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The growing interest in human-grade total body positron emission tomography (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, animal-based 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 (J-PET) Collaboration. Two main PET characteristics: sensitivity and spatial resolution were mainly inspected to evaluate their performance. Moreover, the impact of the scintillator dimension and time-of-flight on the latter parameter was 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 tradeoff between enhancing spatial resolution and reducing sensitivity.

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.

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.

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.

Research conducted in the framework of the 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, wchich 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 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 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., Comment: Accepted for publication in IEEE Transactions on Instrumentation and Measurement

In this article, a new method for the reconstruction of hit-position and hit-time of photons in long scintillator detectors is investigated. This research 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 Multi-Voltage-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 5x9x300 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 Linear Fitting method. The best TOF resolution was obtained with this method at four pre-defined threshold levels which was comparable to the resolution achieved from the Mahalanobis distance at two pre-defined threshold levels. Although the algorithm of 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 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: (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using $2\gamma$ 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 labelled with $^{44}Sc$ 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 three cases were considered assuming that CRT is equal to 140ps, 50ps and 10ps. The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences is larger by a factor of 12.2 (for LYSO PET) and by factor of 4.7 (for plastic PET) with respect to the sensitivity for the standard $2\gamma$ imaging by LYSO PET scanners with AFOV=20cm.

A detection system of the conventional PET tomograph is set-up to record data from e+ e- 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 quantum. 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 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 about 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., Comment: accepted in PMB (http://iopscience.iop.org/article/10.1088/1361-6560/aafe20)

The possibility to separate signals caused by 511 keV photons created in annihilation of electron-positron pairs and the so-called prompt photons from nuclei de- excitation is investigated. It could potentially be used to improve the quality of reconstructed images in the J-PET scanner in 2+1 photon tomography. Firstly, a research is conducted for several radioisotopes that decay via \b{eta}+ decay followed by de-excitation of an excited nucleus. Efficiency, purity and false positive rate are calculated for each isotope as a function of energy deposited threshold, with a hypothesis that signals caused by 511 keV photons deposit smaller values of energy than 1 z 13the selected threshold, while prompt photons deposit larger energy than the threshold. Analysis of the results accompanied with physical properties of radioisotopes suggests using 44 Sc, which is the most promising candidate for medical applications. With the use of GATE and J-POS simulation software, in-phantom scattering was introduced and the best energy deposited threshold value was estimated to be approximately 375 keV. It corresponds to almost 100% efficiency for 511 keV signals, 75% purity for 511 keV photons, and approximately 70% efficiency and purity for prompt photons., Comment: 13 pages, 11 figures, 2 tables, proceedings from "Young Scientists" conferences in Warsaw, Poland, 2017

Samples of uterine leiomyomatis and normal tissues taken from patients after surgery were investigated using the Positron Annihilation Lifetime Spectroscopy (PALS). Significant differences in all PALS parameters between normal and diseased tissues were observed. For all studied patients, it was found that the values of the free annihilation and ortho-positronium lifetime are larger for the tumorous tissues than for the healthy ones. For most of the patients, the intensity of the free annihilation and ortho-positronium annihilation was smaller for the tumorous than for the healthy tissues. For the first time, in this kind of studies, the $3\gamma$ fraction of positron annihilation was determined to describe changes in the tissue porosity during morphologic alteration., Comment: Presented at the 2nd Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, Krak\'ow, Poland, June 4-9, 2017

In this paper we extend the state-of-the-art filtered backprojection (FBP) method with application of the concept of Total Variation regularization. We compare the performance of the new algorithm with the most common form of regularizing in the FBP image reconstruction via apodizing functions. The methods are validated in terms of cross-correlation coefficient between reconstructed and real image of radioactive tracer distribution using standard Derenzo-type phantom. We demonstrate that the proposed approach results in higher cross-correlation values with respect to the standard FBP method., Comment: Presented at the 2nd Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, Krak\'ow, Poland, June 4-9, 2017. To be published in Acta Phys. Pol. B

The Jagiellonian Positron Emission Tomograph (J-PET) is the first PET built from plastic scintillators. J-PET prototype consists of 192 detection modules arranged axially in three layers forming a cylindrical diagnostic chamber with the inner diameter of 85 cm and the axial field-of-view of 50 cm. An axial arrangement of long strips of plastic scintillators, their small light attenuation, superior timing properties, and relative ease of the increase of the axial field-of-view opens promising perspectives for the cost effective construction of the whole-body PET scanner, as well as construction of MR and CT compatible PET inserts. Present status of the development of the J-PET tomograph will be presented and discussed., Comment: Presented at the 2nd Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, Krak\'ow, Poland, June 4-9, 2017. To be published in Acta Phys. Pol. B

The Jagiellonian Positron Emission Tomograph (J-PET) is a detector for medical imaging of the whole human body as well as for physics studies involving detection of electron-positron annihilation into photons. J-PET has high angular and time resolution and allows for measurement of spin of the positronium and the momenta and polarization vectors of annihilation quanta. In this article, we present the potential of the J-PET system for background rejection in the decays of positronium atoms., Comment: Presented at the 2nd Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, Krak\'ow, Poland, June 4-9, 2017. To be published in Acta Phys. Pol. B

We present a method and preliminary results of the image reconstruction in the Jagiellonian PET tomograph. Using GATE (Geant4 Application for Tomographic Emission), interactions of the 511 keV photons with a cylindrical detector were generated. Pairs of such photons, flying back-to-back, originate from e+e- annihilations inside a 1-mm spherical source. Spatial and temporal coordinates of hits were smeared using experimental resolutions of the detector. We incorporated the algorithm of the 3D Filtered Back Projection, implemented in the STIR and TomoPy software packages, which differ in approximation methods. Consistent results for the Point Spread Functions of ~5/7,mm and ~9/20, mm were obtained, using STIR, for transverse and longitudinal directions, respectively, with no time of flight information included., Comment: Presented at the 2nd Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, Krak\'ow, Poland, June 4-9, 2017. To be published in Acta Phys. Pol. B

In this article it is presented an FPGA based $M$ulti-$V$oltage $T$hreshold (MVT) system which allows of sampling fast signals ($1-2$ ns rising and falling edge) in both voltage and time domain. It is possible to achieve a precision of time measurement of $20$ ps RMS and reconstruct charge of signals, using a simple approach, with deviation from real value smaller than 10$\%$. Utilization of the differential inputs of an FPGA chip as comparators together with an implementation of a TDC inside an FPGA allowed us to achieve a compact multi-channel system characterized by low power consumption and low production costs. This paper describes realization and functioning of the system comprising 192-channel TDC board and a four mezzanine cards which split incoming signals and discriminate them. The boards have been used to validate a newly developed Time-of-Flight Positron Emission Tomography system based on plastic scintillators. The achieved full system time resolution of $\sigma$(TOF) $\approx 68$ ps is by factor of two better with respect to the current TOF-PET systems., Comment: Accepted for publication in JINST, 10 pages, 8 figures

In this paper we estimate the time resolution of the J-PET scanner built from plastic scintillators. We incorporate the method of signal processing using the Tikhonov regularization framework and the Kernel Density Estimation method. We obtain simple, closed-form analytical formulas for time resolutions. The proposed method is validated using signals registered by means of the single detection unit of the J-PET tomograph built out from 30 cm long plastic scintillator strip. It is shown that the experimental and theoretical results, obtained for the J-PET scanner equipped with vacuum tube photomultipliers, are consistent., Comment: 25 pages, 11 figures