Realistic Total-Body J-PET Geometry Optimization--Monte Carlo Study
J. Baran, W. Krzemień, L. Raczyński, M. Bała, A. Coussat, S. Parzych, N. Chug, E. Czerwiński, C. Oana Curceanu, M. Dadgar, K. Dulski, K. Eliyan, J. Gajewski, A. Gajos, B. Hiesmayr, K. Kacprzak, Ł. Kapłon, K. Klimaszewski, G. Korcyl, T. Kozik, D. Kumar, S. Niedźwiecki, D. Panek, E. Perez del Rio, A. Ruciński, S. Sharma, Shivani, R.Y. Shopa, M. Skurzok, E. Stępień, F. Tayefiardebili, K. Tayefiardebili, W. Wiślicki, P. Moskal
abstract
Total-Body PET imaging is one of the most promising newly introduced modalities in the medical diagnostics. State-of-the-art PET scanners use inorganic scintillators such as L(Y)SO or BGO, however, those technologies are very expensive, prohibitng the broad total-body PET applications. We present the comparative studies of performance characteristics of the cost-effective Total-Body PET scanners using Jagiellonian PET (J-PET) technology that is based on plastic scintillators. Here, we investigated in silico five realistic Total-Body scanner geometries, varying the number of rings, scanner radius, and distance between the neighbouring rings. Monte Carlo simulations of two NEMA phantoms (2-meter sensitivity line source and image quality) and the anthropomorphic XCAT phantom, were used to assess the performance of the tested geometries. We compared the sensitivity profiles and we performed the quantitative analysis of the reconstructed images by using the quality metrics such as contrast recovery coefficient, background variability and root mean squared error. The optimal scanner design was selected for the first Total-Body J-PET scanner configuration.
Feasibility of the J-PET to monitor range oftherapeutic proton beams
J. Baran, D. Borys, K. Brzeziński, J. Gajewski, M. Silarski, N. Chug, A. Coussat, E. Czerwiński, M. Dadgar, K. Dulski, K.V. Eliyan, A. Gajos, K. Kacprzak, Ł. Kapłon, K. Klimaszewski, P. Konieczka, R. Kopeć, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, A.J. Lomax, K. McNamara, S. Niedźwiecki, P. Olko, D. Panek, S. Parzych, E. Perez del Rio, L. Raczyński, M. Simbarashe, S. Sharma, Shivani, R.Y. Shopa, T. Skóra, M. Skurzok, P. Stasica, E.Ł. Stępień, K. Tayefi, F. Tayefi, D.C. Weber, C. Winterhalter, W. Wiślicki, P. Moskal, A. Ruciński
abstract
Objective: The aim of this work is to investigate the feasibility of the JagiellonianPositron Emission Tomography (J-PET) scanner for intra-treatment proton beamrange monitoring. Approach: The Monte Carlo simulation studies with GATE and PET imagereconstruction with CASToR were performed in order to compare six J-PET scannergeometries (three dual-heads and three cylindrical). We simulated proton irradiationof a PMMA phantom with a Single Pencil Beam (SPB) and Spread-Out BraggPeak (SOBP) of various ranges. The sensitivity and precision of each scanner werecalculated, and considering the setup?s cost-effectiveness, we indicated potentiallyoptimal geometries for the J-PET scanner prototype dedicated to the proton beamrange assessment. Main results: The investigations indicate that the double-layer cylindrical andtriple-layer double-head configurations are the most promising for clinical application.We found that the scanner sensitivity is of the order of 10?5coincidences per primaryproton, while the precision of the range assessment for both SPB and SOBP irradiationplans was found below 1 mm. Among the scanners with the same number of detectormodules, the best results are found for the triple-layer dual-head geometry. Significance: We performed simulation studies demonstrating that the feasibilityof the J-PET detector for PET-based proton beam therapy range monitoring ispossible with reasonable sensitivity and precision enabling its pre-clinical tests in theclinical proton therapy environment. Considering the sensitivity, precision and cost-effectiveness, the double-layer cylindrical and triple-layer dual-head J-PET geometryconfigurations seem promising for the future clinical application. Experimental testsare needed to confirm these findings.
Comparative studies of the sensitivities of sparse and full geometries of Total-Body PET scanners built from crystals and plastic scintillators
M. Dadgar, S. Parzych, J. Baran, N. Chug, C. Curceanu, E. Czerwiński, K. Dulski, K. Elyan, A. Gajos, B.C. Hiesmayr, Ł. Kapłon, K. Klimaszewski, P. Konieczka, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, S. Niedźwiecki, D. Panek, E. Perez del Rio, L. Raczyński, S. Sharma, Shivani, R.Y. Shopa, M. Skurzok, E. L. Stępień, F. Tayefi Ardebili, K. Tayefi Ardebili, S. Vandenberghe, W. Wiślicki and P. Moskal
abstract
Background: Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for
constructing a Total-Body PET scanner based on plastic scintillators.
Methods: For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configuration (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), the different cross-sections of plastic scintillator, and the multiple numbers of the
plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm.
Results: With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance (? 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body
with additional gain on its sides and provides the possibility for high-quality brain
imaging.
Conclusion: Taking into account not only the sensitivity but also the price of the Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.
Detection of range shifts in proton beam therapy using the J-PET scanner: a patient simulation study
K. Brzeziński, J. Baran, D. Borys, J. Gajewski, N. Chug, A. Coussat, E. Czerwiński, M. Dadgar, K. Dulski, K.V. Eliyan, A. Gajos, K. Kacprzak, Ł. Kapłon, K. Klimaszewski, P. Konieczka, R. Kopeć, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, A.J. Lomax, K. McNamara, S. Niedźwiecki, P. Olko, D. Panek, S. Parzych, E. Perez del Rio, L. Raczyński, S. Sharma, Shivani, R.Y. Shopa, T. Skóra, M. Skurzok, P. Stasica, E.Ł. Stępień, K. Tayefi, F. Tayefi, D.C. Weber, C. Winterhalter, W. Wiślicki, P. Moskal, A. Ruciński
abstract
Objective. The Jagiellonian positron emission tomography (J-PET) technology, based on plastic scintillators, has been proposed as a cost effective tool for detecting range deviations during proton therapy. This study investigates the feasibility of using J-PET for range monitoring by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Approach. Discrepancies between prescribed and delivered treatments were artificially introduced in the simulations by means of shifts in patient positioning and in the Hounsfield unit to the relative proton stopping power calibration curve. A dual-layer, cylindrical J-PET geometry was simulated in an in-room monitoring scenario and a triple-layer, dual-head geometry in an in-beam protocol. The distribution of range shifts in reconstructed PET activity was visualized in the beam's eye view. Linear prediction models were constructed from all patients in the cohort, using the mean shift in reconstructed PET activity as a predictor of the mean proton range deviation. Main results. Maps of deviations in the range of reconstructed PET distributions showed agreement with those of deviations in dose range in most patients. The linear prediction model showed a good fit, with coefficient of determination r2 = 0.84 (in-room) and 0.75 (in-beam). Residual standard error was below 1 mm: 0.33 mm (in-room) and 0.23 mm (in-beam). Significance. The precision of the proposed prediction models shows the sensitivity of the proposed J-PET scanners to shifts in proton range for a wide range of clinical treatment plans. Furthermore, it motivates the use of such models as a tool for predicting proton range deviations and opens up new prospects for investigations into the use of intra-treatment PET images for predicting clinical metrics that aid in the assessment of the quality of delivered treatment.
Comparative studies of plastic scintillator strips with high technical attenuation length for the total-body J-PET scanner
Ł. Kapłon, J. Baran, N. Chug, A. Coussat, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, B. Hiesmayr, E. Kavya Valsan, K. Klimaszewski, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, G. Moskal, S. Niedźwiecki, D. Panek, S. Parzych, E. Pérez del Rio, L. Raczyński, A. Ruciński, S. Sharma, S. Shivani, R. Shopa, M. Silarski, M. Skurzok, E. Stępień, F. Tayefi Ardebili, K. Tayefi Ardebili, W. Wiślicki, P. Moskal
abstract
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 total-body 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 × 6 mm, 12 mm × 6 mm, 24 mm × 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 × 6 mm cross-section.
Efficiency determination of J-PET: first plastic scintillators-based PET scanner
S. Sharma, J. Baran, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, K. Eliyan, A. Gajos, N. Gupta-Sharma, B. C. Hiesmayr, K. Kacprzak, Ł. Kapłon, K. Klimaszewski, P. Konieczka, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, Sz. Niedźwiecki, D. Panek, S. Parzych, E. Perez del Rio, L. Raczyński, Shivani, R. Y. Shopa, M. Skurzok, E. Ł. Stępień, F. Tayefi, K. Tayefi , W. Wiślicki and P. Moskal
abstract
Background:
The Jagiellonian Positron Emission Tomograph is the 3-layer prototype
of the first scanner based on plastic scintillators, consisting of 192 half-metre-long strips with readouts at both ends. Compared to crystal-based detectors, plastic scintillators
are several times cheaper and could be considered as a more economical alternative to crystal scintillators in future PETs. JPET is also a first multi-photon PET prototype. For the development of multi-photon detection, with photon characterized by the continuous energy spectrum, it is important to estimate the efficiency of J-PET as a function of energy deposition. The aim of this work is to determine the registration efficiency of the J-PET tomograph as a function of energy deposition by incident photons and the intrinsic efficiency of the J-PET scanner in detecting photons of different incident energies. In this study, 3-hit events are investigated, where 2-hits are caused by 511 keV
photons emitted in e+e- annihilations, while the third hit is caused by one of the scattered photons. The scattered photon is used to accurately measure the scattering angle and thus the energy deposition. Two hits by a primary and a scattered photon are sufficient to calculate the scattering angle of a photon, while the third hit ensures
the precise labeling of the 511 keV photons.
Results:
By comparing experimental and simulated energy distribution spectra, the registration efficiency of the J-PET scanner was determined in the energy deposition range of 70-270 keV, where it varies between 20 and 100%. In addition, the intrinsic efficiency of the J-PET was also determined as a function of the energy of the incident photons.
Conclusion:
A method for determining registration efficiency as a function of energy deposition and intrinsic efficiency as a function of incident photon energy of the J-PET scanner was demonstrated. This study is crucial for evaluating the performance of the scanner based on plastic scintillators and its applications as a standard and multi-photon PET systems. The method may be also used in the calibration of Compton-cameras developed for the ion-beam therapy monitoring and simultaneous multi-radionuclide imaging in nuclear medicine.
TOF MLEM Adaptation for the Total-Body J-PET with a Realistic Analytical System Response Matrix
R.Y. Shopa, J. Baran, K. Klimaszewski, W. Krzemień, L. Raczyński, W. Wiślicki, K. Brzeziński, N. Chug, A. Coussat, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, J. Gajewski, A. Gajos, B.C. Hiesmayr, E. Kavya Valsan, G. Korcyl, T. Kozik, D. Kumar, Ł. Kapłon, G. Moskal, S. Niedźwiecki, D. Panek, S. Parzych, E. Pérez del Rio, A. Ruciński, S. Sharma, Shivani, M. Silarski, M. Skurzok, E. Stepień, F. Tayefi Ardebili, K. Tayefi Ardebili, P. Moskal
abstract
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.
Investigation of novel preclinical Total Body PET designed with J-PET technology: A simulation study
M. Dadgar, S. Parzych, F. Tayefi Ardebili, J. Baran, N. Chug, C. Curceanu, E. Czerwiński, K. Dulski, K. Eliyan, A. Gajos, B.C. Hiesmayr, K. Kacprzak, K. Klimaszewski, P. Konieczka, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, S. Niedźwiecki, D. Panek, E. Perez del Rio, L. Raczyński, S. Sharma, R.Y. Shopa, M. Skurzok, K. Tayefi Ardebili, S. Vandenberghe, W. Wiślicki, E.Ł. Stępień, P. Moskal
abstract
The growing interest in human-grade Total Body 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, animalbased 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 Collaboration (J-PET). Two main PET characteristics: sensitivity and spatial resolution were mainly inspected to evaluate their performance. Moreover, the impact of the scintillator dimension and time-offlight on the latter parameter were 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 trade-off between enhancing spatial resolution and reducing sensitivity.
Transcriptomic data analysis of melanocytes and melanoma cell lines of LAT transporter genes for precise medicine
M. Szczepanek, D. Panek, M. Przybyło, P. Moskal, E. Stępień
abstract
Background: Boron Neutron Capture Therapy (BNCT) is a two-step treatment that can be used in some types of cancers. It involves administering a compound containing boron atoms to the patient and irradiating the affected area of the body with a neutron beam. The success of the therapy depends mainly on the delivery of the boron isotope (10B) to the tumor using an appropriate boron carrier. One of the boron carriers used is boronophenylalanine (BPA). Therefore, in research on the use of boron carriers, it is also important to know the mechanisms of its uptake by cells. Aim: To study the expression of LAT family genes in two melanoma (high melanotic WM115 and low melanotic WM266-4) cell lines and melanocytes (HEMa-Lp) which are responsible for the transport the BPA into cells. Methods: To normalize data from the transcriptomic analysis, the ratio of the median method was used. This allowed the samples to be compared with each other. Comparison metrics included log-fold change (LFC) values. The heatmap of LFC values and the cluster map were created. These graphs show the similarities and differences between the samples. Results: Transcriptomic data show that in melanocytes, LFC for SLC7A5 (LAT1) and SLC3A2 (4Fhc) was higher than in melanoma cell lines, which corresponded with their melanin content. Conclusion: Our results indicate overexpression of BPA transporter genes in normal cells (melanocytes), which may suggest the highest level of these proteins in melanocytes compared to less melanotic melanoma. Therefore, for BNCT, the use of BPA as the 10B carrier will require additional qualifying tests of amino acid transporter expression for patients and specific tumors to develop a personalized BNCT.
Comparison of Lugol's solution and Fe3O4 nanoparticles as contrast agents for tumor spheroid imaging using microcomputed tomography
D. Panek, M. Szczepanek, B. Leszczyński, P. Moskal, E. Stępień
abstract
Background Lugol's solution is well known for its unique contrasting properties to biological samples in in microcomputed tomography imaging. On the other hand, iron oxide nanoparticles (IONPs), which have much lower attenuation capabilities to X-ray radiation show decent cell penetration and accumulation properties, are increasingly being used as quantitative contrast agents in biology and medicine. In our research, they were used to stain 3D cell structures called spheroids. Aim In this study, the micro computed tomography (microCT) technique was used to visualize and compare the uptake and accumulation of two contrast agents, Lugol's solution and iron (II, III) oxide nanoparticles (IONPs) in the in vitro human spheroid tumour model. Methods The metastatic human melanoma cell line WM266-4 was cultured, first under standard 2D conditions, and after reaching 90% confluence cells was seeded in a low adhesive plate, which allows spheroid formation. On the 7th day of growth, the spheroids were transferred to the tubes and stained with IONPs or Lugol's solution and subjected to microCT imaging. Results Our research allows visualization of the regions of absorption at the level of single cells, with relatively short incubation times - 24h - for Lugol's solution. IONPs proved to be useful only in high concentrations (1 mg/ml) and long incubation times (96h). Conclusions When comparing the reconstructed visualizations of the distribution of these stating agents, it is worth noting that Lugol's solution spreads evenly throughout the spheroids, whereas IONPs (regardless of their size 5 and 30 nm) accumulate only in the outer layer of the spheroid structure.
ProTheRaMon - a GATE simulation framework for proton therapy range monitoring using PET imaging
D. Borys, J. Baran, K.W. Brzezinski, J. Gajewski, N. Chug, A. Coussat, E. Czerwiński, M. Dadgar, K. Dulski, K. Valsan Eliyan, A. Gajos, K. Kacprzak, Ł. Kapłon, K. Klimaszewski, P. Konieczka, R. Kopec, G. Korcyl, T. Kozik, W. Krzemień, D. Kumar, A. John Lomax, K. McNamara, S. Niedźwiecki, P. Olko, D. Panek, S. Parzych, E. Pérez del Río, L. Raczyński, S. Sharma, S. Shivani, R.Y. Shopa, T. Skóra, M. Skurzok, P. Stasica, E. Stępień, K. Tayefi Ardebili, F. Tayefi, D. Charles Weber, C. Winterhalter, W. Wiślicki, P. Moskal, A. Rucinski
abstract
Objective: This paper reports on the implementation and shows examples of the use of the ProTheRaMon framework for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility. We present the ProTheRaMon framework and illustrate its potential use case and data processing steps for a patient treated at the Cyclotron Centre Bronowice (CCB) proton therapy center in Krakow, Poland. Approach: The ProTheRaMon framework is based on GATE Monte Carlo software, the CASToR reconstruction package and in-house developed Python and bash scripts. The framework consists of five separated simulation and data processing steps, that can be further optimized according to the user's needs and specific settings of a given proton therapy facility and PET scanner design. Main results: ProTheRaMon is presented using example data from a patient treated at CCB and the J-PET scanner to demonstrate the application of the framework for proton therapy range monitoring. The output of each simulation and data processing stage is described and visualized. Significance: We demonstrate that the ProTheRaMon simulation platform is a high-performance tool, capable of running on a computational cluster and suitable for multi-parameter studies, with databases consisting of large number of patients, as well as different PET scanner geometries and settings for range monitoring in a clinical environment. Due to its modular structure, the ProTheRaMon framework can be adjusted for different proton therapy centers and/or different PET detector geometries. It is available to the community via github.
