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1. A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy

Author

Chacon, Andrew, Rutherford, Harley, Hamato, Akram, Nitta, Munetaka, Nishikido, Fumihiko, Iwao, Yuma, Tashima, Hideaki, Yoshida, Eiji, Akamatsu, Go, Takyu, Sodai, Kang, Han Gyu, Franklin, Daniel R., Parodi, Katia, Yamaya, Taiga, Rosenfeld, Anatoly, Guatelli, Susanna, and Safavi-Naeini, Mitra

Subjects
Physics - Computational Physics, Physics - Medical Physics
Abstract

Purpose: To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy. Materials and Methods: Phantoms of polyethylene, gelatin or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent $^{11}$C, $^{10}$C and $^{15}$O radionuclides contributions in each voxel were determined from the extracted time activity curves. Experiments were simulated in Geant4 Monte Carlo versions 10-11.1, with three different fragmentation models: binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 combinations. Total/parent isotope positron annihilation yields were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Depth of maximum/distal 50\% peak position yield were also compared. Results: Performance varied considerably across versions and models, with no one best predicting all positron-emitting fragments. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50\%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions. Conclusions: Best spatial prediction of annihilation yield and positron-emitting fragment production during carbon and oxygen ion therapy was found to be 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research., Comment: This manuscript has been submitted to IOP's Journal of Physics in Medicine and Biology, on the 5th of February 2024

Published
2024

9. Quantitative PET in the 2020s: a roadmap

Author

Meikle, Steven R, Sossi, Vesna, Roncali, Emilie, Cherry, Simon R, Banati, Richard, Mankoff, David, Jones, Terry, James, Michelle, Sutcliffe, Julie, Ouyang, Jinsong, Petibon, Yoann, Ma, Chao, El Fakhri, Georges, Surti, Suleman, Karp, Joel S, Badawi, Ramsey D, Yamaya, Taiga, Akamatsu, Go, Schramm, Georg, Rezaei, Ahmadreza, Nuyts, Johan, Fulton, Roger, Kyme, André, Lois, Cristina, Sari, Hasan, Price, Julie, Boellaard, Ronald, Jeraj, Robert, Bailey, Dale L, Eslick, Enid, Willowson, Kathy P, and Dutta, Joyita

Subjects
Medical and Biological Physics, Physical Sciences, Biomedical Imaging, Bioengineering, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Generic health relevance, Artificial Intelligence, History, 20th Century, History, 21st Century, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Kinetics, Medical Oncology, Neoplasms, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Prognosis, Radiopharmaceuticals, Systems Biology, Tomography, X-Ray Computed, Positron emission tomography, magnetic resonance imaging, time-of-flight PET, total-body PET, motion correction, dosimetry, quantification, Other Physical Sciences, Biomedical Engineering, Clinical Sciences, Nuclear Medicine & Medical Imaging, Medical and biological physics
Abstract

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

Published
2021

11. A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy

Author

Chacon, Andrew, primary, Rutherford, Harley, additional, Mohammadi, Akram, additional, Nitta, Munetaka, additional, Nishikido, Fumihiko, additional, Iwao, Yuma, additional, Tashima, Hideaki, additional, Yoshida, Eiji, additional, Akamatsu, Go, additional, Takyu, Sodai, additional, Kang, Han Gyu, additional, Franklin, Daniel Robert, additional, Parodi, Katia, additional, Yamaya, Taiga, additional, Rosenfeld, Anatoly B, additional, Guatelli, Susanna, additional, and Safavi-Naeini, Mitra, additional

Published
2024
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23. Exploratory human PET study of the effectiveness of 11C-ketoprofen methyl ester, a potential biomarker of neuroinflammatory processes in Alzheimer's disease

Author

Ohnishi, Akihito, Senda, Michio, Yamane, Tomohiko, Mikami, Tomoko, Nishida, Hiroyuki, Nishio, Tomoyuki, Akamatsu, Go, Ikari, Yasuhiko, Kimoto, Shogo, Aita, Kazuki, Sasaki, Masahiro, Shinkawa, Hiroko, Yamamoto, Yasuji, Shukuri, Miho, Mawatari, Aya, Doi, Hisashi, Watanabe, Yasuyoshi, and Onoe, Hirotaka

Published
2016
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32. Evaluation of a Hamamatsu TOF-PET detector module with 3.2-mm pitch LFS scintillators and a 256-channel SiPM array

Author

Akamatsu, Go, Takyu, Sodai, Yoshida, Eiji, Iwao, Yuma, Tashima, Hideaki, Nishikido, Fumihiko, Yamaya, Taiga, Go, Akamatsu, Sodai, Takyu, Eiji, Yoshida, Yuma, Iwao, Hideaki, Tashima, Fumihiko, Nishikido, and Taiga, Yamaya

Abstract

Using time-of-flight (TOF) information in image reconstruction improves image signal-to-noise ratio and quantitative accuracy in positron emission tomography (PET). A new TOF-PET detector module with a 3.2 mm pitch lutetium fine silicate (LFS) scintillator array one-to-one coupled to a 16×16 (256-ch) silicon photomultiplier (SiPM) array was made commercially available (C13500 series, Hamamatsu Photonics K.K.). In this study, as a candidate detector module for the next generation brain-dedicated PET, we changed the scintillator length of 20 mm to 10 mm according to our helmet-type PET geometry and investigated the basic performance of the PET detector module, including its energy resolution, sensitivity, coincidence response function (CRF) and coincidence timing resolution (CTR). All performance values were compared with those of the 4.2 mm pitch 144-ch detector module which was selected for our current helmet-type PET prototype. The energy resolution was 12% at 511 keV. The sensitivity was about 10% lower compared with those of the 4.2 mm pitch module. The average full width at half maximum (FWHM) of the CRFs was 1.9 mm. The CTRs had values of 235–241 ps with various energy windows after applying timing calibration. The CTR was not significantly changed (

Published
2021

35. Usefulness of PET-guided surgery with 64Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer

Author

Igarashi, Chika, Yoshii, Yukie, Tashima, Hideaki, Iwao, Yuma, Sakurai, Kohei, Hihara, Fukiko, Tachibana, Tomoko, Yoshida, Eiji, Wakizaka, Hidekatsu, Akamatsu, Go, Yamaya, Taiga, Yoshimoto, Mitsuyoshi, Matsumoto, Hiroki, Ming-Rong, Zhang, Nagatsu, Kotaro, Sugyo, Aya, Tsuji, Atsushi, Higashi, Tatsuya, Chika, Igarashi, Yukie, Yoshii, Hideaki, Tashima, Yuma, Iwao, Kohei, Sakurai, Fukiko, Hihara, Tomoko, Tachibana, Eiji, Yoshida, Hidekatsu, Wakizaka, Go, Akamatsu, Taiga, Yamaya, Hiroki, Matsumoto, Zhang, Ming-Rong, Kotaro, Nagatsu, Aya, Sugyo, Atsushi, Tsuji, and Tatsuya, Higashi

Abstract

In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery.

Published
2021

42. Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer's disease.

Author

Ohnishi, Akihito, Akamatsu, Go, Ikari, Yasuhiko, Nishida, Hiroyuki, Shimizu, Keiji, Matsumoto, Keiichi, Aita, Kazuki, Sasaki, Masahiro, Yamamoto, Yasuji, Yamane, Tomohiko, and Senda, Michio

Abstract

Objective: A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [18F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [18F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer's disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese. Methods: Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [18F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [18F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments. Results: No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 μGy/MBq) and the urinary bladder (127.3 ± 11.7 μGy/MBq). The effective dose was 26.8 ± 1.4 μSv/MBq. The parent form ([18F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [18F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01). Conclusion: The findings supported safety and efficacy of [18F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [18F]MK-6240 were consistent with those for non-Japanese populations. Trial registration: Japan Pharmaceutical Information Center ID, JapicCTI-194972. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Simulation study of high-sensitivity cardiac-dedicated PET systems with different geometries

Author

Akamatsu, Go, Tashima, Hideaki, Iwao, Yuma, Takahashi, Miwako, Yoshida, Eiji, and Yamaya, Taiga

Subjects
Physics::Medical Physics
Abstract

Noninvasive quantification of myocardial blood flow with PET is a vital tool for detecting and monitoring of coronary artery disease. However, current standard cylindrical PET scanners are not optimized for cardiac imaging because they are designed mainly for whole-body imaging. In this study, we proposed two compact geometries, the elliptical geometry and the D-shape geometry, for cardiac-dedicated PET systems. We then evaluated their performance compared with a whole-body-size cylindrical geometry by using the Geant4 Monte Carlo simulation toolkit. In the simulation, an elliptical water phantom was scanned for 10-sec, and we calculated the sensitivity and the noise-equivalent count rate (NECR). Subsequently, a digital chest phantom was scanned for 30-sec and the coincidence data were reconstructed by in-house image reconstruction software. We evaluated the image noise in the liver region and the contrast recoveries in the heart region. Even with the limited number of detectors, the proposed compact geometries showed higher sensitivity than the whole-body geometry. The D-shape geometry achieved 47% higher NECR and 44% lower image noise compared with the whole-body cylindrical geometry. However, the contrast in the hot area obtained by the proposed compact geometries were not as good as that obtained by the whole-body cylindrical geometry. There was no considerable difference in image quality between the elliptical geometry and the D-shape geometry. In conclusion, the compact geometries we have proposed are promising designs for a high-sensitivity and low-cost cardiac-dedicated PET system. A further study using a defect phantom model is required to evaluate the contrast of cold areas.

Published
2020

46. Experimental investigation of the characteristics of radioactive beams for heavy ion therapy

Author

Chacon, Andrew, James, Benjamin, Linh Tran, Thuy, Guatelli, Susanna, Chartier, Lachlan, Prokopvich, Dale, R. Franklin, Daniel, Mohammadi, Akram, Nishikido, Fumihiko, Iwao, Yuma, Akamatsu, Go, Takyu, Sodai, Tashima, Hideaki, Yamaya, Taiga, Parodi, Katia, Rosenfeld, Anatoly, Mitra, Safavi‐Naeini, Lachlan, Chartier, Fumihiko, Nishikido, Yuma, Iwao, Go, Akamatsu, Sodai, Takyu, Hideaki, Tashima, and Taiga, Yamaya

Abstract

Purpose This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired postirradiation using an in‐beam whole‐body positron emission tomography scanner for range verification quality assurance. Methods The energy deposited by monoenergetic beams of urn:x-wiley:00942405:media:mp14177:mp14177-math-0001C at 350 MeV/u, urn:x-wiley:00942405:media:mp14177:mp14177-math-0002O at 250 MeV/u, urn:x-wiley:00942405:media:mp14177:mp14177-math-0003C at 350 MeV/u, and urn:x-wiley:00942405:media:mp14177:mp14177-math-0004O at 430 MeV/u was measured using a cruciform transmission ionization chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose‐mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon‐on‐insulator mushroom microdosimeter. Using the modified microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the postirradiation distributions of positron annihilations resulting from the decay of positron‐emitting nuclei were measured for each beam in a gelatin phantom using the in‐beam whole‐body positron emission tomography scanner at HIMAC. The depth of maximum positron‐annihilation density was compared with the depth of maximum dose deposition and the signal‐to‐background ratios were calculated and compared for images acquired over 5 and 20 min postirradiation of the phantom. Results In the entrance region, the urn:x-wiley:00942405:media:mp14177:mp14177-math-0005 was 1.2 ± 0.1 for both urn:x-wiley:00942405:media:mp14177:mp14177-math-0006C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0007C beams, while for urn:x-wiley:00942405:media:mp14177:mp14177-math-0008O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0009O it was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. At the Bragg peak, the urn:x-wiley:00942405:media:mp14177:mp14177-math-0010 was 2.7 ± 0.4 for urn:x-wiley:00942405:media:mp14177:mp14177-math-0011C and 2.9 ± 0.4 for urn:x-wiley:00942405:media:mp14177:mp14177-math-0012C, while for urn:x-wiley:00942405:media:mp14177:mp14177-math-0013O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0014O it was 2.7 ± 0.4 and 2.8 ± 0.4, respectively. In the tail region, urn:x-wiley:00942405:media:mp14177:mp14177-math-0015 could only be evaluated for carbon; the urn:x-wiley:00942405:media:mp14177:mp14177-math-0016 was 1.6 ± 0.2 and 1.5 ± 0.1 for urn:x-wiley:00942405:media:mp14177:mp14177-math-0017C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0018C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal‐to‐background ratios compared to those obtained from targets irradiated by nonradioactive ion beams, with 5‐fold and 11‐fold increases in the ratios calculated for the urn:x-wiley:00942405:media:mp14177:mp14177-math-0019O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0020C images compared with the values obtained for urn:x-wiley:00942405:media:mp14177:mp14177-math-0021O and urn:x-wiley:00942405:media:mp14177:mp14177-math-0022C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0023C, compared to −5.6 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0024C and 0.9 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0025O vs −6.6 ± 0.8 mm for urn:x-wiley:00942405:media:mp14177:mp14177-math-0026O. Conclusions The urn:x-wiley:00942405:media:mp14177:mp14177-math-0027 values for urn:x-wiley:00942405:media:mp14177:mp14177-math-0028C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0029O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, urn:x-wiley:00942405:media:mp14177:mp14177-math-0030C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0031O beams produce much better quality images for range verification compared with urn:x-wiley:00942405:media:mp14177:mp14177-math-0032C and urn:x-wiley:00942405:media:mp14177:mp14177-math-0033O, in particular with regard to estimating the location of the Bragg peak.

Published
2020

50. Feasibility of triple gamma ray imaging of 10 C for range verification in ion therapy.

Author

Mohammadi, Akram, Tashima, Hideaki, Takyu, Sodai, Iwao, Yuma, Akamatsu, Go, Kang, Han Gyu, Obata, Fujino, Nishikido, Fumihiko, Parodi, Katia, and Yamaya, Taiga

Subjects
GAMMA rays, ION beams, HEAVY ion accelerators, POSITRON emission tomography, REAR-screen projection
Abstract

Objective. In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive 15O and 11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of 10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient’s body during ion therapy. Approach. In this work, we focus on investigating the performance of WGI for 10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a 10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a 10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba. Main results. The average spatial resolution and sensitivity for the simulated 10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the 10C ion beam was measured, and the triple gamma image of 10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas. Significance. The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of 10C ion beams. [ABSTRACT FROM AUTHOR]

Published
2022
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