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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 (

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.

The quality and uniformity of positron emission tomography (PET) images can be improved significantly using a PET scanner, which has both time-of-flight (TOF) and depth-of-interaction (DOI) capabilities. We have already developed a DOI dual-end detector using segmented crystal bars by applying a subsurface laser engraving (SSLE) technique, and the DOI was determined by the ratio of the detected light between two readouts using the Anger calculation. In this study, we investigated the influence of the number of DOI segments on the performance of DOI identification and the coincidence timing performance of the detector. The detector consisted of a single lutetium fine silicate (LFS) crystal bar (3×3×20 mm3) with various numbers of DOI segments that were made by applying the SSLE technique and Hamamatsu silicon photomultiplier (SiPM) modules. The maximum number of DOI segments was six, and the SiPM module included one hundred forty four 4 mm × 4 mm SiPM readouts. The coincidence resolving time (CRT) of each DOI segment was obtained from the side irradiation of the dual-end detector. All DOI segments of the detector with 2, 3, 4, 5 or 6 DOI segments were clearly identified, and average energy resolutions of 9.8 ± 0.5% and 12.5 ± 1.4% were obtained at the 511 keV photo peak for the detectors with 2 DOI and 6 DOI segments, respectively. The minimum and maximum estimated CRT of 180 ± 6 ps and 236 ± 6 ps were obtained for the detectors with 2 DOI and 6 DOI segments, respectively. Insignificant differences were observed between the CRT values of different segments of one detector. Greater CRT values were obtained for detectors with larger DOIs. The results of this study prove that there is a high potential for segmented crystal bars using the SSLE technique as a good candidate for PET scanners with TOF and DOI capabilities, which can significantly improve the quality of PET images.

PET装置は通常フルリング型の構成となっているが、一部を開放化したオープンリング型の構成にすることができれば、これまで装置同士の干渉等のため困難であった他のモダリティとの融合など、これまでにない応用が期待できる。一方で、同時計数により測定可能な方向が制限されるため、不完全な逆問題となり、再構成像に強いアーチファクトが生じる問題がある。本研究では、開放部と対向する位置にコンプトン検出器を挿入し、欠損方向の情報をコンプトンイメージングの技術により補完することで、開放部を持ちつつ高精度なイメージングが可能な装置を提案し、その有効性をモンテカルロシミュレーションによって検討した。具体的には、半径20cm、開放部の角度を115°としたオープンリング型PETの内側に、半径15cm、中心角135°の円弧状の散乱検出器を配置し、直径20cmの円柱ファントムのイメージングを模擬した。その結果、散乱検出器がない場合と比べ、提案装置ではアーチファクトが低減され、円柱内の均質性が向上したことから、提案装置の有効性が示唆された。, 第60回日本核医学会学術総会

【目的】乳房用PET装置は対向平板型とリング型の2種類がある。対向平板型はマンモグラフィと比較しやすいなどの利点があるが、投影データが大きく欠損することから、対向する検出器方向のボケは避けられない。本研究では、対向型の利点を残しつつ投影角度の欠損を抑えた、ラウンドエッジ型(平板の両端に位置する検出器に36度傾斜をつけ視野中心に向けた配置)を考案し、その有用性を検証した。【方法】Geant4を用いて平板型、ラウンドエッジ型、リング型のPET装置をシミュレートし、感度、空間分解能、画質を評価した。検出器はGAGGシンチレータ(結晶サイズ1.5×1.5×15mm3)を模擬した。【結果】ラウンドエッジ型はリング型より感度は劣るものの、平板型と比べ画像のボケが減少して垂直方向の空間分解能が大きく改善(4.0mm→1.9mm)し、視野中心付近の4mm集積のコントラストが28%上昇した。TOF情報によりさらに画像のボケが低減し、DOI情報により小集積のコントラストが上昇した。【結論】ラウンドエッジ型ジオメトリは乳房用PET装置として有望であることが示された。, 第60回日本核医学会学術総会

添付のとおり, IEEE NSS&MIC 2020

添付ファイルを参照, 第81回応用物理学会秋季学術講演会

The use of positron-emitting radioactive isotopes for heavy ion therapy has been proposed as a means to increase the number of annihilation photons available for Positron Emission Tomography (PET)-based quality assurance (QA) imaging. The particle stopping point itself, which highly correlates to point of maximum dose, can be directly obtained from PET images with the use of these isotopes. An important step for clinical realisation of this idea is to evaluate the relative biological effectiveness (RBE) of the positron-emitting radioactive heavy ions and compare them to those of the corresponding stable nuclides. In this study, the RBE at 10% survival of two positron-emitting radioactive beams, 11C and 15O, and their corresponding non-radioactive isotopes 12C and 16O, were experimentally evaluated by measuring microdosimetric lineal energy deposition using a silicon-on-insulator mushroom microdosimeter. It was found that the RBE10 of the radioactive beams were statistically indistinguishable from their respective stable counterparts in each of the the entrance, Bragg peak and tail regions. The microdosimetric dose-mean lineal energy, yD was also evaluated for each ion species, with multiple measurements made along the path of the beam, and post-irradiation PET images were acquired and compared between the radioactive and stable beams, demonstrating the greatly improved signal to noise ratio (SNR) which can be achieved with positron-emitting radioactive ion beams., 2019 IEEE Nuclear Science Symposium and Medical Imaging Conference

Coronary artery disease (CAD) is one of the leading causes of death world-wide. Noninvasive quantification of myocardial blood flow with PET is a key tool for detection and monitoring of CAD. 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 a cardiac-dedicated PET system. We compared their performance with a conventional cylindrical geometry by using the Geant4 simulation toolkit. Furthermore, we evaluated two detector designs with different LYSO crystal thicknesses (20-mm and 10-mm) and appropriate practical coincidence timing resolutions (CTRs) (300 ps for 20 mm LYSO and 250 ps for 10 mm LYSO) to investigate a suitable detector design. In the simulation, an elliptical water phantom (10 MBq) was scanned for 10 s. We evaluated the sensitivity, the noise-equivalent count rate (NECR), and image noise (coefficient of variation: CV) of the water phantom. The D-shape geometry with the 20 mm long LYSO showed the highest sensitivity and NECR. This geometry achieved 71% higher sensitivity and 44% higher NECR compared with the conventional cylindrical geometry. The image noise (CV) was decreased by 24%. The number of detectors was reduced to 3/8 (37.5%). On the other hand, the system with the half-thickness crystal did not show any improvement in the image noise compared with the whole-body cylindrical geometry. With the 20 mm long LYSO, our proposed D-shape geometry is a promising design for a high-sensitivity cardiac-dedicated PET system., 2019 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC)

In heavy ion therapy, visualization of the range of incident ions in a patient body is important to exploit the advantages of this therapy. It is ideal to use radioactive beams for in-beam positron emission tomography (PET) imaging in ion therapy because the particle stopping position itself can be visualized with sufficient number of measured radiation counts. We have already demonstrated this idea for both 11C and 15O ion beams using our OpenPET system. In another simulation study, however, we found there was a slight difference between the beam stopping position and the dose peak position, which is caused by energy spread of the ion beams. In this research, we focused on confirmation of the potential difference between the Bragg peak position and the position of the maximum detected positron-emitting fragments by a PET system for radioactive ion beams of 11C (210 MeV/u) and 15O (312 MeV/u) with momentum acceptance of 5% and 0.5% using measurement results. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The differences between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 2.2 mm and 0.5 mm for momentum acceptances of 5% and 0.5%, respectively. The positional differences between two peaks for the 11C ion beam were 2.6 mm and 0.4 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger positional differences between the Bragg peak and the PET peak for momentum acceptance of 5% for both beams, which were consistent with the reported simulation results. The results of this study demonstrated that the position of the Bragg peak is predictable from the PET peak position for the known momentum acceptance (energy spread)., The 2019 IEEE Nuclear Science Symposium (NSS) and Medical Imaging Conference (MIC)

PET detectors with both time-of-flight (TOF) and depth-of-interaction (DOI) capabilities are ideal, but DOI-TOF PET detectors have not been studied well. In this paper, we develop a 4-layer DOI TOF detector. The key item is a recently commercialized module of multi pixel photon counters (MPPCs) (C13500 series, Hamamatsu Photonics K. K., Japan). The MPPC array is the through silicon via (TSV) type with an effective area of 6 x 6 mm 3 (0.075 mm pitch sub pixels), which is arranged as an 8 x 8 array. At first, a pair of lutetium fine silicate (LFS) crystals each sized in 4 x 4 x 10 mm 3 was placed on the center of each one MPPC channel. The CRT value was 252 ps. Afterward one of those detectors was used as the reference detector. Then cerium doped lutetium yttrium orthosilicate (LYSO) crystals sized in 2.8 x 2.8 x 5 mm 3 were arranged in 8 x 8 x 4-layer based on our special reflector arrangement. The 4-layer LYSO array were coupled to the MPPC modules via a light guide. In the position map of the 4-layer LYSO crystal block, most of crystals could be identified. The averaged CRT value for crystals of the central part in the position map for the reference detector was 486 ± 106 ps. In timing spectrum of the third layer and the fourth layer, other components were observed. This was presumed to be due to contamination caused by incomplete crystal identification. Individual specificity for each MPPC channel was required to be calibrated for complete crystal identification. In conclusion, we developed a 4-layer DOI TOF detector and obtained around 500 ps averaged CRT value for the reference detector.

During heavy ion therapy, some particles in the beam undergo atomic nuclear inelastic collisions with other nuclei in the target, resulting in the production of a range of nuclear fragments, including neutrons. The neutron component is moderated by matter in the target, causing them to lose energy and thermalise. These neutrons are of particular interest as they offer the potential for therapeutic applications via neutron capture. Accurate and reliable quantification of the thermal neutron fluence produced during particle therapy will provide valuable information regarding the feasibility of therapeutic exploitation of this thermal neutron field. However, measurement of thermal neutron fluence is extremely challenging due to the intense and diverse mixed radiation field in the target volume. In this work, we present the results of experimental quantification of thermal neutron fluence, performed using the gold activation method, during carbon and helium beam therapy. Geant4 Monte Carlo simulations were used to validate the approach, establishing that the activation of gold is almost exclusively due to neutron capture, and that nearly all gamma photons detected in the vicinity of 411 keV result from the decay of the activated gold. The method was then applied to experimentally measure the fluence of thermal neutrons per Gy(RBE) of delivered dose during carbon and helium beam therapy, both inside and outside of the beam in a poly(methyl methacrylate) (PMMA) phantom. Thermal neutron fluence was measured at four different depths: at the entrance, distal edge, middle of the SOBP and in the tail region of the spread-out Bragg peak (SOBP). o our knowledge, this is the first time that this method has been used in particle therapy., The 2019 IEEE Nuclear Science Symposium (NSS) and Medical Imaging Conference (MIC)

Radioactive ion (RI) beams such as 11C or 15O are useful for in situ range verification by in-beam PET for heavy ion therapy due to the complete agreement between the PET peak and the Bragg peak for an ideal mono energy RI beam. On the other hand, there is a shortened Bragg peak for RI beams because of a wider energy spread than the conventional stable beam. Therefore, quality control of the RI beam is important, but no practical methods which can be done routinely have been realized yet. Recently, an optical imaging technique was proposed as a high-resolution beam range estimation method for heavy ion beams. The aim of this study was to estimate the Bragg peak and energy spread of the 15O ion beam by using the optical imaging technique at submillimeter resolution. The same method can be applied to other RI beams such as 11C. A PMMA phantom (10 × 10 × 9.9 cm3) was irradiated by the 15O ion beam with different momentum acceptances of 1, 2, and 4% at the Heavy Ion Medical Accelerator in Chiba (HIMAC). In-beam luminescence and offline-beam Cerenkov-light images were obtained by using a CCD camera sequentially. The energy spread of the 15O ion beam could be estimated from the positional difference between the Bragg peak measured by luminescence imaging and the beam stopping position measured by Cerenkov imaging. The GATE optical simulation results showed good agreement with the experimental results with a maximum error of 0.3 mm in the Bragg peak position. In conclusion, the feasibility of optical imaging was demonstrated for the energy spread estimation of 15O ion beam., 2019 IEEE Nuclear Science Symposium and Medical Imaging Conference

添付した関連ファイルを参照。, 第80回応用物理学会秋季学術講演会

Time-of-flight (TOF) PET improves image quality and quantitative accuracy compared with a conventional PET system. While it is true that TOF works better for larger objects, recent improvement in timing resolution has encouraged application of TOF to brain-dedicated PET systems. Thus, as the second prototype of the helmet-type PET, we have developed a new TOF brain-dedicated PET prototype using detector modules of 12×12 lutetium fine silicate (LFS) crystals (4.1×4.1×10 mm3) connected to a 12×12 (4 mm pitch, 144-ch) MPPC array. In this paper, we investigated another detector module, which has the same outer size but smaller crystals: 16×16 LFS of 3.1×3.1×10 mm3 size coupled to 16×16 (3 mm pitch, 256-ch) MPPC array. The 3-mm 256-ch module showed an energy resolution of 12.0%. For the coincidence response function, the 3-mm module showed a better full width at half maximum (FWHM) of 1.9 mm compared with the 4-mm 144-ch module (2.4 mm). The FWHM was improved by 21%. The coincidence resolving time obtained by the 3-mm 256-ch module was 241 ps. The energy resolution and coincidence resolving time were almost the same between the two modules. The 3-mm 16×16 MPPC-based TOF-PET module can be expected to improve spatial resolution without compromising the energy resolution and coincidence resolving time compared with the 4-mm 12×12 module.

Objectives: Development of a staggered three-layer DOI PET detector with a 1 mm crystal pitch for realizing a 0.7 mm resolution small animal PET imager of 52 mm ring diameter. Methods: The proposed small animal DOI PET detector consists of three-layer staggered LYSO crystal arrays, an acrylic light guide with a thickness of 1 mm, and 4×4 SiPM (Hamamatsu, S13360-3050NE-04, Japan) array with a pixel pitch of 3.2 mm. The LYSO crystal had a dimension of 0.9 × 0.9 × 5.0 mm3 with a pitch of 1 mm. The 1st (10 × 9), the 2nd (10 × 10), and the 3rd (11 × 11) LYSO layers were stacked with a staggered configuration to provide DOI information in the 2D crystal map. In order to investigate the optimal reflector and light guide thickness, the performance of the PET detector module was evaluated with different reflectors (ESR and BaSO4), and different light guide thicknesses (0.5, 1.0, and 2.0 mm). A 22Na source was used to irradiate 511 keV photon to the detector module. The sixteen SiPM output signals were multiplexed into four position signals by using the Anger logic circuit, and a trigger signal was generated by using the common cathode signals. The SiPM signals were digitized by CAMAC DAQ. Results: The BaSO4 reflector resulted in better crystal identification for the three-layer staggered LYSO crystal arrays as compared to the ESR. However, the energy resolution with BaSO4 (38.8%) was worse than that of the ESR (20.3%). The acrylic light guide thickness of 1 mm resulted in the best crystal identification for both BaSO4 and ESR reflector cases. Conclusions: A staggered three-layer DOI PET detector with a 1 mm crystal pitch was developed. All the LYSO crystals could be identified clearly on the 2D flood histogram by using the BaSO4 reflector. In future, a prototype high resolution small animal DOI PET scanner will be developed by using the proposed three-layer staggered DOI PET detector module., 2019 Annual Meeting of Society of Nuclear Medicine and Moldecular Imaging

[Purpose] Heavy ion therapy has been used as a promising cancer therapy technique due to its Bragg peak characteristics. Recently, the potential of radioactive ion beam therapy has been investigated with a combination of the OpenPET system to improve the accuracy of in vivo beam range verification. The aim of this study is to estimate the O-15 beam range in an acrylic phantom by using luminescence- and Cerenkov-light for beam quality control. [Methods] In this study, an acrylic phantom (10 × 10 × 10 cm3) was irradiated by O-15 beam for 8 min. The energy, lateral beam size (FWHM), and total number of the O-15 ion beam were 250 MeV/n, 19.8 mm, and 2.4×1010, respectively. In order to obtain the luminescence image and Cerenkov image, an optical system which consisted of lens and a cooled CCD camera (Bitran, BS-40L, Japan) was used. The distance between the surface of the acrylic phantom and the optical lens was set to 52 cm. The luminescence image and Cerenkov image were obtained for 2 min with in-beam and offline-beam condition, respectively The CCD image was acquired with various PMMA range shifter thicknesses (0, 10, 25, 30, 35, 40 mm) to evaluate the range estimation accuracy of the luminescence and Cerenkov imaging. [Results] The stopping position of O-15 ion and the lateral FWHM of the O-15 beam could be visualized using Cerenkov and luminescence imaging, respectively. The Bragg peak shift caused by the PMMA range shifter could be estimated by using Cerenkov and luminescence imaging with accuracies of 0.33 mm, and 0.45 mm, respectively. However, the line profile peak of the Cerenkov image was 2.8 ± 0.5 mm deeper than that of the luminescence image. [Conclusion] In conclusion, the optical imaging could be used for high resolution beam profile monitoring. In the future, in-beam PET and systematic dose profile measurement will be performed to investigate the practical method of beam quality control using the optical imaging technique., 第117回日本医学物理学会学術大会