研究者情報

マスター

アカウント（マスター）

• 氏名

  松浦　妙子(マツウラ　タエコ), マツウラ　タエコ

所属（マスター）

• 工学研究院　応用量子科学部門　量子生命工学

所属（マスター）

• 工学研究院　応用量子科学部門　量子生命工学

独自項目

syllabus

• 2021, 基礎放射線治療物理学, Basic Physics for Radiation Therapy, 修士課程, 医理工学院, 放射線治療、放射線物理学、加速器
• 2021, 大学院共通授業科目（一般科目）：自然科学・応用科学, Inter-Graduate School Classes(General Subject):Natural and Applied Sciences, 修士課程, 大学院共通科目, radiation treatment, particle therapy, medical physics, radiobiology, radiomics
• 2021, Medical Physics School, Medical Physics School, 修士課程, 医理工学院, radiation treatment, particle therapy, medical physics, radiobiology, radiomics
• 2021, 粒子線治療工学特論, Physics and Techniques for Particle Therapy, 修士課程, 工学院, 粒子線治療，医学物理学
• 2021, 粒子線治療工学特論, Physics and Techniques for Particle Therapy, 博士後期課程, 工学院, 粒子線治療，医学物理学
• 2021, 応用数学演習Ⅰ, Exercise in Applied Mathematics I, 学士課程, 工学部, 常微分方程式、ベクトル解析
• 2021, 量子力学, Quantum Mechanics, 学士課程, 工学部, 粒子性・波動性、波動関数、不確定性原理、フーリエ展開、演算子、シュレディンガー方程式、調和振動子、水素原子構造、多電子原子の構造、パウリの原理
• 2021, 応用数学Ⅰ, Applied Mathematics I, 学士課程, 工学部, 常微分方程式，ベクトル解析

researchmap

プロフィール情報

学位

• 博士（理学）（東京大学）

プロフィール情報

• 姓

  松浦, マツウラ

• 名

  妙子, タエコ

• ID各種

  201301008105794896

対象リソース

http://kaken.nii.ac.jp/d/r/90590266.ja.html

業績リスト

研究キーワード

• 陽子線治療   

研究分野

• ライフサイエンス / 放射線科学

経歴

• 2015年 - 現在 北海道大学大学院工学研究院
• 2010年 - 2015年 北海道大学 医学(系)研究科(研究院) その他
• 2008年 - 2010年 国立がん研究センター東病院
• 2006年 - 2008年 European Centre for Theoretical Studies in Nuclear Physics and Related Areas (ECT*)

学歴

• 2001年04月 - 2006年03月   東京大学   大学院理学系研究科   物理学専攻
• 1979年04月 - 2001年03月   東京大学   理学部   物理学科

論文

• Investigation of interfractional range variation owing to anatomical changes with beam directions based on water equivalent thickness in proton therapy for pancreatic cancer.

  Yuhei Kikkawa, Hideaki Ueda, Yusuke Uchinami, Norio Katoh, Hidefumi Aoyama, Yoichi M Ito, Kohei Yokokawa, Ye Chen, Taeko Matsuura, Naoki Miyamoto, Seishin Takao

  Journal of radiation research 2024年10月08日 

  To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET } }^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE},{\mathrm{T } }^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40 Gy(RBE)/5 fractions: 'Plan A', using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and 'Plan B', using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss.
• A simulation study of MR-guided proton therapy system using iron-yoked superconducting open MRI: a conceptual study.

  Yusuke Fujii, Hideaki Ueda, Taisuke Takayanagi, Kentaro Nishioka, Takashi Mori, Takayuki Hashimoto, Hidefumi Aoyama, Kikuo Umegaki, Taeko Matsuura

  Journal of radiation research 2024年10月04日 

  Radiotherapy platforms integrated with magnetic resonance imaging (MRI) have been significantly successful and widely used in X-ray therapy over the previous decade. MRI provides greater soft-tissue contrast than conventional X-ray techniques, which enables more precise radiotherapy with on-couch adaptive treatment planning and direct tracking of moving tumors. The integration of MRI into a proton beam irradiation system (PBS) is still in the research stage. However, this could be beneficial as proton therapy is more sensitive to anatomical changes and organ motion. In this simulation study, we considered the integration of PBS into the 0.3-T superconducting open MRI system. Our proposed design involves proton beams traversing a hole at the center of the iron yoke, which allows for a reduced fringe field in the irradiation nozzle while maintaining a large proton scan field of the current PBS. The shape of the bipolar MRI magnets was derived to achieve a large MRI field-of-view. To monitor the beam position and size accurately while maintaining a small beam size, the beam monitor installation was redesigned from the current system. The feasibility of this system was then demonstrated by the treatment plan quality, which showed that the magnetic field did not deteriorate the plan quality from that without the magnetic field for both a rectangular target and a prostate case. Although numerous challenges remain before the proposed simulation model can be implemented in a clinical setting, the presented conceptual design could assist in the initial design for the realization of the MR-guided proton therapy.
• Geometric target margin strategy of proton craniospinal irradiation for pediatric medulloblastoma.

  Takaaki Yoshimura, Keigo Kondo, Takayuki Hashimoto, Kentaro Nishioka, Takashi Mori, Takahiro Kanehira, Taeko Matsuura, Seishin Takao, Hiroshi Tamura, Takuya Matsumoto, Kenneth Sutherland, Hidefumi Aoyama

  Journal of radiation research 2024年09月15日 

  In proton craniospinal irradiation (CSI) for skeletally immature pediatric patients, a treatment plan should be developed to ensure that the dose is uniformly delivered to all vertebrae, considering the effects on bone growth balance. The technical (t) clinical target volume (CTV) is conventionally set by manually expanding the CTV from the entire intracranial space and thecal sac, based on the physician's experience. However, there are differences in contouring methods among physicians. Therefore, we aimed to propose a new geometric target margin strategy. Nine pediatric patients with medulloblastoma who underwent proton CSI were enrolled. We measured the following water equivalent lengths for each vertebra in each patient: body surface to the dorsal spinal canal, vertebral limbus, ventral spinal canal and spinous processes. A simulated tCTV (stCTV) was created by assigning geometric margins to the spinal canal using the measurement results such that the vertebral limb and dose distribution coincided with a margin assigned to account for the uncertainty of the proton beam range. The stCTV with a growth factor (correlation between body surface area and age) and tCTV were compared and evaluated. The median values of each index for cervical, thoracic and lumber spine were: the Hausdorff distance, 9.14, 9.84 and 9.77 mm; mean distance-to-agreement, 3.26, 2.65 and 2.64 mm; Dice coefficient, 0.84, 0.81 and 0.82 and Jaccard coefficient, 0.50, 0.60 and 0.62, respectively. The geometric target margin setting method used in this study was useful for creating an stCTV to ensure consistent and uniform planning.
• Application of motion prediction based on a long short-term memory network for imaging dose reduction in real-time tumor-tracking radiation therapy.

  Kazuki Numakura, Seishin Takao, Taeko Matsuura, Kouhei Yokokawa, Ye Chen, Yusuke Uchinami, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama, Satoshi Tomioka, Naoki Miyamoto

  Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) 125 104507 - 104507 2024年09月 

  PURPOSE: To demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy. METHODS: Time-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms. RESULTS: Except for outliers in the superior-inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more. CONCLUSIONS: Motion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy.
• A Single-Institution Prospective Study To Evaluate the Safety and Efficacy of Real- Time Image-Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer.

  Kentaro Nishioka, Takayuki Hashimoto, Takashi Mori, Yusuke Uchinami, Rumiko Kinoshita, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Yoichi M Ito, Seishin Takao, Masaya Tamura, Taeko Matsuura, Shinichi Shimizu, Hiroki Shirato, Hidefumi Aoyama

  Advances in radiation oncology 9 5 101464 - 101464 2024年05月 [査読有り]
   

  PURPOSE: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. METHODS AND MATERIALS: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE. RESULTS: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%). CONCLUSIONS: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.
• Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

  Takaaki Yoshimura, Ryota Yamada, Rumiko Kinoshita, Taeko Matsuura, Takahiro Kanehira, Hiroshi Tamura, Kentaro Nishioka, Koichi Yasuda, Hiroshi Taguchi, Norio Katoh, Keiji Kobashi, Takayuki Hashimoto, Hidefumi Aoyama

  Journal of radiation research 2024年03月17日 

  This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.
• Application of an optical hydrophone to ionoacoustic range detection in a tissue-mimicking agar phantom

  Shota Sueyasu, Koki Kasamatsu, Taisuke Takayanagi, Ye Chen, Yasutoshi Kuriyama, Yoshihiro Ishi, Tomonori Uesugi, Wolfgang Rohringer, Mehmet Burcin Unlu, Nobuki Kudo, Kohei Yokokawa, Seishin Takao, Naoki Miyamoto, Taeko Matsuura

  Medical Physics 2024年01月 [査読有り]
  
• Study of hepatic toxicity in small liver tumors after photon or proton therapy based on factors predicting the benefits of proton.

  Yusuke Uchinami, Norio Katoh, Daisuke Abo, Ryo Morita, Hiroshi Taguchi, Yoshihiro Fujita, Takahiro Kanehira, Ryusuke Suzuki, Naoki Miyamoto, Seishin Takao, Taeko Matsuura, Takuya Sho, Koji Ogawa, Tatsuya Orimo, Tatsuhiko Kakisaka, Keiji Kobashi, Hidefumi Aoyama

  The British journal of radiology 96 1144 20220720 - 20220720 2023年01月12日 

  OBJECTIVES: In a previous study of hepatic toxicity, the following three factors were identified to predict the benefits of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (one vs ≥2), the location of tumors (hepatic hilum or others), and the sum of the diameters of lesions. The aim of this study is to analyze the association between these three factors and hepatic toxicity. METHODS: We retrospectively reviewed patients of CP-A treated with PBT or photon stereotactic body radiotherapy (X-ray radiotherapy, XRT) for HCC ≤5 cm. For normal liver dose, the V5, V10, V20 (volumes receiving 5, 10, and 20 Gy at least), and the mean dose was evaluated. The albumin-bilirubin (ALBI) and CP score changes from the baseline were evaluated at 3 and 6 months after treatment. RESULTS: In 89 patients (XRT: 48, PBT: 41), those with two or three (2-3) predictive factors were higher normal liver doses than with zero or one (0-1) factor. In the PBT group, the ALBI score worsened more in patients with 2-3 factors than those with 0-1 factor, at 3 months (median 0.26 vs 0.02, p = 0.032) and at 6 months (median: 0.35 vs 0.10, p = 0.009). The ALBI score change in the XRT group and CP score change in either modality were not significantly different in the number of predictive factors. CONCLUSIONS: The predictive factor numbers predicted the ALBI score change in PBT but not in XRT. ADVANCES IN KNOWLEDGE: This study suggest that the number of predictive factors previously identified (0-1 vs 2-3) were significantly associated with dosimetric parameters of the normal liver in both modalities. In the proton group, the number of predictive factors was associated with a worsening ALBI score at 3 and 6 months, but these associations were not found in the photon SBRT group.
• Ionoacoustic application of an optical hydrophone to detect proton beam range in water

  Shota Sueyasu, Taisuke Takayanagi, Koichi Miyazaki, Yasutoshi Kuriyama, Yoshihiro Ishi, Tomonori Uesugi, Mehmet Burcin Unlu, Nobuki Kudo, Ye Chen, Koki Kasamatsu, Masayuki Fujii, Masanori Kobayashi, Wolfgang Rohringer, Taeko Matsuura

  Medical Physics 50 4 2438 - 2449 2023年01月06日 [査読有り]
   

  Abstract Background Proton range uncertainty has been the main factor limiting the ability of proton therapy to concentrate doses to tumors to their full potential. Ionoacoustic (IA) range verification is an approach to reducing this uncertainty by detecting thermoacoustic waves emitted from an irradiated volume immediately following a pulsed proton beam delivery; however, the signal weakness has been an obstacle to its clinical application. To increase the signal‐to‐noise ratio (SNR) with the conventional piezoelectric hydrophone (PH), the detector‐sensitive volume needs to be large, but it could narrow the range of available beam angles and disturb real‐time images obtained during beam delivery. Purpose To prevent this issue, we investigated a millimeter‐sized optical hydrophone (OH) that exploits the laser interferometric principle. For two types of IA waves [γ‐wave emitted from the Bragg peak (BP) and a spherical IA wave with resonant frequency (SPIRE) emitted from the gold fiducial marker (GM)], comparisons were made with PH in terms of waveforms, SNR, range detection accuracy, and signal intensity robustness against the small detector misalignment, particularly for SPIRE. Methods A 100‐MeV proton beam with a 27 ns pulse width and 4 mm beam size was produced using a fixed‐field alternating gradient accelerator and was irradiated to the water phantom. The GM was set on the beam's central axis. Acrylic plates of various thicknesses, up to 12 mm, were set in front of the phantoms to shift the proton range. OH was set distal and lateral to the beam, and the range was estimated using the time‐of‐flight method for γ‐wave and by comparing with the calibration data (SPIRE intensity versus the distance between the GM and BP) derived from an IA wave transport simulation for SPIRE. The BP dose per pulse was 0.5–0.6 Gy. To measure the variation in SPIRE amplitude against the hydrophone misalignment, the hydrophone was shifted by ± 2 mm at a maximum in lateral directions. Results Despite its small size, OH could detect γ‐wave with a higher SNR than the conventional PH (diameter, 29 mm), and a single measurement was sufficient to detect the beam range with a submillimeter accuracy in water. In the SPIRE measurement, OH was far more robust against the detector misalignment than the focused PH (FPH) used in our previous study [5%/mm (OH) versus 80%/mm (FPH)], and the correlation between the measured SPIRE intensity and the distance between the GM and BP agreed well with the simulation results. However, the OH sensitivity was lower than the FPH sensitivity, and about 5.6‐Gy dose was required to decrease the intensity variation among measurements to less than 10%. Conclusion The miniature OH was found to detect weak IA signals produced by proton beams with a BP dose used in hypofractionated regimens. The OH sensitivity improvement at the MHz regime is worth exploring as the next step.
• Deformed dose restoration to account for tumor deformation and position changes for adaptive proton therapy.

  Koichi Miyazaki, Yusuke Fujii, Takahiro Yamada, Takahiro Kanehira, Naoki Miyamoto, Taeko Matsuura, Koichi Yasuda, Yusuke Uchinami, Manami Otsuka, Hidefumi Aoyama, Seishin Takao

  Medical physics 50 2 675 - 687 2022年12月11日 [査読有り]
   

  BACKGROUND: Online adaptation during intensity-modulated proton therapy (IMPT) can minimize the effect of inter-fractional anatomical changes, but remains challenging because of the complex workflow. One approach for fast and automated online IMPT adaptation is dose restoration, which restores the initial dose distribution on the updated anatomy. However, this method may fail in cases where tumor deformation or position changes occur. PURPOSE: To develop a fast and robust IMPT online adaptation method named "deformed dose restoration (DDR)" that can adjust for inter-fractional tumor deformation and position changes. METHODS: THE DDR METHOD COMPRISES TWO STEPS: : (1) calculation of the deformed dose distribution, and (2) restoration of the deformed dose distribution. First, the deformable image registration (DIR) between the initial clinical target volume (CTV) and the new CTV were performed to calculate the vector field. To ensure robustness for setup and range uncertainty and the ability to restore the deformed dose distribution, an expanded CTV-based registration to maintain the dose gradient outside the CTV was developed. The deformed dose distribution was obtained by applying the vector field to the initial dose distribution. Then, the voxel-by-voxel dose difference optimization was performed to calculate beam parameters that restore the deformed dose distribution on the updated anatomy. The optimization function was the sum of total dose differences and dose differences of each field to restore the initial dose overlap of each field. This method only requires target contouring, which eliminates the need for organs at risk (OARs) contouring. Six clinical cases wherein the tumor deformation and/or position changed on repeated CTs were selected. DDR feasibility was evaluated by comparing the results with those from three other strategies, namely, not adapted (continuing the initial plan), adapted by previous dose restoration, and fully optimized. RESULTS: In all cases, continuing the initial plan was largely distorted on the repeated CTs and the dose-volume histogram (DVH) metrics for the target were reduced due to the tumor deformation or position changes. On the other hand, DDR improved DVH metrics for the target to the same level as the initial dose distribution. Dose increase was seen for some OARs because tumor growth had reduced the relative distance between CTVs and OARs. Robustness evaluation for setup and range uncertainty (3 mm/3.5%) showed that deviation in DVH-bandwidth for CTV D95% from the initial plan was 0.4 ± 0.5% (Mean ± S.D.) for DDR. The calculation time was 8.1 ± 6.4 min. CONCLUSIONS: An online adaptation algorithm was developed that improved the treatment quality for inter-fractional anatomical changes and retained robustness for intra-fractional setup and range uncertainty. The main advantage of this method is that it only requires target contouring alone and saves the time for OARs contouring. The fast and robust adaptation method for tumor deformation and position changes described here can reduce the need for offline adaptation and improve treatment efficiency. This article is protected by copyright. All rights reserved.
• Technical Note: Performance evaluation of volumetric imaging based on motion modeling by principal component analysis

  Suzuka Asano, Keishi Oseki, Seishin Takao, Koichi Miyazaki, Kohei Yokokawa, Taeko Matsuura, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama, Kikuo Umegaki, Naoki Miyamoto

  Medical Physics 2022年12月03日
• Hyperfractionated intensity-modulated proton therapy for pharyngeal cancer with variable relative biological effectiveness: A simulation study.

  Koki Kasamatsu, Taeko Matsuura, Koichi Yasuda, Koichi Miyazaki, Seishin Takao, Masaya Tamura, Manami Otsuka, Yusuke Uchinami, Hidefumi Aoyama

  Medical physics 49 12 7815 - 7825 2022年10月27日 [査読有り]
   

  BACKGROUND: The relative biological effectiveness (RBE) of proton is considered to be dependent on biological parameters and fractional dose. While hyperfractionated photon therapy was effective in the treatment of patients with head and neck cancers, its effect in intensity-modulated proton therapy (IMPT) under the variable RBE has not been investigated in detail. PURPOSE: To study the effect of variable RBE on hyperfractionated IMPT for the treatment of pharyngeal cancer. We investigated the biologically effective dose (BED) to determine the theoretical effective hyperfractionated schedule. METHODS: The treatment plans of three pharyngeal cancer patients were used to define the ΔBED for the clinical target volume (CTV) and soft tissue (acute and late reaction) as the difference between the BED for the altered schedule with variable RBE and conventional schedule with constant RBE. The ΔBED with several combinations of parameters (treatment days, number of fractions, and prescribed dose) was comprehensively calculated. Of the candidate schedules, the one that commonly gave a higher ΔBED for CTV was selected as the resultant schedule. The BED volume histogram was used to compare the influence of variable RBE and fractionation. RESULTS: In the conventional schedule, compared with the constant RBE, the variable RBE resulted in a mean 2.6 and 2.7 Gy reduction of BEDmean for the CTV and soft tissue (acute reaction) of the three plans, respectively. Moreover, the BEDmean for soft tissue (late reaction) increased by 7.4 Gy, indicating a potential risk of increased RBE. Comprehensive calculation of the ΔBED resulted in the hyperfractionated schedule of 80.52 Gy (RBE = 1.1)/66 fractions in 6.5 weeks. When variable RBE was used, compared with the conventional schedule, the hyperfractionated schedule increased the BEDmean for CTV by 7.6 Gy; however, this was associated with a 7.8 Gy increase for soft tissue (acute reaction). The BEDmean for soft tissue (late reaction) decreased by 2.4 Gy. CONCLUSION: The results indicated a potential effect of the variable RBE on IMPT for pharyngeal cancer but with the possibility that hyperfractionation could outweigh this effect. Although biological uncertainties require conservative use of the resultant schedule, hyperfractionation is expected to be an effective strategy in IMPT for pharyngeal cancer.
• A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity

  Yusuke Uchinami, Norio Katoh, Ryusuke Suzuki, Takahiro Kanehira, Masaya Tamura, Seishin Takao, Taeko Matsuura, Naoki Miyamoto, Yoshihiro Fujita, Fuki Koizumi, Hiroshi Taguchi, Koichi Yasuda, Kentaro Nishioka, Isao Yokota, Keiji Kobashi, Hidefumi Aoyama

  Clinical and Translational Radiation Oncology 35 70 - 75 2022年07月
• A Consistent Protocol Reveals a Large Heterogeneity in the Biological Effectiveness of Proton and Carbon-Ion Beams for Various Sarcoma and Normal-Tissue-Derived Cell Lines.

  Masashi Yagi, Yutaka Takahashi, Kazumasa Minami, Taeko Matsuura, Jin-Min Nam, Yasuhito Onodera, Takashi Akagi, Takuya Maeda, Tomoaki Okimoto, Hiroki Shirato, Kazuhiko Ogawa

  Cancers 14 8 2022年04月15日 

  This study investigated variations in the relative biological effectiveness (RBE) values among various sarcoma and normal-tissue-derived cell lines (normal cell line) in proton beam and carbon-ion irradiations. We used a consistent protocol that specified the timing of irradiation after plating cells and detailed the colony formation assay. We examined the cell type dependence of RBE for proton beam and carbon-ion irradiations using four human sarcoma cell lines (MG63 osteosarcoma, HT1080 fibrosarcoma, SW872 liposarcoma, and SW1353 chondrosarcoma) and three normal cell lines (HDF human dermal fibroblast, hTERT-HME1 mammary gland, and NuLi-1 bronchus epithelium). The cells were irradiated with gamma rays, proton beams at the center of the spread-out Bragg peak, or carbon-ion beams at 54.4 keV/μm linear energy transfer. In all sarcoma and normal cell lines, the average RBE values in proton beam and carbon-ion irradiations were 1.08 ± 0.11 and 2.08 ± 0.36, which were consistent with the values of 1.1 and 2.13 used in current treatment planning systems, respectively. Up to 34% difference in the RBE of the proton beam was observed between MG63 and HT1080. Similarly, a 32% difference in the RBE of the carbon-ion beam was observed between SW872 and the other sarcoma cell lines. In proton beam irradiation, normal cell lines had less variation in RBE values (within 10%), whereas in carbon-ion irradiation, RBE values differed by up to 48% between hTERT-HME1 and NuLi-1. Our results suggest that specific dose evaluations for tumor and normal tissues are necessary for treatment planning in both proton and carbon-ion therapies.
• An initial systematic study of the linear energy transfer distributions of a proton beam under a transverse magnetic field.

  Yusuke Fujii, Hideaki Ueda, Kikuo Umegaki, Taeko Matsuura

  Medical physics 2022年02月05日 [査読有り]
   

  PURPOSE: To evaluate the biological effectiveness of magnetic resonance (MR)-guided proton beam therapy, comprehensively characterizing the dose and dose-averaged linear energy transfer (LETd ) distributions under a magnetic field is necessary. Although detailed analysis has characterized curved beam paths and distorted dose distributions, the impact of a magnetic field on LETd should also be explored to determine the proton relative biological effectiveness (RBE). Hence, this initial study aims to present a basic analysis of LETd distributions in the presence of a magnetic field using Monte Carlo simulation (MCS). METHODS: Geant4 MCS (v. 10.1.p01) was performed to calculate the LETd distribution of proton beams. The incident beam energies were set to 70.2, 140.8, and 220 MeV, and both zero- and finite-emittance pencil beams as well as scanned field were simulated. A transverse magnetic field of 0-3 T was applied within a water phantom placed at the isocenter, and the three-dimensional dose and LETd distributions in the phantom were calculated. Then, the depth profiles of LETd along the curved trajectory and the lateral LETd profile at the Bragg peak (BP) depth were analyzed under changing energies and magnetic fields. In addition, for zero- and finite-emittance beams, the correlation of the lateral asymmetries between the dose and LETd distributions were analyzed. Finally, spread-out Bragg peak (SOBP) fields were simulated to assess the depth-dependent asymmetry of the LETd distributions. RESULTS: A transverse magnetic field distorted the lateral LETd distribution of a pencil beam at close to the BP, and the magnitude of the distortion at the BP increased for higher energy beams and larger magnetic fields. For a zero-emittance beam, the differences in LETd between the left and right D20 positions were relatively large; the difference in LETd was 1.5 and 2.3 keV/μm at 140.8 and 220 MeV, respectively, at a magnetic field of 1.5 T. These asymmetries were pronounced at positions where the dose asymmetries were large. The size of the asymmetry was less substantial for a finite-emittance beam and even less for a scanned field. However, a 1.5-keV/μm difference still remained between the left and right D20 positions of a scanned field penumbra for a 220 MeV beam under the same magnetic field. For the SOBP field, it was found that the distal region of SOBP had the highest LETd distortions, followed by the central and proximal regions for the middle-sized SOBP (5 × 5 × 5 cm3 ), whereas the degree of LETd distortion did not vary much with depth for the 10 × 10 × 10-cm3 SOBP field. CONCLUSION: Our results indicate that not only the dose but also LETd distortions should be considered to accurately evaluate the biological effectiveness of MR-guided proton beam therapy. This article is protected by copyright. All rights reserved.
• Impact of a spatially dependent dose delivery time structure on the biological effectiveness of scanning proton therapy.

  Koki Kasamatsu, Sodai Tanaka, Koichi Miyazaki, Seishin Takao, Naoki Miyamoto, Shusuke Hirayama, Kentaro Nishioka, Takayuki Hashimoto, Hidefumi Aoyama, Kikuo Umegaki, Taeko Matsuura

  Medical physics 49 1 702 - 713 2021年11月18日 [査読有り]
   

  PURPOSE: In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. This research aimed to evaluate the spatially dependent biological effectiveness of protracted irradiation in scanning proton therapy. METHODS: One and two parallel opposed fields plans were created in water phantom with the prescribed dose of 2 Gy. Three scenarios (instantaneous, continuous, and layered scans) were used with the corresponding beam delivery models. The biological dose (physical dose × relative biological effectiveness) was calculated using the linear quadratic model and the theory of dual radiation action to quantitatively evaluate the dose delivery time effect. In addition, simulations using clinical plans (postoperative seminoma and prostate tumor cases) were conducted to assess the impact of the effects on the dose volume histogram parameters and homogeneity coefficient (HC) in targets. RESULTS: In a single-field plan of water phantom, when the treatment time was 19 min, the layered-scan scenario showed a decrease of <0.2% (almost 3.3%) in the biological dose from the plan on the distal (proximal) side because of the high (low) dose rate. This is in contrast to the continuous scenario, where the biological dose was almost uniformly decreased over the target by approximately 3.3%. The simulation with clinical geometry showed that the decrease rates in D99% were 0.9% and 1.5% for every 10 min of treatment time prolongation for postoperative seminoma and prostate tumor cases, respectively, whereas the increase rates in HC were 0.7% and 0.2%. CONCLUSIONS: In protracted irradiation in scanning proton therapy, the spatially dependent dose delivery time structure in scanning beam delivery can be an important factor for accurate evaluation of biological effectiveness. This article is protected by copyright. All rights reserved.
• Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.

  Takayuki Hashimoto, Yusuke Demizu, Haruko Numajiri, Tomonori Isobe, Shigekazu Fukuda, Masaru Wakatsuki, Haruo Yamashita, Shigeyuki Murayama, Shigeyuki Takamatsu, Hiroyuki Katoh, Kazutoshi Murata, Ryosuke Kohno, Takeshi Arimura, Taeko Matsuura, Yoichi M Ito

  Japanese journal of radiology 40 5 525 - 533 2021年11月15日 

  PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.
• A treatment planning study of urethra-sparing intensity-modulated proton therapy for localized prostate cancer

  Takaaki Yoshimura, Kentaro Nishioka, Takayuki Hashimoto, Kazuya Seki, Shouki Kogame, Sodai Tanaka, Takahiro Kanehira, Masaya Tamura, Seishin Takao, Taeko Matsuura, Keiji Kobashi, Fumi Kato, Hidefumi Aoyama, Shinichi Shimizu

  Physics and Imaging in Radiation Oncology 20 23 - 29 2021年10月
• Prediction of target position from multiple fiducial markers by partial least squares regression in real-time tumor-tracking radiation therapy.

  Kanako Ukon, Yohei Arai, Seishin Takao, Taeko Matsuura, Masayori Ishikawa, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki, Naoki Miyamoto

  Journal of radiation research 62 5 926 - 933 2021年09月13日 

  The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers' positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior-inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.
• First experimental results of gated proton imaging using x-ray fluoroscopy to detect a fiducial marker.

  Sodai Tanaka, Naoki Miyamoto, Yuto Matsuo, Takaaki Yoshimura, Seishin Takao, Taeko Matsuura

  Physics in medicine and biology 66 18 2021年09月09日 

  Increasing numbers of proton imaging research studies are being conducted for accurate proton range determination in proton therapy treatment planning. However, there is no proton imaging system that deals with motion artifacts. In this study, a gated proton imaging system was developed and the first experimental results of proton radiography (pRG) were obtained for a moving object without motion artifacts. A motion management system using dual x-ray fluoroscopy for detecting a spherical gold fiducial marker was introduced and the proton beam was gated in accordance with the motion of the object. To demonstrate the performance of the gated proton imaging system, gated pRG images of a moving phantom were acquired experimentally, and the motion artifacts clearly were diminished. Also, the factors causing image deteriorations were evaluated focusing on the new gating system developed here, and the main factor was identified as the latency (with a maximum value of 93 ms) between the ideal gating signal according to the actual marker position and the actual gating signal. The possible deterioration due to the latency of the proton imaging system and proton beam irradiation was small owing to appropriate setting of the time structure.
• Real-time CT image generation based on voxel-by-voxel modeling of internal deformation by utilizing the displacement of fiducial markers.

  Risa Hayashi, Koichi Miyazaki, Seishin Takao, Kohei Yokokawa, Sodai Tanaka, Taeko Matsuura, Hiroshi Taguchi, Norio Katoh, Shinichi Shimizu, Kikuo Umegaki, Naoki Miyamoto

  Medical physics 48 9 5311 - 5326 2021年09月 

  PURPOSE: To show the feasibility of real-time CT image generation technique utilizing internal fiducial markers that facilitate the evaluation of internal deformation. METHODS: In the proposed method, a linear regression model that can derive internal deformation from the displacement of fiducial markers is built for each voxel in the training process before the treatment session. Marker displacement and internal deformation are derived from the four-dimensional computed tomography (4DCT) dataset. In the treatment session, the three-dimensional deformation vector field is derived according to the marker displacement, which is monitored by the real-time imaging system. The whole CT image can be synthesized by deforming the reference CT image with a deformation vector field in real-time. To show the feasibility of the technique, image synthesis accuracy and tumor localization accuracy were evaluated using the dataset generated by extended NURBS-Based Cardiac-Torso (XCAT) phantom and clinical 4DCT datasets from six patients, containing 10 CT datasets each. In the validation with XCAT phantom, motion range of the tumor in training data and validation data were about 10 and 15 mm, respectively, so as to simulate motion variation between 4DCT acquisition and treatment session. In the validation with patient 4DCT dataset, eight CT datasets from the 4DCT dataset were used in the training process. Two excluded inhale CT datasets can be regarded as the datasets with large deformations more than training dataset. CT images were generated for each respiratory phase using the corresponding marker displacement. Root mean squared error (RMSE), normalized RMSE (NRMSE), and structural similarity index measure (SSIM) between the original CT images and the synthesized CT images were evaluated as the quantitative indices of the accuracy of image synthesis. The accuracy of tumor localization was also evaluated. RESULTS: In the validation with XCAT phantom, the mean NRMSE, SSIM, and three-dimensional tumor localization error were 7.5 ± 1.1%, 0.95 ± 0.02, and 0.4 ± 0.3 mm, respectively. In the validation with patient 4DCT dataset, the mean RMSE, NRMSE, SSIM, and three-dimensional tumor localization error in six patients were 73.7 ± 19.6 HU, 9.2 ± 2.6%, 0.88 ± 0.04, and 0.8 ± 0.6 mm, respectively. These results suggest that the accuracy of the proposed technique is adequate when the respiratory motion is within the range of the training dataset. In the evaluation with a marker displacement larger than that of the training dataset, the mean RMSE, NRMSE, and tumor localization error were about 100 HU, 13%, and <2.0 mm, respectively, except for one case having large motion variation. The performance of the proposed method was similar to those of previous studies. Processing time to generate the volumetric image was <100 ms. CONCLUSION: We have shown the feasibility of the real-time CT image generation technique for volumetric imaging.
• Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction.

  Takahiro Yamada, Seishin Takao, Hidenori Koyano, Hideaki Nihongi, Yusuke Fujii, Shusuke Hirayama, Naoki Miyamoto, Taeko Matsuura, Kikuo Umegaki, Norio Katoh, Isao Yokota, Hiroki Shirato, Shinichi Shimizu

  Journal of radiation research 62 4 626 - 633 2021年07月10日 

  In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5-D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%-2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: -0.5%-0.7%). The mean differences of D99, D5-D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.
• Technical Note: Range verification of pulsed proton beams from fixed‐field alternating‐gradient accelerator by means of time‐of‐flight measurement of ionoacoustic waves

  Yuta Nakamura, Taisuke Takayanagi, Tomoki Uesaka, Mehmet Burcin Unlu, Yasutoshi Kuriyama, Yoshihiro Ishi, Tomonori Uesugi, Masanori Kobayashi, Nobuki Kudo, Sodai Tanaka, Kikuo Umegaki, Satoshi Tomioka, Taeko Matsuura

  Medical Physics 48 9 5490 - 5500 2021年06月26日 [査読有り]
   

  PURPOSE: Ionoacoustics is one of the promising approaches to verify the beam range in proton therapy. However, the weakness of the wave signal remains a main hindrance to its application in clinics. Here we studied the potential use of a fixed-field alternating gradient accelerator (FFA), one of the accelerator candidates for future proton therapy. For such end, magnitude of the pressure wave and range accuracy achieved by the short-pulsed beam of FFA were assessed, using both simulation and experimental procedure. METHODS: A 100 MeV proton beam from the FFA was applied on a water phantom, through the acrylic wall. The beam range measured by the Bragg peak (BP)-ionization chamber (BPC) was 77.6 mm, while the maximum dose at BP was estimated to be 0.35 Gy/pulse. A hydrophone was placed 20 mm downstream of the BP, and signals were amplified and stored by a digital oscilloscope, averaged, and low-pass filtered. Time-of-flight (TOF) and two relative TOF values were analyzed in order to determine the beam range. Furthermore, an acoustic wave transport simulation was conducted to estimate the amplitude of the pressure waves. RESULTS: The range calculated when using two relative TOF was 78.16 ± 0.01 and 78.14 ± 0.01 mm, respectively, both values being coherent with the range measured by the BPC (the difference was 0.5-0.6 mm). In contrast, utilizing the direct TOF resulted in a range error of 1.8 mm. Fivefold and 50-fold averaging were required to suppress the range variation to below 1 mm for TOF and relative TOF measures, respectively. The simulation suggested the magnitude of pressure wave at the detector exceeded 7 Pascal. CONCLUSION: A submillimeter range accuracy was attained with a pulsed beam of about 21 ns from an FFA, at a clinical energy using relative TOF. To precisely quantify the range with a single TOF measurement, subsequent improvement in the measuring system is required.
• Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

  Hideki Minatogawa, Koichi Yasuda, Yasuhiro Dekura, Seishin Takao, Taeko Matsuura, Takaaki Yoshimura, Ryusuke Suzuki, Isao Yokota, Noriyuki Fujima, Rikiya Onimaru, Shinichi Shimizu, Hidefumi Aoyama, Hiroki Shirato

  Journal of applied clinical medical physics 22 1 174 - 183 2021年01月 

  PURPOSE: To investigate potential advantages of adaptive intensity-modulated proton beam therapy (A-IMPT) by comparing it to adaptive intensity-modulated X-ray therapy (A-IMXT) for nasopharyngeal carcinomas (NPC). METHODS: Ten patients with NPC treated with A-IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A-IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A-IMXT with A-IMPT. RESULTS: The means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A-IMPT are lower than those of A-IMXT, with statistical significance. The means of, D0.03cc , and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A-IMPT are significantly lower than those of A-IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1). CONCLUSIONS: An adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.
• Proton dose calculation based on converting dual-energy CT data to stopping power ratio (DEEDZ-SPR): a beam-hardening assessment.

  Sodai Tanaka, Yoshiyuki Noto, Satoru Utsunomiya, Takaaki Yoshimura, Taeko Matsuura, Masatoshi Saito

  Physics in medicine and biology 65 23 235046 - 235046 2020年12月18日 

  To achieve an accurate stopping power ratio (SPR) prediction in particle therapy treatment planning, we previously proposed a simple conversion to the SPR from dual-energy (DE) computed tomography (CT) data via electron density and effective atomic number (Z eff) calibration (DEEDZ-SPR). This study was conducted to carry out an initial implementation of the DEEDZ-SPR conversion method with a clinical treatment planning system (TPS; VQA, Hitachi Ltd., Tokyo) for proton beam therapy. Consequently, this paper presents a proton therapy plan for an anthropomorphic phantom to evaluate the stability of the dose calculations obtained by the DEEDZ-SPR conversion against the variation of the calibration phantom size. Dual-energy x-ray CT images were acquired using a dual-source CT (DSCT) scanner. A single-energy CT (SECT) scan using the same DSCT scanner was also performed to compare the DEEDZ-SPR conversion with the SECT-based SPR (SECT-SPR) conversion. The scanner-specific parameters necessary for the SPR calibration were obtained from the CT images of tissue substitutes in a calibration phantom. Two calibration phantoms with different sizes (a 33 cm diameter phantom and an 18 cm diameter phantom) were used for the SPR calibrations to investigate the beam-hardening effect on dosimetric uncertainties. Each set of calibrated SPR data was applied to the proton therapy plan designed using the VQA TPS with a pencil beam algorithm for the anthropomorphic phantom. The treatment plans with the SECT-SPR conversion exhibited discrepancies between the dose distributions and the dose-volume histograms (DVHs) of the 33 cm and 18 cm phantom calibrations. In contrast, the corresponding dose distributions and the DVHs obtained using the DEEDZ-SPR conversion method coincided almost perfectly with each other. The DEEDZ-SPR conversion appears to be a promising method for providing proton dose plans that are stable against the size variations of the calibration phantom and the patient.
• Quantitative analysis of treatments using real-time image gated spot-scanning with synchrotron-based proton beam therapy system log data.

  Takaaki Yoshimura, Shinichi Shimizu, Takayuki Hashimoto, Kentaro Nishioka, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Taeko Matsuura, Seishin Takao, Masaya Tamura, Sodai Tanaka, Yoichi M Ito, Yuto Matsuo, Hiroshi Tamura, Kenji Horita, Kikuo Umegaki, Hiroki Shirato

  Journal of applied clinical medical physics 21 12 10 - 19 2020年12月 

  A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.
• Normal Tissue Complication Probability for Hematologic and Gastrointestinal Toxicity in Postoperative Whole Pelvic Radiotherapy for Gynecologic Malignancies using Intensity Modulated Proton Therapy with Robust Optimization

  T. Yoshimura, R. Yamada, R. Kinoshita, H. Tamura, T. Matsuura, S. Takao, M. Tamura, S. Tanaka, N. Nagae, K. Kobashi, H. Aoyama, S. Shimizu

  International Journal of Radiation Oncology*Biology*Physics 108 3 e494 - e494 2020年11月
• On-line range verification for proton beam therapy using spherical ionoacoustic waves with resonant frequency

  Taisuke Takayanagi, Tomoki Uesaka, Yuta Nakamura, Mehmet Burcin Unlu, Yasutoshi Kuriyama, Tomonori Uesugi, Yoshihiro Ishi, Nobuki Kudo, Masanori Kobayashi, Kikuo Umegaki, Satoshi Tomioka, Taeko Matsuura

  Scientific Reports 10 1 20385 - 20385 2020年11月 [査読有り]
   

  In contrast to conventional X-ray therapy, proton beam therapy (PBT) can confine radiation doses to tumours because of the presence of the Bragg peak. However, the precision of the treatment is currently limited by the uncertainty in the beam range. Recently, a unique range verification methodology has been proposed based on simulation studies that exploit spherical ionoacoustic waves with resonant frequency (SPIREs). SPIREs are emitted from spherical gold markers in tumours initially introduced for accurate patient positioning when the proton beam is injected. These waves have a remarkable property: their amplitude is linearly correlated with the residual beam range at the marker position. Here, we present proof-of-principle experiments using short-pulsed proton beams at the clinical dose to demonstrate the feasibility of using SPIREs for beam-range verification with submillimetre accuracy. These results should substantially contribute to reducing the range uncertainty in future PBT applications.
• The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters.

  Koki Kasamatsu, Taeko Matsuura, Sodai Tanaka, Seishin Takao, Naoki Miyamoto, Jin-Min Nam, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki

  Medical physics 47 9 4644 - 4655 2020年07月11日 [査読有り][通常論文]
   

  PURPOSE: The purpose of this study is to evaluate the sub-lethal damage (SLD) repair effect in prolonged proton irradiation using the biophysical model with various cell-specific parameters of (α/β)x and T1/2 (repair half time). At present, most of the model-based studies on protons have focused on acute radiation, neglecting the reduction in biological effectiveness due to SLD repair during the delivery of radiation. Nevertheless, the dose-rate dependency of biological effectiveness may become more important as advanced treatment techniques, such as hypofractionation and respiratory gating, come into clinical practice, as these techniques sometimes require long treatment times. Also, while previous research using the biophysical model revealed a large repair effect with a high physical dose, the dependence of the repair effect on cell-specific parameters has not been evaluated systematically. METHODS: Biological dose (relative biological effectiveness (RBE) × physical dose) calculation with repair included was carried out using the linear energy transfer (LET)-dependent linear-quadratic (LQ) model combined with the theory of dual radiation action (TDRA). First, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the TDRA. Using the LQ model, the decrease in biological dose due to SLD repair was systematically evaluated for spread-out Bragg peak (SOBP) irradiation in a water phantom with the possible ranges of both (α/β)x and repair parameters ((α/β)x = 1-15 Gy, T1/2 = 0-90 min). Then, to consider more realistic irradiation conditions, clinical cases of prostate, liver, and lung tumors were examined with the cell-specific parameters for each tumor obtained from the literature. Biological D99% and biological dose homogeneity coefficient (HC) were calculated for the clinical target volumes (CTVs), assuming dose-rate structures with a total irradiation time of 0-60 min. RESULTS: The differences in the cell-specific parameters resulted in considerable variation in the repair effect. The biological dose reduction found at the center of the SOBP with 30 min of continuous irradiation varied from 1.13% to 14.4% with a T1/2 range of 1-90 min when (α/β)x is fixed as 10 Gy. It varied from 2.3% to 6.8% with an (α/β)x range of 1-15 Gy for a fixed value of T1/2 = 30 min. The decrease in biological D99% per 10 min was 2.6, 1.2, and 3.0% for the prostate, liver, and lung tumor cases, respectively. The value of the biological D99% reduction was neither in the order of (α/β)x nor prescribed dose, but both comparably contributed to the repair effect. The variation of HC was within the range of 0.5% for all cases; therefore, the dose distribution was not distorted. CONCLUSION: The reduction in biological dose caused by the SLD repair largely depends on the cell-specific parameters in addition to the physical dose. The parameters should be considered carefully in the evaluation of the repair effect in prolonged proton irradiation.
• Difference in LET-based biological doses between IMPT optimization techniques: Robust and PTV-based optimizations.

  Shusuke Hirayama, Taeko Matsuura, Koichi Yasuda, Seishin Takao, Takaaki Fujii, Naoki Miyamoto, Kikuo Umegaki, Shinichi Shimizu

  Journal of applied clinical medical physics 21 4 42 - 50 2020年04月 [査読有り]
   

  PURPOSE: While a large amount of experimental data suggest that the proton relative biological effectiveness (RBE) varies with both physical and biological parameters, current commercial treatment planning systems (TPS) use the constant RBE instead of variable RBE models, neglecting the dependence of RBE on the linear energy transfer (LET). To conduct as accurate a clinical evaluation as possible in this circumstance, it is desirable that the dosimetric parameters derived by TPS ( D RBE = 1.1 ) are close to the "true" values derived with the variable RBE models ( D v RBE ). As such, in this study, the closeness of D RBE = 1.1 to D v RBE was compared between planning target volume (PTV)-based and robust plans. METHODS: Intensity-modulated proton therapy (IMPT) treatment plans for two Radiation Therapy Oncology Group (RTOG) phantom cases and four nasopharyngeal cases were created using the PTV-based and robust optimizations, under the assumption of a constant RBE of 1.1. First, the physical dose and dose-averaged LET (LETd ) distributions were obtained using the analytical calculation method, based on the pencil beam algorithm. Next, D v RBE was calculated using three different RBE models. The deviation of D v RBE from D RBE = 1.1 was evaluated with D99 and Dmax , which have been used as the evaluation indices for clinical target volume (CTV) and organs at risk (OARs), respectively. The influence of the distance between the OAR and CTV on the results was also investigated. As a measure of distance, the closest distance and the overlapped volume histogram were used for the RTOG phantom and nasopharyngeal cases, respectively. RESULTS: As for the OAR, the deviations of D max v RBE from D max RBE = 1.1 were always smaller in robust plans than in PTV-based plans in all RBE models. The deviation would tend to increase as the OAR was located closer to the CTV in both optimization techniques. As for the CTV, the deviations of D 99 v RBE from D 99 RBE = 1.1 were comparable between the two optimization techniques, regardless of the distance between the CTV and the OAR. CONCLUSION: Robust optimization was found to be more favorable than PTV-based optimization in that the results presented by TPS were closer to the "true" values and that the clinical evaluation based on TPS was more reliable.
• Difference in LET-based biological doses between IMPT optimization techniques: robust and PTV-based optimizations

  S. Hirayama, T. Matsuura, K. Yasuda, S. Takao, T. Fujii, N. Miyamoto, K. Umegaki, S. Shimizu

  J. Appl. Clin. Med. Phys. 2020年03月 [査読有り][通常論文]
  
• Dynamic gating window technique for the reduction of dosimetric error in respiratory-gated spot-scanning particle therapy: An initial phantom study using patient tumor trajectory data.

  Naoki Miyamoto, Kouhei Yokokawa, Seishin Takao, Taeko Matsuura, Sodai Tanaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki

  Journal of applied clinical medical physics 21 4 13 - 21 2020年02月18日 [査読有り][通常論文]
   

  Spot-scanning particle therapy possesses advantages, such as high conformity to the target and efficient energy utilization compared with those of the passive scattering irradiation technique. However, this irradiation technique is sensitive to target motion. In the current clinical situation, some motion management techniques, such as respiratory-gated irradiation, which uses an external or internal surrogate, have been clinically applied. In surrogate-based gating, the size of the gating window is fixed during the treatment in the current treatment system. In this study, we propose a dynamic gating window technique, which optimizes the size of gating window for each spot by considering a possible dosimetric error. The effectiveness of the dynamic gating window technique was evaluated by simulating irradiation using a moving target in a water phantom. In dosimetric characteristics comparison, the dynamic gating window technique exhibited better performance in all evaluation volumes with different effective depths compared with that of the fixed gate approach. The variation of dosimetric characteristics according to the target depth was small in dynamic gate compared to fixed gate. These results suggest that the dynamic gating window technique can maintain an acceptable dose distribution regardless of the target depth. The overall gating efficiency of the dynamic gate was approximately equal or greater than that of the fixed gating window. In dynamic gate, as the target depth becomes shallower, the gating efficiency will be reduced, although dosimetric characteristics will be maintained regardless of the target depth. The results of this study suggest that the proposed gating technique may potentially improve the dose distribution. However, additional evaluations should be undertaken in the future to determine clinical applicability by assuming the specifications of the treatment system and clinical situation.
• OC-078: Development of Gated Proton Imaging System for Moving Target

  S. Tanaka, N. Miyamoto, T. Nishio, T. Yoshimura, S. Takao, Y. Matsuo, S. Shimizu, H. Shirato, T. Matsuura

  Radiotherapy and Oncology 141 S32 - S33 2019年12月
• Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.

  Yoshimura T, Shimizu S, Hashimoto T, Nishioka K, Katoh N, Inoue T, Taguchi H, Yasuda K, Matsuura T, Takao S, Tamura M, Ito YM, Matsuo Y, Tamura H, Horita K, Umegaki K, Shirato H

  Journal of applied clinical medical physics 21 2 38 - 49 2019年12月 [査読有り][通常論文]
   

  We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.
• The Potential Benefit of Adaptive Intensity Modulated Proton Therapy in Nasopharyngeal Carcinoma: Planning Comparison Study

  H. Minatogawa, K. Yasuda, T. Matsuura, R. Onimaru, T. Yoshimura, S. Takao, Y. Matsuo, Y. Dekura, R. Suzuki, M. Tamura, N. Miyamoto, S. Shimizu, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 105 1 E394 - E394 2019年09月
• Initial Clinical Outcomes of Real-Time-Image Gated Spot-Scanning Proton Beam Therapy for Hepatocellular Carcinomas

  N. Katoh, Y. Uchinami, D. Abo, S. Takao, T. Inoue, H. Taguchi, R. Morita, T. Soyama, T. Hashimoto, R. Onimaru, A. Prayongrat, M. Tamura, T. Matsuura, S. Shimizu, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 105 1 E222 - E223 2019年09月
• Quantitative evaluation of image recognition performance of fiducial markers in real-time tumor-tracking radiation therapy.

  Miyamoto N, Maeda K, Abo D, Morita R, Takao S, Matsuura T, Katoh N, Umegaki K, Shimizu S, Shirato H

  Physica Medica 65 33 - 36 2019年08月 [査読有り][通常論文]
  
• Clinical experience of craniospinal intensity-modulated spot-scanning proton therapy using large fields for central nervous system medulloblastomas and germ cell tumors in children, adolescents, and young adults

  Takayuki Hashimoto, Shinichi Shimizu, Seishin Takao, Shunsuke Terasaka, Akihiro Iguchi, Hiroyuki Kobayashi, Takashi Mori, Takaaki Yoshimura, Yuto Matsuo, Masaya Tamura, Taeko Matsuura, Yoichi M. Ito, Rikiya Onimaru, Hiroki Shirato

  Journal of radiation research 60 4 527 - 537 2019年07月01日 [査読有り][通常論文]
   

  © The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-body-sparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s ± 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.
• Physical and biological impacts of collimator-scattered protons in spot-scanning proton therapy.

  Ueno K, Matsuura T, Hirayama S, Takao S, Ueda H, Matsuo Y, Yoshimura T, Umegaki K

  Journal of applied clinical medical physics 20 7 48 - 57 2019年07月 [査読有り][通常論文]
  
• A novel range-verification method using ionoacoustic wave generated from spherical gold markers for particle-beam therapy: a simulation study.

  Takayanagi T, Uesaka T, Kitaoka M, Unlu MB, Umegaki K, Shirato H, Xing L, Matsuura T

  Scientific reports 9 1 4011  2019年03月 [査読有り][通常論文]
  
• A Literature Review of Proton Beam Therapy for Prostate Cancer in Japan.

  Hoshina RM, Matsuura T, Umegaki K, Shimizu S

  Journal of clinical medicine 8 1 2019年01月 [査読有り][通常論文]
  
• Intensity-Modulated Proton Therapy with Dose Painting based on Hypoxia Imaging for Nasopharyngeal Cancer

  K. Yasuda, S. Takao, Y. Matsuo, T. Yoshimura, M. Tamura, H. Minatogawa, Y. Dekura, T. Matsuura, R. Onimaru, T. Shiga, S. Shimizu, K. Umegaki, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 102 3 e378 - e378 2018年11月
• Analysis of Beam Delivery Times and Dose Rates for the Treatment of Mobile Tumors Using Real Time Image Gated Spot-Scanning Proton Beam Therapy

  S. Shimizu, T. Yoshimura, N. Katoh, T. Inoue, T. Hashimoto, K. Nishioka, S. Takao, T. Matsuura, N. Miyamoto, Y.M. Ito, K. Umegaki, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 102 3 S182 - S183 2018年11月
• Investigation of energy absorption by clustered gold nanoparticles

  Jihun Kwon, Kenneth Sutherland, Anastasia Makarova, Taeko Matsuura, Takayuki Hashimoto, Hao Peng, Toshiyuki Toshito, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu

  Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms 429 34 - 41 2018年08月15日 [査読有り][通常論文]
   

  © 2018 Elsevier B.V. The utilization of gold nanoparticles (GNPs) as a radiation sensitizer has received broad attention. Although GNPs form clusters in living cells, most previous simulation studies have assumed a homogeneous distribution of GNPs. In this study, a GNP cluster was constructed for simulations and the impact of cluster formation on dose enhancement was examined. Energy absorption by the GNPs was compared between clustered and homogeneous distributions for several different GNP concentrations and diameters under 100 keV X-ray irradiations. Our simulations showed that clusters more efficiently absorbed the secondary electrons and photons produced by GNPs themselves. Furthermore, the impact of cluster formation on dose enhancement was more significant for smaller GNPs and higher concentrations. Our results suggest that previous simulations assuming a homogeneous GNP distribution have overestimated the dose enhancement, especially for smaller GNPs and higher concentrations. These findings should guide the selection of GNP size and concentration for effectively optimizing dose enhancement in future studies.
• An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

  Hirayama S, Matsuura T, Ueda H, Fujii Y, Fujii T, Takao S, Miyamoto N, Shimizu S, Fujimoto R, Umegaki K, Shirato H

  Medical physics 45 7 3404 - 3416 2018年07月 [査読有り][通常論文]
   

  PURPOSE: To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LETd ) is required. In this study, we have developed the analytical LETd calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. METHODS: In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LETd value for the lateral distribution of a pencil beam, the actual LETd increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LETd behavior, we have assumed that the LETs of primary and halo components can take different values (LETp and LEThalo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LETd distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LETd distributions and mean LETd (LETd,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. RESULTS: In the homogeneous phantom, the LETd profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LETd profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LETd,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/μm in homogeneous phantoms and 0.08 keV/μm in patient geometries under all tested conditions, respectively. CONCLUSIONS: We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LETd was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs.
• Theoretical analysis of angular distribution of scattering in nozzle components using a response-function method for proton spot-scanning therapy

  Hideaki Ueda, Michihiro Furusaka, Taeko Matsuura, Shusuke Hirayama, Kikuo Umegaki

  Physics in Medicine and Biology 63 3 035005  2018年02月01日 [査読有り][通常論文]
   

  In spot-scanning proton therapy, highly precise beam control is required in the treatment nozzle such that the proton beam does not spread out during transportation by restraining the divergence of the beam angle and spot size, simultaneously. In order to evaluate the beam-broadening behaviour induced by passing through the various nozzle components, we have developed a new method to calculate the angular divergence profile of a proton beam in the nozzle. The angular divergence of the proton beam for each nozzle component is calculated by the Monte Carlo simulation code, Geant4, assuming that the initial beam has no divergence. The angular divergence profiles generated in the various nozzle components are then fitted by the analytic function formula with triple Gaussian distributions. The fitted profiles can be treated like analytic response functions and the angular divergence profile in the nozzle can be easily and systematically calculated by using a convolution theorem. The beam-broadening behaviour during transportation in the nozzle is carefully evaluated. The beam profiles are well-characterized by the proposed angular divergence analysis, i.e. triple Gaussian profile analysis. The primary Gaussian part of the beam profile is mainly generated by air and dose monitors with plate electrode components. The secondary and tertiary Gaussian parts are so-called wide-angle scattering and generated mainly by spot-position and profile monitors with metal window and wire components. The scattering of the nozzle component can be analysed using the proposed response function method for the angular distribution. Multiple convolved angular scattering can be determined from the response function of the individual nozzle components. The angular distribution from small to large angle regions can then be quantitatively evaluated by the proposed method. The method is quite simple and generalized, and is a straightforward way to understand the nozzle and component characteristics related to the beam-broadening behaviour.
• A simulation study on the dosimetric benefit of real-time motion compensation in spot-scanning proton therapy for prostate

  Yusuke Fujii, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Takaaki Fujii, Naoki Miyamoto, Kikuo Umegaki, Kentaro Nishioka, Shinichi Shimizu, Hiroki Shirato

  JOURNAL OF RADIATION RESEARCH 58 4 591 - 597 2017年07月 [査読有り][通常論文]
   

  For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique. For each scenario, dose distributions were simulated using the CT images of nine prostate cancer patients. Treatment plans were generated using a single-field proton beam with 3-mm and 6-mm lateral margins. During beam delivery, the prostate was assumed to move by 5 mm in four directions that were perpendicular to the beam direction at one of three separate timings (i.e. after the completion of the first, second and third quartiles of the total delivery of spot irradiation). Using a 3-mm margin and second quartile motion timing, the averaged values for Delta D-99, Delta D-95, Delta D-5 and D5-95 were 5.1%, 3.3%, 3.6% and 9.0%, respectively, for Scenario (i) and 2.1%, 1.5%, 0.5% and 4.1%, respectively, for Scenario (ii). The margin expansion from 3 mm to 6 mm reduced the size of Delta D-99, Delta D-95, Delta D-5 and D5-95 only with Scenario (i). These results indicate that patient positioning during beam delivery is an effective way to obtain better target coverage and uniformity while reducing the target margin when the prostate moves during irradiation.
• Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study.

  Kanehira T, Matsuura T, Takao S, Matsuzaki Y, Fujii Y, Fujii T, Ito YM, Miyamoto N, Inoue T, Katoh N, Shimizu S, Umegaki K, Shirato H

  International journal of radiation oncology, biology, physics 97 1 173 - 181 2017年01月 [査読有り][通常論文]
   

  Purpose: To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW). Methods and Materials: A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of +/- 1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 > 95% and D5 to D95 < 5%, V20 for the normal lung, and treatment times were evaluated. Results: Gating windows <= +/- 2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs >= +/- 3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs >= +/- 4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the +/- 1-mm GW, but less than 226 seconds (292 seconds) for the +/- 2-mm GW. The maximum increased considerably at +/- 1-mm GW. Conclusion: Real-time-image gated proton beam therapy with a GW of +/- 2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time. (C) 2016 Elsevier Inc. All rights reserved.
• A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-β-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam.

  Maeda K, Yasui H, Yamamori T, Matsuura T, Takao S, Suzuki M, Matsuda A, Inanami O, Shirato H

  PloS one 11 11 e0166848  2016年11月01日 [査読有り][通常論文]
   

  The effect of 1-(3-C-ethynyl-innodatabeta-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton-induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair. This study demonstrated that ECyd enhances proton-induced cell killing at all positions of SOBP, except for the distal region and minimizes the site-dependent differences in RBE within SOBP. Thus, ECyd is a unique radiosensitizer for proton therapy that may be useful because it levels the biological dose within SOBP, which improves tumor control and reduces the risk of adverse effects at the distal edge of SOBP.
• NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies – A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT)

  Takaaki Yoshimura, Rumiko Kinoshita, Shunsuke Onodera, Chie Toramatsu, Ryusuke Suzuki, Yoichi M. Ito, Seishin Takao, Taeko Matsuura, Yuka Matsuzaki, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu

  Physica Medica 32 9 1095 - 1102 2016年09月01日 [査読有り][通常論文]
   

  Purpose This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). Methods and materials The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. Results The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 ± 0.01 and 0.19 ± 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 ± 0.01 and 0.96 ± 0.02, p = 0.3177, and HI = 1.24 ± 0.11 and 1.27 ± 0.05, p = 0.8473, respectively). Conclusion The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT.
• Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique

  Takahiro Yamada, Naoki Miyamoto, Taeko Matsuura, Seishin Takao, Yusuke Fujii, Yuka Matsuzaki, Hidenori Koyano, Masumi Umezawa, Hideaki Nihongi, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki

  Physica Medica 32 7 932 - 937 2016年07月01日 [査読有り][通常論文]
   

  Purpose To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. Methods A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, Tw. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable Tw value. 271 gate signal data sets from 58 patients were used for the simulation. Results The highest mean efficiency 0.52 was obtained in TW = 0.2 s. The irradiation efficiency was approximately 21% higher than at TW = 0 s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the TW value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at Tw = 0.2 s, 4.48 GyE irradiation was completed within 250 s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420 s. Conclusions The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time.
• Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro

  Kenichiro Maeda, Hironobu Yasui, Taeko Matsuura, Tohru Yamamori, Motofumi Suzuki, Masaki Nagane, Jin-Min Nam, Osamu Inanami, Hiroki Shirato

  JOURNAL OF RADIATION RESEARCH 57 3 307 - 311 2016年06月 [査読有り][通常論文]
   

  Variations in relative biological effectiveness (RBE) from a fixed value of 1.1 are critical in proton beam therapy. To date, studies estimating RBE at multiple positions relative to the spread-out Bragg peak (SOBP) have been predominantly performed using passive scattering methods, and limited data are available for spot-scanning beams. Thus, to investigate the RBE of spot-scanning beams, Chinese hamster fibroblast V79 cells were irradiated using the beam line at the Hokkaido University Hospital Proton Therapy Center. Cells were placed at six different depths, including the entrance of the proton beam and the proximal and distal part of the SOBP. Surviving cell fractions were analyzed using colony formation assay, and cell survival curves were obtained by the curve fitted using a linear-quadratic model. RBE10 and RBE37 were 1.15 and 1.21 at the center of the SOBP, respectively. In contrast, the distal region showed higher RBE values (1.50 for RBE10 and 1.85 for RBE37). These results are in line with those of previous studies conducted using passive scattering proton beams. Taken together, these data strongly suggest that variations in RBE should be considered during treatment planning for spot-scanning beams as well as for passive scattering proton beams.
• Development and evaluation of a short-range applicator for treating superficial moving tumors with respiratory-gated spot-scanning proton therapy using real-time image guidance

  Taeko Matsuura, Yusuke Fujii, Seishin Takao, Takahiro Yamada, Yuka Matsuzaki, Naoki Miyamoto, Taisuke Takayanagi, Shinichiro Fujitaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki

  PHYSICS IN MEDICINE AND BIOLOGY 61 4 1515 - 1531 2016年02月 [査読有り][通常論文]
   

  Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.
• Intrafractional baseline shift or drift of lung tumor motion during gated radiation therapy with a real-time tumor-tracking system a preliminary version of this study was presented at the 55th Annual Meeting of the American Society for Radiation Oncology, September 22-25, 2013, Atlanta, GA.

  Seishin Takao, Naoki Miyamoto, Taeko Matsuura, Rikiya Onimaru, Norio Katoh, Tetsuya Inoue, Kenneth Lee Sutherland, Ryusuke Suzuki, Hiroki Shirato, Shinichi Shimizu

  International Journal of Radiation Oncology Biology Physics 94 1 172 - 180 2016年01月01日 [査読有り][通常論文]
   

  © 2016 Elsevier Inc. Purpose To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. Methods and Materials Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. Results The average change in position of the treatment couch during the treatment time was 0.45 ± 2.23 mm (mean ± standard deviation), -1.65 ± 5.95 mm, and 1.50 ± 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. Conclusions Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers.
• Proton-induced x-ray fluorescence CT imaging

  Magdalena Bazalova-Carter, Moiz Ahmad, Taeko Matsuura, Seishin Takao, Yuto Matsuo, Rebecca Fahrig, Hiroki Shirato, Kikuo Umegaki, Lei Xing

  MEDICAL PHYSICS 42 2 900 - 907 2015年02月 [査読有り][通常論文]
   

  Purpose: To demonstrate the feasibility of proton-induced x-ray fluorescence CT (pXFCT) imaging of gold in a small animal sized object by means of experiments and Monte Carlo (MC) simulations. Methods: First, proton-induced gold x-ray fluorescence (pXRF) was measured as a function of gold concentration. Vials of 2.2 cm in diameter filled with 0%-5% Au solutions were irradiated with a 220 MeV proton beam and x-ray fluorescence induced by the interaction of protons, and Au was detected with a 3x3 mm(2) CdTe detector placed at 90 degrees. with respect to the incident proton beam at a distance of 45 cm from the vials. Second, a 7-cm diameter water phantom containing three 2.2-diameter vials with 3%-5% Au solutions was imaged with a 7-mm FWHM 220 MeV proton beam in a first generation CT scanning geometry. X-rays scattered perpendicular to the incident proton beam were acquired with the CdTe detector placed at 45 cm from the phantom positioned on a translation/ rotation stage. Twenty one translational steps spaced by 3 mm at each of 36 projection angles spaced by 10. were acquired, and pXFCT images of the phantom were reconstructed with filtered back projection. A simplified geometry of the experimental data acquisition setup was modeled with the MC TOPAS code, and simulation results were compared to the experimental data. Results: A linear relationship between gold pXRF and gold concentration was observed in both experimental and MC simulation data (R-2 > 0.99). All Au vials were apparent in the experimental and simulated pXFCT images. Specifically, the 3% Au vial was detectable in the experimental [contrast-to-noise ratio (CNR) = 5.8] and simulated (CNR = 11.5) pXFCT image. Due to fluorescence x-ray attenuation in the higher concentration vials, the 4% and 5% Au contrast were underestimated by 10% and 15%, respectively, in both the experimental and simulated pXFCT images. Conclusions: Proton-induced x-ray fluorescence CT imaging of 3%-5% gold solutions in a small animal sized water phantom has been demonstrated for the first time by means of experiments and MC simulations. (C) 2015 American Association of Physicists in Medicine.
• Development of a wavelength-separated type scintillator with optical fiber (SOF) dosimeter to compensate for the Cerenkov radiation effect

  Masayori Ishikawa, Naomi Nagase, Taeko Matsuura, Junichi Hiratsuka, Ryusuke Suzuki, Naoki Miyamoto, Kenneth Lee Sutherland, Katsuhisa Fujita, Hiroki Shirato

  Journal of Radiation Research 56 2 372 - 381 2015年 [査読有り][通常論文]
   

  The scintillator with optical fiber (SOF) dosimeter consists of a miniature scintillator mounted on the tip of an optical fiber. The scintillator of the current SOF dosimeter is a 1-mm diameter hemisphere. For a scintillation dosimeter coupled with an optical fiber, measurement accuracy is influenced by signals due to Cerenkov radiation in the optical fiber. We have implemented a spectral filtering technique for compensating for the Cerenkov radiation effect specifically for our plastic scintillator-based dosimeter, using a wavelength-separated counting method. A dichroic mirror was used for separating input light signals. Individual signal counting was performed for high- and low-wavelength light signals. To confirm the accuracy, measurements with various amounts of Cerenkov radiation were performed by changing the incident direction while keeping the Ir-192 source-to-dosimeter distance constant, resulting in a fluctuation of < 5%. Optical fiber bending was also addressed no bending effect was observed for our wavelength-separated SOF dosimeter.
• 【放射線治療活用BOOK 2014】 (DIVISION-3)これからの放射線治療の展望 最新の動体追跡放射線治療装置

  宮本 直樹, 石川 正純, 松浦 妙子, 井上 哲也, 加藤 徳雄, 清水 伸一, 鬼丸 力也, 梅垣 菊男, 白土 博樹

  Rad Fan 12 15 75 - 77 (株)メディカルアイ 2014年12月 [査読無し][通常論文]
   

  動体追跡法は、日本が世界に先駆けて実現してきた治療法であり、多くの実績を有する。本稿では、最新の迎撃照射型動体追跡装置として、島津製作所からリリースされたX線治療用動体追跡装置「SyncTraX」、日立製作所からリリースされた動体追跡陽子線スポットスキャニングシステム「PROBEAT-RT」について、その特徴と利点を紹介する。(著者抄録)
• Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study

  Yoshitaka Matsumoto, Taeko Matsuura, Mami Wada, Yusuke Egashira, Teiji Nishio, Yoshiya Furusawa

  JOURNAL OF RADIATION RESEARCH 55 4 816 - 822 2014年07月 [査読有り][通常論文]
   

  In the clinic, the relative biological effectiveness (RBE) value of 1.1 has usually been used in relation to the whole depth of the spread-out Bragg-peak (SOBP) of proton beams. The aim of this study was to confirm the actual biological effect in the SOBP at the very distal end of clinical proton beams using an in vitro cell system. A human salivary gland tumor cell line, HSG, was irradiated with clinical proton beams (accelerated by 190 MeV/u) and examined at different depths in the distal part and the center of the SOBP. Surviving fractions were analyzed with the colony formation assay. Cell survival curves and the survival parameters were obtained by fitting with the linear-quadratic (LQ) model. The RBE at each depth of the proton SOBP compared with that for X-rays was calculated by the biological equivalent dose, and the biological dose distribution was calculated from the RBE and the absorbed dose at each position. Although the physical dose distribution was flat in the SOBP, the RBE values calculated by the equivalent dose were significantly higher (up to 1.56 times) at the distal end than at the center of the SOBP. Additionally, the range of the isoeffective dose was extended beyond the range of the SOBP (up to 4.1 mm). From a clinical point of view, this may cause unexpected side effects to normal tissues at the distal position of the beam. It is important that the beam design and treatment planning take into consideration the biological dose distribution.
• A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor-tracking radiotherapy system

  Naoki Miyamoto, Masayori Ishikawa, Kenneth Sutherland, Ryusuke Suzuki, Taeko Matsuura, Chie Toramatsu, Seishin Takao, Hideaki Nihongi, Shinichi Shimizu, Kikuo Umegaki, Hiroki Shirato

  Journal of Radiation Research 56 1 186 - 196 2014年05月15日 [査読有り][通常論文]
   

  In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within ±2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction.
• A Proton Beam Therapy System Dedicated to Spot-Scanning Increases Accuracy with Moving Tumors by Real-Time Imaging and Gating and Reduces Equipment Size

  Shinichi Shimizu, Naoki Miyamoto, Taeko Matsuura, Yusuke Fujii, Masumi Umezawa, Kikuo Umegaki, Kazuo Hiramoto, Hiroki Shirato

  PLOS ONE 9 4 94971  2014年04月 [査読有り][通常論文]
   

  Purpose: A proton beam therapy (PBT) system has been designed which dedicates to spot-scanning and has a gating function employing the fluoroscopy-based real-time-imaging of internal fiducial markers near tumors. The dose distribution and treatment time of the newly designed real-time-image gated, spot-scanning proton beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam therapy (FBPT) in a simulation. Materials and Methods: In-house simulation tools and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating the dose distribution and treatment time. Simulations were performed for 48 motion parameters (including 8 respiratory patterns and 6 initial breathing timings) on CT data from two patients, A and B, with hepatocellular carcinoma and with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were derived from the actual trajectory of internal fiducial markers taken in X-ray real-time tumor-tracking radiotherapy (RTRT). Results: With FBPT, 9/48 motion parameters achieved the criteria of successful delivery for patient A and 0/48 for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the mean liver dose was smaller with RGPT with statistical significance (p<0.001); it decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A and B, respectively. The relative lengthening of treatment time to administer 3 Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s) for patients A and B, respectively. Conclusions: This simulation study demonstrated that the RGPT was able to improve the dose distribution markedly for moving tumors without very large treatment time extension. The proton beam therapy system dedicated to spot-scanning with a gating function for real-time imaging increases accuracy with moving tumors and reduces the physical size, and subsequently the cost of the equipment as well as of the building housing the equipment.
• Preliminary analysis for integration of spot-scanning proton beam therapy and real-time imaging and gating

  S. Shimizu, T. Matsuura, M. Umezawa, K. Hiramoto, N. Miyamoto, K. Umegaki, H. Shirato

  Physica Medica 30 5 555 - 558 2014年 [査読有り][通常論文]
   

  Purpose: Spot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning. Materials and methods: Using log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed. Results/conclusions: Total facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014. © 2014 Associazione Italiana di Fisica Medica.
• Integration of a real-time tumor monitoring system into gated proton spot-scanning beam therapy: An initial phantom study using patient tumor trajectory data

  Taeko Matsuura, Naoki Miyamoto, Shinichi Shimizu, Yusuke Fujii, Masumi Umezawa, Seishin Takao, Hideaki Nihongi, Chie Toramatsu, Kenneth Sutherland, Ryusuke Suzuki, Masayori Ishikawa, Rumiko Kinoshita, Kenichiro Maeda, Kikuo Umegaki, Hiroki Shirato

  MEDICAL PHYSICS 40 7 071729  2013年07月 [査読有り][通常論文]
   

  Purpose: In spot-scanning proton therapy, the interplay effect between tumor motion and beam delivery leads to deterioration of the dose distribution. To mitigate the impact of tumor motion, gating in combination with repainting is one of the most promising methods that have been proposed. This study focused on a synchrotron-based spot-scanning proton therapy system integrated with real-time tumor monitoring. The authors investigated the effectiveness of gating in terms of both the delivered dose distribution and irradiation time by conducting simulations with patients' motion data. The clinically acceptable range of adjustable irradiation control parameters was explored. Also, the relation between the dose error and the characteristics of tumor motion was investigated. Methods: A simulation study was performed using a water phantom. A gated proton beam was irradiated to a clinical target volume (CTV) of 5 x 5 x 5 cm(3), in synchronization with lung cancer patients' tumor trajectory data. With varying parameters of gate width, spot spacing, and delivered dose per spot at one time, both dose uniformity and irradiation time were calculated for 397 tumor trajectory data from 78 patients. In addition, the authors placed an energy absorber upstream of the phantom and varied the thickness to examine the effect of changing the size of the Bragg peak and the number of required energy layers. The parameters with which 95% of the tumor trajectory data fulfill our defined criteria were accepted. Next, correlation coefficients were calculated between the maximum dose error and the tumor motion characteristics that were extracted from the tumor trajectory data. Results: With the assumed CTV, the largest percentage of the data fulfilled the criteria when the gate width was +/- 2 mm. Larger spot spacing was preferred because it increased the number of paintings. With a prescribed dose of 2 Gy, it was difficult to fulfill the criteria for the target with a very small effective depth (the sum of an assumed energy absorber's thickness and the target depth in the phantom) because of the sharpness of the Bragg peak. However, even shallow targets could be successfully irradiated by employing an adequate number of paintings and by placing an energy absorber of sufficient thickness to make the effective target depth more than 12 cm. The authors also observed that motion in the beam direction was the main cause of dose distortion, followed by motion in the lateral plane perpendicular to the scan direction. Conclusions: The results suggested that by properly adjusting irradiation control parameters, gated proton spot-scanning beam therapy can be robust to target motion. This is an important first step toward establishing treatment plans in real patient geometry. (C) 2013 American Association of Physicists in Medicine.
• What is the appropriate size criterion for proton radiotherapy for hepatocellular carcinoma? A dosimetric comparison of spot-scanning proton therapy versus intensity-modulated radiation therapy

  Chie Toramatsu, Norio Katoh, Shinichi Shimizu, Hideaki Nihongi, Taeko Matsuura, Seishin Takao, Naoki Miyamoto, Ryusuke Suzuki, Kenneth Sutherland, Rumiko Kinoshita, Rikiya Onimaru, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato

  Radiation Oncology 8 1 2013年03月05日 [査読有り][通常論文]
   

  Background: We performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD).Methods: A number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm3. Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model.Results: For IMRT the risk of RILD increased drastically between 6.3-7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT.Conclusions: Regarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm. © 2013 Toramatsu et al.; licensee BioMed Central Ltd.
• Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

  Taeko Matsuura, Kenichiro Maeda, Kenneth Sutherland, Taisuke Takayanagi, Shinichi Shimizu, Seishin Takao, Naoki Miyamoto, Hideaki Nihongi, Chie Toramatsu, Yoshihiko Nagamine, Rintaro Fujimoto, Ryusuke Suzuki, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato

  MEDICAL PHYSICS 39 9 5584 - 5591 2012年09月 [査読有り][通常論文]
   

  Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). Methods: A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCPr) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, alpha/beta values of 1.5, 3, and 10 Gy (RBE) were considered. Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all alpha/beta values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCPr by less than 3%. This is especially true when multiple (two or three) markers are used for alignment of a patient. Conclusions: It is recommended that 1.5-mm markers be used to avoid the reduction of TCP as well as to spare the surrounding critical organs, as long as the markers are visible on x-ray fluoroscopy. When 2-mm markers are implanted, more than two fields should be used and the markers should not be placed close to the distal edge of any of the beams. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4745558]
• In-treatment 4D cone-beam CT with image-based respiratory phase recognition.

  Satoshi Kida, Yoshitaka Masutani, Hideomi Yamashita, Toshikazu Imae, Taeko Matsuura, Naoya Saotome, Kuni Ohtomo, Keiichi Nakagawa, Akihiro Haga

  Radiological physics and technology 5 2 138 - 47 2012年07月 [査読有り][通常論文]
   

  The use of respiration-correlated cone-beam computed tomography (4D-CBCT) appears to be crucial for implementing precise radiation therapy of lung cancer patients. The reconstruction of 4D-CBCT images requires a respiratory phase. In this paper, we propose a novel method based on an image-based phase recognition technique using normalized cross correlation (NCC). We constructed the respiratory phase by searching for a region in an adjacent projection that achieves the maximum correlation with a region in a reference projection along the cranio-caudal direction. The data on 12 lung cancer patients acquired just prior to treatment and on 3 lung cancer patients acquired during volumetric modulated arc therapy treatment were analyzed in the search for the effective area of cone-beam projection images for performing NCC with 12 combinations of registration area and segment size. The evaluation was done by a "recognition rate" defined as the ratio of the number of peak inhales detected with our method to that detected by eye (manual tracking). The average recognition rate of peak inhale with the most efficient area in the present method was 96.4%. The present method was feasible even when the diaphragm was outside the field of view. With the most efficient area, we reconstructed in-treatment 4D-CBCT by dividing the breathing signal into four phase bins; peak exhale, peak inhale, and two intermediate phases. With in-treatment 4D-CBCT images, it was possible to identify the tumor position and the tumor size in moments of inspiration and expiration, in contrast to in-treatment CBCT reconstructed with all projections.
• Experimental evaluation of a spatial resampling technique to improve the accuracy of pencil-beam dose calculation in proton therapy.

  Yusuke Egashira, Teiji Nishio, Taeko Matsuura, Satoru Kameoka, Mitsuru Uesaka

  Medical physics 39 7 4104 - 14 2012年07月 [査読有り][通常論文]
   

  PURPOSE: In proton therapy, pencil-beam algorithms (PBAs) are the most widely used dose calculation methods. However, the PB calculations that employ one-dimensional density scaling neglect the effects of lateral density heterogeneity on the dose distributions, whereas some particles included in such pencil beams could overextend beyond the interface of the density heterogeneity. We have simplified a pencil-beam redefinition algorithm (PBRA), which was proposed for electron therapy, by a spatial resampling technique toward an application for proton therapy. The purpose of this study is to evaluate the calculation results of the spatial resampling technique in terms of lateral density heterogeneity by comparison with the dose distributions that were measured in heterogeneous slab phantoms. METHODS: The pencil beams are characterized for multiple residual-range (i.e., proton energy) bins. To simplify the PBRA, the given pencil beams are resampled on one or two transport planes, in which smaller sub-beams that are parallel to each other are generated. We addressed the problem of lateral density heterogeneity comparing the calculation results to the dose distributions measured at different depths in heterogeneous slab phantoms using a two-dimensional detector. Two heterogeneity slab phantoms, namely, phantoms A and B, were designed for the measurements and calculations. In phantom A, the heterogeneity slab was placed close to the surface. On the other hand, in phantom B, it was placed close to the Bragg peak in the mono-energetic proton beam. RESULTS: In measurements, lateral dose profiles showed a dose reduction and increment in the vicinity of x = 0 mm in both phantoms at depths z = 142 and 161 mm due to lateral particle disequilibrium. In phantom B, these dose reduction∕increment effects were higher∕lower, respectively, than those in phantom A. This is because a longer distance from the surface to the heterogeneous slab increases the strength of proton scattering. Sub-beams, which were generated from the resampling plane, formed a detouring∕overextending path that was different from that of elemental pencil beams. Therefore, when the spatial resampling was implemented at the surface and immediately upstream of the lateral heterogeneity, the calculation could predict these dose reduction∕increment effects. Without the resampling procedure, these dose reduction∕increment effects could not be predicted in both phantoms owing to the blurring of the pencil beam. We found that the PBA with the spatial resampling technique predicted the dose reduction∕increment at the dose profiles in both phantoms when the sampling plane was defined immediately upstream of the heterogeneous slab. CONCLUSIONS: We have demonstrated the implementation of a spatial resampling technique for pencil-beam calculation to address the problem of lateral density heterogeneity. While further validation is required for clinical use, this study suggests that the spatial resampling technique can make a significant contribution to proton therapy.
• In vivo proton dosimetry using a MOSFET detector in an anthropomorphic phantom with tissue inhomogeneity.

  Ryosuke Kohno, Kenji Hotta, Kana Matsubara, Shie Nishioka, Taeko Matsuura, Mitsuhiko Kawashima

  Journal of applied clinical medical physics 13 2 3699 - 3699 2012年03月08日 [査読有り][通常論文]
   

  When in vivo proton dosimetry is performed with a metal-oxide semiconductor field-effect transistor (MOSFET) detector, the response of the detector depends strongly on the linear energy transfer. The present study reports a practical method to correct the MOSFET response for linear energy transfer dependence by using a simplified Monte Carlo dose calculation method (SMC). A depth-output curve for a mono-energetic proton beam in polyethylene was measured with the MOSFET detector. This curve was used to calculate MOSFET output distributions with the SMC (SMC(MOSFET)). The SMC(MOSFET) output value at an arbitrary point was compared with the value obtained by the conventional SMC(PPIC), which calculates proton dose distributions by using the depth-dose curve determined by a parallel-plate ionization chamber (PPIC). The ratio of the two values was used to calculate the correction factor of the MOSFET response at an arbitrary point. The dose obtained by the MOSFET detector was determined from the product of the correction factor and the MOSFET raw dose. When in vivo proton dosimetry was performed with the MOSFET detector in an anthropomorphic phantom, the corrected MOSFET doses agreed with the SMC(PPIC) results within the measurement error. To our knowledge, this is the first report of successful in vivo proton dosimetry with a MOSFET detector.
• Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

  Ryosuke Kohno, Kenji Hotta, Taeko Matsuura, Kana Matsubara, Shie Nishioka, Teiji Nishio, Mitsuhiko Kawashima, Takashi Ogino

  Journal of applied clinical medical physics 12 2 3431 - 3431 2011年04月04日 [査読有り][通常論文]
   

  We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.
• Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau.

  Taeko Matsuura, Yusuke Egashira, Teiji Nishio, Yoshitaka Matsumoto, Mami Wada, Sachiko Koike, Yoshiya Furusawa, Ryosuke Kohno, Shie Nishioka, Satoru Kameoka, Katsuya Tsuchihara, Mitsuhiko Kawashima, Takashi Ogino

  Medical physics 37 10 5376 - 81 2010年10月 [査読有り][通常論文]
   

  PURPOSE: Respiration-gated irradiation for a moving target requires a longer time to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate (UDR) proton beam, which is 10-100 times higher than that is used in current clinical practice, has been investigated to deliver daily dose in single breath hold duration. The purpose of this study is to investigate the survival curve and relative biological effectiveness (RBE) of such an ultrahigh dose rate proton beam and their linear energy transfer (LET) dependence. METHODS: HSG cells were irradiated by a spatially and temporally uniform proton beam at two different dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau. To study LET dependence, the cells were positioned at the Bragg peak, where the absorbed dose-averaged LET was 3.19 keV/microm, and at the plateau, where it was 0.56 keV/microm. After the cell exposure and colony assay, the measured data were fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10% survival were compared. RESULTS: No significant difference was observed in the survival curves between the two proton dose rates. The ratio of the RBE for CDR/UDR was 0.98 +/- 0.04 at the Bragg peak and 0.96 +/- 0.06 at the plateau. On the other hand, Bragg peak/plateau RBE ratio was 1.15 +/- 0.05 for UDR and 1.18 +/- 0.07 for CDR. CONCLUSIONS: Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required.
• Evaluation of the usefulness of a MOSFET detector in an anthropomorphic phantom for 6-MV photon beam.

  Ryosuke Kohno, Eriko Hirano, Satoshi Kitou, Tomonori Goka, Kana Matsubara, Satoru Kameoka, Taeko Matsuura, Takaki Ariji, Teiji Nishio, Mitsuhiko Kawashima, Takashi Ogino

  Radiological physics and technology 3 2 104 - 12 2010年07月 [査読有り][通常論文]
   

  In order to evaluate the usefulness of a metal oxide-silicon field-effect transistor (MOSFET) detector as a in vivo dosimeter, we performed in vivo dosimetry using the MOSFET detector with an anthropomorphic phantom. We used the RANDO phantom as an anthropomorphic phantom, and dose measurements were carried out in the abdominal, thoracic, and head and neck regions for simple square field sizes of 10 x 10, 5 x 5, and 3 x 3 cm(2) with a 6-MV photon beam. The dose measured by the MOSFET detector was verified by the dose calculations of the superposition (SP) algorithm in the XiO radiotherapy treatment-planning system. In most cases, the measured doses agreed with the results of the SP algorithm within +/-3%. Our results demonstrated the utility of the MOSFET detector for in vivo dosimetry even in the presence of clinical tissue inhomogeneities.
• Improved dose-calculation accuracy in proton treatment planning using a simplified Monte Carlo method verified with three-dimensional measurements in an anthropomorphic phantom.

  Kenji Hotta, Ryosuke Kohno, Yoshihisa Takada, Yousuke Hara, Ryohei Tansho, Takeshi Himukai, Satoru Kameoka, Taeko Matsuura, Teiji Nishio, Takashi Ogino

  Physics in medicine and biology 55 12 3545 - 56 2010年06月21日 [査読有り][通常論文]
   

  Treatment planning for proton tumor therapy requires a fast and accurate dose-calculation method. We have implemented a simplified Monte Carlo (SMC) method in the treatment planning system of the National Cancer Center Hospital East for the double-scattering beam delivery scheme. The SMC method takes into account the scattering effect in materials more accurately than the pencil beam algorithm by tracking individual proton paths. We confirmed that the SMC method reproduced measured dose distributions in a heterogeneous slab phantom better than the pencil beam method. When applied to a complex anthropomorphic phantom, the SMC method reproduced the measured dose distribution well, satisfying an accuracy tolerance of 3 mm and 3% in the gamma index analysis. The SMC method required approximately 30 min to complete the calculation over a target volume of 500 cc, much less than the time required for the full Monte Carlo calculation. The SMC method is a candidate for a practical calculation technique with sufficient accuracy for clinical application.
• WE‐A‐BRA‐05: Proton Ultra High Dose‐Rate Effect on HSG Cell Survival Curve

  T. Matsuura, Y. Egashira, T. Nishio, R. Kohno, S. Kameoka, R. Ohta, K. Matsumura, H. Suzuki, T. Taniyama, T. Toda, T. Shimoju, A. Sakamoto, K. Yamazaki, M. Kawashima, T. Ogino, Y. Matsumoto, M. Wada, Y. Furusawa

  Medical Physics 37 6 3410  2010年 [査読有り][通常論文]
   

  Purpose: One of the important issues that we are facing in the current radiation process is the long treatment time for irradiating protons to the tumor moving with respiration. In order to improve this problem, we are currently developing the highly precise and very short time proton IGRT using the high intensity beam from cyclotron and the real‐time images acquired by two flat panel detectors attached to the gantry. The dose‐rate by using this method will reach 10 to 100 times of the present one. The purpose of this study is to investigate the relative biological effectiveness (RBE) of HSG cell in such an ultra high dose‐rate regime and its LET dependence by using the colony assay method. Material and method: We attached the HSG cells at the bottom of the plastic chamber, and irradiated the spatially and temporally homogeneous proton beam. We used 235MeV proton beams with the different beam current of 10nA and 300nA in order to study the dose‐rate effect. The chamber was molded in a Polyethylene block with a hole which fits tightly to the chamber. It was placed at plateau(1.75, 114Gy/min, yD=0.56keV/ m), then at Bragg‐peak(8, 325Gy/min, yD=3.19keV/ m) to see the LET dependence of RBE at high dose‐rate. Result: There were no significant splits observed in survival curves of HSG cell over the proton dose‐rate. The ratio of RBE at lower dose‐rate to that at higher dose‐rate was 0.98−+0.08 at Bragg‐peak and was 0.96−+0.11 at plateau. On the other hand, the RBE ratio at Bragg‐peak to plateau was 1.13–1.20, which suggests that the position dependence of RBE cannot be neglected. Conclusion: We conclude that in the therapeutic planning of high dose‐rate radiation, the present RBE can be consistently used. Instead, the RBE enhancement toward the Bragg‐peak and beyond should be reconsidered. © 2010, American Association of Physicists in Medicine. All rights reserved.
• Interactions of non-Abelian global strings

  Eiji Nakano, Muneto Nitta, Taeko Matsuura

  Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics 672 1 61 - 64 2009年02月09日 [査読有り][通常論文]
   

  Non-Abelian global strings are expected to form during the chiral phase transition. They have orientational zero modes in the internal space, associated with the vector-like symmetry SU (N)L + R broken in the presence of strings. The interaction among two parallel non-Abelian global strings is derived for general relative orientational zero modes, giving a non-Abelian generalization of the Magnus force. It is shown that when the orientations of the strings are the same, the repulsive force reaches the maximum, whereas when the relative orientation becomes the maximum, no force exists between the strings. For the Abelian case we find a finite volume correction to the known result. The marginal instability of the previously known Abelian η′ strings is discussed. © 2008.
• Non-Abelian strings in high-density QCD: Zero modes and interactions

  Eiji Nakano, Muneto Nitta, Taeko Matsuura

  Physical Review D - Particles, Fields, Gravitation and Cosmology 78 4 2008年08月04日 [査読有り][通常論文]
   

  The most fundamental strings in high-density color superconductivity are the non-Abelian semisuperfluid strings which have color-gauge flux tubes but behave as superfluid vortices in the energetic point of view. We show that in addition to the usual translational zero modes, these vortices have normalizable orientational zero modes in the internal space, associated with the color-flavor locking symmetry broken in the presence of the strings. The interaction among two parallel non-Abelian semisuperfluid strings is derived for general relative orientational zero modes to show the universal repulsion. This implies that the previously known superfluid vortices, formed by spontaneously broken U(1)B, are unstable to decay. Moreover, our result proves the stability of color superconductors in the presence of external color-gauge fields. © 2008 The American Physical Society.
• Non-Abelian strings in hot or dense QCD

  Eiji Nakano, Muneto Nitta, Taeko Matsuura

  Progress of Theoretical Physics Supplement 174 254 - 257 2008年 [査読有り][通常論文]
   

  Different types of non-Abelian vortex-strings appear in dense or hot QCD, both of which possess non-Abelian internal orientation zero modes. We calculate the interaction between them and find the universal repulsion for dense QCD (color superconductivity) and the dependence on the orientations for hot QCD (chirally broken phase). This is a review article based on our papers [E. Nakano, M. Nitta and T. Matsuura, arXiv:0708.4092 arXiv:0708.4096].
• Semisuperfluid strings in high density QCD

  A. P. Balachandran, S. Digal, T. Matsuura

  Physical Review D - Particles, Fields, Gravitation and Cosmology 73 7 2006年 [査読有り][通常論文]
   

  We show that topological semisuperfluid strings exist in the color-flavor locked (CFL) phase of color superconductors. These semisuperfluid strings carry quantized flux of ordinary and color magnetic fields. Away from the core the behavior of the string is that of a superfluid string. Using a Ginzburg-Landau free energy we find the configurations of these strings. These strings can form during the transition from the normal phase to the CFL phase at the core of very dense stars. We discuss an interesting scenario for a network of strings and its evolution at the core of dense stars. © 2006 The American Physical Society.
• Thermal phase transitions and gapless quark spectra in quark matter at high density

  K. Iida, T. Matsuura, M. Tachibana, T. Hatsuda

  Physical Review D - Particles, Fields, Gravitation and Cosmology 71 5 1 - 15 2005年03月01日 [査読有り][通常論文]
   

  Thermal color superconducting phase transitions in three-flavor quark matter at high baryon density are investigated in the Ginzburg-Landau (GL) approach. We constructed the GL potential near the boundary with a normal phase by taking into account nonzero quark masses, electric charge neutrality, and color charge neutrality. We found that the density of states averaged over paired quarks plays a crucial role in determining the phases near the boundary. By performing a weak coupling calculation of the parameters characterizing the GL potential terms of second order in the pairing gap, we show that three successive second-order phase transitions take place as the temperature increases: a modified color-flavor locked phase (ud, ds, and us pairings) → a dSC phase (ud and ds pairings) → an isoscalar pairing phase (ud pairing) → a normal phase (no pairing). The Meissner masses of the gluons and the number of gapless quark modes are also studied analytically in each of these phases. © 2005 The American Physical Society.
• Melting pattern of diquark condensates in quark matter

  K. Iida, T. Matsuura, M. Tachibana, T. Hatsuda

  Physical Review Letters 93 13 1 - 132001 2004年09月24日 [査読有り][通常論文]
   

  Thermal color superconducting phase transitions in high density three-flavor quark matter, in the Ginzburg-Landau approach are discussed. The effects of electric and color change neutrality, nonzero strange quark mass and direct instantons are considered. As shown by the weak coupling calculations, an interplay between the mass and electric neutrality effects near the critical temperature gives rise to three successive second-order phase transitions on increasing temperature. It is found that a d-quark superconducting (dSC) phase is novel in the sense that three out of nine quark quasiparticles are always gapless, while all eight gluons are Meissner screened as in the mCFL phase.
• Ginzburg-Landau approach to color superconductivity

  Kei Iida, Gordon Baym, Taeko Matsuura, Tetsuo Hatsuda

  Progress of Theoretical Physics Supplement 153 230 - 240 2004年 [査読有り][通常論文]
   

  We study, within Ginzburg-Landau theory, the equilibrium properties of a color super-conductor of three-flavor massless quarks near the transition temperature. We first draw the phase diagram in the space of the parameters controlling the thermodynamic-potential terms of fourth order in the pairing gap. Within the color and flavor antitriplet channel with zero total angular momentum, the phase diagram contains the color-flavor locked and two-flavor pairing phases the limit of weak coupling is included in the color-flavor locked phase. The responses of the color-flavor locked and two-flavor condensates to external magnetic fields and rotation are then investigated by calculating the induced supercurrents. In equilibrium, rotation can produce vortices only in the color-flavor locked condensate. We finally discuss the effects of fluctuations in gauge fields and order parameters on the finite temperature phase transition.
• Thermal fluctuations of gauge fields and first order phase transitions in color superconductivity

  Taeko Matsuura, Kei Iida, Tetsuo Hatsuda, Gordon Baym

  Physical Review D - Particles, Fields, Gravitation and Cosmology 69 7 10  2004年 [査読有り][通常論文]
   

  We study the effects of thermal fluctuations of gluons and the diquark pairing field on the superconducting-to-normal state phase transition in a three-flavor color superconductor, using the Ginzburg-Landau free energy. At high baryon densities, where the system is a type I superconductor, gluonic fluctuations, which dominate over diquark fluctuations, induce a cubic term in the Ginzburg-Landau free energy, as well as large corrections to quadratic and quartic terms of the order parameter. The cubic term leads to a relatively strong first order transition, in contrast with the very weak first order transitions in metallic type I superconductors. The strength of the first order transition decreases with increasing baryon density. In addition gluonic fluctuations lower the critical temperature of the first order transition. We derive explicit formulas for the critical temperature and the discontinuity of the order parameter at the critical point. The validity of the first order transition obtained in the one-loop approximation is also examined by estimating the size of the critical region. © 2004 The American Physical Society.

MISC

• Automatic Bladder Delineation on MR Images Using a Convolution Neural Network for Online Image-Guided Radiotherapy

  K. Nishioka, Y. Nomura, T. Hashimoto, R. Kinoshita, N. Katoh, H. Taguchi, K. Yasuda, T. Mori, Y. Uchinami, M. Otsuka, T. Matsuura, S. Takao, R. Suzuki, S. Tanaka, T. Yoshimura, H. Aoyama, S. Shimizu International Journal of Radiation Oncology*Biology*Physics 108 (3) e288 -e289 2020年11月 [査読有り]
  
• 種々の細胞特異的パラメータによる長期陽子照射に対するSLD修復の影響【JST・京大機械翻訳】|||

  KASAMATSU Koki, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, TAKAO Seishin, TANAKA Sodai, TANAKA Sodai, MIYAMOTO Naoki, MIYAMOTO Naoki, NAM Jin-Min, SHIRATO Hiroki, SHIRATO Hiroki, UMEGAKI Kikuo, UMEGAKI Kikuo 日本医学物理学会学術大会報文集 119th 2020年
• Big Data Analysis of Treatment Process Time for the Real-Time-Image Gated-Spot-Scanning Proton-Beam Therapy (RGPT) System

  T. Yoshimura, S. Shimizu, T. Hashimoto, N. Katoh, T. Inoue, K. Nishioka, T. Matsuura, S. Takao, M. Tamura, H. Tamura, K. Horita, K. Umegaki, H. Shirato International Journal of Radiation Oncology*Biology*Physics 102 (3) e501 -e502 2018年11月 [査読有り]
  
• 前立腺癌治療の新たな展開:ハイリスク前立腺癌に対する拡大手術、粒子線治療、ネオアジュバント治療 ハイリスク前立腺がんに対する強度変調放射線治療・陽子線治療 現状と可能性

  清水 伸一, 橋本 孝之, 西岡 健太郎, 安部 崇重, 大澤 崇宏, 松本 隆児, 松浦 妙子, 宮本 直樹, 高尾 聖心, 鈴木 隆介, 梅垣 菊男, 篠原 信雄, 白土 博樹 日本癌治療学会学術集会抄録集 56回 SY5 -2 2018年10月 [査読無し][通常論文]
  
• 動体追跡陽子線治療における前立腺位置変動の解析

  TAMURA Hiroshi, TAMURA Hiroshi, SHIMIZU Shinichi, NISHIOKA Kentaro, HASHIMOTO Takayuki, YOSHIMURA Takaaki, MATSUO Yuto, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, UMEGAKI Kikuo, UMEGAKI Kikuo, SHIRATO Hiroki 医学物理 Supplement 38 (1) 2018年
• Benefits of Craniospinal Intensity-modulated Proton Beam Therapy in Reducing the Myelosuppression for Adolescent Germ Cell Tumors: Two Case Reports

  Takayuki Hashimoto, Syunsuke Terasaka, Akihiro Iguchi, Shigeru Yamaguchi, Hiroyuki Kobayashi, Minako Sugiyama, Yuko Cho, Takashi Mori, Seishin Takao, Taeko Matsuura, Rikiya Onimaru, Shinichi Shimizu, Hiroki Shirato PEDIATRIC BLOOD & CANCER 64 S87 -S88 2017年11月 [査読無し][通常論文]
  
• 簡易モンテカルロ計算を用いた陽子スポットスキャニング治療の患者QA省力化

  YAMADA Takahiro, TAKAYANAGI Taisuke, MATSUURA Taeko, TAKAO Seishin, YOSHIMURA Takaaki, HIRAYAMA Shusuke, FUJII Takaaki, UMEGAKI Kikuo 医学物理 Supplement 37 (1) 2017年
• Feasibility Study of Using Dual-Energy Cone Beam Computed Tomography (DE-CBCT) in Proton Therapy Treatment Planning

  H. Peng, T. Kanehira, S. Takao, T. Matsuura, K. Umegaki, H. Shirato, L. Xing INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 96 (2) E697 -E697 2016年10月 [査読無し][通常論文]
  
• Analysis of Durations and Dose Rates for Treatment of Moving Liver Tumors Using Real-Time Image Gated Spot Scanning Proton Beam Therapy

  S. Shimizu, N. Katoh, T. Hashimoto, K. Nishioka, T. Yoshimura, S. Takao, T. Matsuura, N. Miyamoto, K. Umegaki, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 96 (2) S211 -S212 2016年10月 [査読無し][通常論文]
  
• Simulation Study of Real-Time-Image Gating On Spot Scanning Proton Therapy for Lung Tumors

  T. Kanehira, T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, T. Fujii, N. Miyamoto, T. Inoue, N. Katoh, S. Shimizu, K. Umegaki, H. Shirato MEDICAL PHYSICS 43 (6) 2016年06月 [査読無し][通常論文]
  
• Feasibility Study of Using a Dual-Energy Cone Beam CT (DECBCT) in Proton Therapy Treatment Planning

  H. Peng, T. Kanehira, S. Takao, T. Matsuura, K. Umegaki, H. Shirato, L. Xing MEDICAL PHYSICS 43 (6) 3457 -3458 2016年06月 [査読無し][通常論文]
  
• Particle Therapy Using Protons or Carbon Ions for Cancer Patients With Cardiac Implantable Electronic Devices (CIEDs): A Retrospective Japan Radiological Society Multi-institutional Study

  T. Hashimoto, Y. Demizu, T. Isobe, H. Numajiri, S. Fukuda, M. Wakatsuki, H. Yamashita, S. Murayama, S. Takamatsu, H. Katoh, K. Murata, R. Kohno, T. Arimura, T. Matsuura, Y. M. Ito INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 93 (3) E563 -E564 2015年11月 [査読無し][通常論文]
  
• Target Residual Motion During Beam Delivery in Gated Irradiation Using Real Time Tumor Tracking Radiation Therapy System: Analysis of Simultaneous Motion of Multiple Internal Fiducial Markers

  N. Miyamoto, M. Ishikawa, R. Suzuki, A. Makinaga, T. Matsuura, S. Takao, Y. Matsuzaki, T. Inoue, N. Katoh, S. Shimizu, R. Onimaru, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 93 (3) E554 -E554 2015年11月 [査読無し][通常論文]
  
• Influence of the Intrafraction Patient Repositioning On Spot Scanning Proton Therapy for Prostate Cancer

  Y. Fujii, T. Matsuura, S. Takao, Y. Matsuzaki, T. Yamada, N. Miyamoto, S. Shimizu, K. Umegaki, H. Shirato MEDICAL PHYSICS 42 (6) 3449 -3449 2015年06月 [査読無し][通常論文]
  
• Development of Evaluation System of Optimal Synchrotron Controlling Parameter for Spot Scanning Proton Therapy with Multiple Gate Irradiations in One Operation Cycle

  T. Yamada, N. Miyamoto, T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, H. Koyano, H. Nihongi, M. Umezawa, K. Matsuda, K. Umegaki, H. Shirato MEDICAL PHYSICS 42 (6) 3394 -3394 2015年06月 [査読無し][通常論文]
  
• Development of An Applicator for Treating Shallow and Moving Tumors with Respiratory-Gated Spot-Scanning Proton Therapy Using Real-Time Image Guidance

  T. Matsuura, Y. Fujii, S. Takao, T. Yamada, Y. Matsuzaki, N. Miyamoto, T. Takayanagi, S. Fujitaka, S. Shimizu, H. Shirato, K. Umegaki MEDICAL PHYSICS 42 (6) 3207 -3208 2015年06月 [査読無し][通常論文]
  
• Realization of the Cone Beam CT by FPDs That Mounted on the Spot-Scanning Dedicated Proton Beam Gantry

  S. Shimizu, S. Takao, T. Matsuura, N. Miyamoto, R. Baba, T. Umekawa, K. Matsuda, T. Sasaki, Y. Nagamine, K. Umegaki, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 90 S920 -S920 2014年09月 [査読無し][通常論文]
  
• Spatial Re-Sampling of Pencil Beams to Improve the Dose-Calculation Accuracy in Proton Therapy

  Y. Egashira, T. Nishio, T. Matsuura, S. Kameoka, M. Uesaka MEDICAL PHYSICS 38 (6) 2011年06月 [査読無し][通常論文]
  
• 【最新の放射線治療の動向 IMRTガイドライン改定をふまえて】頭頸部腫瘍に対するIMRTの現況と問題点

  河島 光彦, 有路 貴樹, 上田 隆司, 亀岡 覚, 全田 貞幹, 荒平 聡子, 金井 一能, 伍賀 友紀, 木藤 哲史, 福原 里恵, 遠山 尚紀, 大山 正哉, 宮岸 朋子, 松浦 妙子, 河野 良介, 西尾 禎治 Rad Fan 8 (12) 46,13 -48,13 2010年10月
• Thermal phase transition of dense QCD

  T Matsuura, T Hatsuda, K Iida, G Baym INTERNATIONAL CONFERENCE ON COLOR CONFINEMENT AND HADRONS IN QUANTUM CHROMODYNAMICS 346 -357 2004年 [査読有り][通常論文]
   

  Using the Ginzburg-Landau (GL) free energy, we study the effects of thermal fluctuations of gluons and the diquark pairing field on the superconducting-to-normal state phase transition in a three-flavor color superconductor. At high baryon densities, the system becomes a Type I superconductor and the gluonic fluctuations dominate over diquark fluctuations. The thermal gluons induce a cubic term in the GL free energy, as well as large corrections to quadratic and quartic terms of the order parameter. The cubic term leads to a relatively strong first order transition in comparison to the very weak first order transitions in metallic Type I superconductors. The strength of the first order transition decreases with increasing baryon density. In addition, gluonic fluctuations lower the critical temperature of the first order transition. We derive explicit formulae for the critical temperature and the discontinuity of the order parameter at the critical point. The validity of the first order transition obtained in the one-loop approximation is also examined by estimating the size of the critical region.

共同研究・競争的資金等の研究課題

• MR画像誘導陽子線治療システムおよび磁場下の治療計画・検証技法に関する基盤開発

  日本学術振興会：科学研究費助成事業

  研究期間 : 2024年04月 -2028年03月 

  代表者 : 松浦 妙子, 宮本 直樹, 打浪 雄介, 高尾 聖心, 陳 叶, 橋本 孝之, 栗山 靖敏, 加藤 徳雄
• 超高線量率陽子線治療に適したリアルタイム飛程検出法の開発

  日本学術振興会：科学研究費助成事業

  研究期間 : 2021年07月 -2024年03月 

  代表者 : 松浦 妙子, 田中 創大, 富岡 智, 橋本 孝之, 栗山 靖敏

   

  FLASH放射線治療は，通常の放射線治療の線量率の数百倍から数千倍高い線量率（40 Gy/s程度以上）を用いる超高線量率照射法である。抗腫瘍効果を変えずに正常組織の障害発生を顕著に抑制できることが知られており，これまでの治療様式を大きく変えるインパクトがある．本研究では，数年以内に臨床利用が期待される超高線量率陽子線治療に適用する心電図検査式リアルタイム飛程検出法の実用化に向けた基盤技術開発を行うことを目標とした研究開発を行っている．本年度はまず，シミュレーション検討に用いるためにCT及び超音波の両方のイメージングに対応した人体ファントムを選定し（Model 057A，CIRS社製），音波伝搬シミュレーションの構築を開始した．まず人体ファントムを陽子線治療計画用のCT装置で撮影し，各ボクセルのCT値に対して陽子線治療に用いられているCT-相対阻止能テーブルを用いて水密度を割り当て，モンテカルロシミュレーションによって陽子線線量分布を計算した．一方で，音波発生・伝搬シミュレーションの準備として，文献を参照しながら各ボクセルに対してCT値に応じた音響特性（音速や音響インピーダンス，グルネイセン係数など）を割り当てた．人体ファントムに対して，FLASH線量率で陽子線を照射し，これを音源とした音波伝搬をシミュレーションした．音波は体表面に配置した複数のセンサーで受信する設定とした．本年度はまた，次年度予定している陽子線照射実験に用いる予定の寒天をベースとしたファントムの構造と形状の検討を行い，試作を行った．
• 陽子線CT搭載型ヘリウム・陽子線混合治療装置と免疫賦活照射法の研究開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2019年04月 -2024年03月 

  代表者 : 白土 博樹, 宮本 直樹, 平田 雄一, 田中 創大, 高尾 聖心, 梅垣 菊男, 茶本 健司, 清水 伸一, Nam JinMin, 小野寺 康仁, 松浦 妙子

   

  ① 2019年度に決定した、短時間（0.1秒以下）でエネルギー変更可能な小型加速器の基本設計に基づき、小型加速器の要素技術の設計を行い、短時間（0.1秒以下）でエネルギー変更を可能とする回転ガントリーを含む照射・輸送系の磁場制御設計を行った。 ② 陽子からヘリウムに短時間で加速粒子を変更できる混合加速方式を検討、2023年度に制作開始するべく、陽子線CTの機器としての仕様を検討した。 ③ 陽子線CT値-ヘリウムSPR変換プロセスと、X線CT値利用時の精度を比較し、高エネルギー陽子線CTに必要な要素機器と制御方式の仕様を明確化した。 ④ 高エネルギー陽子線ビームを照射する場合に、ビームの人体への入射方向を意図的に偏心させ、ノズルの外側から照射野中心に向かったビームアングルとするための加速器・照射系の検討を行った。 ⑤ PD-1阻害剤およびPD-L1阻害剤を用いて、がん細胞の制御に最適なLET、ROSとミトコンドリアの分布を計測し、放射線と阻害剤の組み合わせによる相関を検討した。T細胞のPD-1阻害に関する条件検討を行っていたところ、当初の想定に反し、がん細胞での観察と類似の条件ではT細胞の観察が困難であることが判明した。T細胞を観察した上で条件決定することが不可欠であるため、T細胞のPD-1阻害に関する条件決定のための追加検討事項として、培養条件や使用する蛍光色素の種類を複数追加し、T細胞を観察するための至適条件の検討を行った。
• MR画像誘導と併用可能なリアルタイム陽子線飛程検出法の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2021年04月 -2024年03月 

  代表者 : 松浦 妙子, 宮本 直樹, 高尾 聖心, 栗山 靖敏
• 超高線量率の動体追跡照射に対応するマーカーレスボリュームイメージング技術の開発

  日本学術振興会：科学研究費助成事業

  研究期間 : 2020年04月 -2023年03月 

  代表者 : 宮本 直樹, 田中 創大, 高尾 聖心, 富岡 智, 松浦 妙子, 清水 伸一

   

  本研究では、放射線治療中に得られる2方向X線透視画像を利用し、体内マーカを利用することなく（マーカーレス）、リアルタイムに体内の3次元構造を取得するボリュームイメージング技術を開発することを目的とする。この提案技術の実現により、体内にマーカーを留置するという侵襲性のあるプロセスを無くすことができ、加えて、ボリュームイメージを得ることによる高精度な呼吸性移動対策をFLASH などの超高線量率照射を含むあらゆる照射において実施可能となる。本研究では、研究期間内に各要素技術の開発を進め、十分な質と量のデータにより精度検証を実施し、ボリュームイメージングを利用した治療ビーム照射制御の臨床的有用性を明らかにする。 2021年度は、昨年度のデジタルファントムによる画像合成精度評価に続き、実際の患者の4DCTデータによる評価を進めた。同一患者で異なる日に撮影された4DCTデータを利用し、1つの4DCTデータを変形モデリング用、残りの4DCTデータを検証に用い、モデリングの課程で得られた固有体内変形ベクトルの線形結合にもとづくボリュームイメージングにより、検証データをどこまで再現できるか評価した。合成画像の画素値と構造の再現性を評価した結果、先行研究（主にデジタルファントムでの評価）と同等の性能が得られた。したがって、放射線治療中に正確な固有値を評価することにより、標的の位置や体内構造の評価に応用できるボリュームイメージをリアルタイムで合成できると考えられ、提案手法の臨床的な実行可能性を示すことができた。
• 陽子線治療におけるパラメトリックDVH予測モデルの構築と治療高度化の試み

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2019年04月 -2022年03月 

  代表者 : 高尾 聖心, 田村 昌也, 松浦 妙子, 清水 伸一

   

  前年度に実施した、臨床パラメータを指標とした類似症例選択に基づく新たなDose Volume Histogram（DVH）予測モデル構築をさらに発展させるため、臨床パラメータとDVH予測精度の詳細な評価を行った。 臨床パラメータとして、前年度に導入した、標的と周辺正常組織（OAR）の近接の状態を表すOverlap Volume Histogram(OVH)を引き続き用いた。前立腺がん陽子線治療症例においてOVHとDVHの関係を調査したところ、OVHにおいて標的から遠位の割合が大きい症例ほどDVHが低線量側で急峻となり、OVHがなだらかな増加傾向を示す症例ではDVHも同様の傾向を示すことが明らかとなった。この知見に基づき、DVH予測精度とOVHの関係をより詳細に評価するため、DVH予測モデルにおける歪正規分布を記述する各パラメータのばらつきとOVHの相関の評価を行った。全体的には明確な相関関係は認められなかったものの、標的近位から2～5番目のsub volumeにおいて、歪正規分布の平均を表すパラメータであるμおよび歪度を表すλについて、OVHに対するばらつきが顕著に大きいことが明らかとなった。これにより、OVHを指標とした類似症例選択に基づくDVH予測の精度向上において、2～5番目のsub volumeのOVHに注目し類似症例を選択することが重要であることが示され、前年度のモデル構築が妥当であることが確認された。 今後は本知見に基づく予測モデルの更なる精度向上の検討および臨床データに基づく検証を実施する予定である。
• 微小空間画像による極低侵襲・マーカーレス実時間画像誘導放射線治療技法の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 清水 伸一, 宮本 直樹, 高尾 聖心, 梅垣 菊男, 橋本 孝之, 木下 留美子, 吉村 高明, 西岡 健太郎, 加藤 徳雄, 田口 大志, 松浦 妙子

   

  本研究は、陽子線治療ガントリー設置動体追跡装置の2軸X線透視装置を発展させ、現状より更に低侵襲で尚且つ腫瘍や体内臓器の空間的・時間的変動や呼吸性移動を考慮したがん治療が実現できる実時間画像誘導放射線治療システムを創造することを目的としている。動体追跡装置では2方向X線透視画像から特徴点の3次元位置座標をリアルタイムに計算し、様々な呼吸位相から治療計画に用いたのものと同じ呼吸位相を時間的に演算によって切り出しゲーティング治療を実現している。透視X線は治療放射線を照射する時間以外にも待機的に用いられているため本来不要な被曝が生じており、特徴点の抽出・認識にマーカを使用する必要があるため、観血的手技が必要などの患者負担が生じている。 本年度の実績として、マーカを用いずにゲーティング治療を行う手法についての特許出願を行った(特願2019-056069, 2019)。この特許出願は本研究で想定している特徴点近傍に領域を絞って情報を得、判断を行う画像認識手法を用い実際に治療を行う際に必須の物となる。正常組織の線量負荷を低減することの臨床的意義を検証する研究を実施した。
• 陽子線照射の線量率とLET変動を同時に考慮した治療効果評価システムの開発

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 松浦 妙子, 平山 嵩祐, 安井 博宣, 高尾 聖心

   

  当初の研究実施計画に従い、本研究課題のベースとなる時間依存LQモデルの亜致死損傷回復関数およびそのLET依存性を明らかにするために、生物モデルおよび細胞照射実験に関する文献調査を行い、これらに基づいて細胞照射実験計画を完成させ、陽子線を用いた実験を開始した。また、体内の各位置における、線量率とLET変動に基づき、治療効果を評価するシステムの構築を開始した。 細胞照射実験には、ヒト唾液腺のがん細胞であるHSG細胞を用いることとした。細胞の生存率は、陽子線照射後の細胞の増殖能を見るコロニーフォーメーションアッセイ法により評価した。陽子線の照射エネルギーは140.8 MeVとした。LETは我々のグループが開発したDual-LETモデルを用いて評価を行い、エネルギー吸収材によって位置を調整した。 まずLQモデルの生物パラメータ（α,β）についてLET依存性を調べるため、異なるLETでの瞬間照射を行った。次に、損傷回復のLET依存性を調べるために、細胞に対し時間を空けて2回線量を付与する間歇照射を行い、回復に対するLET変動の影響を評価した。本実験では1回の治療中に起こる損傷回復を想定し、照射の時間間隔は最大で90分とした。 最終的には、全部で5種類のLETに対する実験を行い、亜致死損傷回復関数およびそのLET依存性を明らかにする予定であるが、現在のところ、0.74 keV/μmと10.2 keV/μmの2点での測定が完了している。
• 標的の非均質性と動きを考慮したロバストな陽子線スキャニング治療技術の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2016年04月 -2020年03月 

  代表者 : 梅垣 菊男, 宮本 直樹, 高尾 聖心, 清水 伸一, 松浦 妙子

   

  平成28、29年度の研究成果に基づき、実際の臨床における標的マーカの呼吸性移動データを用い、陽子線照射スポット位置誤差の統計的/確率的評価に基づく線量分布解析、ロバスト性評価技術を開発した。また、標的移動と陽子線ビーム照射方向との相関を考慮し、一方向、多方向照射に対応した照射ゲーティングの方法、4次元線量分布最適化方法を開発した。線量誤差を考慮したがん病巣と重要臓器(Critical Organ)のロバストな線量分布評価方法を開発し、標的がん病巣線量・正常臓器線量ならびに照射効率（治療時間）のトレードオフスタディの方法を検討した。 (1)スポットスキャニングの特徴を活かした標的目標線量分布の設定と照射方法 ：実際の臨床における標的マーカの呼吸性移動データを用い、ゲーティングで生じるスポット位置誤差の確率的/統計的評価を実施した。その結果に基づき、線量分布誤差低減と照射効率向上の観点でロバストなスキャニング線量分布形成方法を提案した。また、生物学的効果等を考慮した一方向、多方向照射陽子線線量分布形成法に基づくロバストな治療計画策定方法を検討した。 (2)動く標的の空間移動方向とビーム照射方向を考慮した線量分布最適化方法 ：実際の臨床における標的マーカの呼吸性移動をモデル化し、移動方向と照射ビームの方向の相関に基づいて、4次元線量分布誤差を統計的に評価し、線量分布誤差を低減する陽子線特有の照射ゲーティング法による線量分布最適化方法を提案した。 (3) 臨床的観点からの治療計画最適化とトレードオフスタディの実現：位置誤差の確率的/統計的評価に基づき、線量誤差と照射効率（治療時間）をパラメータとしたトレードオフスタディの方法を開発した、臨床データを用いて比較検討した。
• CBCT画像を用いた線量評価に基づく治療効果誘導放射線治療技術の開発

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2016年04月 -2020年03月 

  代表者 : 高尾 聖心, 宮本 直樹, 清水 伸一, 松浦 妙子

   

  陽子線治療において、治療期間中の患者様態の変化に対して治療計画を適合させるadaptive陽子線治療の要否判断を的確に行うためには、治療期間中の患者の体形等の変化が線量分布すなわち治療効果に与える影響を定量的に掌握することが重要である。本研究では、陽子線治療の患者位置合わせの目的で取得されたコーンビームCT（CBCT）画像を用いた水等価厚の評価に基づく線量分布への影響の推測手法を開発した。水等価厚の評価には、得られたCBCT画像をそのまま用いる方法およびCBCT画像に対する治療計画CT画像の変形レジストレーションによって得られた変形CT画像を用いる方法が一般的であるが、本研究では治療計画CT画像とのヒストグラムマッチングによりCT値の定量性を改善させたCBCT画像を用いる手法を採用した。水等価厚の評価は陽子線スポットスキャニング照射の各スポット照射ビームを想定し、各門の入射角度における全スポットに対して行った。水等価厚比の算出には治療計画装置に登録されているCT値-水等価厚比変換テーブルを用いた。本手法の有効性検証として、頭頚部癌患者のCBCT画像および経過観察CT画像を用いた水等価厚算出の精度評価を行った。CT値改善後のCBCT画像を用いた水等価厚と経過観察CT画像を用いた水等価厚の差分の平均は最深部が10cm程度に位置する腫瘍において3mm程度であり、誤差3%程度での算出が可能であった。しかし、全スポットの水等価厚算出誤差の標準偏差は5mm程度であり、特に鼻腔等の密度が急峻に変化する領域を通過するビームにおいて不確定性が高くなるためであると推察された。また、水等価厚の算出誤差と標的のcoverageには相関が確認された。
• ヘリウム・陽子線ハイブリッド治療の研究開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2015年04月 -2019年03月 

  代表者 : 白土 博樹, 高尾 聖心, 梅垣 菊男, 清水 伸一, 鬼丸 力也, 松浦 妙子, 牧永 綾乃

   

  炭素線と同じく浅部でシャープで、体の動きに対応することができる動体追跡技術を有し、ガントリーを用いた治療が可能な次世代型放射線治療装置として、ヘリウム・陽子線ハイブリッド治療装置の開発研究に必要な基礎概念を確立し、これを国際特許化した。同治療を選択する場合に、個々の患者に最適な放射線治療の選択を可能とする、統計学的な信頼度を持つインシリコ・バイオマーカーとして、ΔNTCPを活用するための方法論を確立した。
• 4D-CBCTと治療計画CTの容積マッチング法による4D-IGRTの試み

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 清水 伸一, 梅垣 菊男, 高尾 聖心, 松浦 妙子, 宮本 直樹, 西岡 健太郎, 木下 留美子, 加藤 徳雄

   

  陽子線治療ガントリー内に設置した動体追跡装置の2軸X線透視装置を活用し、腫瘍の空間的・時間的変動や呼吸性移動を考慮したがん治療ができる4D-IGRT放射線治療システム構築を目的として、動体追跡装置の透視画像から4次元コーンビームCT(4D-CBCT)画像を得て、複数の呼吸位相で構成される4D-CBCT画像群の中から、治療計画に用いたCT画像と同じ呼吸位相にあるCT画像から選択するとともに、選択されたCBCT画像を構成する元画像群を用いてマーカーレス4D-RTを目指す発展的画像誘導システムを開発することを目標とした。
• 動体追跡スポットスキャニング陽子線治療に適合した生物線量計算システムの開発

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 松浦 妙子

   

  本研究では、呼吸性移動腫瘍に対するスポットスキャニング陽子線治療に焦点を当て、実際に照射された物理線量分布を正確に算出するための方法論を構築した。これを、別途開発したシステムに搭載し、患者への日々の実績投与線量評価を可能にした。また、生物学的影響を含めた治療効果を評価するために、患者体内のLET分布を短時間で計算する解析アルゴリズムを開発した。一般的に用いられてきたモンテカルロ法と比較して、格段に短時間で、同程度の計算精度が達成されることを確認した。最後に、治療効果に影響する因子として線量率に着目し、体内各位置における線量率構造を算出するための仕組みを構築することで、将来的な発展に備えた。
• 移動標的に対するスポット陽子線照射の精度向上に関する研究

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2013年04月 -2015年03月 

  代表者 : 松浦 妙子

   

  動体追跡スポットスキャニング陽子線治療は、動きのある腫瘍に対して、腫瘍近傍に置かれた金マーカーを透視X線によってリアルタイムでモニターし、マーカーが所定の位置に来た時のみ照射を行うことで、周辺正常臓器への余分な被ばくを抑制しつつ腫瘍に十分な線量を付与することを目的としている。この方法を、肺がんのような体内浅部にある腫瘍に対して適用するため、陽子線エネルギーを減速させるエネルギー吸収体と、線量分布を動きに強くしつつ、治療時間を短縮するためのミニリッジフィルタから構成されるアプリケーターを開発した。
• スポット陽子線照射における体内金属マーカー存在下の照射精度向上に関する研究

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2011年 -2012年 

  代表者 : 松浦 妙子

   

  放射線治療において、呼吸やその他の原因によって治療中に移動する腫瘍への高精度照射法の開発が望まれている。本研究では、動体追跡スポットスキャニング陽子線治療法において、腫瘍の正確な3次元位置特定の為に患部に刺入される金マーカーが線量分布や腫瘍制御確率(TCP)に与える影響を、高精度線量計算法であるモンテカルロ法を用いて正確に評価し、多門照射による解決策を提案した。
• ギンツブルグ・ランダウ理論を用いたカラー超伝導相の相構造の研究

  日本学術振興会：科学研究費助成事業 特別研究員奨励費

  研究期間 : 2005年 -2006年 

  代表者 : 松浦 妙子

   

  BCS理論が提唱されて以来、超伝導・超流動現象は、固相(金属超伝導)、液相(超流動ヘリウム)では観測されてきたものの、気相においての実現は実験的な困難のために憚られてきた。しかし、近年遂に、超低温でのアルカリ原子気体を用いての超流動現象が観測され、話題をよんでいる。この系の特徴は原子間の相互作用の大きさを実験的にも自由に調整できることであり、これにより実験による観測と理論計算との比較が広範囲の相互作用領域にわたって行えるところにある。理論的にはこの系は相互作用の弱い極限ではBCS理論で、強い極限ではボース凝縮として良く記述されているが、この二つの全く異なる理論が相互作用の大きさという一つのパラメータで連続的に結ばれる。 私は本年度、ヨーロッパ核物理センター(ECT*,イタリア)において、理論的立場から厳密繰り込み群という手法を用いて全ての相互作用領域にわたってこの現象を記述する試みを行っている。今まで行われてきた手法では特定の相互作用の大きさだけでの記述や揺らぎの考慮が不十分なものであったが、この手法ではあらゆる相互作用の大きさの領域が記述できるので系の連続的変化が明瞭になり、しかも従来よりも精度の高い計算が可能となる。現在、この手法の核となる繰り込み群方程式の数値的解析を進めている。この手法は非摂動的なものであり、標準的な摂動論ではわからない比較的強い相互作用領域での系の振る舞いや理論の根本的な構造が明らかにされると期待される。 今後更に、クォーク物質や核物質にもこの解析を応用して様々な密度領域での物質の振る舞いを明らかにしていきたい。