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Recently, ultra-high dose rate (> 40 Gy/s, uHDR; FLASH) radiation therapy (RT) has attracted interest, because the FLASH effect that is, while a cell-killing effect on cancer cells remains, the damage to normal tissue could be spared has been reported. This study aimed to compare the immune-related protein expression on cancer cells after γ-ray, conventionally used dose rate (Conv) carbon ion (C-ion), and uHDR C-ion. B16F10 murine melanoma and Pan02 murine pancreas cancer were irradiated with γ-ray at Osaka University and with C-ion at Osaka HIMAK. The dose rates at 1.16 Gy/s for Conv and 380 Gy/s for uHDR irradiation. The expressed calreticulin (CRT), major histocompatibility complex class (MHC)-I, and programmed cell death 1 ligand (PD-L1) were evaluated by flow cytometry. Western blotting and PCR were utilized to evaluate endoplasmic reticulum (ER) stress, DNA damage, and its repair pathway. CRT, MHC-I on B16F10 was also increased by irradiation, while only C-ion increased MHC-I on Pan02. Notably, PD-L1 on B16F10 was increased after irradiation with both γ-ray and C-ion, while uHDR C-ion suppressed the expression of PD-L1 on Pan02. The present study indicated that uHDR C-ion has a different impact on the repair pathway of DNA damage and ER than the Conv C-ion. This is the first study to show the immune-related protein expressions on cancer cells after uHDR C-ion irradiation. [ABSTRACT FROM AUTHOR]

Background Purpose Method Result Conclusion All Hitachi proton pencil beam scanning facilities currently use discrete spot scanning (DSS). Mayo Clinic Florida (MCF) is installing a Hitachi particle therapy system with advanced technologies, including fast scan speeds, high beam intensity, rapid beam off control (RBOC), a skip spot function, and proton pencil beam scanning using dose driven continuous scanning (DDCS). A potential concern of RBOC is the generation of a shoulder at the end of the normal spot delivery due to a flap spot (FS) with a flap dose (FD), which has been investigated for carbon synchrotron but not for proton delivery. While investigated, for instance, for Hitachi's installation at MCF, this methodology could be applicable for all future high intensity proton deliveries.No Hitachi proton facility currently uses the proposed RBOC. This study aimed to understand the dosimetric impact of proton FD at MCF by simulating the FS with a Hitachi proton machine in research mode, reflecting the higher proton intensities expected with RBOC at MCF.Experiments were conducted to simulate MCF RBOC at Kyoto Prefecture University of Medicine (KPUM) in research mode, reducing delay time (Td) from 1.5 ms to 0.1 ms. 5,000 contiguous spots were delivered on the central axis for proton energies of 70.2, 142.5, and 220.0 MeV; at normal, high dose rate (HDR), and ultra‐high dose rate (uHDR) intensities; and at vertical and horizontal gantry angles for different Td. Measurements were taken using a fast oscilloscope and the nozzle's spot position monitor (SPM) and dose monitor (DM). A model was developed to predict FD dependence on beam intensity and assess the dosimetric impact for prostate and brain treatment plans. Two simulation types were planned: a flap DSS plan with FS at every spot and a flap DDCS plan with FS only at the end of each layer.FD was observed for RBOC with Td = 0.1 ms, showing no gantry angle dependence. FD increased with higher delayed dose rate (DDR), that is, beam intensity. The planning study showed dose volume histogram deterioration with increased FD compared to the clinical plan, but it was only significant for uHDR intensities. Deterioration was marginal in flap DSS plans for the HDR intensities planned at MCF, and flap DDCS plans were even less sensitive than flap DSS plans.MCF is installing proton DDCS with higher beam intensities, a skip spot function, and fast beam‐off control. The resulting FD had an insignificant impact on dose distribution for two patient plans with both DSS and DDCS at the anticipated MCF intensities. However, significant dependence was observed in the case of uHDR. A method to measure the position and dose of the FS during commissioning is described in addition to recommendations for regular QA and log‐based proton patient‐specific quality assurance. [ABSTRACT FROM AUTHOR]

Background: In carbon ion radiation therapy (CIRT) the predominant method of irradiation is raster scanning, called dose driven continuous scanning (DDCS) by Hitachi, allowing for continuous synchrotron extraction. The reduction in irradiation time is highly beneficial in minimizing the impact of patient and target movement on dose distribution. The RF knock out (RFKO) slow‐extraction method is commonly used for beam on/off control. When the Hitachi synchrotron receives a beam off signal the control system stops the RFKO and after some delay time (t‐delay) during which the beam intensity declines, a high‐speed steering magnet (HSST) is used to sweep the remaining beam from isocenter to a beam dump for safety reasons. Mayo Clinic Florida (MCF) will use a very short delay of the HSST operation from the RFKO beam OFF signal to minimize the delay time and delayed dose. MCF clinical beam intensity, a tenfold increase over HIMAK, is still less than 100 mMU/ms (approximately 4.9 × 109 pps for 430 MeV/u). Purpose: The rapid beam off control (RBOC) proposed for MCF is associated with the occurrence of flap dose (FD), which refers to the asymmetric shoulder of the spot dose profile formed from the beam bent by HSST deviating from its planned spot position on the isocenter plane. In this study, we quantitatively assessed FD, proposed a treatment planning system (TPS) implementation using a flap spot (FS) and evaluated its impact on dose distribution. Method: The experiments were conducted at the Osaka Heavy Ion Therapy Center (HIMAK) varying the t‐delay from 0.01 to 1 ms in a research environment to simulate the MCF RBOC. We studied the dependence of FD position on beam transport and its dependence on energy and beam intensity. FD was generated by delivering 10000 continuous spots on the central axis that are occasionally triggered by an external 10 Hz gate signal. Measurements were conducted using an oscilloscope, and the nozzle's spot position monitor (SPM) and dose monitor (DM). Result: All spot profile data were corrected for the gain of the SPM's beam intensity dependence. FD was determined by fitting the (SPM) Profile data to a double Gaussian. The position of the FS was found to be transport path dependent, with FS occurring on the opposite sides of the scanning x‐direction for vertical and horizontal ports, respectively, as predicted by transport calculations. It was observed that the FD increases with beam intensity and did not exhibit a significant dependence on energy. The effect of FD on treatment planning is shown to have no significant dose impact on the organs at risk (OARs) near the target for clinical beam intensities and a modest increase for very high intensities. Conclusion: Using HIMAK in research mode the implications are that the FD has no clinical impact on the clinical CIRT beam intensities for MCF and maybe planned for higher intensities by incorporating FS into the TPS to predict the modest increased dose to OARs. A method for commissioning and quality assurance of FD has been proposed. [ABSTRACT FROM AUTHOR]

Background: Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose‐Driven‐Continuous‐Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or "break points," allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam‐off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump. Purpose: The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS. Method: We conducted fixed‐point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed‐point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam‐off and beam‐on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam‐off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model. Result: We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam‐off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose. Conclusion: We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam‐off control. [ABSTRACT FROM AUTHOR]

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose–volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a −0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost. [ABSTRACT FROM AUTHOR]

In this study, we report our experience in commissioning a commercial treatment planning system (TPS) for fast-raster scanning of carbon-ion beams. This TPS uses an analytical dose calculation algorithm, a pencil-beam model with a triple Gaussian form for the lateral-dose distribution, and a beam splitting algorithm to consider lateral heterogeneity in a medium. We adopted the mixed beam model as the relative biological effectiveness (RBE) model for calculating the RBE values of the scanned carbon-ion beam. To validate the modeled physical dose, we compared the calculations with measurements of various relevant quantities as functions of the field size, range and width of the spread-out Bragg peak (SOBP), and depth–dose and lateral-dose profiles for a 6-mm SOBP in water. To model the biological dose, we compared the RBE calculated with the newly developed TPS to the RBE calculated with a previously validated TPS that is in clinical use and uses the same RBE model concept. We also performed patient-specific measurements to validate the dose model in clinical situations. The physical beam model reproduces the measured absolute dose at the center of the SOBP as a function of field size, range, and SOBP width and reproduces the dose profiles for a 6-mm SOBP in water. However, the profiles calculated for a heterogeneous phantom have some limitations in predicting the carbon-ion-beam dose, although the biological doses agreed well with the values calculated by the validated TPS. Using this dose model for fast-raster scanning, we successfully treated more than 900 patients from October 2018 to October 2020, with an acceptable agreement between the TPS-calculated and measured dose distributions. We conclude that the newly developed TPS can be used clinically with the understanding that it has limited accuracies for heterogeneous media. [ABSTRACT FROM AUTHOR]

Simple Summary: Using a consistent experimental protocol, we found a large heterogeneity in the relative biological effectiveness (RBE) values of both proton and carbon-ion beams in various sarcomas and normal-tissue-derived cell lines. Our data suggest that proton beam therapy may be more beneficial for some types of tumors. In carbon-ion therapy, for some types of tumors, large heterogeneity in RBE should prompt consideration of dose reduction or an increased dose per fraction. In particular, a higher RBE value in normal tissues requires caution. Specific dose evaluations for tumor and normal tissues are needed for both proton and carbon-ion therapies. 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. [ABSTRACT FROM AUTHOR]

Purpose: Herein, we report the methods and results of the Hitachi carbon‐ion therapy facility commissioning to determine the optimum values of the magnitude of movement and repaint number in respiratory‐gated irradiation. Methods: A virtual‐cylinder target was created using the treatment‐planning system (VQA Plan), and measurements were performed to study the effects of respiratory movements using a two‐dimensional ionization‐chamber array detector and a phantom with movable wedge and stage. For simulations, we selected a 10 × 10 × 10 cm3 cubic irradiation pattern with a uniform physical dose and two actual cases of liver‐cancer treatments, whose prescribed doses were 60 Gy(RBE)/4 fraction (Case 1) and 60 Gy(RBE)/12 fraction (Case 2). We employed two types of repainting methods, one produced by the algorithm of VQA Plan (VQA algorithm) and the other by ideal repainting. The latter completely repeats all spots with set number of repaintings. We performed flatness calculations and gamma analysis to evaluate the effects of each condition. Results: From the measurements, the gamma passing rates for which the criteria were 3%/3 mm exceeded 95% for displacements in the head‐to‐tail direction if the repaint number was greater than 3 and the magnitude of the residual motions was less than 5.0 mm. In simulations with the cubic irradiation pattern, the gamma passing rates (with criteria of 2%/2 mm) exceeded 95% when the magnitude of the residual motions was 3.0 mm and the repaint number was greater than 3. When the repaint number was set to 4 in the VQA with the actual liver cases, the flatness results for Case 2 was minimal. For ideal repainting, the flatness results for all ports fell within ∼3.0% even when the magnitude of the residual motions was 5.0 mm if the repaint number was 6. However, the flatness was less than 3.0% for almost all ports if the magnitude of the residual motions was less than 3.0 mm with a repaint number of 4 in case of both types of repaint methods. Conclusions: At our facility, carbon‐ion radiotherapy can be provided safely to a moving target with residual motions of 3.0 mm magnitude and with a repaint number of 4. [ABSTRACT FROM AUTHOR]

Purpose: Carbon ion radiotherapy for prostate cancer was performed using two fine needle Gold Anchor (GA) markers for patient position verification in Osaka Heavy Ion Medical Accelerator in Kansai (Osaka HIMAK). The present study examined treatment plans for prostate cases using beam‐specific planning target volume (bsPTV) based on the effect of the markers on dose distribution and analysis of target movements. Materials and Methods: Gafchromic EBT3 film was used to measure dose perturbations caused by markers. First, the relationships between the irradiated film density and absolute dose with different linear energy transfer distributions within a spread‐out Bragg peak (SOBP) were confirmed. Then, to derive the effect of markers, two types of markers, including GA, were placed at the proximal, center, and distal depths within the same SOBP, and dose distributions behind the markers were measured using the films. The amount of internal motion of prostate was derived from irradiation results and analyzed to determine the margins of the bsPTV. Results: The linearity of the film densities against absolute doses was constant within the SOBP and the amount of dose perturbations caused by the markers was quantitatively estimated from the film densities. The dose perturbation close behind the markers was smallest (<10% among depths within the SOBP regardless of types of markers) and increased with depth. The effect of two types of GAs on dose distributions was small and could be ignored in the treatment planning. Based on the analysis results of internal motions of prostate, required margins of the bsPTV were found to be 8, 7, and 7 mm in left–right (LR), anterior–posterior (AP), and superior–inferior (SI) directions, respectively. Conclusion: We evaluated the dose reductions caused by markers and determined the margins of the bsPTV, which was applied to the treatment using fiducial markers, using the analysis results of prostate movements. [ABSTRACT FROM AUTHOR]

We have developed physical and biological beam modeling for carbon scanning therapy at the Osaka Heavy Ion Therapy Center (Osaka HIMAK). Carbon beam scanning irradiation is based on continuous carbon beam scanning, which adopts hybrid energy changes using both accelerator energy changes and binary range shifters in the nozzles. The physical dose calculation is based on a triple Gaussian pencil‐beam algorithm, and we thus developed a beam modeling method using dose measurements and Monte Carlo simulation for the triple Gaussian. We exploited a biological model based on a conventional linear‐quadratic (LQ) model and the photon equivalent dose, without considering the dose dependency of the relative biological effectiveness (RBE), to fully comply with the carbon passive dose distribution using a ridge filter. We extended a passive ridge‐filter design method, in which carbon and helium LQ parameters are applied to carbon and fragment isotopes, respectively, to carbon scanning treatment. We then obtained radiation quality data, such as the linear energy transfer (LET) and LQ parameters, by Monte Carlo simulation. The physical dose was verified to agree with measurements to within ±2% for various patterns of volume irradiation. Furthermore, the RBE in the middle of a spread‐out Bragg peak (SOBP) reproduced that from passive dose distribution results to within ±1.5%. The developed carbon beam modeling and dose calculation program was successfully applied in clinical use at Osaka HIMAK. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to develop a deep learning (DL) method for generating virtual noncontrast (VNC) computed tomography (CT) images from contrast‐enhanced (CE) CT images (VNCDL) and to evaluate its performance in dose calculations for head and neck radiotherapy in comparison with VNC images derived from a dual‐energy CT (DECT) scanner (VNCDECT). Methods: This retrospective study included data for 61 patients who underwent head and neck radiotherapy. All planning CT images were obtained with a single‐source DECT scanner (80 and 140 kVp) with rapid kVp switching. The DL‐based method used a pair of virtual monochromatic images (VMIs) at 70 keV with and without contrast materials. VMIs without contrast materials were used as reference true noncontrast (TNC) images. Deformable image registration was used between the TNC and CE images. We used the data of 45 patients, chosen randomly, for training (7922 paired images), and data from the other 16 patients as test data. We generated the VNCDL images with a densely connected convolutional network. As the VNCDECT images, we used VMIs with the iodine signal suppressed, reconstructed from the CE images of the 16 test patients. The CT numbers of the tumor, common carotid artery, internal jugular vein, muscle, fat, bone marrow, cortical bone, and mandible of each VNC image were compared with those of the TNC image. The dose of the reference TNC plan was recalculated using the CE, VNCDL, and VNCDECT images. Difference maps of the dose distributions and dose–volume histograms were evaluated. Results: The mean prediction time for the VNCDL images was 3.4 s per patient, and the mean number of slices was 204. The absolute differences in CT numbers of the VNCDL images were significantly smaller than those of the VNCDECT images for the bone marrow (8.0 ± 6.5 vs 175.1 ± 40.9 HU; P < 0.001) and mandible (20.3 ± 19.3 vs 106.2 ± 80.5 HU; P = 0.002). The DL‐based model provided the dose distribution most similar to that of the TNC plan. With the VNCDECT plans, dose errors >1.0% were observed in bone regions. The dose–volume histogram analysis showed that the VNCDL plans yielded the smallest errors for the primary target, although dose differences were <1.0% for all the approaches. For the maximum dose to the mandible, the mean ± SD errors for the CE, VNCDL, and VNCDECT plans were –0.13% ± 0.23% (range: −0.46% to 0.31%; P = 0.037), –0.01% ± 0.22% (range: −0.40% to 0.36%; P = 1.0), and 0.53% ± 0.47% (range: −0.21% to 1.41%; P < 0.001), respectively. Conclusions: In this study, we developed a method based on DL that can rapidly generate VNC images from CE images without a DECT scanner. Compared with the DECT approach, the DL‐based method improved the prediction accuracy of CT numbers in bone regions. Consequently, there was greater agreement between the VNCDL and TNC plan dose distributions than with the CE and VNCDECT plans, achieved by suppressing the contrast material signals while retaining the CT numbers of bone structures. [ABSTRACT FROM AUTHOR]

The aim of this work is to generate synthetic computed tomography (sCT) images from multi-sequence magnetic resonance (MR) images using an adversarial network and to assess the feasibility of sCT-based treatment planning for brain radiotherapy. Datasets for 15 patients with glioblastoma were selected and 580 pairs of CT and MR images were used. T1-weighted, T2-weighted and fluid-attenuated inversion recovery MR sequences were combined to create a three-channel image as input data. A conditional generative adversarial network (cGAN) was trained using image patches. The image quality was evaluated using voxel-wise mean absolute errors (MAEs) of the CT number. For the dosimetric evaluation, 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans were generated using the original CT set and recalculated using the sCT images. The isocenter dose and dose–volume parameters were compared for 3D-CRT and VMAT plans, respectively. The equivalent path length was also compared. The mean MAEs for the whole body, soft tissue and bone region were 108.1 ± 24.0, 38.9 ± 10.7 and 366.2 ± 62.0 hounsfield unit, respectively. The dosimetric evaluation revealed no significant difference in the isocenter dose for 3D-CRT plans. The differences in the dose received by 2% of the volume (D 2%), D 50% and D 98% relative to the prescribed dose were <1.0%. The overall equivalent path length was shorter than that for real CT by 0.6 ± 1.9 mm. A treatment planning study using generated sCT detected only small, clinically negligible differences. These findings demonstrated the feasibility of generating sCT images for MR-only radiotherapy from multi-sequence MR images using cGAN. [ABSTRACT FROM AUTHOR]

Purpose: A contrast‐enhancing agent is imperative for the accurate target delineation of pancreatic tumors. This study demonstrates the potential use of treatment planning for patients with pancreatic tumors based on the water density image (WDI) generated by dual‐energy computed tomography (DECT). Methods: Tissue characterization and multi‐energy phantom scanning were performed through DECT and the physical characteristics of the WDI and a virtual monochromatic image (VMI) were assessed. The measured and the corresponding theoretical electron density relative to water (RED) and mass density (MD) were compared. Treatment plans based on the WDI (TPWDI) and VMI (TPVMI) were compared for 22 pancreatic cancer patients who underwent contrast‐enhanced DECT scan. Results: The total absolute difference in the HU value between the conventional 120 kVp images and the VMI was the smallest at the energy level of 77 keV (3.3 HU), and the VMI at 77 keV was used for subsequent analysis. The difference between the measured and theoretical values of RED and MD for iodine using the VMI (>15%) was larger than that using WDI (<4%). In clinical cases, the maximum difference in the dosimetric parameters between TPWDI and TPWDI for the planning target volume was 3.0% when the doses were calculated using AXB, and for the duodenum, it was 1.7%. Conclusions: The WDI estimated the RED and MD accurately and could form the basis for a new treatment planning approach for pancreatic cancer using contrast‐enhancing agent. [ABSTRACT FROM AUTHOR]

Background: The incomplete repair (IR) model expresses the cell repair effect from radiation-induced damage over time, which is given little consideration in actual treatment planning. By incorporating the IR model into the normal tissue complication probability (NTCP), the accuracy and safety of treatment plan evaluations concerning the effect of repair can be improved. This study aims to evaluate the impact of incorporating the IR model into the NTCP by varying time-related factors such as the repair half-time (T1/2) and the junction-shift sc3hedule in craniospinal irradiation (CSI).Methods: CSI was planned retrospectively, and the NTCP of the spinal cord was calculated with the IR model for values of T1/2 from 1 to 10 h. The NTCP in the case of changing the junction-shift schedule was also examined in the same manner.Results: The NTCP with the IR model increased with increasing T1/2, which is prominent for the larger T1/2. By changing the junction-shift schedule, the NTCP with the IR model decreased when adjacent fields overlapped.Conclusions: The IR model is a valuable addition to treatment planning because it enables the NTCP to be evaluated including the effect of repair and differences in scheduling to be reflected in the NTCP. However, these are largely dependent on the value of the T1/2. [ABSTRACT FROM AUTHOR]

The ground fault experiment for the 275-kV high-temperature superconductor cable was conducted in the project “Demonstration studies of the stability and reliability of next-generation transmission systems,” sponsored by NEDO. A short piece of the cable, which had an artificial ground fault point with an iron pin, was stood and poured with liquid nitrogen, and then conducted alternating current for three cycles, 60 ms. As a result, the current flowed in the ground fault path and caused an arc discharge. When the effective current was less than 5 kA, the arc lasted only half a cycle to invert the polarity. When the current was over 5 kA, the samples were damaged severely. The cryostat pipes were vented completely, and the cable cores were cratered deeply. [ABSTRACT FROM PUBLISHER]

A simulation has been developed for estimating the transient temperature and pressure distributions in a high-temperature superconducting (HTS) power cable with a fault current accident cooled by a forced flow of subcooled liquid nitrogen (LN2). This simulation is an essential tool for realizing a practical HTS power cable in order to assess the effects of short-circuit accidents. When a fault occurs in a 275 kV class power transmission system in Japan, an excessive current of 63 kA may flow in the cable for 0.6 s. When faults occur, it is important to estimate the temperature and pressure profiles in a cable cooled by the forced flow of subcooled LN2. The temperature profiles of the LN2 coolant and the cable cores were analyzed by solving nonlinear partial differential equations of the heat transfer phenomenon through heat conduction using finite-difference method. The GASPAK software package (Cryodata) was used to evaluate the fluid properties. The simulation results for 275 kV class 20 m model cable show fairly good agreement with the experimental results obtained by Fukukawa Electric. [ABSTRACT FROM PUBLISHER]

High-temperature superconducting (HTS) power cable has significant merits of compactness and large power transmission capacity. Although the stability of the HTS cable system was verified by in-grid operation, the verification of its safety and reliability against various accidents is required for practical use of this system. A ground fault accident is one of the typical accidents of a conventional cable. If this fault occurs by breakdown of the dielectric layer, the generated arc energy is dissipated into the environment in various forms. As a result, the safety of the public may be jeopardized. Arc energy relates to arc voltage, which is dependent on the inherent physical properties of the faulted equipment. The use of coolant and the structure of the HTS cable differentiate it from a conventional cable, so it should be verified how these differences influence the arc voltage. Accordingly, ground fault tests using the HTS cable were conducted and the arc voltages were compared to that of a conventional cable. The results obtained proved that the arc voltage on the HTS cable is similar to that of a conventional cable, in spite of the differences concerning the use of coolant and the cable structure. [ABSTRACT FROM PUBLISHER]

The unintended side effects of cancer treatment are increasing recognized. Among these is a syndrome of long-term neurocognitive dysfunction called cancer/chemotherapy related cognitive impairment. To date, all studies examining the cognitive impact of cancer treatment have emphasized chemotherapy. Radiation-induced bystander effects have been described in cell culture and, to a limited extent, in rodent model systems. The purpose of this study was to examine, for the first time, the impact of non-brain directed radiation therapy on the brain in order to elucidate its potential relationship with cancer/chemotherapy related cognitive impairment. To address this objective, female BALB/c mice received either a single 16 gray fraction of ionizing radiation to the right hind limb or three doses of methotrexate, once per week for three consecutive weeks. Mice were sacrificed either 3 or 30 days post-treatment and brain injury was determined via quantification of activated astrocytes and microglia. To characterize the effects of non-brain directed radiation on brain glucose metabolism, mice were evaluated by fluorodeoxygluocose positron emission tomography. A single fraction of 16 gray radiation resulted in global decreases in brain glucose metabolism, a significant increase in the number of activated astrocytes and microglia, and increased TNF-α expression, all of which lasted up to 30 days post-treatment. This inflammatory response following radiation therapy was statistically indistinguishable from the neuroinflammation observed following methotrexate administration. In conclusion, non-brain directed radiation was sufficient to cause significant brain bystander injury as reflected by multifocal hypometabolism and persistent neuroinflammation. These findings suggest that radiation induces significant brain bystander effects distant from the irradiated cells and tissues. These effects may contribute to the development of cognitive dysfunction in treated human cancer patients and warrant further study. [ABSTRACT FROM AUTHOR]

Purpose: During radiotherapy, maintaining the patient in a relaxed and comfortable state helps ensure respiratory regularity and reproducibility, thereby supports accurate respiratory tracking/gating treatment. Criteria to evaluate respiratory naturalness, regularity, and phase robustness are therefore needed to aid for the treatment system numerically and medical observers visually. This study introduces a new concept of respiratory tumor kinematics that describes the trajectory of tumor motion with respiration, leading to the minimum jerk theory. Using this theory, this study proposes novel respiratory criteria for respiratory naturalness, regularity, and phase robustness. Methods: According to respiratory tumor kinematics, tumor motion follows the minimum curvature/ jerk trajectory in 4D spacetime. Using this theory, the following three respiratory criteria are proposed: (1) respiratory naturalness (Us), the residual sum of the squared difference between the normalized average free respiratory wave (single inhalation/exhalation averaged over each 10 phases) and the normalized minimum jerk theoretical respiratory wave; (2) respiratory regularity (Cj16), the cumulative jerk squared cost function sampling every 0.2 s with a peak adjustment coefficient, 16; and (3) respiratory phase robustness (LΔ), a second-order partial differential in the respiratory position for regarded Cj16 as the respiratory position function. To verify these respiratory criteria, values obtained from CyberKnife tracking marker log data for 15 patients were compared with regard to the correlation error between the correlation model and the imaged tumor position, as well as with the number of remodels. The Cj16 growth curve was also compared between 15 patients and 15 healthy volunteers. Results: In the 15 patients, data with Us < 1 and Cj16(60 s) < 10 000 satisfied average/maximum correlation errors of less than 1/3 mm. Data with higher Us values (less respiratory naturalness) and higher Cj16(60 s) values (less respiratory regularity) demonstrated more than 3 mm average/5 mm maximum correlation errors and an increased number of remodels. The data for the 15 patients and 15 volunteers demonstrated that the Cj16 growth curve over 120 s from the start of sampling indicated patient-specific respiratory trends and that the distribution of LΔ clearly showed the respiratory phase shift. In 22 of 30 subjects, the degree of change in the Cj growth curve trends from 60 to 120 s was 22%±13% (average ± SD). In contrast, the residual data observed when Cj16 > 1000 showed minimum and mean changes of 91% and 180%, respectively. Conclusions: The authors developed and verified novel respiratory criteria for respiratory naturalness, regularity, and phase robustness obtained using respiratory tumor kinematics and minimum jerk analysis. These criteria should be useful in monitoring respiratory trends on a real-time basis during treatment, as well as in selecting optimal breathing for tracking/gating radiation treatment and defining numerical goals for respiratory training/gating. [ABSTRACT FROM AUTHOR]

Purpose: CyberKnife® robotic surgery system has the ability to deliver radiation to a tumor subject to respiratory movements using Synchrony® mode with less than 2 mm tracking accuracy. However, rapid and rough motion tracking causes mechanical tracking errors and puts mechanical stress on the robotic joint, leading to unexpected radiation delivery errors. During clinical treatment, patient respiratory motions are much more complicated, suggesting the need for patient-specific modeling of respiratory motion. The purpose of this study was to propose a novel method that provides a reference respiratory wave to enable smooth tracking for each patient. Methods: The minimum jerk model, which mathematically derives smoothness by means of jerk, or the third derivative of position and the derivative of acceleration with respect to time that is proportional to the time rate of force changed was introduced to model a patient-specific respiratory motion wave to provide smooth motion tracking using CyberKnife®. To verify that patient-specific minimum jerk respiratory waves were being tracked smoothly by Synchrony® mode, a tracking laser projection from CyberKnife® was optically analyzed every 0.1 s using a webcam and a calibrated grid on a motion phantom whose motion was in accordance with three pattern waves (cosine, typical freebreathing, and minimum jerk theoretical wave models) for the clinically relevant superior-inferior directions from six volunteers assessed on the same node of the same isocentric plan. Results: Tracking discrepancy from the center of the grid to the beam projection was evaluated. The minimum jerk theoretical wave reduced the maximum-peak amplitude of radial tracking discrepancy compared with that of the waveforms modeled by cosine and typical free-breathing model by 22% and 35%, respectively, and provided smooth tracking for radial direction. Motion tracking constancy as indicated by radial tracking discrepancy affected by respiratory phase was improved in the minimum jerk theoretical model by 7.0% and 13% compared with that of the waveforms modeled by cosine and free-breathing model, respectively. Conclusions: The minimum jerk theoretical respiratory wave can achieve smooth tracking by CyberKnife® and may provide patient-specific respiratory modeling, which may be useful for respiratory training and coaching, as well as quality assurance of the mechanical CyberKnife® robotic trajectory. [ABSTRACT FROM AUTHOR]

Purpose The marrow composition throughout the body is heterogeneous and changes with age. Due to heterogeneity, invasive biopsies of the iliac crest do not truly represent the complete physiological status, impeding the clinical effectiveness of this method. Therefore, we aim to provide verification for an in vivo imaging technique using co-registered histologic examinations for assessment of marrow adiposity. Methods Five recently expired (i.e. < 24 h) human cadavers were scanned with a dual source CT (DECT) scanner in order to measure marrow fat in the lumbar vertebrae. These donors were also imaged using water–fat MRI (wfMRI) which was used to estimate the fraction of yellow marrow. After imaging, lumbar columns were excised and the superior and inferior aspects of 21 vertebrae were removed. The remaining center section was processed for histological examination to find the ratio of adipocyte volume per tissue volume (AV/TV). Results Results of DECT and wfMRI had a high correlation (r = 0.88). AV/TV ranged from 0.18 to 0.75 with a mean (SD) of 0.36 (0.18). Inter-evaluator reliability for AV/TV was r > 0.984. There were similar correlations between AV/TV and the imaging modalities, DECT-derived MF and wfMRI (r = 0.802 and 0.772, respectively). Conclusions A high MF variation was seen among the 25 vertebrae imaged. Both DECT and wfMRI have a good correlation with the histologic adipocyte proportion and can be used to measure MF. This makes longitudinal studies possible without painful, less-effective, invasive biopsies. [ABSTRACT FROM AUTHOR]

Recent studies have proven that skeleton-wide functional assessment is essential to comprehensively understand physiological aspects of the skeletal system. Therefore, in contrast to regional imaging studies utilizing a multiple-animal holder (mouse hotel), we attempted to develop and characterize a multiple-mouse imaging system with micro-PET/CT for high-throughput whole-skeleton assessment. Using items found in a laboratory, a simple mouse hotel that houses four mice linked with gas anesthesia was constructed. A mouse-simulating phantom was used to measure uniformity in a cross sectional area and flatness ( A max / A min *100) along the axial, radial and tangential directions, where A max and A min are maximum and minimum activity concentration in the profile, respectively. Fourteen mice were used for single- or multiple-micro-PET/CT scans. NaF uptake was measured at eight skeletal sites (skull to tibia). Skeletal 18 F activities measured with mice in the mouse hotel were within 1.6 ± 4% (mean ± standard deviation) of those measured with mice in the single-mouse holder. Single-holder scanning yields slightly better uniformity and flatness over the hotel. Compared to use of the single-mouse holder, scanning with the mouse hotel reduced study time (by 65%), decreased the number of scans (four-fold), reduced cost, required less computer storage space (40%), and maximized 18 F usage. The mouse hotel allows high-throughput, quantitatively equivalent scanning compared to the single-mouse holder for micro-PET/CT imaging for whole-skeleton assessment of mice. [ABSTRACT FROM AUTHOR]

Background: Recent work by Saito (2012) has demonstrated a simple conversion from energy-subtracted computed tomography (CT) values (ΔHU) obtained using dual-energy CT to relative electron density (RED) via a single linear relationship. The purpose of this study was to investigate the feasibility of this method to obtain RED from virtual monochromatic CT images obtained by the gemstone spectral imaging (GSI) mode with fast-kVp switching. Methods: A tissue characterization phantom with 13 inserts made of different materials was scanned using the GSI mode on a Discovery CT750 HD. Four sets of virtual monochromatic CT images (60, 77, 100 and 140 keV) were obtained from a single GSI acquisition. When we define Δ HU in terms of the weighting factor for the subtraction α, Δ HU = (1 + α)H - αL (H and L represent the CT values for high and low energy respectively), the relationship between Δ HU and RED is approximated as a linear function, α x Δ HU/1000 + b (a, b = unity). We evaluated the agreement between the determined and nominal RED. We also have investigated reproducibility over short and long time periods. Results: For the 13 insert materials, the RED determined by monochromatic CT images agreed with the nominal values within 1.1% and the coefficient of determination for this calculation formula was greater than 0.999. The observed reproducibility (1 standard deviation) of calculation error was within 0.5% for all materials. Conclusions: These findings indicate that virtual monochromatic CT scans at two different energies using GSI mode can provide an accurate method for estimating RED. [ABSTRACT FROM AUTHOR]

The current margin of a jointed model cable of the 275 kV class high-temperature superconductor (HTS) power cable was measured under fault condition. The cable-to-cable joint is necessary to connect long continuous sections of the power cable. At the joint the superconductor is prone to degradation due to an excessive temperature rise caused by the current passing through normal conducting zones of the joint. The jointed, and for the comparison the joint-less cables were subjected to a short-circuited fault current of 63 kA rms for 0.6 s. In the results, the allowable current margins were about the same for both model cables. The jointed cable degraded at the joint area from the result of the magneto-optical (MO) image. The numerical simulations were performed to clarify current distribution and temperature rise at the cable joint area. The temperature rise as a function of the joint gap was also calculated. The experimental and simulation results were showed in this paper. [ABSTRACT FROM PUBLISHER]

YBCO coated conductors are candidate materials for future electric power devices such as transmission cables, transformers, and fault current limiters. In practical applications, YBCO coated conductors are subject to short-circuit fault currents greater than the operating current. These fault currents cause heat generation, resulting in degradation of the characteristics of YBCO coated conductors. It is therefore necessary to identify the maximum temperatures under which YBCO coated conductors can operate without suffering degradation. To date, we have carried out preliminary experiments on the degradation of YBCO coated conductors due to an over-current pulse. We also focused on the relationship between increases in temperature and Ic degradation. In this study, we prepared YBCO coated conductors fabricated by TFA-MOD method. We also carried out over-current tests to investigate the Ic degradation and performed numerical simulations on thermal stress to estimate the stress and strain acting on the YBCO layer. [ABSTRACT FROM AUTHOR]

High-temperature superconducting (HTS) cables are considered the next generation transmission line because they are compact, lightweight, and demonstrate large capacity and low loss compared to conventional cables. In particular, since a coated conductor (YBCO wire) provides high critical current, high magnetic-field property, low AC loss, and low cost, it is expected to make the HTS cable more attractive than other superconducting wire. In Japan, 66/77 kV HTS cables have developed for about 20 years. We started developing 275 kV class HTS cables three years ago based on 66/77 kV HTS cables. The goal is a 275 kV 3 kA cable with a capacity of 1.5 GVA, the same capacity as a typical overhead transmission line, which serves as the backbone of Japanese power networks. [ABSTRACT FROM AUTHOR]

The effects of removing low-Jc edges of coated conductors by a laser for ac loss reduction were studied in two-layer superconducting power transmission cables. By removing the low-Jc edges, narrower coated conductor with more uniform Jc distribution can be obtained. The original 5 mm-wide coated conductors as well as the edge-removed 4 mm-wide and 3 mm-wide coated conductors were assembled spirally around cyrindrical formers in two layers to form a cable. The measured ac losses were compared with the ac losses calculated using a numerical model where the spiral structure is neglected. For ac loss calculations, we used the lateral Jc distribution of the coated conductor measured by the magnetic knife method or those which are assumed based on the losses of the critical current by the edge removal. [ABSTRACT FROM AUTHOR]

In Japan, a project for the development of a 275-kV class YBCO power cable started in 2008. High-temperature superconducting (HTS) power cables typically consist of a copper former, an HTS conductor layer, an electrical insulation layer, an HTS shield layer, and a copper shield layer. In practical applications, the 275-kV class transmission line may be subjected to short-circuit fault currents such as 63 kArms for a duration of 0.6 s. Therefore, in order to ensure the stability and demonstrate the feasibility of the cable, it is important to estimate the current distribution and temperature increase under the fault condition. We designed the copper former, copper shield layer, and copper plating of the YBCO coated conductor carefully so as to fulfill the requirements of practical applications. In this study, we carried out over-current experiments on a 2-m long YBCO model cable and performed numerical simulations by a computer program developed using the finite element method (FEM) and an electric circuit model. We investigated the electromagnetic and thermal behaviors of the cable under fault conditions from the experimental and simulation results. [ABSTRACT FROM AUTHOR]

In Japan, the development of a 275 kV/3 kA class YBa2Cu3O7 (YBCO) power cable was started in 2008. A high-temperature superconducting (HTS) power cable typically consists of a copper former, HTS conductor layers, an electrical insulation layer, HTS shield layers, and copper shield layers. 275 kV/3 kA class YBCO power cables may be subjected to a fault current of 63 kArms for 0.6 s. Therefore, in order to ensure stability and feasibility of superconducting power cables, we need to investigate the thermal characteristics and current distribution in the cable under fault conditions. In this study, we performed numerical simulations on a YBCO model cable under fault conditions by using a computer program we developed on the basis of 3D finite element method (FEM) and electrical circuit model. [ABSTRACT FROM AUTHOR]

YBCO tapes are expected to be used in future high temperature superconducting (HTS) applications because of their good Jc characteristics at high temperatures and in high applied magnetic fields. In applications to electric power devices such as transmission cables, transformers, and fault current limiters, the HTS conductors will be subjected to short-circuit fault currents that are 10 to 30 times the normal operating current. These over-currents are greater than the critical current, and degrade or burn-out the HTS conductors. Therefore, it is important to clarify the mechanism of the degradation caused by such over-current pulses. We carried out preliminary experiments on damage caused by over-current pulse drive, focusing on the temperature limitation without suffering degradation for over-current pulse operation. A 10-mm-wide YECO tape was cut into 2-mm-wide sample tapes by a laser beam, and the sample tapes were soldered on silver-deposited 100-μm-thick copper plates. Over-current tests were carried out on these sample tapes and Ic degradation was investigated. In addition the contact interface between YBCO and the Ag layer or buffer layer before and after the over-current drives has been investigated in order to clarify the correlation between the degradation and delamination of sample tapes. [ABSTRACT FROM AUTHOR]

To achieve large current capacity and mechanical flexibility, high-temperature superconductor (HTS) power transmission cables consist of a number of YBCO coated conductors, which are assembled and wound spirally on a Cu former. In practical applications, superconducting cables might be subjected to short-circuit fault currents that are 10 to 30 times the operating current. Therefore, in order to ensure the stability and feasibility of HTS power cables and protect them from fault currents, it is important to estimate the redistribution of the transport current and electromagnetic coupling among the conductor layer, shield layer, and Cu former. In this study, we carried out experiments on a 20-rn-long YBCO model cable, which was composed of two jointed 10-rn-long YBCO model cables. Over-current with a peak of 31.8 k-Arms and a duration of 2.02 s was applied to the model cable. We performed numerical simulations using a newly developed computer program based on the 3D finite element method (FEM) in order to clarify the electromagnetic and thermal behaviors of the YBCO model cable in the presence of an over-current. [ABSTRACT FROM AUTHOR]

YBCO tapes are expected to be used in future high temperature superconductor (HTS) applications as they have better Jc characteristics at high temperatures and in high magnetic fields. For power applications such as transmission cables, YBCO tapes and a copper former are connected in parallel and they might be subjected to a short-circuit fault current that is 10 to 30 times the normal operating current. Therefore, the over-current behavior, including the hot-spot and the distribution of transport current between the copper-laminated YBCO tapes and the copper former, is very important to examine the stability and feasibility of the cable. This paper describes the experimental results for over-current pulses of a 1-m single-layer cable fabricated with five copper-laminated YBCO tapes and a copper former. Further, we performed numerical simulations by using a newly developed computer program based on the 3D finite element method. [ABSTRACT FROM AUTHOR]

AC losses in power transmission cables composed of coated conductors could be potentially small. A strategy to approach their potentially small AC loss was studied. AC losses in mono-layer conductors for cables were calculated numerically in order to show the principle for AC loss reduction: use of narrower coated conductors and/or decrease in space between conductors reduce the magnetic field component perpendicular to the wide face of coated conductors, and they are effective for AC loss reduction. This principle was confirmed experimentally by using short monolayer conductors. Based on the principle, 1 kArms-class three-layer conductors were fabricated, and AC loss of 0.054 W/m at 1 kArms was achieved in a three-layer conductor whose outer diameter is 19.6 mm. The influence of a magnetic substrate on the AC losses in a single coated conductor and a mono-layer conductor for a cable was studied numerically. [ABSTRACT FROM AUTHOR]

The 500 m high temperature superconducting cable (HTS cable) is 77 kV 1 kA single-core cable with LN2-impregnated paper insulation. Demonstration and verification test of 500 m HTS cable has been started from March 2004 and many useful results can be obtained in the test for future practical uses. Furukawa Electric has mainly taken charge of designing, manufacturing and installation of the 500 m cable. In the manufacturing process, the cable could be fabricated without Ic degradation in Ag/Bi-2223 tapes. Moreover, various factory tests were carried out for the 500 m cable. The result of tests showed that the cable has sufficiently satisfied the quality requirement. In the installation, the cable was successfully pulled into a cable duct of 170 m long like actual underground cable installations. [ABSTRACT FROM AUTHOR]