Faculty of Physics, Astronomy
and Applied Computer Science

Author: Meysam Dadgar

Supervisor: prof. Paweł Moskal

Defence year: 2022

Metastasis as the major reason for 90 % of cancer-related deaths, occurs when cancerous cells detach from their primary tissue and spread to the other part of the body through blood vessels or the lymphatic system. Detection of these malignant lesions in their early stages can increase the patient?s survival rate by taking proper treatment strategies. Due to their low sensitivity, conventional PET scanners cannot detect metastatic lesions in the early stages.
In 2019, a new Total-Body PET (TB PET) scanner called uEXPLORER with higher sensitivity thanks to the full detector coverage along the patient?s body was constructed. The main obstacle in the worldwide utilization of this generation of scanners is their higher construction and maintenance price. Since 2013, there has been continuous research to develop a novel economic type of PET scanner named Jagiellonian Positron Emission Tomography (J-PET) based on plastic scintillators. This technology, by providing a cost-efficient solution in the construction of the Total-Body PET scanners opens possibilities for worldwide utilization of these systems and improves the survival rate of patients significantly with precise diagnosis. The research presented in this thesis evaluated the lesion detectability of Total-Body J-PET scanners by accomplishing the GATE simulation from XCAT anthropomorphic digital phantoms. This thesis?s main aim is to investigate the lesion detectability of the Total-Body J-PET scanner and improve this feature by optimizing event selection criteria and the spatial resolution of the tomograph. The liver is the organ under study to determine the lesion detectability of Total-Body J-PET.
For the case of the presented thesis, a series of simulations with point sources and cylindrical phantoms has been performed for the determination of optimum characteristics of Total-Body J-PET. The second group of the simulations has been performed by utilization of human-grade XCAT anthropomorphic phantoms. The results of the simulations have been analyzed by Gate Output J-PET Analyzer (Goja) which has been developed by the J-PET collaboration. Due to the unique configuration of the J-PET-based scanners and their special detection principle, conventional image reconstruction software could not be compatible. In the case of the image reconstruction Quantitative Emission Tomography Iterative Reconstruction (QETIR) in collaboration with the Medisip research group from Gent, Belgium has been used.
The results showed that the Total-Body J-PET tomograph can detect centimeter-grade lesions in the various ranges of the XCAT phantoms with different body mass index (BMI). However applying acceptance angle criteria to remove the contribution of the most oblique coincidences in the image reconstruction, provided the possibility of detecting sub-centimeter (5mm) lesions in a higher number of the iterations of image reconstruction.

Author: Kamil Dulski

Supervisor: prof. Paweł Moskal, prof. Bożena Jasińska

Defence year: 2022

The thesis describes the basics of a new imaging technique - positronium imaging. Positronium imaging is a technique that combines the metabolic information obtained in a standard Positron Emission Tomography (PET) scan with the structural indices examined by the Positron Annihilation Lifetime Spectroscopy (PALS) technique. In particular, proof of concept of the positronium imaging, by means of the 192-strip J-PET detector is presented. A research hypothesis was formulated which stated that it is possible to simultaneously measure the distribution of the radioisotope inside the sample and to determine the structural index (mean ortho-positronium lifetime) in each part of the sample. According to this hypothesis, it is possible to distinguish samples with a di erent structure. Therefore, positronium imaging can nd application not only in PET scans by delivering additional information, potentially improving PET diagnosis e ectiveness, but also in material research as a technique to characterize the nanostructure in every part of the large sample. In order to demonstrate that positronium imaging can be an important technique and prove the research hypothesis, comprehensive studies were carried out using the 192-strip J-PET detector. To ensure the high quality of the collected data, the J-PET detector was calibrated for time and position reconstruction, and a set of data selection conditions was developed. It was also checked how developed selection criteria and dedicated measurement simulations re ect the measurement conditions and at the same time maintain high purity of the data sample. In order to check how well the J-PET detector is able to examine the properties of positronium, an additional analysis was carried out in terms of the separation of various states and types of positronium decay. The results of the analysis shows the possibilities of the J-PET detector in the context of fundamental studies, on the example of the precise determination of the ortho-positronium decay constant. The main part of the work focuses on testing the research hypothesis on two systems that covered two potential applications of positronium imaging - material and medical studies. The positronium image of a system composed of samples of di erent porosity shows that it is possible to distinguish the samples in terms of structure, despite the lack of visible di erences on the analogue to the standard image of annihilation density distribution. The developed method of estimating the mean o-Ps lifetime for single voxels allows to obtain quite good agreement, even for voxels with a relatively low o-Ps intensity. A clear separation in terms of structure is also presented in the positronium image from the in-vitro measurement of the human tissues. Measurement setup consisted of four samples of two types of tissue - cardiac myxoma and adipose tissue. Despite relatively low di erences in the mean lifetime of o-Ps, the positronium image of these samples also con rms the research hypothesis, successfully separating di erent types of tissues, with quite good compatibility of tissues of the same type.

Author: Hanieh Karimi

Supervisor: prof. Paweł Moskal, prof. Ewa Stępień

Defence year: 2022

The presented thesis is devoted to evaluating the three-dimensional (3D) spheroid characteristics using imaging techniques and examining the positron annihilation lifetime spectroscopy (PALS) as a novel biomedical approach to identify the cancer malignancy level. A 3D spheroid mimics important properties of a real tumor and may soon become a reasonable substitute for animal models and human tissue. In this thesis, the morphological analysis of spheroid cell cultures was conducted using micro-CT and compared to that of confocal microscopy. An approach is proposed that can potentially open new diagnostic opportunities to determine the characteristics of cancer cells cultured in 3D structures instead of using actual tumors. Micro-CT analysis of a spheroid showed that the spheroid size and shape differed depending on the cell line, initial cell number, and duration of culture. The micro-CT allows for high-resolution visualization of the spheroids? structure. In this study, it was hypothesized whether the difference between the grade of malignancy of cancer cell lines can be probed by positronium biomarker. The hypothesis was tested on the 3D spheroid model. Positron annihilation lifetime spectroscopy is known as an appropriate technique to evaluate the properties of different organic and inorganic materials based on the determination of the void size within and between molecules. To test the proposed hypothesis, the lifetime of ortho-Positronium (o-Ps) was evaluated in 3D melanoma spheroids from two melanoma cell lines differing in the stage of malignancy. Obtained results show that the o-Ps lifetime and intensity are different between 3D melanoma spheroids with different malignancy level. The presented method paves the way for the application of the 3D spheroids for the in-vitro tests of positronium biomarker. The result of the method applied to studies of positronium in melanoma cancer cells revealed that positronium is a promising biomarker that may be applied in PET diagnostics for the assessment of the degree of cancer malignancy.

Author: Ewelina Kubicz

Supervisor: prof. Paweł Moskal, prof. Ewa Stępień

Defence year: 2020

This thesis is devoted to examining a possible biomedical application of Positron Annihilation Lifetime Spectroscopy (PALS), for the characterisation of normal and cancer cells and tissues. PALS allows to study molecular structure at the nano- and subnanometer levels, by measurement of positronium properties in intra-molecular voids. Studies conducted in the framework of this thesis aim to test the research hypothesis that positronium can be used as a novel biomarker for cancer diagnostics. The working hypothesis assumes that cancer cells differ from normal ones, in their nanostructure and molecular interactions. These changes are significant enough to affect positronium properties to a degree observable with the PALS technique. Correlations between the cellular organisation, its relation to the cell morphology and signalling with positronium are examined in connection with positronium properties to carcinogenesis and metastatic processes. The proposed hypothesis is tested in two models: benign cardiac myxoma specimens and malignant melanoma cultured cell lines. In both cases, positronium properties are compared to an appropriate normal tissue and cell line. Studies are performed for both fixed and living cells and tissues to investigate the influence of water and cell viability on the PALS signal. Obtained results show significant differences in positronium lifetime and its production intensity between cancer and normal cells and tissues in all studied cases, regardless of hydration and fixation of specimens. Therefore, obtained results validate the working hypothesis that positronium can be applied as a novel biomarker in cancer diagnostics.

Author: Julia Nizioł

Supervisor: prof. Ewa Stępień

Defence year: 2023

Investigating the ortho-positronium (o-Ps) lifetime in biological materials holds promise for enhancing our understanding of biological processes and pathologies. This master?s thesis aimed to develop experimental conditions for the measurement of the o-Ps lifetime in extracellular vesicles (EVs) isolated using the low-pressure filtration method. EVs in question were derived from a largescale 2D human pancreatic beta cell culture (1.1B4 cell line) maintained under normoglycemic conditions. In order to check the effectiveness of the chosen method of isolation, environmental scanning electron microscopy (ESEM) images of the dialysis membrane were taken, which allowed to determine the size of its pores. Fourier transform infrared spectroscopy (FTIR) was employed to characterise the chemical composition of EVs. The qNano device, which operates on the principle of tunable resistive pulse sensing (TRPS), was used to determine the size distribution and concentration of EVs. Transmission electron microscopy (TEM) was employed to visualise the morphological features of EVs and validate their structural integrity. Finally, positron annihilation lifetime spectroscopy (PALS) was used to investigate the o-Ps lifetime in the EV sample. In addition, the PALS technique was also used to study the lifetime of o-Ps in pancreatic beta cells from which the vesicles were derived, and in PBS buffer in which they were suspended after the isolation. The o-Ps lifetime and intensity for the sample containing EVs measured at 22°C were 1.87 ns and 15.4%. The same sample investigated at 34.2 °C gave results of 1.83 ns and 15.0%, respectively. These results were not significantly different from the results of the PBS measurement. This study allowed to test several technical solutions to measure the positronium lifetime in EV samples. It underscores the need for continued efforts in exploring EVs with progressive methods such as PALS, as they hold immense potential, for example as carriers of biological cargo or biomarkers.

Author: Agnieszka Babińska

Supervisor: prof. Ewa Stępień

Defence year: 2023

This master thesis aims to present a study using Positron Annihilation Lifetime Spectroscopy (PALS), which allows the study of matter at the nano- and subnanometer level, to analyze the ortho-Positronium (o-Ps) lifetime and intensity in healthy and cancerous colorectal tissues. The study presented in this research investigated the possibility of using positronium as a new biomarker in the diagnosis of colorectal cancer. The study aimed to verify the following research hypothesis: in healthy colorectal tissues, the average lifetime of ortho-Positronium (o-Ps) is longer than in cancerous tissues. The measurements carried out allowed us to determine the average lifetime and average intensity of o-Ps in healthy and cancerous colorectal tissues. The sensitivity and specificity of the diagnostic test showed that 27,3% of colorectal cancer patients were correctly diagnosed with a positive test result, while 15% of healthy patients (those without colorectal cancer) were correctly diagnosed with a negative test result. The results do not allow us to indicate clear differences in the o-Ps lifetime and intensity in healthy and cancerous colorectal tissues. In order to confirm the proposed research hypothesis, more measurements of colon sections would be necessary.

Author: Mateusz Bała

Supervisor: dr Michał Silarski

Defence year: 2022

Quantum entanglement of the group of particles, is a fascinating quantum mechanical phenomenon, without the classical analogy, which happens when the system state can be treated only as a whole, and the constituent particles cannot be described separately. The simplest example in which the quantum entanglement can be manifested is the polarized two -photon system.Indeed such a case was analyzed both theoretically and experimentally many times. However, most of the studies were concentrated on the optical photons regime. For higher-energetic photons, the polarization cannot be measured by using standard devices such as polarizers. However, the partial polarization estimation is possible by exploiting the Compton scatterings process. In this work the analysis of high-energetic, polarized two-photon system is considered, probed by the doubly Compton scattering process. The model is described using the quantum information theory formalism. In addition, the model is incorporated to the Monte Carlo C++ library. The simulations of the various quantum states are performed and the results are compared with the expectations from the theory.

Author: Szymon Parzych

Supervisor: prof. Paweł Moskal

Defence year: 2021

The main aim of presented thesis is to investigate sensitivity of the Total Body J-PET scanners as a function of their axial field of view and inner module construction, as well as assessing the influence of the angular acceptance criterion (used for PET performance optimization) on this characteristic. In order to achieve this goal a simulation-based study was carried out with a use of the standard Monte-Carlo simulation software - Geant4 Application for Tomography Emission (GATE). Moreover, a Toy Monte-Carlo model has been developed as a simplified approach to the sensitivity investigation. Its principle of operation, as well as detailed validation by comparison with GATE software is presented in this work. The obtained results demonstrate that the standard imaging total sensitivity achievable with the Total Body J-PET scanners equals to 25.92(05+/-04) [cps/kBq] for the 2 meter long two-layer tomograph and 84.74(0.9+/-1.1) [cps/kBq] for the 2.5 meter long fourlayer tomograph. Such results exceed the conventional PET systems (represented by the Biograph Vision) by a factor of ~4.5 and ~15 respectively. At the same time sensitivity at the center of the tomograph can reach up to 124.1(1.0+/-1.1) [cps/kBq]. Furthermore, due to the possibility of the positronium mean lifetime imaging guaranteed by the J-PET technology, its sensitivity based on the triple coincidence technique has been evaluated. The acquired maximal total sensitivity of 30.63(06+/-31) [cps/kBq] proves to again surpass the traditional crystal-based system up to ~5 times. Ultimately, the sensitivity achieved with the studied Total Body scanners is almost uniform along the whole patient with an additional increase on its sides for both double and triple coincidence imaging. This creates a possibility for high-quality simultaneous imaging of the whole human body.

Author: Maciej Bakalarek

Supervisor: dr Grzegorz Korcyl

Defence year: 2020

The aim of the thesis was to design and implement a preprocessing system for tomographic data in FPGA devices. The system has been designed with high parallelism of calculations in mind, thanks to which it works in real-time. Additionally, applications were prepared for live-visualization of the results (i.e. Lines of Response). The paper describes the architecture of the CM-PET scanner (with which the implemented system has been integrated) and the technologies used. In the paper results of tests with the use of four CM-PET?s modules are presented. The estimated maximum system throughput is around 14 MSps.

Author: Zuzanna Bura

Supervisor: prof. Paweł Moskal

Defence year: 2020

Currently, cancer is the second cause of death worldwide. The most effective method for cancer prevention is early diagnosis. This thesis describes an innovative method for cancer diagnosis that provides not only information about the localization of tumor in the human body but also about its structure. The purpose of this work was to examine the correlation between orth-positronium (o-Ps) mean lifetime and the degree of malignancy, size, type of cells and other factors which can be associated with colorectal cancer, contemporaneously demonstrate the potential of simultaneous PALS (Positron Annihilation Lifetime Spectroscopy) and PET scan (conduct on Jagiellonian Positron Emission Tomograph, developed at the Jagiellonian University). For this purpose, a series of measurements were performed on normal and cancerous colon tissues. This work also describes details of measurements and their analysis (chapter 4). Chapter 5 shows the results of PALS measurements on living tissues (and fixed in formalin), as well as the impact of environmental factors such as temperature and humidity on the mean lifetime of o-Ps.

Author: Kamil Rakoczy

Supervisor: dr Wojciech Krzemień

Defence year: 2019

The main aim of this thesis is the implementation of various analytic image reconstruction algorithms in the frame of the J-PET Framework analysis package. The implemented algorithms: Kernel Density Estimation, Filtered Back-Projection and Time-Of-Flight-Filtered Back-Projection have been tested both using Monte Carlo simulations and experimental data gathered by the scanner. Obtained results show that the implemented algorithms reconstruct correctly the shape of the phantoms. Comparison studies between implemented algorithms have been performed. In reconstruction of the NEMA phantom, the best results have been obtained using the Shepp-Logan filter with the cut-off parametr equal to 0.75 of Nyquist frequency (corresponding to the Background Variability of 0.13 and the Contrast Recovery Coefficient equal to 1.03 for high activity region of radius 22 mm). For the Time of-Fligth Filtered Back-Projection algorithm, the best reconstruction was obtained using the Hamming filter with the cut-off parameter equal to Nyquist frequency (corresponding to the Background Variability of 0.17 and the Contrast Recovery Coefficient equal to 0.96 for high activity region of radius 22 mm).

Author: Karol Farbaniec

Supervisor: dr Grzegorz Korcyl

Defence year: 2019

The aim of this work is to implement selected data processing stages for Digital J-PET detector readout and explore feasibility of hardware acceleration of image reconstruction. Moreover this work covers main aspects of FPGA design process. First chapter contains introduction to PET tomography, data processing followed by image reconstruction. Second chapter present fundamentals of digital electronics in reference to FPGA technology. Later Digital J-PET detecting system is described with system architecture and readout procedure. In fourth chapter implementation details are presented on data processing for detecting module and image reconstruction kernel. Next chapter contains results of implemented components.

Author: Julia Nizioł

Supervisor: prof. Ewa Stępień

Defence year: 2021

The phenomenon of positronium formation in biological material brings new possibilities formedical diagnostics. This thesis presents a method for determining mean positronium lifetme in microvesicles isolated from the culture of beta-pancreatic cells using low-vacuum filtration technique combined with the ultracentrifugation. The concentration of microvesicles in the prepared samples was tested with qNano particle analyzer, the operation of which is based on the TRPS (Tunable Resistive Pulse Sensing) technology. Before starting the actual measurements, Positron Annihilation Lifetime Spectrometer was adjusted accordingly, e.g. by equipping it with a thermostat which allows to precisely control the temperature in the system. A series of measurements was performed to check the temperature stability and a calibration curve was obtained, on the basis of which it is possible to accurately determine the temperature of the sample during the measurement. The positron source was additionally secured against leakage, which may occur when testing with liquid samples. Parafilm was used for this purpose, the positronium lifetime in it changes with temperature, what was taken into account in data analysis. The positronium lifetime in microvesicles cultured under normoglycemic and hyperglycemic conditions was investigated. The values were 1.80 ns and 1.77 ns respectively, thus not significantly different from the lifetime determined in the PBS buffer in which microvesicles were suspended (g = 1.80 ns). On the basis of the obtained results, it can be concluded that to conduct research with microvesicles using the presented method, it is necessary that the samples have a higher concentration of vesicles.

Author: Agata Jędruszczak

Supervisor: prof. Paweł Moskal

Defence year: 2021

Positronium imaging is a new method that can be used for PET scanning. This method allows not only to determine the location of the tumor, but also to analyze the structure of the tissue. What is important is how many gamma quanta from a positronium atom reach the detector. The main goal of this work is to study the absorption in the brain of gamma quanta from a positronium atom. The brain in this study is approximated by a sphere with water. The 3 gamma / 2 gamma ratio, a parameter that reflects the tissue structure, is determined. For this purpose, Monte Carlo simulations of positron decays into 2 gamma and 3 gamma and photon absorption in the brain and skull were performed. The simulation results were compared with theoretical calculations. The results of the percent events for which none of photons scattered in the head are as follows: 26.10 +/- 0.05% for para-positronium and 8.40 +/- 0.03% for ortho-positronium (absorption in the brain), 20.84 +/- 0.05% for para-positronium, 5.46 +/- 0,02% for ortho-positronium (absorption in the brain and in skull). The values of the 3 gamma / 2 gamma ratio from the simulation are: 0.322 +/- 0.002 for absorption in the brain and 0.262 +/- 0.002 for absorption in the brain and skull. The dependence of absorption probability of photons in the head on the location of positronium atom decay in the brain is determined.

Author: Agnieszka Babińska

Supervisor: prof. Ewa Stępień
Auxilliary supervisor: dr inż. Magdalena Marzec

Defence year: 2021

Niniejsza praca ma na celu przedstawienie wyników wykorzystujących spektrometrię masową jonów wtórnych z analizatorem czasu przelotu (ToF-SIMS) do analizy składu lipidowego pęcherzyków zewnątrzkomórkowych, pochodzących z ludzkich komórek beta trzustki hodowanych w warunkach hiperglikemii. ToF-SIMS jest czułą metodą spektrometryczną, stosowaną do jakościowego określania składu powierzchni. Dzięki jej zaawansowanemu rozwojowi, została zaadoptowana do badań biologicznych, gdzie wykorzystywana jest przede wszystkim do analizy lipidów oraz protein. Zawartość prenoli i steroli w pęcherzykach zewnątrzkomórkowych komórek beta trzustki jest regulowana wieloma czynnikami środowiskowymi, jak i genetycznymi. W części eksperymentalnej, czynnikiem wywołującym widoczne zmiany składu lipidowego były warunki hiperglikemiczne. Z przeprowadzonej jednoczynnikowej analizy wariancji ANOVA oraz testu Tukey?a wynika, iż dla wszystkich wybranych jonów dla prenoli i steroli występują istotne różnice statystyczne pomiędzy średnimi wartościami intensywności dla warunków normalnych oraz hiperglikemicznych przy p?0,05. Przeprowadzona analiza potwierdziła, iż wykorzystana technika ToF-SIMS jest skuteczna, zaś jej zaawansowany rozwój sprawił, iż jest coraz częściej stosowana do badań biologicznych, gdzie wykorzystywana jest przede wszystkim do analizy lipidów oraz protein.