Ps parameters in plasma blood clots, underscoring the sensitivity of PALS to preparation-induced nanoscale changes. To the best of our knowledge, this study provides the first systematic PALS-based comparison of plasma clots across multiple physical states, highlighting the importance of protocol selection when applying positronium-based techniques to biological materials.

Positronium (Ps), an exotic atom composed of an electron and a positron, provides a unique system for testing fundamental physics and verifying quantum electrodynamic predictions. At Jagiellonian University, the J-PET detector enables high-precision studies of positronium decays and the search for dark matter. This work focuses on mirror matter, a hypothetical dark matter candidate, by comparing measured o-Ps lifetimes with quantum electrodynamic predictions to probe potential deviations.

Objective: Quantitative PET requires accurate attenuation correction (AC), which is conventionally achieved using CT-derived maps, incurring extra dose and complexity. This study explores a CT-less AC approach for the plastic scintillator-based J-PET scanner by investigating whether detector-scattered photons (DS-LORs) can serve as an intrinsic transmission source. Methods: Simulation Setup: The study utilized GATE v9.1 software to simulate the modular J-PET scanner, which consists of plastic scintillator strips where 511 keV photons predominantly undergo Compton scattering. Two configurations were evaluated: a uniform water cylinder and a NEMA IQlike phantom containing a cold lung insert and six hot spheres to simulate heterogeneous activity. Analysis & reconstruction: The study isolated triple-hit coincidences to analyze angular deviations. DS-LORs were identified using a specific scatter test metric based on interaction positions and detection times. Attenuation maps were reconstructed using Filtered Back Projection (FBP) applied to the ratio of water-to-air sinograms. Results: Due to the properties of plastic scintillators, DS-LORs constituted approximately 50% of all detected prompts, providing a substantial dataset for analysis. In a simulated 10-minute acquisition, the noise propagation analysis yielded a Signal-to-Noise Ratio (SNR) of ? 33.9 for water. This is significantly higher than conventional crystal-based PET, which yields only ? 5% DS-LORs and a lower SNR. Reconstructions successfully resolved the NEMA phantom features, including the cold lung insert and hot spheres, particularly when phantom-scattered events were rejected. Conclusions and future directions: This study confirms that DS-LORs retain sufficient attenuation information to estimate ?-maps, demonstrating the potential for fully CT-less PET imaging. While the current implementation faces limitations like reliance on blank scans and activity-attenuation crosstalk, the high statistics of DS-LORs are a foundation for developing joint reconstruction algorithms aiming towards clinical application.

Objective: Positron emission tomography (PET) scanners with plastic scintillators offer more cost-effective instrumentation to image the distribution of radiopharmaceuticals. However, inter-detector scatters among plastic scintillators can lead to more false coincidences than in conventional PET scanners, since annihilation photons in plastic scintillators dominantly interact via Compton scattering, which deposits only a portion of the photon energy. A scatter test (ST), combined with a lower energy deposition threshold of 200 keV, has been used to preselect the coincidence events. Methods: In this work, we investigate the impact of temporal and spatial resolution limitations as well as a variation of the energy threshold on the preselection and different subsequent coincidence event selection policies via Monte Carlo simulations. We simulate the total-body Jagiellonian-PET (TB-J-PET), combined with a brain PET insert imaging a human-sized water phantom. Results: We find that coincidence time resolution (CTR) worse than 200 ps poses limitations on the ST for scanners close to the patient, such as the brain PET. Also, coincidence event selection requiring energy loss higher than 200 keV performs suboptimally, whereas a lower energy threshold (50 keV), combined with a time-based selection policy, can capture a higher percentage of true events, even under realistic time resolution. Conclusions: We recommend the adaptation of a time-based event selection policy together with a lowered energy threshold, which can also significantly increase sensitivity, as the latter rises faster than the fraction of true and non-phantom- -scattered events decreases. Dedicated analyses in the scatter-corrected image domain are necessary to further investigate this potential.

Positronium imaging was recently proposed to image the properties of positronium atoms in the patient body. Positronium properties depend on the size of intramolecular voids and oxygen concentration; therefore, they deliver information different and complementary to the anatomic, morphological, and metabolic images. Thus far, the mean ortho-positronium lifetime imaging has been at the center of research interest. The first ex vivo and in vivo positronium lifetime images of humans have been demonstrated with the dedicated J-PET scanner enabling simultaneous registration of annihilation photons and prompt gamma from beta+gamma emitters. Annihilation photons are used to reconstruct the annihilation place and time while prompt gamma is used to reconstruct the time of positronium formation. This review describes recent achievements in the translation of positronium imaging into clinics. The first measurements of positronium lifetime in humans with commercial PET scanners modernized to register triple coincidences are reported. The in vivo observations of differences in ortho-positronium lifetime between tumor and healthy tissues and between different oxygen concentrations are discussed. So far, the positronium lifetime measurements in humans were completed with clinically available 68Ga, 82Rb, and 124I radionuclides. Status and challenges in developing positronium imaging on a way to a clinically useful procedure are presented and discussed.

Purpose: Measuring the ortho-positronium (oPs) lifetime in human tissue bears the potential of adding clinically relevant information about the tissue microenvironment to conventional positron emission tomography (PET). Through phantom measurements, we investigate the voxel-wise measurement of oPs lifetime using a commercial long-axial field-of-view (LAFOV) PET scanner. Methods: We prepared four samples with mixtures of Amberlite XAD4, a porous polymeric adsorbent, and water and added between 1.12 and 1.44 MBq of 124I. The samples were scanned in two different setups: once with a couple of centimeters between each sample (15 min scan time) and once with all samples taped together (40 min scan time). For each scan, we determine the oPs lifetime for the full samples and at the voxel level. The voxel sizes under consideration are 10.03 mm3, 7.13 mm3 and 4.03 mm3. Results: Amberlite XAD4 allows the preparation of samples with distinct oPs lifetime. Using a Bayesian fitting procedure, the oPs lifetimes in the whole samples are 2.52 +- 0.03 ns, 2.37 +- 0.03 ns, 2.27 +- 0.04 ns and 1.82 +- 0.02 ns, respectively. The voxel-wise oPs lifetime fits showed that even with 4.03 mm3 voxels the samples are clearly distinguishable and a central voxels have good count statistics. However, the situation with the samples close together remains challenging with respect to the spatial distinction of regions with different oPs lifetimes. Conclusions: Our study shows that positronium lifetime imaging on a commercial LAFOV PET/CT is feasible using 124I.

Introduction: Positron emission tomography (PET) has undergone transformative advancements, evolving from a research tool into a cornerstone of precision medicine. Objective: This review highlights key developments in PET imaging, including the introduction of specialized systems such as brain and breast-dedicated scanners, total-body PET, and hybrid PET/CT and PET/MRI technologies. Methods: These innovations have significantly enhanced diagnostic accuracy and patient management across oncology, neurology and cardiology. The emergence of novel radiotracers beyond fluorodeoxyglucose (FDG) has expanded PET's clinical applications by targeting specific molecular pathways, improving sensitivity and specificity in disease characterization. Notable tracers include those for tumor proliferation, hypoxia and receptor-specific imaging, which facilitate personalized treatment strategies. The integration of artificial intelligence (AI) has revolutionized PET imaging by improving image reconstruction, noise reduction, motion correction and lesion segmentation. AI-driven tools enhance diagnostic precision while reducing scan times and radiation exposure, making PET safer and more efficient. Furthermore, AI accelerates radiotracer development by optimizing molecular design and enabling personalized dosimetry planning for theranostic applications. Total-body PET scanners represent a technological milestone, offering unparalleled sensitivity, reduced radiation doses, faster scans, the ability to track systemic diseases comprehensively and to enhance diagnosis by novel imaging biomarkers. These advancements enable earlier disease detection, precise monitoring of treatment efficacy and deeper insights into disease mechanisms. Results: Collectively, these innovations underscore PET's transformative role in advancing precision medicine through early diagnosis, disease monitoring and tailored therapeutic interventions. Conclusions: This review concludes that ongoing technological progress will continue to redefine the capabilities of PET imaging in clinical practice and research.

In the state-of-the-art Positron Emission Tomography (PET), information about the polarization of annihilation photons is not available. Current PET systems track molecules labeled with positron-emitting radioisotopes by detecting the propagation direction of two photons from positron-electron annihilation. However, annihilation photons carry more information than just the site where they originated. Here we present a novel J-PET scanner built from plastic scintillators, in which annihilation photons interact predominantly via the Compton effect, providing information about photon polarization in addition to information on photon direction of propagation. Theoretically, photons from the decay of positronium in a vacuum are maximally entangled in polarization. However, in matter, when the positron from positronium annihilates with the electron bound to the atom, the question arises whether the photons from such annihilation are maximally entangled. In this work, we determine the distribution of the relative angle between polarization orientations of two photons from positron-electron annihilation in a porous polymer. Contrary to prior results for positron annihilation in aluminum and copper, where the strength of observed correlations is as expected for maximally entangled photons, our results show a significant deviation. We demonstrate that in porous polymer, photon polarization correlation is weaker than for maximally entangled photons but stronger than for separable photons. The data indicate that more than 40% of annihilations in Amberlite resin lead to a non-maximally entangled state. Our result indicates the degree of correlation depends on the annihilation mechanism and the molecular arrangement. We anticipate that the introduced Compton interaction-based PET system opens a promising perspective for exploring polarization correlations in PET as a novel diagnostic indicator.

Total-Body PET imaging is one of the most promising newly introduced modalities in the medical diagnostics. State-of-the-art PET scanners use inorganic scintillators such as L(Y)SO or BGO, however, those technologies are very expensive, prohibitng the broad total-body PET applications. We present the comparative studies of performance characteristics of the cost-effective Total-Body PET scanners using Jagiellonian PET (J-PET) technology that is based on plastic scintillators. Here, we investigated in silico five realistic Total-Body scanner geometries, varying the number of rings, scanner radius, and distance between the neighbouring rings. Monte Carlo simulations of two NEMA phantoms (2-meter sensitivity line source and image quality) and the anthropomorphic XCAT phantom, were used to assess the performance of the tested geometries. We compared the sensitivity profiles and we performed the quantitative analysis of the reconstructed images by using the quality metrics such as contrast recovery coefficient, background variability and root mean squared error. The optimal scanner design was selected for the first Total-Body J-PET scanner configuration.

Objective: Positron Emission Tomography (PET) is a widely used medical imaging technique that allows for non-invasive imaging of metabolic processes. However, traditional PET scanners rely on costly inorganic scintillators, which limit their accessibility ? especially in light of emerging long axial field-of-view devices. The modular J-PET scanner, an innovative alternative, uses 50-cm long plastic scintillator strips, offering a cost-effective and modular solution. In this study, we develop and assess the PET data correction techniques required for quantitative image reconstruction. Methods: We present methods for attenuation correction, random coincidence correction using the Delayed Time Window (DTW) technique, and scatter correction based on Monte Carlo simulations. Phantom studies using the NEMA IQ phantom were performed to qualitatively evaluate these corrections. Results: The results demonstrate that our implemented corrections for attenuation, randoms, and scattered coincidences successfully improve the uniformity of tracer distribution in homogenous volumes and significantly reduce undesired activity in cold regions. Despite limitations in sensitivity and axial resolution, the applied correction techniques effectively enhance image quality, providing promising results for future applications. Conclusions: These findings highlight the potential of the modular J-PET system to offer affordable PET imaging and to pave the way towards a total-body PET scanner based on plastic scintillators. Future work will focus on quantitative validation and the implementation of these corrections for human subject imaging.

Objective: The paper presents the prospects for increasing the availability of PET diagnostic by combining low-cost, lightweight, and easily portable modular J-PET with the 44Ti/44Sc generator. Methods: J-PET is constructed based on the low-cost axially arranged plastic scintillators that may enable construction of PET scanners 5 to 10 times less expensive compared to current PET systems which are based on crystal detectors. Development of the radionuclide 44Ti/44Sc generator with the 60 years half-lifetime would facilitates long-term onsite production of 44Sc labelled radiopharmaceuticals, eliminating the need for extensive and costly infrastructure typically associated with nuclear medicine. Presently applied 68Ge/68Ga generators with the 270 days half-lifetime require renewal every year. 44Ti/44Sc generator could in principle be purchased once for half a century. Results: The lightweight and portable J-PET scanner, combined with the 44Ti/44Sc generator, can be deployed in remote and underserved regions, thus democratising access to advanced medical imaging technologies. Conclusions: This research highlights the transformative potential of combining innovative J-PET technology with the 44Ti/44Sc generator to make advanced diagnostics more accessible and affordable worldwide, potentially benefiting millions of patients and driving further innovations in medical imaging including in low- and medium-income countries.

Objective and method: Positron annihilation lifetime spectroscopy (PALS) is a powerful technique in material science that allows the investigation of the properties and behavior of positrons in various materials. PALS can be used to investigate solid structures at the nanometer scale and enable the use of positronium properties as an additional diagnostic parameter. Here we present results from calibration of the PALS system with certificated reference materials (CRM). Materials: Source of 22Na covered with layer of Kapton film, and after that parafilm from both sides was used in all experiments. Certified materials of No_5602-a (polycarbonate) and No_5601-a (fused silica) were used to ascertain if parameters were correctly identified. Results: In an experiment three lifetime components were correctly identified. All of those components will always be present in the data in further experiments on biological samples. Lifetime components consist of: 196 ps for annihilations in AI an aluminium cover of the chamber, 386 ps for annihilations in thesource and in the Kapton foil, 463 ps for reactions with parafilm. Conclusions: These parameters will be further used to correctly identify positron lifetimes in biological samples. Recently, a new method for imaging of positronium properties was invented and the first in-vivo images of positronium lifetime in humans were demonstrated with the multi-photon J-PET scanner. In order to correlate the positronium properties in tissue with the medically useful parameters, and to translate positronium imaging to clinics, comprehensive research of positronium properties in biological samples is needed.

For in vivo dose delivery monitoring in proton therapy the positron emission tomography can be applied because the positron emitters are being produced by the nuclear reactions of protons with atomic nuclei in a human body. The estimation of cross-sections of proton-induced nuclear reactions in the body is, therefore, one of the important steps on the way to develop proton beam range monitoring with positron emission tomography. Here, we calculate cross-sections for all open nuclear reaction channels initiated by 150 MeV protons and featured with 10C and 11C formation in the output channels. Taking into account the composition of elements in the human body and the data from the literature, we estimated 10C and 11C cumulative production cross-sections for proton-induced reactions in the human body.

The presented study evaluates the spatial resolution of the Modular J-PET scanner using the National Electrical Manufacturers Association (NEMA) NU2-2018 standard. The Modular J-PET, constructed with BC-404 plastic scintillators in an axial arrangement and coupled with analogue Silicon Photomultipliers (SiPMs) at both ends, offers a 50 cm axial field of view and a bore diameter of 73.9 cm. The study compares results from GATE simulations with experimental data.

The quantum entanglement of photons used in positron emission tomography (PET) scans has been shown to be surprisingly robust, opening prospects for developing quantum-enhanced PET schemes.

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.

Objective: The aim of this work is to investigate the feasibility of the JagiellonianPositron Emission Tomography (J-PET) scanner for intra-treatment proton beamrange monitoring. Approach: The Monte Carlo simulation studies with GATE and PET imagereconstruction with CASToR were performed in order to compare six J-PET scannergeometries (three dual-heads and three cylindrical). We simulated proton irradiationof a PMMA phantom with a Single Pencil Beam (SPB) and Spread-Out BraggPeak (SOBP) of various ranges. The sensitivity and precision of each scanner werecalculated, and considering the setup?s cost-effectiveness, we indicated potentiallyoptimal geometries for the J-PET scanner prototype dedicated to the proton beamrange assessment. Main results: The investigations indicate that the double-layer cylindrical andtriple-layer double-head configurations are the most promising for clinical application.We found that the scanner sensitivity is of the order of 10?5coincidences per primaryproton, while the precision of the range assessment for both SPB and SOBP irradiationplans was found below 1 mm. Among the scanners with the same number of detectormodules, the best results are found for the triple-layer dual-head geometry. Significance: We performed simulation studies demonstrating that the feasibilityof the J-PET detector for PET-based proton beam therapy range monitoring ispossible with reasonable sensitivity and precision enabling its pre-clinical tests in theclinical proton therapy environment. Considering the sensitivity, precision and cost-effectiveness, the double-layer cylindrical and triple-layer dual-head J-PET geometryconfigurations seem promising for the future clinical application. Experimental testsare needed to confirm these findings.

Studies based on imaging the annihilation of the electron (e-) and its antiparticle positron (e+) open up several interesting applications in nuclear medicine and fundamental research. The annihilation process involves both the direct conversion of ee into photons and the formation of their atomically bound state, the positronium atom (Ps), which can be used as a probe for fundamental studies. With the ability to produce large quantities of Ps, manipulate them in long-lived Ps states, and image their annihilations after a free fall or after passing through atomic interferometers, this purely leptonic antimatter system can be used to perform inertial sensing studies in view of a direct test of Einstein equivalence principle. It is envisioned that modular multistrip detectors can be exploited as potential detection units for this kind of studies. In this work, we report the results of the first feasibility study performed on a e beamline using two detection modules to evaluate their reconstruction performance and spatial resolution for imaging ee annihilations and thus their applicability for gravitational studies of Ps.

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 methodfor random events, which is essential for real applications. Both simulation andexperimental 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.

Discrete symmetries play an important role in particle physics with violation of CP connected to the matter-antimatter imbalance in the Universe. We report the most precise test of P, T and CP invariance in decays of ortho-positronium, performed with methodology involving polarization of photons from these decays. Positronium, the simplest bound state of an electron and positron, is of recent interest with discrepancies reported between measured hyperfine energy structure and theory at the level of 10^-4 signaling a need for better understanding of the positronium system at this level. We test discrete symmetries using photon polarizations determined via Compton scattering in the dedicated J-PET tomograph on an event-by-event basis and without the need to control the spin of the positronium with an external magnetic field, in contrast to previous experiments. Our result is consistent with QED expectations at the level of 0.0007 and one standard deviation.

The application of PET scanners to proton-beam-therapy monitoring is a promising solution to obtain the range of the beam and hence the positions of a Bragg peak - maximum dose deposition point. A proton beam induces nuclear reactions in the tissue, leading to the production of isotopes that emit beta+ radiation. This enables the imaging of the density distribution of beta+ isotopes produced in the body, allowing the reconstruction of the proton beam range. Moreover, PET detectors may open the possibility for in-beam monitoring, which would offer an opportunity to verify the range during irradiation. PET detectors may also allow positronium imaging, which would be the indicator of the tissue conditions. However, the image of annihilation points does not represent the range of the proton beam. There are several factors influencing the translation from annihilation points to obtain the Bragg peak position. One of them is the kinetic energy of the positron. This energy corresponds to some range of the positron within the tissue. In this manuscript we estimate positron energy and its range and discuss its influence on proton therapy monitoring.

The modular J-PET scanner, comprising 24 compact and versatile modules, each consisting of 13 plastic strips with four SiPM detectors at the ends, represents a powerful tool for clinical applications in nuclear medical imaging. This study presents preliminary results from the exploration of simultaneous dual-isotope imaging using the modular J-PET system. Our approach involved two isotopes: 68Ge, characterized by a ringlike shape, and 22Na, exhibiting a point-like shape. The imaging was based on double-coincidence and triple-coincidence events. In the double coincidence case, both isotopes contributed comparably, whereas in the triple coincidence case 22Na dominated due to the prompt gamma being emitted with 100% of positron emissions, unlike 68Ga, where the prompt gamma was emitted in only 1.3% of cases after positron emission. In this work we present direct 2? images determined for two-signal events and images for three-signal events, with two signals from annihilation photons and one from a prompt gamma. These results showcase the preliminary findings from simultaneous dual-isotope imaging of 68Ga and 22Na isotopes using the modular J-PET scanner, which will be presented and discussed.

The positronium imaging technique represents a potential enhancement of the PET imaging method. Its core principle involves employing a beta+ radiation source that emits additional gamma quanta referred to as prompt gamma. Our aim is to evaluate the capability to differentiate between annihilation and prompt gamma emissions, a vital aspect of positronium imaging. For this purpose, the selected isotopes should enable high efficiency and purity in detecting both prompt gamma and annihilation gamma. The assessment of the efficiency in identifying prompt and annihilation photons for various isotopes, which are potentially superior candidates for beta++ gamma emitters, is conducted through toy Monte-Carlo simulation utilizing the cross-section formula for photon-electron scattering. In this article, we have performed calculations for efficiency and purity values across different isotopes under ideal conditions and examined how these values evolve as we incorporate the fractional energy resolution into the analysis. Ultimately, the primary goal is to determine the energy threshold that optimizes both efficiency and purity, striking a balance between accurately identifying and recording events of interest while minimizing contamination from undesired events.

Total-body Positron Emission Tomography (PET) scanning is a promising new method for rapidly acquiring comprehensive wide-volume metabolic data with a lower radiation dosage compared to discrete whole-body PET imaging. PET scanners are generally used with Computed Tomography (CT) scanners to precisely understand tumor location and composition with the help of anatomical images. However, PET/CT sequential imaging methods for simultaneous total-body imaging are impractical for claustrophobic patients due to the enclosed gantry design and require large examination rooms because of the need for an exceptionally long patient table. To address this challenge, the Jagiellonian--PET Tomography (J-PET) Total-body scanner employs an innovative approach: utilizing both PET and CT devices on the same patient table but from different axes. The motion system of the J-PET Total Body scanner requires custom linear stages to move both PET and CT gantries. In this study, a novel cross-staged linear guiding solution is proposed by combining scanners on intersecting separable stages. The proposed sliding system is a combination of different machine elements and will be produced for the J-PET Total-body PET/CT Scanner. Concept designs are shown, and the proposed system is described. The application of the system for the J-PET total-body PET/CT scanner is discussed. The proposed solution is still in the development phase. The system holds the potential to achieve combining CT and PET scanners from different axes and enables motion artifact-free imaging for total-body imaging.

The Modular J-PET represents the latest advancement in the Jagiellonian-PET series, utilizing extended plastic scintillator strips. This prototype's modular design enables cost-effective imaging of multi-photon annihilation and positronium, allowing for easy assembly, portability, and versatility. Additionally, its lightweight construction facilitates static bed examinations with a mobile detection system that can be positioned conveniently alongside the patient, negating the requirement for spacious clinical settings. Comprising 24 modules arranged in regular 24- sided polygons circumscribing a 73.9 cm diameter circle, each module integrates 13 scintillator strips, measuring 50 cm in length and 6mm×24mm in cross-section. Scintillation light is captured at both ends through analog Silicon Photomultipliers (SiPMs). This research presents Sensitivity of the Modular J-PET tomograph, adhering to the NEMA_NU 2-2018 standards. Sensitivity measurement was performed with Ge line source inside the 5 sleeves aluminium phantom placed at center of the detector`s FOV and 10 cm offset from the center of detector. Analyzing the gathered data involved employing the specialized J-PET Framework software, developed within the C++ architecture. To validate the experimental findings, comparisons were made with GATE simulations, wherein the source and phantom were emulated in the same configuration as employed in the actual experiment. The system sensitivity of the Modular J-PET was assessed to be 1.03 ? 0.02 cps/kBq in the center of the detector`s FOV with the peak sensitivity of 2.1 cps/kBq. However, the simulations indicate that at the center of the detector's FOV, the Modular J-PET achieves a system sensitivity of 1.32 ? 0.03 cps/kBq, with a peak sensitivity of 2.9 cps/kBq.

Background: Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. Methods: For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configuration (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), the different cross-sections of plastic scintillator, and the multiple numbers of the plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. Results: With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance (? 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. Conclusion: Taking into account not only the sensitivity but also the price of the Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

In positron emission tomography (PET) studies, convolutional neural networks (CNNs) may be applied directly to the reconstructed distribution of radioactive tracers injected into the patient's body, as a pattern recognition tool. Nonetheless, unprocessed PET coincidence data exist in tabular format. This paper develops the transformation of tabular data into -dimensional matrices, as a preparation stage for classification based on CNNs. This method explicitly introduces a nonlinear transformation at the feature engineering stage and then uses principal component analysis to create the images. We apply the proposed methodology to the classification of simulated PET coincidence events originating from NEMA IEC and anthropomorphic XCAT phantom. Comparative studies of neural network architectures, including multilayer perceptron and convolutional networks, were conducted. The developed method increased the initial number of features from 6 to 209 and gave the best precision results (79.8) for all tested neural network architectures; it also showed the smallest decrease when changing the test data to another phantom.

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 r2 = 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.

Plastic scintillator strips are considered as one of the promising solutions for the cost-effective construction of total-body positron emission tomography, (PET) system. The purpose of the performed measurements is to compare the transparency of long plastic scintillators with dimensions 6 mm x 24 mm x 1000 mm and with all surfaces polished. Six different types of commercial, general purpose, blue-emitting plastic scintillators with low attenuation of visible light were tested, namely: polyvinyl toluene-based BC-408, EJ-200, RP-408, and polystyrene-based Epic, SP32 and UPS-923A. For determination of the best type of plastic scintillator for total-body Jagiellonian positron emission tomograph (TB-J-PET) construction, emission and transmission spectra, and technical attenuation length (TAL) of blue light-emitting by the scintillators were measured and compared. The TAL values were determined with the use of UV lamp as excitation source, and photodiode as light detector. Emission spectra of investigated scintillators have maxima in the range from 420 nm to 429 nm. The BC-408 and EJ-200 have the highest transmittance values of about 90% at the maximum emission wavelength measured through a 6 mm thick scintillator strip and the highest technical attenuation length reaching about 2000 mm, allowing assembly of long detection modules for time-of-flight (TOF) J-PET scanners. Influence of the 6 mm × 6 mm, 12 mm × 6 mm, 24 mm × 6 mm cross-sections of the 1000 mm long EJ-200 plastic scintillator on the TAL and signal intensity was measured. The highest TAL value was determined for samples with 24 mm × 6 mm cross-section.

It was recently demonstrated that newly invented positronium imaging may be used for improving cancer diagnostics by providing additional information about tissue pathology with respect to the standardized uptake value currently available in positron emission tomography (PET). Positronium imaging utilizes properties of a positronium atoms, which are built from the electron and positron produced in the body during PET examinations. We hypothesized whether positronium imaging would be sensitive to in vitro discrimination of tumour-like three-dimensional structures (spheroids) build of melanoma cell lines with different cancer activity and biological properties. The lifetime of ortho-Positronium (o-Ps) was evaluated in melanoma spheroids from two cell lines (WM266-4 and WM115) differing in the stage of malignancy. Additionally, we considered such parameters: as cell size, proliferation rate and malignancy to evaluate their relationship with o-Ps lifetime. We demonstrate the pilot results for the o-Ps lifetime measurement in extracellular matrix free spheroids. With the statistical significance of two standard deviations, we demonstrated that the higher the degree of malignancy and the rate of proliferation of neoplastic cells the shorter the lifetime of ortho-positronium. In particular we observed following indications encouraging further research: (i) WM266-4 spheroids characterized with higher proliferation rate and malignancy showed shorter o-Ps lifetime compared to WM115 spheroids characterized by lower growth rate, (ii) Both cell lines showed a decrease in the lifetime of o-Ps after spheroid generation in 8th day comparing to 4th day in culture and the mean o-Ps lifetime is longer for spheroids formed from WM115 cells than these from WM266-4 cells, regardless spheroid age. The results of these study revealed that positronium is a promising biomarker that may be applied in PET diagnostics for the assessment of the degree of cancer malignancy.

Positronium is the simplest bound state, built of an electron and a positron. Studies of positronium in vacuum and its decays in medium tell us about quantum electrodynamics (QED) and about the structure of matter and biological processes of living organisms at the nanoscale, respectively. Spectroscopic measurements constrain our understanding of QED bound state theory. Searches for rare decays and measurements of the effect of gravitation on positronium are used to look for new physics phenomena. In biological materials positronium decays are sensitive to the intermolecular and intramolecular structure and to the metabolism of living organisms ranging from single cells to human beings. This leads to new ideas of positronium imaging in medicine using the fact that during positron emission tomography (PET) as much as 40% of positron annihilation occurs through the production of positronium atoms inside the patient?s body. A new generation of the high sensitivity and multiphoton total-body PET systems opens perspectives for clinical applications of positronium as a biomarker of tissue pathology and the degree of tissue oxidation.

Background: The Jagiellonian Positron Emission Tomograph is the 3-layer prototype of the first scanner based on plastic scintillators, consisting of 192 half-metre-long strips with readouts at both ends. Compared to crystal-based detectors, plastic scintillators are several times cheaper and could be considered as a more economical alternative to crystal scintillators in future PETs. JPET is also a first multi-photon PET prototype. For the development of multi-photon detection, with photon characterized by the continuous energy spectrum, it is important to estimate the efficiency of J-PET as a function of energy deposition. The aim of this work is to determine the registration efficiency of the J-PET tomograph as a function of energy deposition by incident photons and the intrinsic efficiency of the J-PET scanner in detecting photons of different incident energies. In this study, 3-hit events are investigated, where 2-hits are caused by 511 keV photons emitted in e+e- annihilations, while the third hit is caused by one of the scattered photons. The scattered photon is used to accurately measure the scattering angle and thus the energy deposition. Two hits by a primary and a scattered photon are sufficient to calculate the scattering angle of a photon, while the third hit ensures the precise labeling of the 511 keV photons. Results: By comparing experimental and simulated energy distribution spectra, the registration efficiency of the J-PET scanner was determined in the energy deposition range of 70-270 keV, where it varies between 20 and 100%. In addition, the intrinsic efficiency of the J-PET was also determined as a function of the energy of the incident photons. Conclusion: A method for determining registration efficiency as a function of energy deposition and intrinsic efficiency as a function of incident photon energy of the J-PET scanner was demonstrated. This study is crucial for evaluating the performance of the scanner based on plastic scintillators and its applications as a standard and multi-photon PET systems. The method may be also used in the calibration of Compton-cameras developed for the ion-beam therapy monitoring and simultaneous multi-radionuclide imaging in nuclear medicine.

Purpose: Cardiac myxoma (CM), the most common cardiac tumor in adults, accounts for 50?75% of benign cardiac tumors. The diagnosis of CM is often elusive, especially in young stroke survivors and transthoracic echocardiography (TTE) is the initial technique for the differential diagnostics of CM. Less invasive cardiac computed tomography (CT) and magnetic resonance imaging (MRI) are not available for the majority of cardiac patients. Here, a robust imaging approach, ortho-Positronium (o-Ps) imaging, is presented to determine cardiac myxoma extracted from patients undergoing urgent cardiac surgery due to unexpected atrial masses. We aimed to assess if the o-Ps atom, produced copiously in intramolecular voids during the PET imaging, serves as a biomarker for CM diagnosing. Methods: Six perioperative CM and normal (adipose) tissue samples from patients, with primary diagnosis confirmed by the histopathology examination, were examined using positron annihilation lifetime spectroscopy (PALS) and micro-CT. Additionally, cell cultures and confocal microscopy techniques were used to picture cell morphology and origin. Results: We observed significant shortening in the mean o-Ps lifetime in tumor with compare to normal tissues: an average value of 1.92(02) ns and 2.72(05) ns for CM and the adipose tissue, respectively. Microscopic differences between tumor samples, confirmed in histopathology examination and micro-CT, did not influenced the major positronium imaging results. Conclusions: Our findings, combined with o-Ps lifetime analysis, revealed the novel emerging positronium imaging marker (o-PS) for cardiovascular imaging. This method opens the new perspective to facilitate the quantitative in vivo assessment of intracardiac masses on a molecular (nanoscale) level.

We report a study of the original image reconstruction algorithm based on the time-of-flight maximum likelihood expectation maximisation (TOF MLEM), developed for the total-body (TB) Jagiellonian PET (J-PET) scanners. The method is applicable to generic cylindrical or modular multi-layer layouts and is extendable to multi-photon imaging. The system response matrix (SRM) is represented as a set of analytical functions, uniquely defined for each pair of plastic scintillator strips used for the detection. A realistic resolution model (RM) in detector space is derived from fitting the Monte Carlo simulated emissions and detections of annihilation photons on oblique transverse planes. Additional kernels embedded in SRM account for TOF, parallax effect and axial smearing. The algorithm was tested on datasets, simulated in GATE for the NEMA IEC and static XCAT phantoms inside a 24-module 2-layer TB J-PET. Compared to the reference TOF MLEM with none or a shift-invariant RM, an improvement was observed, as evaluated by the analysis of image quality, difference images and ground truth metrics. We also reconstructed the data with additive contributions, pre-filtered geometrically and with non-TOF scatter correction applied. Despite some deterioration, the obtained results still capitalise on the realistic RM with better edge preservation and superior ground truth metrics. The envisioned prospects of the TOF MLEM with analytical SRM include its application in multi-photon imaging and further upgrade to account for the non-collinearity, positron range and other factors.

The growing interest in human-grade Total Body PET systems has also application in small animal research. Due to the existing limitations in human-based studies involving drug development and novel treatment monitoring, animalbased research became a necessary step for testing and protocol preparation. In this simulation-based study two unconventional, cost effective small animal Total Body PET scanners (for mouse and rat studies) have been investigated in order to inspect their feasibility for preclinical research. They were designed with the novel technology explored by the Jagiellonian PET Collaboration (J-PET). Two main PET characteristics: sensitivity and spatial resolution were mainly inspected to evaluate their performance. Moreover, the impact of the scintillator dimension and time-offlight on the latter parameter were examined in order to design the most efficient tomographs. The presented results show that for mouse TB J-PET the achievable system sensitivity is equal to 2.35% and volumetric spatial resolution to 9.46 +- 0.54 mm3, while for rat TB J-PET they are equal to 2.6% and 14.11 ? 0.80 mm3, respectively. Furthermore, it was shown that the designed tomographs are almost parallax-free systems, hence they resolve the problem of the acceptance criterion trade-off between enhancing spatial resolution and reducing sensitivity.

Pioneering investigations on the usage of positron-emission-tomography (PET) for the monitoring of ion beam therapy with light (protons, helium) and heavier (stable and radioactive neon, carbon and oxygen) ions started shortly after the first realization of planar and tomographic imaging systems, which were able to visualize the annihilation of positrons resulting from irradiation induced or implanted positron emitting nuclei. And while the first clinical experience was challenged by the utilization of instrumentation directly adapted from nuclear medicine applications, new detectors optimized for this unconventional application of PET imaging are currently entering the phase of (pre)clinical testing for more reliable monitoring of treatment delivery during irradiation. Moreover, recent advances in detector technologies and beam production open several new exciting opportunities which will not only improve the performance of PET imaging under the challenging conditions of in-beam applications in ion beam therapy, but will also likely expand its field of application. In particular, the combination of PET and Compton imaging can enable the most efficient utilization of all possible radiative emissions for both stable and radioactive ion beams, while positronium lifetime imaging may enable probing new features of the underlying tumour and normal tissue environment. Thereby, PET imaging will not only provide means for volumetric reconstruction of the delivered treatment and in-vivo verification of the beam range, but can also shed new insights for biological optimization of the treatment or treatment response assessment.

Positron-electron annihilation in living organisms occurs in about 30% via the formation of a metastable ortho-positronium atom that annihilates into two 511 keV photons in tissues because of the pick-off and conversion processes. Positronium (Ps) annihilation lifetime and intensities can be used to determine the size and quantity of defects in a material's microstructure, such as voids or pores in the range of nanometers. This is particularly true for blood clots. Here we present pilot investigations of positronium properties in fibrin clots. The studies are complemented by the use of SEM Edax and micro-computed tomography (microCT) to evaluate the extracted thrombotic material's properties. microCT is a versatile characterization method offering in situ and in operando possibilities and is a qualitative diagnostic tool. With microCT the presence of pores, cracks, and structural errors can be verified, and hence the 3D inner structure of samples can be investigated.

We develop a positronium imaging method for the Jagiellonian PET (J-PET) scanners based on the time-of-flight maximum likelihood expectation maximisation (TOF MLEM). The system matrix elements are calculated on-the-fly for the coincidences comprising two annihilation and one de-excitation photons that originate from the ortho-positronium (o-Ps) decay. Using the Geant4 library, a Monte Carlo simulation was conducted for four cylindrical 22Na sources of ?+ decay with diverse o-Ps mean lifetimes, placed symmetrically inside the two JPET prototypes. The estimated time differences between the annihilation and the positron emission were aggregated into histograms (one per voxel), updated by the weights of the activities reconstructed by TOF MLEM. The simulations were restricted to include only the o-Ps decays into back-to-back photons, allowing a linear fitting model to be employed for the estimation of the mean lifetime from each histogram built in the log scale. To suppress the noise, the exclusion of voxels with activity below 2% ? 10% of the peak was studied. The estimated o-Ps mean lifetimes were consistent with the simulation and distributed quasi-uniformly at high MLEM iterations. The proposed positronium imaging technique can be further upgraded to include various correction factors, as well as be modified according to realistic o-Ps decay models.

Objective: This paper reports on the implementation and shows examples of the use of the ProTheRaMon framework for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility. We present the ProTheRaMon framework and illustrate its potential use case and data processing steps for a patient treated at the Cyclotron Centre Bronowice (CCB) proton therapy center in Krakow, Poland. Approach: The ProTheRaMon framework is based on GATE Monte Carlo software, the CASToR reconstruction package and in-house developed Python and bash scripts. The framework consists of five separated simulation and data processing steps, that can be further optimized according to the user's needs and specific settings of a given proton therapy facility and PET scanner design. Main results: ProTheRaMon is presented using example data from a patient treated at CCB and the J-PET scanner to demonstrate the application of the framework for proton therapy range monitoring. The output of each simulation and data processing stage is described and visualized. Significance: We demonstrate that the ProTheRaMon simulation platform is a high-performance tool, capable of running on a computational cluster and suitable for multi-parameter studies, with databases consisting of large number of patients, as well as different PET scanner geometries and settings for range monitoring in a clinical environment. Due to its modular structure, the ProTheRaMon framework can be adjusted for different proton therapy centers and/or different PET detector geometries. It is available to the community via github.

This review introduce extracellular vesicles (EVs) to a molecular imaging field. The idea of modern analyses based on the use of omics studies, using highthroughput methods to characterize the molecular content of a single biological system, vesicolomics seems to be the new approach to collect molecular data about EV content, to find novel biomarkers or therapeutic targets. The use of various imaging techniques, including those based on radionuclides as positron emission tomography (PET) or single photon emission computed tomography (SPECT), combining molecular data on EVs, opens up the new space for radiovesicolomics?a new approach to be used in theranostics.

The image of positronium properties created in the patient?s body during PET examination tells about the inter- and intra-molecular structure of the tissue and the concentration of bio-active molecules in the tissue [2?4]. In this article, we advocate the opinion that total-body PET systems, thanks to their high imaging sensitivity and high time resolution, open up the prospect of translating positronium imaging into clinics.

The entanglement of photons originating from electron-positron annihilation has not been experimentally proven. owever, the independent experiments performed so far unanimously confirm that the correlation between the linear polarizations of back-to-back photons from electron?positron annihilation is consistent with the assumption that these photons are entangled in the polarization. Yet, unexpectedly, recent experiments differ as regards the correlation of polarization direction of back-to-back photons after the decoherence induced by the scattering of one of these photons on the electron in the scattering material. In one of the experiments, the correlation before and after the decoherence of the photon state is the same, and in the other experiment, the scattering of one photon leads to a significant decrease in this correlation. Here we discuss this puzzle. Decoherent states were ensured provided by forcing one of the annihilation photons to scatter earlier before measuring the polarization correlation based on Compton kinematics. The comparison is made between the experimental setups used for the different measurements, and the results obtained are briefly discussed, highlighting the parameters that are important in performing such measurements. Finally, the main features of the J-PET detector are presented, along with the schemes for performing similar studies, so that the conclusive results can be used as remarks to solve the puzzle in question. Solving the decoherence puzzle will have crucial consequences for basic studies of entanglement, as well as for the proposed application of the photon polarization in positron emission tomography. If the correlation of the polarization of back-to-back photons from the electron?positron annihilation is the same before and after the scattering of these photons, then it will not be useful for the reduction of scatter fraction in positron emission tomography diagnostics.

The positronium system ? a bound state of an electron and a positron ? is suitable for testing the predictions of quantum electrodynamics, since its properties can be perturbatively calculated to high accuracy and, unlike the hydrogen system, it is not affected by the finite size or quantum chromodynamics effects at the current level of experimental precision. Experiments searching for invisible decays of the positronium triplet state ? the ortho-positronium ? which mainly decays to three photons, are being conducted since they are sensitive to new physics scenarios, e.g., mirror matter, milli-charged particles, and extra space-time dimensions. The particular case of mirror matter and its search with the novel total-body positron emission tomography scanner at the Jagiellonian University is presented. This J-PET is a large, high precision medical imaging tool based on plastic scintillators.

Positronium lifetime imaging (PLI) [1], an extension of PET, provides insight into the submolecular properties of tissues by imaging the lifetime of the positronium atom [2]. Currently, the method is under rapid development as regards reconstruction [3], [4] and detection systems [5], [6]. The first studies with the J-PET scanner using 68Ga have demonstrated the feasibility of this technique in human subjects [6]. However, the Ga68 isotope has limitations due to its low yield of de-excitation photons necessary for positronium lifetime estimation. In this context, 44Sc emerges as a promising candidate for PLI [7], offering a clinically optimal half-life of 3.97 hours and a high deexcitation photon yield of 94.3 % with an energy of 1157 keV. In this work, we report the results of the successful demonstration of PLI with 44 Sc using the Modular J-PET tomograph, featuring triggerless data acquisition that enables simultaneous multiphoton detection [8]. 44Sc was produced at the Heavy Ion Laboratory in Warsaw and transported to Jagiellonian University in Kraków. A NEMA IQ phantom with six spheres was used. The three largest spheres were filled with 44Sc, and the three smallest with 18 F, both diluted with water, having an initial activity concentration ratio of 1:3. Event selection was based on the simultaneous detection of two 511 keV photons and one de-excitation photon, enabling reconstruction of images of the mean positronium lifetime [2], [6]. The measured mean o-Ps lifetime shows good agreement with previously reported values in water [9]. This study presents the first-ever demonstration of PLI with 44 Sc, marking a significant advancement and opening new possibilities for developing PLI for clinical applications.

Positronium Imaging is gaining interest as a new promising method that may improve the diagnostic specificity of Positron Emission Tomography. Recently, the first ex-vivo and in-vivo positronium lifetime images were demonstrated by means of the dedicated multi-photon J-PET system. The latest upgrades of the Biograph Vision Quadra (Siemens Healthineers) to the singles mode acquisition open the possibility of multi-photon imaging. In this simulation-based work, sensitivity of both systems has been assessed as a function of the energy window applied for registration of the prompt photon. The research was conducted using four radioisotopes: 124 I, 68 Ga, 44 Sc, 22 Na, which were chosen due to their medical or laboratory utilization. Simulations were performed with the GATE software. The result indicates that Biograph Vision Quadra provides about 400 times higher sensitivity with respect to the modular J-PET prototype used to demonstrate the first positronium images, assuming full energy acquisition of the prompt photon.

The positronium atom, a bound state of electron and positron, is a suitable leptonic test site for Charge-Parity (CP) discrete symmetry research. According to the Standard Model, the photon?photon interaction in the final state due to the vacuum polarization may mimic CP violation of the order of 10^-9, while weak interaction effects lead to a violation of the order of 10^-14. So far, the experimental limits on CP symmetry violation in the decay of o-Ps are set at the level of 10^-3. The J-PET detector can be used to explore discrete symmetries by looking for probable non-zero expectation values of the symmetry-odd operators, constructed from spin of ortho-Positronium (o-Ps) and momentum, and polarization vectors of gamma quanta resulting from o-Ps annihilation. The upgraded version of the J-PET detector, with an additional fourth layer of detection modules increases signal acceptance, which allows to triple the efficiency of quanta detection for CP discrete symmetry studies.