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In positron emission tomography acquisition (PET), sensitivity along a line of response can vary due to crystal geometrical arrangements in the scanner and/or detector inefficiencies, leading to severe artefacts in the reconstructed image. To mitigate these effects, data must be corrected by a set of normalization coefficients applied to each line of response. The J-PET Modular scanner is a PET device made of 50 cm long plastic strips arranged axially, currently in operation at the Jagiellonian University in Krak\'ow (Poland). We have implemented a normalization method for the large field-of-view plastic-based J-PET Modular scanner using the component-based approach. We estimated the geometric normalization factors for the J-PET Modular scanner using Monte Carlo simulations. We also analysed the effects of variations in detection efficiency. A dedicated cylindrical phantom was simulated to investigate the impact of various factors on image quality. The image quality was quantified in terms of radial and axial uniformity metrics, and the standard deviation to mean intensity ratio, determined for a set of image slices. Without normalization, reconstructions of a uniform cylinder exhibit artefacts. These artefacts were satisfactorily compensated using the normalization factors. Applying geometrical corrections lowers the non-uniformity of the image expressed as a standard deviation-to-mean ratio to a range between 5.5 % to 8.5 %. Computationally, the technique is straightforward to parallelize, making it time-efficient. Preliminary estimates suggest that the method is appropriate for use with long axial field-of-view scanners, such as the total-body J-PET, currently under development at the Jagiellonian University., Comment: 36 pages, 16 figures, 4 tables

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 tomograph is demonstrated

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.

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 totalbody 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 x 6 mm, 12 mm x 6 mm, 24 mm x 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 x 6 mm cross-section., Comment: 10 pages, 5 figures

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.

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 e$^{+}$e$^{-}$ 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 e$^{+}$e$^{-}$ annihilations and thus their applicability for gravitational studies of Ps.

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 J-PET detector, which consists of inexpensive plastic scintillators, has demonstrated its potential in the study of fundamental physics. In recent years, a prototype with 192 plastic scintillators arranged in 3 layers has been optimized for the study of positronium decays. This allows performing precision tests of discrete symmetries (C, P, T) in the decays of positronium atoms. Moreover, thanks to the possibility of measuring the polarization direction of the photon based on Compton scattering, the predicted entanglement between the linear polarization of annihilation photons in positronium decays can also be studied. Recently, a new J-PET prototype was commissioned, based on a modular design of detection units. Each module consists of 13 plastic scintillators and can be used as a stand-alone, compact and portable detection unit. In this paper, the main features of the J-PET detector, the modular prototype and their applications for possible studies with positron and positronium beams are discussed. Preliminary results of the first test experiment performed on two detection units in the continuous positron beam recently developed at the Antimatter Laboratory (AML) of Trento are also reported.

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

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., Comment: 12 pages, 7 figures

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 interest in the extracellular vesicles (EVs) is rapidly growing as they became reliable biomarkers for many diseases. For this reason, fast and accurate techniques of EVs size characterization are the matter of utmost importance. One increasingly popular technique is the Nanoparticle Tracking Analysis (NTA), in which the diameters of EVs are calculated from their diffusion constants. The crucial assumption here is that the diffusion in NTA follows the Stokes-Einstein relation, i.e. that the Mean Square Displacement (MSD) of a particle grows linearly in time (MSD $\propto t$). However, we show that NTA violates this assumption in both artificial and biological samples, i.e. a large population of particles show a strongly sub-diffusive behaviour (MSD $\propto t^\alpha$, $0<\alpha<1$). To support this observation we present a range of experimental results for both polystyrene beads and EVs. This is also related to another problem: for the same samples there exists a huge discrepancy (by the factor of 2-4) between the sizes measured with NTA and with the direct imaging methods, such as AFM. This can be remedied by e.g. the Finite Track Length Adjustment (FTLA) method in NTA, but its applicability is limited in the biological and poly-disperse samples. On the other hand, the models of sub-diffusion rarely provide the direct relation between the size of a particle and the generalized diffusion constant. However, we solve this last problem by introducing the logarithmic model of sub-diffusion, aimed at retrieving the size data. In result, we propose a novel protocol of NTA data analysis. The accuracy of our method is on par with FTLA for small ($\simeq$200nm) particles. We apply our method to study the EVs samples and corroborate the results with AFM., Comment: Revised version for Colloids and Surfaces B