Ex-Vivo Positronium Lifetime Imaging with 44Sc using J-PET Scanner
Karol Kubat, Manish Das, Sushil Sharma, Bartosz Leszczyński, Ewa Ł. Stępień, and Pawel Moskal
abstract
Positronium Lifetime Imaging (PLI), an advanced extension of Positronium Emission
Tomography (PET), is an emerging diagnostic modality [1,2,3]. It has potential to probe
nano-scale environmental properties such as hypoxia, tumour microenvironment
pathology by mapping the spatial distribution of Ps lifetime in biological tissues [4, 5].
Despite the common consensus on its advantages and ongoing progress in adaptation of
reconstruction algorithms and detector technology, PLI faces slow translation in clinical
applications mainly due to two reasons: (1) measurement of nano-second positronium
lifetimes requires fast gamma-ray detectors, and (2) new radioisotopes that provide both
medically suitable half-life and high positron yield accompanying a prompt gamma signal
for Ps lifetime estimation. The first in-vivo results on PLI of human brain was reported
by J-PET collaboration using 68Ga radioisotope [6] However, the low prompt gamma
yield of 68Ga, only a ~1.34% prompt?? branching ratio, poses challenges for accurate
lifetime estimation due to limited statistics [7].
To address this, 44Sc has emerged as a highly promising isotope for PLI, boasting an
optimal decay profile: a clinically suitable half-life of 4.04 hours, an ultrashort deexcitation delay of 2.61 ps, and a 100% decay probability producing a single, high-energy
(1157 keV) prompt gamma following positron emission [7].
In this work, we report the successful application of PLI using 44Sc, performed with the
state-of-the-art Modular J-PET tomograph, featuring triggerless data acquisition enabling
simultaneous multiphoton detection [8].
For this study 44Sc was produced at the Heavy Ion Laboratory in Warsaw and transported
to Jagiellonian University in Kraków. Four phantoms containing cardiac myxoma tissue,
blood thrombi, adipose tissue, and Fused Silica were used, where the Fused Silica serving
as the certified material with a known o-Ps lifetime for quality control. Event selection
was based on the simultaneous detection of two 511 keV photons and one de-excitation
photon, enabling the reconstruction of positronium lifetime images. The reconstructed
annihilation positions, obtained using the two 511 keV photons along with the positron
lifetime, was used to identify regions of interest (ROIs) in image samples. Whereas the oPs lifetime was estimated utilizing the registration time of an additional prompt gamma
as the o-Ps formation time. The obtained o-Ps lifetime shows good agreement with
previously reported values for biological tissues [3, 9]
In this presentation, we will show the first-ever demonstration PLI with 44Sc, marking a
significant advancement and opening new possibilities for developing PLI for clinical
applications.
Acknowledgments
This work was supported by the National Science Centre of Poland (Grants:
2021/42/A/ST2/00423, 2021/43/B/ST2/02150, 2022/47/I/NZ7/03112), SciMat and
qLife under the Excellence Initiative at Jagiellonian University, and PLGrid (ACK
Cyfronet AGH, PLG/2024/017688).
Reference
[1] P. Moskal, Proc. 2019 IEEE Nucl. Sci. Symp. Med. Imaging Conf. (NSS MIC), Manchester (2019)
1-3, DOI: 10.1109/NSS/MIC42101.2019.9059856
[2] P. Moskal et al., IEEE Transactions on Radiation and Plasma Medical Sciences Early access
(2025), DOI: 10.1109/TRPMS.2025.3583554
[3] P. Moskal et al., Science Advances 7 (2021) eabh439
[4] P. Moskal et al., EJNMMI Physics 10 (2023) 22
[5] P. Moskal et. al., Bio-Algorithms and Med-Systems 17(4) (2021) 311-319
[6] P. Moskal et al., Science Advances 10 (2024) adp2840
[7] M. Das et al., Bio-Algorithms and Med-Systems 19 (2023) 87-95
[8] P. Moskal et al., Nature Communication 12 (2021) 5658
[9] Avachat, A.V., Mahmoud, K.H., Leja, A.G. et al. Ortho-positronium lifetime for soft-tissue
classification. Sci Rep 14, 21155 (2024
Ex-Vivo Positronium Lifetime Imaging with 44Sc using J-PET Scanner
Karol Kubat, Manish Das, Sushil Sharma, Bartosz Leszczyński, Ewa Ł. Stępień, and Pawel Moskal
abstract
Positronium Lifetime Imaging (PLI), an advanced extension of Positronium Emission
Tomography (PET), is an emerging diagnostic modality [1,2,3]. It has potential to probe
nano-scale environmental properties such as hypoxia, tumour microenvironment
pathology by mapping the spatial distribution of Ps lifetime in biological tissues [4, 5].
Despite the common consensus on its advantages and ongoing progress in adaptation of
reconstruction algorithms and detector technology, PLI faces slow translation in clinical
applications mainly due to two reasons: (1) measurement of nano-second positronium
lifetimes requires fast gamma-ray detectors, and (2) new radioisotopes that provide both
medically suitable half-life and high positron yield accompanying a prompt gamma signal
for Ps lifetime estimation. The first in-vivo results on PLI of human brain was reported
by J-PET collaboration using 68Ga radioisotope [6] However, the low prompt gamma
yield of 68Ga, only a ~1.34% prompt?? branching ratio, poses challenges for accurate
lifetime estimation due to limited statistics [7].
To address this, 44Sc has emerged as a highly promising isotope for PLI, boasting an
optimal decay profile: a clinically suitable half-life of 4.04 hours, an ultrashort deexcitation delay of 2.61 ps, and a 100% decay probability producing a single, high-energy
(1157 keV) prompt gamma following positron emission [7].
In this work, we report the successful application of PLI using 44Sc, performed with the
state-of-the-art Modular J-PET tomograph, featuring triggerless data acquisition enabling
simultaneous multiphoton detection [8].
For this study 44Sc was produced at the Heavy Ion Laboratory in Warsaw and transported
to Jagiellonian University in Kraków. Four phantoms containing cardiac myxoma tissue,
blood thrombi, adipose tissue, and Fused Silica were used, where the Fused Silica serving
as the certified material with a known o-Ps lifetime for quality control. Event selection
was based on the simultaneous detection of two 511 keV photons and one de-excitation
photon, enabling the reconstruction of positronium lifetime images. The reconstructed
annihilation positions, obtained using the two 511 keV photons along with the positron
lifetime, was used to identify regions of interest (ROIs) in image samples. Whereas the oPs lifetime was estimated utilizing the registration time of an additional prompt gamma
as the o-Ps formation time. The obtained o-Ps lifetime shows good agreement with
previously reported values for biological tissues [3, 9]
In this presentation, we will show the first-ever demonstration PLI with 44Sc, marking a
significant advancement and opening new possibilities for developing PLI for clinical
applications.
Acknowledgments
This work was supported by the National Science Centre of Poland (Grants:
2021/42/A/ST2/00423, 2021/43/B/ST2/02150, 2022/47/I/NZ7/03112), SciMat and
qLife under the Excellence Initiative at Jagiellonian University, and PLGrid (ACK
Cyfronet AGH, PLG/2024/017688).
Reference
[1] P. Moskal, Proc. 2019 IEEE Nucl. Sci. Symp. Med. Imaging Conf. (NSS MIC), Manchester (2019)
1-3, DOI: 10.1109/NSS/MIC42101.2019.9059856
[2] P. Moskal et al., IEEE Transactions on Radiation and Plasma Medical Sciences Early access
(2025), DOI: 10.1109/TRPMS.2025.3583554
[3] P. Moskal et al., Science Advances 7 (2021) eabh439
[4] P. Moskal et al., EJNMMI Physics 10 (2023) 22
[5] P. Moskal et. al., Bio-Algorithms and Med-Systems 17(4) (2021) 311-319
[6] P. Moskal et al., Science Advances 10 (2024) adp2840
[7] M. Das et al., Bio-Algorithms and Med-Systems 19 (2023) 87-95
[8] P. Moskal et al., Nature Communication 12 (2021) 5658
[9] Avachat, A.V., Mahmoud, K.H., Leja, A.G. et al. Ortho-positronium lifetime for soft-tissue
classification. Sci Rep 14, 21155 (2024
Quality control of plastic scintillators for the total-body J-PET scanner
Ł. Kapłon, E. Beyene, N. Chug, C. Curceanu, E. Czerwiński, M. Das, K. Eliyan, K. Kacprzak, T. Kaplanoglu, G. Korcyl, K. Kubat, D. Kumar, E. Lisowski, F. Lisowski, J. Mędrala-Sowa, G. Moskal, W. Mryka, S. Niedźwiecki, P. Pandey, S. Parzych, E. Pérez del Rio, S. Sharma, M. Skurzok, P. Tanty, K. Tayefi, A. Venadan, E. Stępień and P. Moskal
abstract
The construction of the total-body Jagiellonian positron emission tomography scanner requires component verification before detector assembly. The purpose of this research is to verify the quality of BC-408 plastic scintillators with dimensions 6 mm × 30 mm × 330 mm. The scintillators were inspected for optical and mechanical defects and all dimensions were measured. Scratches, mechanically damaged corners and edges, as well as encapsulated dust and fibers within the scintillators, were identified under ceiling lamp illumination. Line defects on the as-cast surfaces were easily visible in a plane polariscope setup consisting of crossed horizontal and vertical polarizer foils. The transmittance at the wavelength of maximum emission through 6 mm thick scintillator samples and the technical attenuation length along 330 mm long scintillator samples were measured on a linear CCD array spectrometer for randomly selected scintillators from each delivered batch. Selected properties of the emission spectra, such as their FWHM and the values of the emission maxima as a function of the distance between the excitation point and the spectrometer fiber, were measured. Additionally, the scintillators optical homogeneity was measured on a light transfer setup consisting of an LED and photodiode matrix. The majority of the obtained plastic scintillators meets the transparency criteria and falls within the dimensional tolerances.
muPPET: Investigating the Muon Puzzle with J-PET Detectors
A. Porcelli, K. Valsan Eliyan, G. Moskal, N. Nasrin Protiti, D. L. Sirghi, E. Yitayew Beyene, N. Chug, C. Curceanu, E. Czerwiński, M. Das, M. Gorgol, J. Hajduga, S. Jalali, B. Jasińska, K. Kacprzak, T. Kaplanoglu, Ł. Kapłon, K. Kasperska, A. Khreptak, G. Korcyl, T. Kozik, D. Kumar, K. Kubat, E. Lisowski, F. Lisowski, J. Mędrala-Sowa, W. Mryka, S. Moyo, S. Niedźwiecki, S. Parzych, P. Pandey, E. Perez del Rio, B. Rachwał, M. Rädler, S. Sharma, M. Skurzok, E. Ł. Stępień, T. Szumlak, P. Tanty, K. Tayefi Ardebili, S. Tiwari, and P. Moskal
abstract
The muPPET [muon Probe with J-PET] project aims to investigate the Muon
Puzzle seen in cosmic ray air showers. This puzzle arises from the observation of a significantly
larger number of muons on Earth's surface than that predicted by the current
theoretical models. The investigated hypothesis is based on recently observed asymmetries
in the parameters for the strong interaction cross-section and trajectory of an outgoing particle
due to projectile-target polarization. The measurements require detailed information
about muons at the ground level, including their track and charge distributions. To achieve
this, the two PET scanners developed at the Jagiellonian University in Krakow (Poland),
the J-PET detectors, will be employed, taking advantage of their well-known resolution
and convenient location for detecting muons that reach long depths in the atmosphere.
One station will be used as a muon tracker, while the second will reconstruct the core of
the air shower. In parallel, the existing hadronic interaction models will be modified and
fine-tuned based on the experimental results. In this work, we present the conceptualization
and preliminary designs of muPPET.
Development of correction techniques for a J-PET scanner
M. Das, R. Bayerlein, S. Sharma, S. Parzych, S. Niedźwiecki, R. Badawi, E. Yitayew Beyene, N. Chug, C. Curceanu, E. Czerwiński, K. Valsan Eliyan, B. Głowa, A. Hubalewska-Dydejczyk, K. Kacprzak, T. Kaplanoglu, K. Kasperska, G. Korcyl, A. Khreptak, K. Kubat, D. Kumar, E. Lisowski, F. Lisowski, J. Mędrala-Sowa, S. Moyo, W. Mryka, M. Opalińska, P. Pandey, M. Rädler, M. Skurzok, A. Sowa-Staszczak, B. A. Spencer, P. Tanty, K. Tayefi Ardebili, A. Kunimmal Venadan, E. Stępień, P. Moskal
abstract
Objective: Positron Emission Tomography (PET) is a widely used medical imaging technique that allows for non-invasive imaging of metabolic processes. However, traditional PET scanners rely on costly inorganic scintillators, which limit their accessibility ? especially in light of emerging long axial field-of-view devices. The modular J-PET scanner, an innovative alternative, uses 50-cm long plastic scintillator strips, offering a cost-effective and modular solution. In this study, we develop and assess the PET data correction techniques required for quantitative image reconstruction. Methods: We present methods for attenuation correction, random coincidence correction using the Delayed Time Window (DTW) technique, and scatter correction based on Monte Carlo simulations. Phantom studies using the NEMA IQ phantom were performed to qualitatively evaluate these corrections. Results: The results demonstrate that our implemented corrections for attenuation, randoms, and scattered coincidences successfully improve the uniformity of tracer distribution in homogenous volumes and significantly reduce undesired activity in cold regions. Despite limitations in sensitivity and axial resolution, the applied correction techniques effectively enhance image quality, providing promising results for future applications. Conclusions: These findings highlight the potential of the modular J-PET system to offer affordable PET imaging and to pave the way towards a total-body PET scanner based on plastic scintillators. Future work will focus on quantitative validation and the implementation of these corrections for human subject imaging.
Calibration of PALS System with CRM Materials for Biomedical Studies
K. Kubat, Ł. Kapłon, P. Moskal, E. Stępień
abstract
Objective and method: Positron annihilation lifetime spectroscopy (PALS) is a powerful technique in material science that allows the investigation of the properties and behavior of positrons in various materials. PALS can be used to investigate solid structures at the nanometer scale and enable the use of positronium properties as an additional diagnostic parameter. Here we present results from calibration of the PALS system with certificated reference materials (CRM).
Materials: Source of 22Na covered with layer of Kapton film, and after that parafilm from both sides was used in all experiments. Certified materials of No_5602-a (polycarbonate) and No_5601-a (fused silica) were used to ascertain if parameters were correctly identified.
Results: In an experiment three lifetime components were correctly identified. All of those components will always be present in the data in further experiments on biological samples. Lifetime components consist of: 196 ps for annihilations in AI an aluminium cover of the chamber, 386 ps for annihilations in thesource and in the Kapton foil, 463 ps for reactions with parafilm.
Conclusions: These parameters will be further used to correctly identify positron lifetimes in biological samples. Recently, a new method for imaging of positronium properties was invented and the first in-vivo images of positronium lifetime in humans were demonstrated with the multi-photon J-PET scanner. In order to correlate the positronium properties in tissue with the medically useful parameters, and to translate positronium imaging to clinics, comprehensive research of positronium properties in biological samples is needed.
Positronium image of the human brain in vivo
P. Moskal, J. Baran, S. Bass, J. Choiński, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, M. Das, K. Dulski, K.V. Eliyan, K. Fronczewska, A. Gajos, K. Kacprzak, M. Kajetanowicz, T. Kaplanoglu, Ł. Kapłon, K. Klimaszewski, M. Kobylecka, G. Korcyl, T. Kozik, W. Krzemień, K. Kubat, D. Kumar, J. Kunikowska, J. Mączewska, W. Migdał, G. Moskal, W. Mryka, S. Niedźwiecki, S. Parzych, E. Perez del Rio, L. Raczyński, S. Sharma, Shivani, R.Y. Shopa, M. Silarski, M. Skurzok, F. Tayefi, K. Tayefi, P. Tanty, W. Wiślicki, L. Królicki, E. Ł. Stępień
abstract
Positronium is abundantly produced within the molecular voids of a patient?s body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo.
Molecular phenomena related to moisture uptake in amorphous solid dispersion loaded with bosentan monohydrate and copovidone
K. Kubat, D. Strojewski, D. Majda, D. Jakibiec, A. Andrzejowska, A. Bogdał, A. Krupa, H. Harańczyk
abstract
Amorphous bosentan alone lacks dissolution flux that could enhance its bioavailability. Its coamorphization with hydrophilic copovidone (1:1) enables to improve wettability and dissolution rate, but fine amorphous particles are prone to moisture uptake. Water sorbed on the surface of this amorphous solid dispersion can considerably alter its physical properties annihilating benefits of coamorphization. The gravimetric measurements of water uptake, the solid state 1H NMR spectroscopy and relaxometry enabled us to describe for the first time, phase changes initiated by hydration in amorphous bosentan systems. The properties of copovidone greatly impacted water uptake in bosentan solid dispersions. A nonlinear reduction of the Tg upon water sorption resulted in the transformation of the glassy state into the rubbery state at ambient temperature. The state diagrams were developed for optimization of manufacturing conditions, selection of suitable packaging material and storage temperature, ensuring long-term stability of amorphous bosentan products.
How rotational speed of planetary ball mill and polymer load influence the performance and water vapor sorption in solid dispersions composed of tadalafil and soluplus
K. Kubat, A. Krupa, W. Brniak, A. Węgrzyn, D. Majda, A. Bogdał, H. Harańczyk
abstract
Particuology 73, (2023) 37
The presence of residual water may deteriorate the performance of amorphous solid dispersions prepared by ball milling, affecting molecular mobility, crystallinity, particle size and finally, the drug dissolution rate. As the stability of these metastable systems depend on both formulation and process variables, the aim of this study was to assess for the first time, the impact that the polymer load and the rotational speed applied upon high energy ball milling could have on the performance of binary co-milled solid dispersions composed of tadalafil (a hydrophobic crystalline drug) and Soluplus (an amphiphilic, hygroscopic amorphous polymer). Each of these variables was tested at three levels. Scanning electron microscopy, laser diffraction and X-ray powder diffraction were used to analyze morphology, particle size distribution and crystallinity of ball milled formulations respectively. Dissolution studies were also carried out. Advanced tools of applied physics, namely solid state 1H NMR and relaxometry were used to assess the structure and water mobility upon gaseous phase hydration on storage. It was shown that both tested variables determined the particle size of the formulation. When the rotational speed of 400 rpm was used, all solid dispersion were XRD-amorphous, but to ensure the immediate release of tadalafil its micellar solubilization in Soluplus was necessary. While the formulation was exposed to water vapor, the hydration level increased with an increasing polymer load as well. Hence, the rotational speed governed the space available for the adsorption of water molecules and their organization in a monolayer or multilayers. Such behavior may have impact on the kinetics of the amorphous drug recrystallization, and finally deteriorate its dissolution.
Ex-Vivo Positronium Lifetime Imaging with 44Sc using J-PET Scanner
Karol Kubat, Manish Das, Sushil Sharma, Bartosz Leszczyński, Ewa Ł. Stępień, and Pawel Moskal
abstract
Positronium Lifetime Imaging (PLI), an advanced extension of Positronium Emission
Tomography (PET), is an emerging diagnostic modality [1,2,3]. It has potential to probe
nano-scale environmental properties such as hypoxia, tumour microenvironment
pathology by mapping the spatial distribution of Ps lifetime in biological tissues [4, 5, 6].
Despite the common consensus on its advantages and ongoing progress in adaptation of
reconstruction algorithms and detector technology, PLI faces slow translation in clinical
applications mainly due to two reasons: (1) measurement of nano-second positronium
lifetimes requires fast gamma-ray detectors, and (2) new radioisotopes that provide both
medically suitable half-life and high positron yield accompanying a prompt gamma signal
for Ps lifetime estimation. The first in-vivo results on PLI of human brain was reported
by J-PET collaboration using 68Ga radioisotope [7]. However, the low prompt gamma
yield of 68Ga, only a ~1.34% prompt?? branching ratio, poses challenges for accurate
lifetime estimation due to limited statistics [8].
To address this, 44Sc has emerged as a highly promising isotope for PLI [9], boasting an
optimal decay profile: a clinically suitable half-life of 4.04 hours, an ultrashort deexcitation delay of 2.61 ps, and a 100% decay probability producing a single, high-energy
(1157 keV) prompt gamma following positron emission [8].
In this work, we report the successful application of PLI using 44Sc, performed with the
state-of-the-art Modular J-PET tomograph, featuring triggerless data acquisition enabling
simultaneous multiphoton detection [7].
For this study 44Sc was produced at the Heavy Ion Laboratory in Warsaw and transported
to Jagiellonian University in Kraków. Four phantoms containing cardiac myxoma tissue,
blood thrombi, adipose tissue, and Fused Silica were used, where the Fused Silica serving
as the certified material with a known o-Ps lifetime for quality control. Event selection
was based on the simultaneous detection of two 511 keV photons and one de-excitation
photon, enabling the reconstruction of positronium lifetime images. The reconstructed
annihilation positions, obtained using the two 511 keV photons along with the positron
lifetime, was used to identify regions of interest (ROIs) in image samples. Whereas the oPs lifetime was estimated utilizing the registration time of an additional prompt gamma
as the o-Ps formation time. The obtained o-Ps lifetime shows good agreement with
previously reported values for biological tissues [3, 10].
In this presentation, we will show the first-ever demonstration of ex-vivo PLI with 44Sc,
marking a significant advancement and opening new possibilities for developing PLI for
clinical applications.
Acknowledgments
This work was supported by the National Science Centre of Poland (Grants:
2021/42/A/ST2/00423, 2021/43/B/ST2/02150, 2022/47/I/NZ7/03112), SciMat and
qLife under the Excellence Initiative at Jagiellonian University, and PLGrid (ACK
Cyfronet AGH, PLG/2024/017688).
Reference
[1] P. Moskal, Proc. 2019 IEEE Nucl. Sci. Symp. Med. Imaging Conf. (NSS MIC), Manchester (2019)
1-3, DOI: 10.1109/NSS/MIC42101.2019.9059856
[2] P. Moskal et al., IEEE Transactions on Radiation and Plasma Medical Sciences Early access
(2025), DOI: 10.1109/TRPMS.2025.3583554
[3] P. Moskal et al., Science Advances 7 (2021) eabh439
[4] P. Moskal et al., EJNMMI Physics 10 (2023) 22
[5] P. Moskal et. al., Bio-Algorithms and Med-Systems 17(4) (2021) 311-319
[6] P. Moskal et al., Nature Communication 12 (2021) 5658
[7] P. Moskal et al., Science Advances 10 (2024) adp2840
[8] M. Das et al., Bio-Algorithms and Med-Systems 19 (2023) 87-95
[9] P. Moskal, E. Stępień, PET Clinics 15 (2020) 439
[10] Avachat, A.V., Mahmoud, K.H., Leja, A.G. et al. Ortho-positronium lifetime for soft-tissue
classification. Sci Rep 14, 21155 (2024)
