Positronium imaging with the novel multiphoton PET scanner
P. Moskal, K. Dulski, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, J. Gajewski, A. Gajos, G. Grudzień, B.C. Hiesmayr, K. Kacprzak, Ł. Kapłon, H. Karimi, K. Klimaszewski, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, S. Niedźwiecki, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E.Ł. Stępień, M. Szczepanek, F. Tayefi, W. Wiślicki
abstract
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.
Testing CPT symmetry in ortho-positronium decays with positronium annihilation tomography
P. Moskal, A. Gajos, M. Mohammed, J. Chhokar, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, M. Gorgol, J. Goworek, B. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, T. Kozik, E. Kubicz, S. Niedźwiecki, S. Parzych, M. Pawlik-Niedźwiecka, L. Raczyński, J. Raj, S. Sharma, S. Choudhary, R. Shopa, A. Sienkiewicz, M. Silarski, M. Skurzok, E. Stepien, F. Tayefi, W. Wiślicki
abstract
Charged lepton system symmetry under combined charge, parity, and time-reversal transformation (CPT) remain 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 the 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 a magnetic field or polarised positronium source. We use a plastic-scintillator-based positron-emission-tomography scanner to record ortho-positronium (o-Ps) annihilations with a 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.
Simulating NEMA characteristics of the modular total-body J-PET scanner - an economic total-body PET from plastic scintillators
P. Moskal, P. Kowalski, R.Y. Shopa, L. Raczyński, J. Baran, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, A. Gajos, B.C. Hiesmayr, K. Kacprzak, Ł. Kapłon, D. Kisielewska, K. Klimaszewski, P. Kopka, G. Korcyl, N. Krawczyk, W. Krzemień, E. Kubicz, Sz. Niedźwiecki, Sz. Parzych, J. Raj, S. Sharma, S. Shivani, E. Stępień, F. Tayefi, W. Wiślicki
abstract
The purpose of the presented research is the 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 NEMANU-2-2018 standards utilizing the GATE package. The simulated detector consists of 24 modules, each built out of 32 plastic scintillator strips
(each with a 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 a diameter of 78.6 cm. For the TB-J-PET with an axial field-of-view (AFOV) of 200 cm, a spatial resolution (SRs) of 3.7mm (transversal) and 4.9mm (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 amount 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 systemswithAFOVin the range from16 to 26 cm, the TBJ-PET is characterized by an increase inNECRapproximately by a factor of 4 and by the increase of the whole-body sensitivity by a factor of 12.6 to 38. The time-of-flight resolution for the TB-J-PETis expected to be at the level ofCRT=240 ps fullwidth at half-maximum. For the TB-J-PETwith an AFOVof 140 cm, an image quality of the reconstructed images of a NEMAIEC phantom was presented with a contrast recovery coefficient and a background variability parameters. The increase of the whole-body sensitivity andNECRestimated for the TB-J-PET with respect to current commercial PETsystems makes the TB-J-PET a promising cost-effective solution for the broad clinical applications of total-body PET scanners. TB-J-PETmay constitutes an economic alternative for the crystal TB-PET scanners, since plastic scintillators are much cheaper than BGO or LYSO crystals and the axial arrangement of the strips significantly reduces the costs of readout electronics and SiPMs.
The J-PET detector-a tool for precision studies of ortho-positronium decays
K. Dulski, S.D. Bass, J. Chhokar, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, J. Gajewski, A. Gajos, M. Gorgol, R. Del Grande, B.C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K. Klimaszewski, P. Kopka, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemień, E. Kubicz, P. Małczak, M. Mohammed, Sz. Niedźwiecki, M. Pałka, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński7, J. Raj, A. Ruciński, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E. Ł. Stępień, F. Tayefi, W. Wiślicki, B. Zgardzińska, P. Moskal
abstract
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 and its lifetime distribution measurements. 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
Optimisation of the event-based TOF filtered back-projection for online imaging in total-body J-PET
R.Y. Shopa, K. Klimaszewski, P. Kopka, P. Kowalski, W. Krzemień, L. Raczyński, W. Wiślicki, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, A. Gajos, B.C. Hiesmayr, K. Kacprzak, Ł. Kapłon, D. Kisielewska, G. Korcyl, N. Krawczyk, E. Kubicz, Sz. Niedźwiecki, J. Raj, S. Sharma, Shivani, E.Ł. Stępień, F. Tayefi, P. Moskal
abstract
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 scan- ner. 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 real- istic 10-minute scans of NEMA IEC and XCAT, which require a trade-offbetween the noise and spatial resolution, the need for Gaussian TOF kernel components, coupled with median post-filtering, is demon- strated. 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 recon- struction 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.
Synchronisation and calibration of the 24-modules J-PET prototype with 300 mm axial field of view
P. Moskal, T. Bednarski, Sz. Niedźwiecki, M. Silarski, E. Czerwiński, T. Kozik, J. Chhokar, M. Bała, C. Curceanu, R. Del Grande, M. Dadgar, K. Dulski, A. Gajos, M. Gorgol, N. Gupta-Sharma, B. C. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, H. Karimi, D. Kisielewska, K.Klimaszewski, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, E. Kubicz, M. Mohammed, M. Pawlik-Niedźwiecka, L. Raczyński, S. Sharma, Shivani, R. Y. Shopa, M. Skurzok, E. Stępień, W. Wiślicki, B. Zgardzińska
abstract
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 an inner diameter of 360 mm and an 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 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 +- 9 ps. This value can be translated to the position reconstruction accuracy s(Dl) = 18 mm which is fairly position-independent Keywords: positron emission tomography, plastic scintillators, J-PET.
Prospects and clinical perspectives of total-body PET imaging using plastic scintillators
P. Moskal, E. Ł. Stępień
abstract
Total-body PET opens new diagnostic paradigm with prospects for personalized disease treatment, yet the high cost of the current crystal-based PET technology limits dissemination of total-body PET in hospitals and even in the research
clinics.
The J-PET tomography system is based on axially arranged low-cost plastic scintillator strips. It constitutes a realistic cost-effective solution of a total-body PET for broad clinical applications.
High sensitivity of total-body J-PET and trigger-less data acquisition enable multi-photon imaging, opening possibilities for multi-tracer and positronium imaging, thus promising quantitative enhancement of specificity in cancer and inflammatory diseases assessment.
An example of dual tracer analysis, becoming possible with total-body J-PET system, could be a concurrent application of FDA-approved 82Rb-Chloride and [18F]FDG, allowing simultaneous assessment of myocardium metabolic rate and perfusion of the cardiovascular system.
X-ray microtomography as a new approach for imaging and analysis of tumor spheroids
H. Karimi, B. Leszczyński, T. Kołodziej, E. Kubicz, M. Przybyło, E. Stępień
abstract
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.
Performance assessment of the 2gamma positronium imaging with the total-body PET scanners
P. Moskal, D. Kisielewska, Z. Bura, C. Chhokar, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, M. Gorgol, R. Del Grande, B. C. Hiesmayr, B. Jasińska, K. Kacprzak, A. Kamińska, Ł. Kapłon, H. Karimi, G. Korcyl, P. Kowalski, N. Krawczyk, W. Krzemień, T. Kozik, E. Kubicz, P. Małczak, M. Mohammed, Sz. Niedźwiecki, M. Pałka, M. Pawlik-Niedźwiecka, M. Pędziwiatr, L. Raczyński, J. Raj, A. Ruciński, S. Sharma, Shivani, R. Y. Shopa, M. Silarski, M. Skurzok, E. Ł. Stępień, S. Vandenberghe, W. Wiślicki, B. Zgardzińska
abstract
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 2gamma 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 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 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 2gamma imaging by LYSO PET scanners with AFOV=20cm.
Estimating relationship between the Time Over Threshold and energy loss by photons in plastic scintillators used in the J-PET scanner
S. Sharma, J. Chhokar, C. Curceanu, E. Czerwinski, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, M. Gorgol, N. Gupta-Sharma, R. Del Grande, B. C. Hiesmayr, B. Jasinska, K. Kacprzak, L. Kaplon, H. Karimi, D. Kisielewska, K. Klimaszewski, G. Korcyl, P. Kowalski, T. Kozik, N. Krawczyk, W. Krzemien, E. Kubicz, M. Mohammed, Sz. Niedzwiecki, M. Palka, M. Pawlik-Niedzwiecka, L. Raczynski, J. Raj, A. Rucinski, Shivani, R. Y. Shopa, M. Silarski, M. Skurzok, E. L. Stepien, W. Wislicki, B. Zgardzinska, P. Moskal
abstract
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 22Na 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, 22Na 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.
Studies of the ortho-Positronium lifetime for cancer diagnostics
Z. Bura, K. Dulski, E. Kubicz, P. Małczak, M. Pędziwiatr, M. Szczepanek, E.Ł. Stępień, P. Moskal
abstract
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 measurement sand 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.
Melanoma spheroids as a model for cancer imaging study
E. Ł. Stępień, H. Karimi, B. Leszczyński, M. Szczepanek
abstract
In contrast to standard 2D cell cultures, spheroids are three-dimensional (3D) models which can mimic natural conditions of cancer growth and metabolism. Their complex structure can be investigated and analyzed using fluorescence microscopy and micro-tomographic imaging (micro-CT) as a new technique. In this study, we show application of two different melanoma cell lines (WM115 and WM266) with different biological characteristics to form spheroids by a hanging drop method.
Feasibility study of the positronium imaging with the J-PET tomograph
P. Moskal, D. Kisielewska, C. Curceanu, E. Czerwiński, K. Dulski, A. Gajos, M. Gorgol, B. Hiesmayr, B. Jasińska, K. Kacprzak, Ł. Kapłon, G. Korcyl, P. Kowalski, W. Krzemień, T. Kozik, E. Kubicz, M. Mohammed, Sz. Niedźwiecki, M. Pałka, M. Pawlik-Niedźwiecka, L. Raczyński, J. Raj, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, E. Stępień, W. Wiślicki, B. Zgardzińska
abstract
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 average 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 ns to ~2.9 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.
Positronium in medicine and biology
P. Moskal, B. Jasińska, E. Ł. Stępień, S. D. Bass
abstract
In positron emission tomography, as much as 40% of positron annihilation occurs through the production of positronium atoms inside the patient's body. The decay of these positronium atoms is sensitive to metabolism and could provide information about disease progression. New research is needed to take full advantage of what positronium decays reveal.
