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PURPOSE The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.

Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the 7 Li(p,n)7 Be near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the 7 Li(p,n)7 Be reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT.

Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the Li-7(p,n)Be-7 near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the Li-7(p,n)Be-7 reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT.

Purpose: We evaluate an SGRT device (Voxelan HEV-600 M/RMS) installed with Radixact, with the view angle of the Voxelan's camera at 74 degrees. The accuracy of Voxelan with this steep angle was evaluated with phantom experiments and inter-fractional setup errors of patients. Methods: In the phantom experiments, the difference between the measured values of Voxelan from the truth was evaluated for translations and rotations. The inter-fractional setup error between the setup using skin markers with laser localizer (laser setup: LS) and the setup using Voxelan (surface setup: SS) was compared for head and neck (N = 19), chest (N = 7) and pelvis (N = 9) cases. The inter-fractional setup error was calculated by subtracting from bone matching by megavoltage computed tomography (MVCT) as ground truth. Results: From the phantom experiments, the average difference between the measured values of Voxelan from the truth was within 1 mm and 1 degree. In all cases, inter-fractional setup error based on MVCT was not significantly different between LS and SS by Welch's t-test (P > 0.05). The vector offset of the LS for head and neck, chest, and pelvis were 6.5, 9.6, and 9.6 mm, respectively, and that of the SS were 5.8, 8.6, and 12.6 mm, respectively. Slight improvement was observed for the head and neck, and chest cases, however, pelvis cases were not improved because the umbilical region could not be clearly visualized as a reference. Conclusion: The results show that SS in Voxelan with an installation angle of 74 degrees is equal to or better than LS.

Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the Li-7(p,n)Be-7 near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the Li-7(p,n)Be-7 reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT.

Purpose: We evaluate an SGRT device (Voxelan HEV-600 M/RMS) installed with Radixact, with the view angle of the Voxelan's camera at 74 degrees. The accuracy of Voxelan with this steep angle was evaluated with phantom experiments and inter-fractional setup errors of patients. Methods: In the phantom experiments, the difference between the measured values of Voxelan from the truth was evaluated for translations and rotations. The inter-fractional setup error between the setup using skin markers with laser localizer (laser setup: LS) and the setup using Voxelan (surface setup: SS) was compared for head and neck (N = 19), chest (N = 7) and pelvis (N = 9) cases. The inter-fractional setup error was calculated by subtracting from bone matching by megavoltage computed tomography (MVCT) as ground truth. Results: From the phantom experiments, the average difference between the measured values of Voxelan from the truth was within 1 mm and 1 degree. In all cases, inter-fractional setup error based on MVCT was not significantly different between LS and SS by Welch's t-test (P > 0.05). The vector offset of the LS for head and neck, chest, and pelvis were 6.5, 9.6, and 9.6 mm, respectively, and that of the SS were 5.8, 8.6, and 12.6 mm, respectively. Slight improvement was observed for the head and neck, and chest cases, however, pelvis cases were not improved because the umbilical region could not be clearly visualized as a reference. Conclusion: The results show that SS in Voxelan with an installation angle of 74 degrees is equal to or better than LS.

Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the Li-7(p,n)Be-7 near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the Li-7(p,n)Be-7 reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT.

Purpose: We evaluate an SGRT device (Voxelan HEV-600 M/RMS) installed with Radixact, with the view angle of the Voxelan's camera at 74 degrees. The accuracy of Voxelan with this steep angle was evaluated with phantom experiments and inter-fractional setup errors of patients. Methods: In the phantom experiments, the difference between the measured values of Voxelan from the truth was evaluated for translations and rotations. The inter-fractional setup error between the setup using skin markers with laser localizer (laser setup: LS) and the setup using Voxelan (surface setup: SS) was compared for head and neck (N = 19), chest (N = 7) and pelvis (N = 9) cases. The inter-fractional setup error was calculated by subtracting from bone matching by megavoltage computed tomography (MVCT) as ground truth. Results: From the phantom experiments, the average difference between the measured values of Voxelan from the truth was within 1 mm and 1 degree. In all cases, inter-fractional setup error based on MVCT was not significantly different between LS and SS by Welch's t-test (P > 0.05). The vector offset of the LS for head and neck, chest, and pelvis were 6.5, 9.6, and 9.6 mm, respectively, and that of the SS were 5.8, 8.6, and 12.6 mm, respectively. Slight improvement was observed for the head and neck, and chest cases, however, pelvis cases were not improved because the umbilical region could not be clearly visualized as a reference. Conclusion: The results show that SS in Voxelan with an installation angle of 74 degrees is equal to or better than LS.

We evaluate the track segment yield G′ of typical water radiolysis products (eaq−, ·OH and H2O2) under heavy ions (He, C and Fe ions) using a Monte Carlo simulation code in the Geant4-DNA. Furthermore, we reproduce experimental results of ·OH of He and C ions around the Bragg peak energies (< 6 MeV/u). In the relatively high energy region (e.g., > 10 MeV/u), the simulation results using Geant4-DNA have agreed with experimental results. However, the G-values of water radiolysis species have not been properly evaluated around the Bragg peak energies, at which high ionizing density can be expected. Around the Bragg peak energy, dense continuous secondary products are generated, so that it is necessary to simulate the radical–radical reaction more accurately. To do so, we added the role of secondary products formed by irradiation. Consequently, our simulation results are in good agreement with experimental results and previous simulations not only in the high-energy region but also around the Bragg peak. Several future issues are also discussed regarding the roles of fragmentation and multi-ionization to realize more realistic simulations.

Purpose: The real-time tumor tracking radiotherapy (RTRT) system requires periodic quality assurance (QA) and quality control. The goal of this study is to propose QA procedures from the viewpoint of imaging devices in the RTRT system. Methods: Tracking by the RTRT system (equips two sets of colored image intensifiers (colored I.I.s) fluoroscopy units) for the moving gold-marker (diameter 2.0 mm) in a rotating phantom were performed under various X-ray conditions. To analyze the relationship between fluoroscopic image quality and precision of gold marker coordinate calculation, the standard deviation of the 3D coordinate (sigma 3D [mm]) of the gold marker, the mean of the pattern recognition score (PRS) and the standard deviation of the distance between rays (DBR) (sigma DBR [mm]) were evaluated. Results: When tracking with speed of 10-60 mm/s, sigma DBR increased, though the mean PRS did not change significantly (p>0.05). On the contrary, the mean PRS increased depending on the integral noise equivalent quanta (integral NEQ) that is an indicator of image quality calculated from the modulation transfer function (MTF) as an indicator of spatial resolution and the noise power spectrum (NPS) as an indicator of noise characteristic. Conclusion: The indicators of NEQ, MTF, and NPS were useful for managing the tracking accuracy of the RTRT system. We propose observing the change of these indicators as additional QA procedures for each imaging device from the commissioning baseline.

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.

Monte Carlo track structure simulation is a powerful method for estimating damage induced by water radiolysis products for cell killing. To investigate the influence of multiple ionization for the formation of water radiolysis products under H-1(+), He-4(2+), and C-12(6+) ion beams, a Monte Carlo simulation based on Geant4-DNA was carried out. The G-value of H2O2 increased monotonically with increasing linear energy transfer up to 200 eV/nm. Above 200 eV/nm, the G-value of H2O2 began dropping, but only when the influence of multiple ionization was considered. This trend is in good agreement with the experimental results. Furthermore, we successfully reproduce the experimental results of G-values of HO2 center dot + O-2(center dot-). The role of the multiple ionization in the production of H2O2, HO2 center dot, O-2(center dot-), and O-2 is also discussed.

Purpose: The real-time tumor tracking radiotherapy (RTRT) system requires periodic quality assurance (QA) and quality control. The goal of this study is to propose QA procedures from the viewpoint of imaging devices in the RTRT system. Methods: Tracking by the RTRT system (equips two sets of colored image intensifiers (colored I.I.s) fluoroscopy units) for the moving gold-marker (diameter 2.0 mm) in a rotating phantom were performed under various X-ray conditions. To analyze the relationship between fluoroscopic image quality and precision of gold marker coordinate calculation, the standard deviation of the 3D coordinate (sigma 3D [mm]) of the gold marker, the mean of the pattern recognition score (PRS) and the standard deviation of the distance between rays (DBR) (sigma DBR [mm]) were evaluated. Results: When tracking with speed of 10-60 mm/s, sigma DBR increased, though the mean PRS did not change significantly (p>0.05). On the contrary, the mean PRS increased depending on the integral noise equivalent quanta (integral NEQ) that is an indicator of image quality calculated from the modulation transfer function (MTF) as an indicator of spatial resolution and the noise power spectrum (NPS) as an indicator of noise characteristic. Conclusion: The indicators of NEQ, MTF, and NPS were useful for managing the tracking accuracy of the RTRT system. We propose observing the change of these indicators as additional QA procedures for each imaging device from the commissioning baseline.

Monte Carlo track structure simulation is a powerful method for estimating damage induced by water radiolysis products for cell killing. To investigate the influence of multiple ionization for the formation of water radiolysis products under H-1(+), He-4(2+), and C-12(6+) ion beams, a Monte Carlo simulation based on Geant4-DNA was carried out. The G-value of H2O2 increased monotonically with increasing linear energy transfer up to 200 eV/nm. Above 200 eV/nm, the G-value of H2O2 began dropping, but only when the influence of multiple ionization was considered. This trend is in good agreement with the experimental results. Furthermore, we successfully reproduce the experimental results of G-values of HO2 center dot + O-2(center dot-). The role of the multiple ionization in the production of H2O2, HO2 center dot, O-2(center dot-), and O-2 is also discussed.

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.

To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium., info:eu-repo/semantics/published

Purpose: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. Methods: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. Results: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). Conclusions: Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (Dw,w), this is acceptable., SCOPUS: re.j, info:eu-repo/semantics/published

Purpose To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. Methods The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. Results No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). Conclusions Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution’s planning system can only calculate dose to water in water (Dw,w), this is acceptable.

In our laboratory we have confirmed that the capacitance of barium titanate-based capacitors changes due to radiation. Since a commercially available capacitor is very small and inexpensive, it may be used as a multidimensional dose meter in which a large number of capacitor elements are arranged, or may be embedded in the body and used as an in-vivo dose meter. In this study we examined the usefulness of a dosimeter using the capacitance change of a barium titanate capacitor. As a basic property, it was confirmed that the dose linearity was good. With regard to dose rate characteristics and response to fractionated irradiation, capacitance change due to aging affects measurement accuracy, but online measurement of capacitance change immediately before irradiation can be performed to correct aging effects during irradiation. By doing this, we confirmed that the dose rate characteristics and the response to fractionated radiation are improved.

In our laboratory we have confirmed that the capacitance of barium titanate-based capacitors changes due to radiation. Since a commercially available capacitor is very small and inexpensive, it may be used as a multidimensional dose meter in which a large number of capacitor elements are arranged, or may be embedded in the body and used as an in-vivo dose meter. In this study we examined the usefulness of a dosimeter using the capacitance change of a barium titanate capacitor. As a basic property, it was confirmed that the dose linearity was good. With regard to dose rate characteristics and response to fractionated irradiation, capacitance change due to aging affects measurement accuracy, but online measurement of capacitance change immediately before irradiation can be performed to correct aging effects during irradiation. By doing this, we confirmed that the dose rate characteristics and the response to fractionated radiation are improved.

Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1(-/-) Cry2(-/-) arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice.

Focusing on whole-body uniformity in small-animal single-photon emission computed tomography (SPECT), we examined the optimal helical acquisition parameters using five-pinhole collimators for mouse imaging. SPECT images of an 80-mm-long cylindrical phantom with 99mTc solution were acquired using an Inveon multimodality imaging platform. The bed travels used in this study were 0, 30, 60, 90 and 120 mm, and the numbers of revolutions traversed during the SPECT scan were 1.0, 2.0, 3.0, 4.0, 5.0 and 7.0, respectively. Artifacts that degrade uniformity in reconstructed images were conspicuous when the bed travel was smaller than the object length. Regarding the distal-to-center ratio (DCR) of SPECT values in the object's axial direction, the DCR nearest to the ideal ratio of 1.00 was 1.02 in the optimal uniformity with 4.0 revolutions and a bed travel of 120 mm. Moreover, the helical acquisition using these parameters suppressed the formation of artifacts. We proposed the optimal parameters in whole-body helical SPECT; the bed travel was sufficiently larger than the object length; the 4.0 or more revolutions were required for a pitch of approximately 30 mm/revolution. The optimal acquisition parameters in SPECT to preserve uniformity would contribute to the accurate quantification of whole-body biodistribution. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. Material and methods: Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). Results: The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. Conclusion: Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

Background: Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. Material and methods: Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). Results: The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. Conclusion: Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1(-/-) Cry2(-/-) arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice.

Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 105 n/cm2/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources.

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.

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.

Radiotherapy is effective for treating various types of tumors. However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes that correlate with poor prognosis. It is not known how cancer cells survive and generate malignant tumors after irradiation. Here, we show that activating transcription factor 5 (ATF5) promotes radioresistance and malignancy in cancer cells after irradiation. In the G1-S phase of the cell cycle, cancer cells express high levels of ATF5, which promotes cell cycle progression and thereby increases radioresistance. Furthermore, ATF5 increases malignant phenotypes, such as cell growth and invasiveness, in cancer cells in vitro and in vivo. We have identified a new mechanism for the regeneration of highly malignant tumors after irradiation and shown that ATF5 plays a key role in the process.

Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130-150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans.

Radiotherapy is effective for treating various types of tumors. However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes that correlate with poor prognosis. It is not known how cancer cells survive and generate malignant tumors after irradiation. Here, we show that activating transcription factor 5 (ATF5) promotes radioresistance and malignancy in cancer cells after irradiation. In the G1-S phase of the cell cycle, cancer cells express high levels of ATF5, which promotes cell cycle progression and thereby increases radioresistance. Furthermore, ATF5 increases malignant phenotypes, such as cell growth and invasiveness, in cancer cells in vitro and in vivo. We have identified a new mechanism for the regeneration of highly malignant tumors after irradiation and shown that ATF5 plays a key role in the process.

Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130-150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans.

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.

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.

Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 105 n/cm2/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources.

A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ≤0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ≤0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

東京電力福島第一原子力発電所事故後における広域の詳細な空間線量率マップを作成するために、原子力機構は走行サーベイシステムKURAMA-IIを用いた測定を文部科学省の委託を受けて実施した。KURAMAは、一般乗用車に多数搭載して広範囲の空間線量率を詳細かつ短期間に把握することを目的として京都大学原子炉実験所で開発されたシステムである。KURAMAは、エネルギー補償型gamma線検出器で測定した線量率をGPSの測位データでタグ付けしながら記録する測定器、データを受け取り可視化のための処理や解析を行うサーバ、エンドユーザがデータを閲覧するためのクライアントから構成される。第2世代のKURAMA-IIでは更なる小型化、堅牢性の向上、データ送信の完全自動化等の機能が強化されたことによって、100台の同時測定が可能となり、広域の詳細な線量率マッピングをより短期間で実施することが可能になった。本報告では、KURAMA-IIによる測定データの信頼性を確保するために実施した基盤整備と、KURAMA-IIを空間線量率マッピング事業に適用した結果について述べるとともに、多数のKURAMA-IIを使用した走行サーベイの精度を保証するための効率的なKURAMA-IIの管理方法を提案した。, JAEA has been performing dose rate mapping in air using a car-borne survey system KURAMA-II. The KURAMA system is a GPS-aided mobile radiation monitoring system that has been newly developed by Kyoto University Research Reactor Institute in response to the nuclear disaster. The KURAMA system is composed of an energy-compensated scintillation survey meter for measuring dose rate, electric device for controlling both the dose rates and the position data from a GPS module, a computer server for processing and analyzing data from KURAMA, and client PCs for providing for end users. The KURAMA-II has been improved in small-packaging, durability, and automated data transmission. In consequence, dose rate mapping in wide area has become possible in shorter period of time. This report describes the construction of KURAMA-II, its application and a suggestion of how to manage a large number of KURAMA-II., 著者所属: 日本原子力研究開発機構(JAEA), JAEA-Technology 2013-037

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 cm(3). 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.

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 cm(3). 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.

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG < 1) group and the Grade 2-5 RP (RPG >= 2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RPG >= 2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG < 1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG >= 2 group. There were two advantages gained from the proposed plan for V5 (< 55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.

Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as a contributor to the limited benefit of radiotherapy; however, its mechanism is still unclear. We previously showed that subcloned lung adenocarcinoma A549 cells (P cells), which survived 10 Gy IR (IR cells), acquired high invasiveness in vitro. Here, we tried to identify the mechanism by which IR cells increase their invasiveness by examining altered gene expression and signaling pathways in IR cells compared with those in P cells. To simulate the microenvironment in vivo, cells were embedded in a three-dimensional (3D) collagen type I gel, in which the IR cells were elongated, while the P cells were spherical. The integrin expression pattern was surveyed, and expression levels of the integrin alpha 2 and beta 1 subunits were significantly elevated in IR cells. Knockdown of alpha 2 expression or functional blockade of integrin alpha 2 beta 1 resulted in a round morphology of IR cells, and abrogated their invasion in the collagen matrix, suggesting the molecule's essential role in cell spread and invasion in 3D collagen. Epidermal growth factor receptor (EGFR) also presented enhanced expression and activation in IR cells. Treatment with EGFR tyrosine kinase inhibitor, PD168393, decreased the ratio of elongated cells and cell invasiveness. Signaling molecules, including extracellular signal-regulated kinase-1/2 (Erk1/2) and Akt, exhibited higher activation in IR cells. Inhibition of Akt activation by treating with phosphoinositide 3-kinase (PI3K) inhibitor LY294002 decreased IR cell invasion, whereas inhibition of Erk1/2 activation by mitogen-activated protein kinase kinase (MEK) inhibitor U0126 did not. Our results show that integrin alpha 2 beta 1 and EGFR cooperatively promote higher invasiveness of IR-survived lung cancer cells, mediated in part by the PI3K/Akt signaling pathway, and might serve as alternative targets in combination with radiotherapy.

Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as a contributor to the limited benefit of radiotherapy; however, its mechanism is still unclear. We previously showed that subcloned lung adenocarcinoma A549 cells (P cells), which survived 10 Gy IR (IR cells), acquired high invasiveness in vitro. Here, we tried to identify the mechanism by which IR cells increase their invasiveness by examining altered gene expression and signaling pathways in IR cells compared with those in P cells. To simulate the microenvironment in vivo, cells were embedded in a three-dimensional (3D) collagen type I gel, in which the IR cells were elongated, while the P cells were spherical. The integrin expression pattern was surveyed, and expression levels of the integrin alpha 2 and beta 1 subunits were significantly elevated in IR cells. Knockdown of alpha 2 expression or functional blockade of integrin alpha 2 beta 1 resulted in a round morphology of IR cells, and abrogated their invasion in the collagen matrix, suggesting the molecule's essential role in cell spread and invasion in 3D collagen. Epidermal growth factor receptor (EGFR) also presented enhanced expression and activation in IR cells. Treatment with EGFR tyrosine kinase inhibitor, PD168393, decreased the ratio of elongated cells and cell invasiveness. Signaling molecules, including extracellular signal-regulated kinase-1/2 (Erk1/2) and Akt, exhibited higher activation in IR cells. Inhibition of Akt activation by treating with phosphoinositide 3-kinase (PI3K) inhibitor LY294002 decreased IR cell invasion, whereas inhibition of Erk1/2 activation by mitogen-activated protein kinase kinase (MEK) inhibitor U0126 did not. Our results show that integrin alpha 2 beta 1 and EGFR cooperatively promote higher invasiveness of IR-survived lung cancer cells, mediated in part by the PI3K/Akt signaling pathway, and might serve as alternative targets in combination with radiotherapy.

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG < 1) group and the Grade 2-5 RP (RPG >= 2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RPG >= 2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG < 1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG >= 2 group. There were two advantages gained from the proposed plan for V5 (< 55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.

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 cm(3). 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.

Two treatment planning methods for nasopharyngeal carcinoma were compared: conventional whole-body BGO scintillator positron emission tomography and a new brain PET system using semiconductor detec- tors. The average absolute volume of GTV contoured with the use of the new brain PET system was significantly smaller than that of conven- tional whole-body BGO PET. The new brain PET system using semiconductor detectors can provide more accurate tumor delineation

Two treatment planning methods for nasopharyngeal carcinoma were compared: conventional whole-body BGO scintillator positron emission tomography and a new brain PET system using semiconductor detec- tors. The average absolute volume of GTV contoured with the use of the new brain PET system was significantly smaller than that of conven- tional whole-body BGO PET. The new brain PET system using semiconductor detectors can provide more accurate tumor delineation

A feasibility study of a novel PET-based molecular image guided radiation therapy (m-IGRT) system was conducted by comparing PET-based registration with radiographic registration. We selected a pair of opposing parallel-plane PET systems for the practical implementation. Five different sizes of 18F cylindrical sources (diameter: 8, 12, 16, 24, 32 mm) were used to determine setup errors. PET data acquisition times were 1, 3 and 5 min. Image registration was performed by 5 observers. Setup errors from the PET system were compared with setup errors from image intensifier-based fluoroscopy. The in-plane and cross-plane FWHM of the profile of a 2 mm diameter sources for the parallel-plane PET system were approximately 1.8 mm and 8.1 mm, respectively. The majority of the mean registration errors obtained from the PET-based registration were not significantly different from those obtained from the radiographic registration. Acquisition time did not appear to result in significant differences in the mean registration error. The mean registration error for the PET-based registration was found to be 0.93±0.33 mm. This is not statistically different from the radiographic registration which had mean registration error of 0.92±0.27 mm. Our results suggest that m-IGRT is feasible for clinical use with a parallel plane PET-based registration.

A feasibility study of a novel PET-based molecular image guided radiation therapy (m-IGRT) system was conducted by comparing PET-based registration with radiographic registration. We selected a pair of opposing parallel-plane PET systems for the practical implementation. Five different sizes of 18F cylindrical sources (diameter: 8, 12, 16, 24, 32 mm) were used to determine setup errors. PET data acquisition times were 1, 3 and 5 min. Image registration was performed by 5 observers. Setup errors from the PET system were compared with setup errors from image intensifier-based fluoroscopy. The in-plane and cross-plane FWHM of the profile of a 2 mm diameter sources for the parallel-plane PET system were approximately 1.8 mm and 8.1 mm, respectively. The majority of the mean registration errors obtained from the PET-based registration were not significantly different from those obtained from the radiographic registration. Acquisition time did not appear to result in significant differences in the mean registration error. The mean registration error for the PET-based registration was found to be 0.93±0.33 mm. This is not statistically different from the radiographic registration which had mean registration error of 0.92±0.27 mm. Our results suggest that m-IGRT is feasible for clinical use with a parallel plane PET-based registration.

Results of Monte Carlo calculated dose distributions of proton treatment of ocular melanoma are presented. An efficient spot-scanning method utilizing active energy modulation which also minimizes the number of target spots was developed. We simulated various parameter values for the particle energy spread and the pencil-beam diameter in order to determine values suitable for medical treatment. We found that a 2.5-mm-diameter proton beam with a 5% Gaussian energy spread is suitable for treatment of ocular melanoma while preserving vision for the typical case that we simulated. The energy spectra and required proton current were also calculated and are reported. The results are intended to serve as a guideline for a new class of low-cost, compact accelerators.