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.

The J-PET tomograph is constructed from plastic scintillator strips arranged axially in concentric cylindrical layers. It enables investigations of positronium decays by measurement of the time, position, polarization and energy deposited by photons in the scintillators, in contrast to studies conducted so far with crystal and semiconductor based detection systems where the key selection of events is based on the measurement of the photons' energies. In this article we show that the J-PET tomograph system is capable of exclusive measurements of the decays of ortho-positronium atoms. We present the first positronium production results, its lifetime distribution measurements and discuss estimation of the influence of various background sources. The tomograph's performance demonstrated here makes it suitable for precision studies of positronium decays including entanglement of the final state photons, positron annihilation lifetime spectroscopy plus molecular imaging diagnostics.

In vivo assessment of cancer and precise location of altered tissues at initial stages of molecular disorders are important diagnostic challenges. Positronium is copiously formed in the free molecular spaces in the patient's body during positron emission tomography (PET). The positronium properties vary according to the size of inter- and intramolecular voids and the concentration of molecules in them such as, e.g., molecular oxygen, O2; therefore, positronium imaging may provide information about disease progression during the initial stages of molecular alterations. Current PET systems do not allow acquisition of positronium images. This study presents a new method that enables positronium imaging by simultaneous registration of annihilation photons and deexcitation photons from pharmaceuticals labeled with radionuclides. The first positronium imaging of a phantom built from cardiac myxoma and adipose tissue is demonstrated. It is anticipated that positronium imaging will substantially enhance the specificity of PET diagnostics.

Research conducted in the framework of the Jagiellonian-PET (J-PET) project aims to develop a cost-effective total-body positron emission tomography scanner. As a first step on the way to construct a full-scale J-PET tomograph from long strips of plastic scintillators, a 24-strip prototype was built and tested. The prototype consists of detection modules arranged axially forming a cylindrical diagnostic chamber with the inner diameter of 360 mm and the axial field-of-view of 300 mm. Promising perspectives for a low-cost construction of a total-body PET scanner are opened due to an axial arrangement of strips of plastic scintillators, which have a small light attenuation, superior timing properties, and the possibility of cost-effective increase of the axial field-of-view. The presented prototype comprises dedicated solely digital front-end electronic circuits and a triggerless data acquisition system which required the development of new calibration methods including time, thresholds, and gain synchronization. The system and elaborated calibration methods, including first results of the 24-module J-PET prototype, are presented and discussed. The achieved coincidence resolving time equals to ${\mathrm {CRT}}=490\pm 9$ ps. This value can be translated to the position reconstruction accuracy $\sigma (\Delta l) =18$ mm, which is fairly position independent.

We perform a parametric study of the newly developed time-of-flight (TOF) image reconstruction algorithm, proposed for the real-time imaging in total-body Jagiellonian PET (J-PET) scanners. The asymmetric 3D filtering kernel is applied at each most likely position of electron-positron annihilation, estimated from the emissions of back-to-back $\gamma$-photons. The optimisation of its parameters is studied using Monte Carlo simulations of a 1-mm spherical source, NEMA IEC and XCAT phantoms inside the ideal J-PET scanner. The combination of high-pass filters which included the TOF filtered back-projection (FBP), resulted in spatial resolution, 1.5 $\times$ higher in the axial direction than for the conventional 3D FBP. For realistic $10$-minute scans of NEMA IEC and XCAT, which require a trade-off between the noise and spatial resolution, the need for Gaussian TOF kernel components, coupled with median post-filtering, is demonstrated. The best sets of 3D filter parameters were obtained by the Nelder-Mead minimisation of the mean squared error between the resulting and reference images. The approach allows training the reconstruction algorithm for custom scans, using the IEC phantom, when the temporal resolution is below 50 ps. The image quality parameters, estimated for the best outcomes, were systematically better than for the non-TOF FBP.

The purpose of the presented research is estimation of the performance characteristics of the economic total-body Jagiellonian-PET system (TB-J-PET) constructed from plastic scintillators. The characteristics are estimated according to the NEMA NU-2-2018 standards utilizing the GATE package. The simulated detector consists of 24 modules, each built out of 32 plastic scintillator strips (each with cross section of 6 mm times 30 mm and length of 140 or 200 cm) arranged in two layers in regular 24-sided polygon circumscribing a circle with the diameter of 78.6 cm. For the TB-J-PET with an axial field-of-view (AFOV) of 200 cm, a spatial resolutions (SRs) of 3.7 mm (transversal) and 4.9 mm (axial) are achieved. The noise equivalent count rate (NECR) peak of 630 kcps is expected at 30 kBq cc-1. Activity concentration and the sensitivity at the center amounts to 38 cps kBq-1. The scatter fraction (SF) is estimated to 36.2 %. The values of SF and SR are comparable to those obtained for the state-of-the-art clinical PET scanners and the first total-body tomographs: uExplorer and PennPET. With respect to the standard PET systems with AFOV in the range from 16 to 26 cm, the TB-J-PET is characterized by an increase in NECR approximately by factor of 4 and by the increase of the whole-body sensitivity by factor of 12.6 to 38. The time-of-flight resolution for the TB-J-PET is expected to be at the level of CRT = 240 ps full width at half maximum. For the TB-J-PET with an AFOV of 140 cm, an image quality of the reconstructed images of a NEMA IEC phantom was presented with a contrast recovery coefficient and a background variability parameters. The increase of the whole-body sensitivity and NECR estimated for the TB-J-PET with respect to current commercial PET systems makes the TB-J-PET a promising cost-effective solution for the broad clinical applications of total-body PET scanners. TB-J-PET may constitute an economic alternative for the crystal TB-PET scanners, since plastic scintillators are much cheaper than BGO or LYSO crystals and axial arrangement of the strips significantly reduces the costs of readout electronics and SiPMs.

Charged lepton system symmetry under combined charge, parity, and time-reversal transformation (CPT) remains scarcely tested. Despite stringent quantum-electrodynamic limits, discrepancies in predictions for the electron-positron bound state (positronium atom) motivate further investigation, including fundamental symmetry tests. While CPT noninvariance effects could be manifested in non-vanishing angular correlations between final-state photons and spin of annihilating positronium, measurements were previously limited by knowledge of the latter. Here, we demonstrate tomographic reconstruction techniques applied to three-photon annihilations of ortho-positronium atoms to estimate their spin polarisation without magnetic field or polarised positronium source. We use a plastic-scintillator-based positron-emission-tomography scanner to record ortho-positronium (o-Ps) annihilations with single-event estimation of o-Ps spin and determine the complete spectrum of an angular correlation operator sensitive to CPT-violating effects. We find no violation at the precision level of 10-4, with an over threefold improvement on the previous measurement.

Abstract Background/Introduction Positron Emission Tomography (PET), also a standard in cardiovascular imaging, enables semi-quantitative myocardial perfusion evaluation and assessment of atherosclerosis. PET is based on positron-electro annihilation inside a patient's body and in about 40% events it proceeds via formation of positronium. Positronium is an exotic atom created from an electron and a positron in a patient during standard PET imaging. Positronium is not stable and its life-time depends on molecular environment. Recently, it was shown that with the new generation of high sensitivity long-axial field of view PET systems is possible to perform simultaneous imaging of the metabolism rate of administered pharmaceutical and imaging of positronium life-time. Positronium life-time informs about tissue nanostructure and allows distinguishing pathology. Purpose Purpose of the presented study is the evaluation of positronium life-time as a biomarker for cardiac masses, namely cardiac myxoma (CM) and normal tissues, obtained from symptomatic patients. Methods CM and adipose tissue samples were obtained during a surgery from six symptomatic patients with ECHO confirmed cardiac masses in a left atrium. Immediately after sampling, sample were analyzed with the dedicated positronium-life time measurement system. Samples were irradiated with positrons emitted from the 22Na radionuclide. The system enabled to measure the time-difference spectrum between the formation and annihilation of positronium atom within the studied samples. The life-time spectrum was used for the extraction of a mean positronium life-time. The sample underwent histopathological and micro-computer-tomography (micro-CT) examinations, which confirmed a diagnosis and revealed microstructure of a cardiac mass. Results It was established that positronium life-time in CM tissues is significantly (at the level of 10 standard deviations) smaller than in adipose tissue. At the same time, the determined positronium life-time in CM samples from different patients was the same within two standard deviations. Micro-CT imaging showed that CM samples had different calcification spots, but did not revealed existing microvasculature. Conclusion Obtained results confirm that positronium life-time differentiates between cardiac pathologies (CM) and normal tissues. And may be used as a biomarker in cardiac masses assessment available during PET examination. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Foundation for Polish Science through the TEAM POIR.04.04.00-00-4204/17 Programme, the National Science Centre.

We present results on CPT symmetry tests in decays of positronium performed with the precision at the level of 10${^{-4}}$, and positronium images determined with the prototype of the J-PET tomograph. The first full-scale prototype apparatus consists of 192 plastic scintillator strips readout from both ends with vacuum tube photomultipliers. Signals produced by photomultipliers are probed in the amplitude domain and are digitized by FPGA-based readout boards in triggerless mode. In this contribution we report on the first two- and three-photon positronium images and tests of CPT symmetry in positronium decays.

In this paper we introduce a semi-analytic algorithm for 3-dimensional image reconstruction for positron emission tomography (PET). The method consists of the back-projection of the acquired data into the most likely image voxel according to time-of-flight (TOF) information, followed by the filtering step in the image space using an iterative optimization algorithm with a total variation (TV) regularization. TV regularization in image space is more computationally efficient than usual iterative optimization methods for PET reconstruction with full system matrix that use TV regularization. The efficiency comes from the one-time TOF back-projection step that might also be described as a reformatting of the acquired data. An important aspect of our work concerns the evaluation of the filter operator of the linear transform mapping an original radioactive tracer distribution into the TOF back-projected image. We obtain concise, closed-form analytical formula for the filter operator. The proposed method is validated with the Monte Carlo simulations of the NEMA IEC phantom using a one-layer, 50 cm-long cylindrical device called Jagiellonian PET scanner. The results show a better image quality compared with the reference TOF maximum likelihood expectation maximization algorithm.

Three-dimensional (3D) spheroids mimic important properties of tumors and may soon become a reasonable substitute for animal models and human tissue, eliminating numerous problems related to in vivo and ex vivo experiments and pre-clinical drug trials. Currently, various imaging methods including X-ray microtomography (micro-CT), exist but their spatial resolution is limited. Here, we visualized and provided a morphological analysis of spheroid cell cultures using micro-CT and compared it to that of confocal microscopy. An approach is proposed that can potentially open new diagnostic opportunities to determine the morphology of cancer cells cultured in 3D structures instead of using actual tumors. Spheroids were formed from human melanoma cell lines WM266-4 and WM115 seeded at different cell densities using the hanging drop method. Micro-CT analysis of spheroid showed that spheroid size and shape differed depending on the cell line, initial cell number, and duration of culture. The melanoma cell lines used in this study can successfully be cultured as 3D spheroids and used to substitute human and animal models in pre-clinical studies. The micro-CT allows for high-resolution visualization of the spheroids structure.

In living organisms, the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511 keV photons. In this article, we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include the (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2γ annihilations and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. Simulations are conducted assuming that radiopharmaceutical is labeled with 44Sc isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution, the four cases were considered assuming that CRT is equal to 500 ps, 140 ps, 50 ps, and 10 ps. The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences (2γ+γprompt) is larger by a factor of 13.5 (for LYSO PET) and by factor of 5.2 (for plastic PET) with respect to the sensitivity for the standard 2γ imaging by LYSO PET scanners with AFOV = 20 cm. The spatial resolution of the ortho-positronium image is comparable with the resolution achievable when using TOF-FBP algorithms already for CRT = 50 ps. For the 20-min scan, the resolution better than 20 ps is expected for the mean ortho-positronium lifetime image determination. Ortho-positronium mean lifetime imaging based on the annihilations into two photons and prompt gamma is shown to be feasible with the advent of the high sensitivity total-body PET systems and time resolution of the order of tens of picoseconds.

Positron Annihilation Lifetime Spectroscopy (PALS) is a technique based on the analysis of the lifetime of positronium emitted from implanted or delivered positronium donors. This technique employs the lifetime and intensity dependence on the structure of analyzed material. Due to this specific features, PALS might be used in further research protocols and clinical studies for cancer diagnostic purposes. This article reports the progress in the study design, main objectives of the study, protocols of measurements and data analysis and further perspective of this study. The main goal of this work was to show the effectiveness of this method and progress in its development. For this purpose, colorectal cancer was examined.

The J-PET tomograph is constructed from plastic scintillator strips arranged axially in concentric cylindrical layers. It enables investigations of positronium decays by measurement of the time, position, polarization and energy deposited by photons in the scintillators, in contrast to studies conducted so far with crystal and semiconductor based detection systems where the key selection of events is based on the measurement of the photons' energies. In this article we show that the J-PET tomography system constructed solely from plastic scintillator detectors is capable of exclusive measurements of the decays of ortho-positronium atoms. We present the first positronium production results, its lifetime distribution measurements and estimation of the influence of various background sources. The obtained results prove the capability of the J-PET tomograph for (i) fundamental studies of positronium decays (in particular test of discrete symmetries in purely leptonic systems), (ii) positron annihilation lifetime spectroscopy, as well as (iii) molecular imaging diagnostics and (iv) observation of entanglement.

In this article, a new method for the reconstruction of hit-position and hit-time of photons in long scintillator detectors is investigated. This article is motivated by the recent development of the positron emission tomography scanners based on plastic scintillators. The proposed method constitutes a new way of signal processing in multivoltage-technique. It is based on the determination of the degree of similarity between the registered signals and the synchronized model signals stored in a library. The library was established for a set of well-defined hit-positions along the length of the scintillator. The Mahalanobis distance was used as a measure of similarity between the two compared signals. The method was validated on the experimental data measured using two-strips J-PET prototype with dimensions of $5\times 9\times 300$ mm 3 . The obtained time-of-flight (TOF) and spatial resolutions amount to 325 ps (FWHM) and 25 mm (FWHM), respectively. The TOF resolution was also compared to the results of an analogous study done using the linear fitting method. The best TOF resolution was obtained with this method at four predefined threshold levels which was comparable to the resolution achieved from the Mahalanobis distance at two predefined threshold levels. Although the algorithm of the linear fitting method is much simpler to apply than the Mahalanobis method, the application of the Mahalanobis distance requires a lower number of applied threshold levels and, hence, decreases the costs of electronics used in PET scanner.

Time-Over-Threshold (TOT) technique is being used widely due to its implications in developing the multi channel readouts mainly when fast signal processing is required. Using TOT technique as a measure of energy loss instead of charge integration methods significantly reduces the signals readout cost by combining the time and energy information. Therefore, this approach can potentially be used in J-PET tomograph which is build from plastic scintillators characterized by fast light signals. The drawback in adopting this technique is lying in the non-linear correlation between input energy loss and TOT of the signal. The main motivation behind this work is to develop the relationship between TOT and energy loss and validate it with the J-PET tomograph. The experiment was performed using the $^{22}$Na beta emitter source placed in the center of the J-PET tomograph. One can obtain primary photons of two different energies: 511 keV photon from the annihilation of positron (direct annihilation or through the formation of para-Positronim atom or pick-off process of ortho-Positronium atoms), and 1275 keV prompt photon. This allows to study the correlation between TOT values and energy loss for energy range up to 1000 keV. As the photon interacts dominantly via Compton scattering inside the plastic scintillator, there is no direct information of primary photon energy. However, using the J-PET geometry one can measure the scattering angle of the interacting photon. Since, $^{22}$Na source emits photons of two different energies, it is required to know unambiguously the energy of incident photons and its corresponding scattering angle for the estimation of energy deposition. In this work, the relationship between Time Over Threshold and energy loss by interacting photons inside the plastic scintillators used in J-PET scanner is established for a energy deposited range 100-1000 keV

In this paper we present Monte Carlo N-Particle (MCNP) simulations of the system for underwater threat detection using neutron activation analysis developed in the SABAT project. The simulated system is based on a D-T neutron generator emitting 14 MeV neutrons without associated α particle detection and equipped with a LaBr_3:Ce scintillation detector offering superior energy resolution and allowing for precise identification of activation γ quanta. The performed simulations show that using the neutron activation analysis method with the designed geometry we are able to identify γ-rays from hydrogen, carbon, sulphur and chlorine originating from mustard gas in a sea water environment. Our results show that the most efficient way of mustard gas detection is to compare the integral peak ratio for Cl and H.

J-PET is the first positron-emission tomograph (PET) constructed from plastic scintillators. It was optimized for the detection of photons from electron-positron annihilation. Such photons, having an energy of 511 keV, interact with electrons in plastic scintillators predominantly via the Compton effect. Compton scattering is at most probable at an angle orthogonal to the electric field vector of the interacting photon. Thus registration of multiple photon scatterings with J-PET enables to determine the polarization of the annihilation photons. In this contribution we present estimates on the physical limitation in the accuracy of the polarization determination of 511 keV photons with the J-PET detector.

Positron Annihilation Lifetime Spectroscopy (PALS) allows examining structure of materials in nano and sub-nanometer scale. This technique is based on the lifetime and intensity of ortho-positronium atoms in free volumes of given structures. It is mostly used for studies in material sciences, but it can also be used for in vivo imaging of the cell morphology as proposed in [1], [2]. Cancer cells are characterized by an altered macro structure in comparison to normal cells, thus the main objective of these studies is to compare if these differences can be detected on sub-nanometer level and therefore allows to distinguish between normal and cancer cells with application of PALS technique. This perspective will allow for simultaneous determination of early and advanced stages of carcinogenesis, by observing changes in biomechanical parameters between normal and tumour cells, and standard PET examination. Such simultaneous PET imaging and PALS investigations can be performed with the Jagiellonian Positron Emission Tomograph (J-PET) which is a multi-purpose detector used for investigations with positronium atoms in life-sciences as well as for development of medical diagnostics.

A detection system of the conventional PET tomograph is set-up to record data from annihilation into two photons with energy of 511 keV, and it gives information on the density distribution of a radiopharmaceutical in the body of the object. In this paper we explore the possibility of performing the three gamma photons imaging based on ortho-positronium annihilation, as well as the possibility of positronium mean lifetime imaging with the J-PET tomograph constructed from plastic scintillators. For this purposes simulations of the ortho-positronium formation and its annihilation into three photons were performed taking into account distributions of photons’ momenta as predicted by the theory of quantum electrodynamics and the response of the J-PET tomograph. In order to test the proposed ortho-positronium lifetime image reconstruction method, we concentrate on the decay of the ortho-positronium into three photons and applications of radiopharmaceuticals labeled with isotopes emitting a prompt gamma. The proposed method of imaging is based on the determination of hit-times and hit-positions of registered photons which enables the reconstruction of the time and position of the annihilation point as well as the lifetime of the ortho-positronium on an event-by-event basis. We have simulated the production of the positronium in point-like sources and in a cylindrical phantom composed of a set of different materials in which the ortho-positronium lifetime varied from 2.0 ns to 3.0 ns, as expected for ortho-positronium created in the human body. The presented reconstruction method for total-body J-PET like detector allows to achieve a mean lifetime resolution of  ∼40 ps. Recent positron annihilation lifetime spectroscopy measurements of cancerous and healthy uterine tissues show that this sensitivity may allow to study the morphological changes in cell structures.