Electrochemistry in bicontinuous microemulsions derived from two immiscible electrolyte solutions for a membrane-free redox flow battery.

HYPOTHESES: Bicontinuous microemulsions (BMEs) have attracted attention as unique heterogeneous mixture for electrochemistry. An interface between two immiscible electrolyte solutions (ITIES) is an electrochemical system that straddles the interface between a saline and an organic solvent with a lipophilic electrolyte. Although most BMEs have been reported with nonpolar oils, such as toluene and fatty acids, it should be possible to construct a sponge-like three-dimensionally expanded ITIES comprising a BME phase. EXPERIMENTS: Dichloromethane (DCM)-water microemulsions stabilized by a surfactant were investigated in terms of the concentrations of co-surfactants and hydrophilic/lipophilic salts. A Winsor III microemulsion three-layer system, consisting of an upper saline phase, a middle BME phase, and a lower DCM phase, was prepared, and electrochemistry was conducted in each phase. FINDINGS: We found the conditions for ITIES-BME phases. Regardless of where the three electrodes were placed in the macroscopically heterogeneous three-layer system, electrochemistry was possible, as in a homogeneous electrolyte solution. This indicates that the anodic and cathodic reactions can be divided into two immiscible solution phases. A redox flow battery comprising a three-layer system with a BME as the middle phase was demonstrated, paving the way for applications such as electrolysis synthesis and secondary batteries.

Effect of External Magnetic Fields on Biological Effectiveness of Proton Beams.

PURPOSE: The purpose is to verify experimentally whether application of magnetic fields longitudinal and perpendicular to a proton beam alters the biological effectiveness of the radiation. METHODS AND MATERIALS: Proton beams with linear energy transfer of 1.1 and 3.3 keV/µm irradiated human cancer and normal cells under a longitudinal (perpendicular) magnetic field of BL (BP) = 0, 0.3, or 0.6 T. Cell survival curves were constructed to evaluate the effects of the magnetic fields on the biological effectiveness. The ratio of dose that would result in a survival fraction of 10% without the magnetic field Dwo to the dose with the magnetic field Dw, R10 = Dwo/Dw, was determined for each cell line and magnetic field. RESULTS: For cancer cells exposed to the 1.1- (3.3-) keV/µm proton beams, R10s were increased to 1.10 ± 0.07 (1.11 ± 0.07) and 1.11 ± 0.07 (1.12 ± 0.07) by the longitudinal magnetic fields of BL = 0.3 and 0.6 T, respectively. For normal cells, R10s were increased to 1.13 ± 0.06 (1.17 ± 0.06) and 1.17 ± 0.06 (1.30 ± 0.06) by the BLs. In contrast, R10s were not changed significantly from 1 by the perpendicular magnetic fields of BP = 0.3 and 0.6 T for both cancer and normal cells exposed to 1.1- and 3.3-keV/µm proton beams. CONCLUSIONS: The biological effectiveness of proton beams was significantly enhanced by longitudinal magnetic fields of BL = 0.3 and 0.6 T, whereas the biological effectiveness was not altered by perpendicular magnetic fields of the same strengths. This enhancement effect should be taken into account in magnetic resonance imaging guided proton therapy with a longitudinal magnetic field.

Effects of Magnetic Field Applied Just Before, During or Immediately after Carbon-Ion Beam Irradiation on its Biological Effectiveness.

Previously reported studies have revealed that the application of a magnetic field longitudinal to a carbon-ion beam enhances its biological effectiveness. Here we investigated how timing of the magnetic field application with respect to beam irradiation influenced this effect. Human cancer cells were exposed to carbon-ion beams with linear energy transfer (LET) of 12 and 50 keV/µm. The longitudinal magnetic field of 0.3 T was applied to the cells just before, during or immediately after the beam irradiation. The effects of the timing on the biological effectiveness were evaluated by cell survival. The biological effectiveness increased only if the magnetic field was applied during beam irradiation for both LETs.

Compression and tension variably alter Osteoprotegerin expression via miR-3198 in periodontal ligament cells.

BACKGROUND: Osteoclasts play a critical role in bone resorption due to orthodontic tooth movement (OTM). In OTM, a force is exerted on the tooth, creating compression of the periodontal ligament (PDL) on one side of the tooth, and tension on the other side. In response to these mechanical stresses, the balance of receptor activator of nuclear-factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) shifts to stimulate osteoclastogenesis. However, the mechanism of OPG expression in PDL cells under different mechanical stresses remains unclear. We hypothesized that compression and tension induce different microRNA (miRNA) expression profiles, which account for the difference in OPG expression in PDL cells. To study miRNA expression profiles resulting from OTM, compression force (2 g/cm2) or tension force (15% elongation) was applied to immortalized human PDL (HPL) cells for 24 h, and miRNA extracted. The miRNA expression in each sample was analyzed using a human miRNA microarray, and the changes of miRNA expression were confirmed by real-time RT-PCR. In addition, miR-3198 mimic and inhibitor were transfected into HPL cells, and OPG expression and production assessed. RESULTS: We found that certain miRNAs were expressed differentially under compression and tension. For instance, we observed that miR-572, - 663, - 575, - 3679-5p, UL70-3p, and - 3198 were upregulated only by compression. Real-time RT-PCR confirmed that compression induced miR-3198 expression, but tension reduced it, in HPL cells. Consistent with previous reports, OPG expression was reduced by compression and induced by tension, though RANKL was induced by both compression and tension. OPG expression was upregulated by miR-3198 inhibitor, and was reduced by miR-3198 mimic, in HPL cells. We observed that miR-3198 inhibitor rescued the compression-mediated downregulation of OPG. On the other hand, miR-3198 mimic reduced OPG expression under tension. However, RANKL expression was not affected by miR-3198 inhibitor or mimic. CONCLUSIONS: We conclude that miR-3198 is upregulated by compression and is downregulated by tension, suggesting that miR-3198 downregulates OPG expression in response to mechanical stress.

Influence of a perpendicular magnetic field on biological effectiveness of carbon-ion beams.

Purpose: Our previous study revealed that the application of a magnetic field longitudinal to a carbon-ion beam of 0.1 ≤ B//≤ 0.6 T enhances the biological effectiveness of the radiation. The purpose of this study is to experimentally verify whether the application of a magnetic field perpendicular to the beam also alters the biological effectiveness. Methods and materials: Most experimental conditions other than the magnetic field direction were the same as those used in the previous study to allow comparison of their results. Human cancer and normal cells were exposed to low (12 keV/µm) and high (50 keV/µm) linear energy transfer (LET) carbon-ion beams under the perpendicular magnetic fields of B⊥ = 0, 0.15, 0.3, or 0.6 T generated by a dipole magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in the survival of 10%, D10s, were determined for the exposures and analyzed using Student's t-tests. Results: For both cancer and normal cells treated by low- and high-LET carbon-ion beams, the D10s measured in the presence of the perpendicular magnetic fields of B⊥ ≥ 0.15 T were not statistically different (p ≫ .05) from the D10s measured in the absence of the magnetic fields, B⊥ = 0 T. Conclusions: Exposure of human cancer and normal cells to the perpendicular magnetic fields of B⊥ ≤ 0.6 T did not alter significantly the biological effectiveness of the carbon-ion beams, unlike the exposure to longitudinal magnetic fields of the same strength. Although the mechanisms underlying the observed results still require further exploration, these findings indicate that the influence of the magnetic field on biological effectiveness of the carbon-ion beam depends on the applied field direction with respect to the beam.

Enhancement of biological effectiveness of carbon-ion beams by applying a longitudinal magnetic field.

Purpose: A magnetic field longitudinal to an ion beam will potentially affect the biological effectiveness of the radiation. The purpose of this study is to experimentally verify the significance of such effects. Methods and materials: Human cancer and normal cell lines were exposed to low (12 keV/µm) and high (50 keV/µm) linear energy transfer (LET) carbon-ion beams under the longitudinal magnetic fields of B// = 0, 0.1, 0.2, 0.3, or 0.6 T generated by a solenoid magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in a survival fraction of 10% (D10s) were determined for each cell line and magnetic field. Results: For cancer cells exposed to the low (high)-LET beams, D10 decreased from 5.2 (3.1) Gy at 0 T to 4.3 (2.4) Gy at 0.1 T, while no further decrease in D10 was observed for higher magnetic fields. For normal cells, decreases in D10 of comparable magnitudes were observed by applying the magnetic fields. Conclusions: Significant decreases in D10, i.e. significant enhancements of the biological effectiveness, were observed in both cancer and normal cells by applying longitudinal magnetic fields of B// ≥ 0.1 T. These effects were enhanced with LET. Further studies are required to figure out the mechanism underlying the observed results.

Difference in normal limit values of nerve conduction parameters between Westerners and Japanese people might need to be considered when diagnosing diabetic polyneuropathy using a Point-of-Care Sural Nerve Conduction Device (NC-stat®/DPNCheck™).

AIM/INTRODUCTION: Studies on a novel point-of-care device for nerve conduction study called DPNCheck have been limited to Westerners. We aimed to clarify Japanese normal limits of nerve action potential amplitude (Amp) and conduction velocity by DPNCheck (investigation I), and the validity of DPNCheck to identify diabetic symmetric sensorimotor polyneuropathy (DSPN; investigation II). MATERIALS AND METHODS: For investigation I, 463 non-neuropathic Japanese participants underwent DPNCheck examinations. Regression formulas calculating the normal limits of Amp and conduction velocity (Japanese regression formulas [JRF]) were determined by quantile regression and then compared with regression formulas of individuals from the USA (USRF). For investigation II, in 92 Japanese diabetes patients, 'probable DSPN' was diagnosed and nerve conduction abnormalities (NCA1: one or more abnormalities, and NCA2: two abnormalities in Amp and conduction velocity) were determined. Validity of NCAs to identify 'probable DSPN' was evaluated by determining sensitivity, specificity, reproducibility (kappa-coefficient) and the area under the curve of receiver operating characteristic curves. RESULTS: For investigation I, JRF was different from USRF, and normal limits by JRF were higher than that of USRF. The prevalence of Amp abnormality calculated by JRF was significantly higher than that of USRF. For investigation II, the sensitivity, specificity and reproducibility of NCA1 and NCA2 judged from JRF were 85%, 86% and 0.57, and 43%, 100% and 0.56, respectively. These values of JRF were higher than those of USRF. The area under the curve of JRF (0.89) was larger than USRF (0.82). CONCLUSIONS: A significant difference in the normal limits of nerve conduction parameters by DPNCheck between Japanese and USA individuals was suggested. Validity to identify DSPN of NCAs might improve by changing the judgment criteria from USRF to JRF.

Treatment planning of intensity modulated composite particle therapy with dose and linear energy transfer optimization.

The biological effect of charged-particle beams depends on both dose and particle spectrum. As one of the physical quantities describing the particle spectrum of charged-particle beams, we considered the linear energy transfer (LET) throughout this study. We investigated a new therapeutic technique using two or more ion species in one treatment session, which we call an intensity modulated composite particle therapy (IMPACT), for optimizing the physical dose and dose-averaged LET distributions in a patient as its proof of principle. Protons and helium, carbon, and oxygen ions were considered as ion species for IMPACT. For three cubic targets of 4 × 4 × 4, 8 × 8 × 8, and 12 × 12 × 12 cm3, defined at the center of the water phantom of 20 × 20 × 20 cm3, we made IMPACT plans of two composite fields with opposing and orthogonal geometries. The prescribed dose to the target was fixed at 1 Gy, while the prescribed LET to the target was varied from 1 keV µm-1 to 120 keV µm-1 to investigate the range of LET valid for prescription. The minimum and maximum prescribed LETs, (L T_min, L T_max), by the opposing-field geometry, were (3 keV µm-1, 115 keV µm-1), (2 keV µm-1, 84 keV µm-1),and (2 keV µm-1, 66 keV µm-1), while those by the orthogonal-field geometry were (8 keV µm-1, 98 keV µm-1), (7 keV µm-1, 72 keV µm-1), and (8 keV µm-1, 57 keV µm-1) for the three targets, respectively. To show the proof of principle of IMPACT in a clinical situation, we made IMPACT plans for a prostate case. In accordance with the prescriptions, the LETs in prostate, planning target volume (PTV), and rectum could be adjusted at 80 keV µm-1, at 50 keV µm-1, and below 30 keV µm-1, respectively, while keeping the dose to the PTV at 2 Gy uniformly. IMPACT enables the optimization of the dose and the LET distributions in a patient, which will maximize the potential of charged-particle therapy by expanding the therapeutic window. Further studies and developments will enable this therapeutic technique to be used in clinical practice.

Technical Note: Range verification system using edge detection method for a scintillator and a CCD camera system.

PURPOSE: Three-dimensional irradiation with a scanned carbon-ion beam has been performed from 2011 at the authors' facility. The authors have developed the rotating-gantry equipped with the scanning irradiation system. The number of combinations of beam properties to measure for the commissioning is more than 7200, i.e., 201 energy steps, 3 intensities, and 12 gantry angles. To compress the commissioning time, quick and simple range verification system is required. In this work, the authors develop a quick range verification system using scintillator and charge-coupled device (CCD) camera and estimate the accuracy of the range verification. METHODS: A cylindrical plastic scintillator block and a CCD camera were installed on the black box. The optical spatial resolution of the system is 0.2 mm/pixel. The camera control system was connected and communicates with the measurement system that is part of the scanning system. The range was determined by image processing. Reference range for each energy beam was determined by a difference of Gaussian (DOG) method and the 80% of distal dose of the depth-dose distribution that were measured by a large parallel-plate ionization chamber. The authors compared a threshold method and a DOG method. RESULTS: The authors found that the edge detection method (i.e., the DOG method) is best for the range detection. The accuracy of range detection using this system is within 0.2 mm, and the reproducibility of the same energy measurement is within 0.1 mm without setup error. CONCLUSIONS: The results of this study demonstrate that the authors' range check system is capable of quick and easy range verification with sufficient accuracy.

Carbon-Ion Pencil Beam Scanning Treatment With Gated Markerless Tumor Tracking: An Analysis of Positional Accuracy.

PURPOSE: Having implemented amplitude-based respiratory gating for scanned carbon-ion beam therapy, we sought to evaluate its effect on positional accuracy and throughput. METHODS AND MATERIALS: A total of 10 patients with tumors of the lung and liver participated in the first clinical trials at our center. Treatment planning was conducted with 4-dimensional computed tomography (4DCT) under free-breathing conditions. The planning target volume (PTV) was calculated by adding a 2- to 3-mm setup margin outside the clinical target volume (CTV) within the gating window. The treatment beam was on when the CTV was within the PTV. Tumor position was detected in real time with a markerless tumor tracking system using paired x-ray fluoroscopic imaging units. RESULTS: The patient setup error (mean ± SD) was 1.1 ± 1.2 mm/0.6 ± 0.4°. The mean internal gating accuracy (95% confidence interval [CI]) was 0.5 mm. If external gating had been applied to this treatment, the mean gating accuracy (95% CI) would have been 4.1 mm. The fluoroscopic radiation doses (mean ± SD) were 23.7 ± 21.8 mGy per beam and less than 487.5 mGy total throughout the treatment course. The setup, preparation, and irradiation times (mean ± SD) were 8.9 ± 8.2 min, 9.5 ± 4.6 min, and 4.0 ± 2.4 min, respectively. The treatment room occupation time was 36.7 ± 67.5 min. CONCLUSIONS: Internal gating had a much higher accuracy than external gating. By the addition of a setup margin of 2 to 3 mm, internal gating positional error was less than 2.2 mm at 95% CI.

Experimental verification of gain drop due to general ion recombination for a carbon-ion pencil beam.

PURPOSE: Accurate dose measurement in radiotherapy is critically dependent on correction for gain drop, which is the difference of the measured current from the ideal saturation current due to general ion recombination. Although a correction method based on the Boag theory has been employed, the theory assumes that ionized charge density in an ionization chamber (IC) is spatially uniform throughout the irradiation volume. For particle pencil beam scanning, however, the charge density is not uniform, because the fluence distribution of a pencil beam is not uniform. The aim of this study was to verify the effect of the nonuniformity of ionized charge density on the gain drop due to general ion recombination. METHODS: The authors measured the saturation curve, namely, the applied voltage versus measured current, using a large plane-parallel IC and 24-channel parallel-plate IC with concentric electrodes. To verify the effect of the nonuniform ionized charge density on the measured saturation curve, the authors calculated the saturation curve using a method which takes into account the nonuniform ionized charge density and compared it with the measured saturation curves. RESULTS: Measurement values of the different saturation curves in the different channels of the concentric electrodes differed and were consistent with the calculated values. The saturation curves measured by the large plane-parallel IC were also consistent with the calculation results, including the estimation error of beam size and of setup misalignment. Although the impact of the nonuniform ionized charge density on the gain drop was clinically negligible with the conventional beam intensity, it was expected that the impact would increase with higher ionized charge density. CONCLUSIONS: For pencil beam scanning, the assumption of the conventional Boag theory is not valid. Furthermore, the nonuniform ionized charge density affects the prediction accuracy of gain drop when the ionized charge density is increased by a higher dose rate and/or lower beam size.

Beam Delivery Method for Carbon-ion Radiotherapy with the Heavy-ion Medical Accelerator in Chiba.

The heavy-ion medical accelerator in Chiba (HIMAC), Japan, has been using carbon-ion radiation therapy since 1994, and the number of patients treated with this technique has reached around 10,000. The HIMAC employs single beam wobbling as a beam-delivery method. Based on the broad-beam method, respiratory-gating and layer-stacking irradiation methods were subsequently developed, which have contributed to significantly increasing irradiation accuracy. During the study and research and development to downsize carbon-ion radiation therapy facilities, a spiral beam-wobbling method was developed, which has been employed in compact carbon-ion radiation therapy facilities constructed in Japan. Toward the further development of the HIMAC treatment, the National Institute of Radiological Sciences has developed new treatment technologies, such as phase-controlled rescanning, based on a fast 3-deminsional (3D) scanning method with a pencil beam toward adaptive cancer radiation therapy. A heavy-ion rotating gantry, combined with 3D-scanning, is currently under development. These technologies developed by the National Institute of Radiological Sciences will hopefully boost the use of heavy-ion radiation therapy worldwide.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan.

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy(-1) and ß = 0.0615 Gy(-2) as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ± 1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

Carbon-ion scanning lung treatment planning with respiratory-gated phase-controlled rescanning: simulation study using 4-dimensional CT data.

BACKGROUND: To moving lung tumors, we applied a respiratory-gated strategy to carbon-ion pencil beam scanning with multiple phase-controlled rescanning (PCR). In this simulation study, we quantitatively evaluated dose distributions based on 4-dimensional CT (4DCT) treatment planning. METHODS: Volumetric 4DCTs were acquired for 14 patients with lung tumors. Gross tumor volume, clinical target volume (CTV) and organs at risk (OARs) were delineated. Field-specific target volumes (FTVs) were calculated, and 48Gy(RBE) in a single fraction was prescribed to the FTVs delivered from four beam angles. The dose assessment metrics were quantified by changing the number of PCR and the results for the ungated and gated scenarios were then compared. RESULTS: For the ungated strategy, the mean dose delivered to 95% of the volume of the CTV (CTV-D95) was in average 45.3 ± 0.9 Gy(RBE) even with a single rescanning (1 × PCR). Using 4 × PCR or more achieved adequate target coverage (CTV-D95 = 46.6 ± 0.3 Gy(RBE) for ungated 4 × PCR) and excellent dose homogeneity (homogeneity index =1.0 ± 0.2% for ungated 4 × PCR). Applying respiratory gating, percentage of lung receiving at least 20 Gy(RBE) (lung-V20) and heart maximal dose, averaged over all patients, significantly decreased by 12% (p < 0.05) and 13% (p < 0.05), respectively. CONCLUSIONS: Four or more PCR during PBS-CIRT improved dose conformation to moving lung tumors without gating. The use of a respiratory-gated strategy in combination with PCR reduced excessive doses to OARs.

Function of chemokine (CXC motif) ligand 12 in periodontal ligament fibroblasts.

The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) demonstrated markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs. CXCL12 plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. Expression of CXCL12 in HPDLFs and HDFs was examined by RT-PCR, qRT-PCR and ELISA. Chemotactic ability of CXCL12 was evaluated in both PDLFs and HDFs by migration assay of MSCs. CXCL12 was also immunohistochemically examined in the PDL in vivo. Expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. CXCL12 was immunohistochemically localized in the fibroblasts in the PDL of rat molars. The results suggest that PDLFs synthesize and secrete CXCL12 protein and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL.

Amplitude-based gated phase-controlled rescanning in carbon-ion scanning beam treatment planning under irregular breathing conditions using lung and liver 4DCTs.

Amplitude-based gating aids treatment planning in scanned particle therapy because it gives better control of uncertainty with the gate window. We have installed an X-ray fluoroscopic imaging system in our treatment room for clinical use with an amplitude-based gating strategy. We evaluated the effects of this gating under realistic organ motion conditions using 4 DCT data of lung and liver tumors. 4 DCT imaging was done for 24 lung and liver patients using the area-detector CT. We calculated the field-specific target volume (FTV) for the gating window, which was defined for a single respiratory cycle. Prescribed doses of 48 Gy relative biological effectiveness (RBE)/fraction/four fields and 45 Gy RBE/two fractions/two fields were delivered to the FTVs for lung and liver treatments, respectively. Dose distributions were calculated for the repeated first respiratory cycle (= planning dose) and the whole respiratory data (= treatment dose). We applied eight phase-controlled rescannings with the amplitude-based gating. For the lung cases, D95 of the treatment dose (= 96.0 ± 1.0%) was almost the same as that of the planning dose (= 96.6 ± 0.9%). D(max)/D(min) of the treatment dose (= 104.5 ± 2.2%/89.4 ± 2.6%) was slightly increased over that of the planning dose (= 102.1 ± 1.0%/89.8 ± 2.5%) due to hot spots. For the liver cases, D95 of the treatment dose (= 97.6 ± 0.5%) was decreased by ∼ 1% when compared with the planning dose (= 98.5 ± 0.4%). D(max)/D(min) of the treatment dose was degraded by 3.0%/0.4% compared with the planning dose. Average treatment times were extended by 46.5 s and 65.9 s from those of the planning dose for lung and liver cases, respectively. As with regular respiratory patterns, amplitude-based gated multiple phase-controlled rescanning preserves target coverage to a moving target under irregular respiratory patterns.

Conformity and robustness of gated rescanned carbon ion pencil beam scanning of liver tumors at NIRS.

PURPOSE: Pencil beam scanning offers excellent conformity, but is sensitive to organ motion. We conducted a simulation study to validate our rescanning approach in combination with gating in the irradiation of liver tumors. MATERIALS AND METHODS: 4DCT imaging was performed under free-breathing conditions in 30 patients with hepatocellular carcinoma. Dose distributions for a two-field approach were calculated for layered phase controlled rescannings (PCR) under organ motion conditions. A total dose of 45 Gy(RBE) was delivered to respective field-specific target volumes (FTVs) in two fractions, each composed of two orthogonal uniform fields of 11.25 Gy(RBE) at beam angles of either 0° and 90° or 0° and 270°. The number of rescannings was changed from 1 to 10. RESULTS: Good dose conformity was achieved with 4× PCR or more, and over 95% of the prescribed dose was delivered to the CTV independent of the use of gating. D95, Dmax/min and dose homogeneity were similar with or without gating, whereas V10 dose to the liver as well as maximal doses to healthy tissue (esophagus and cord) were about 40% lower with gating. However, total time increased by about 50% with gating. CONCLUSIONS: Gated rescanning provides good target coverage and homogeneity with maximal sparing of healthy tissue. Our results suggest that carbon-ion pencil beam scanning may soon be available for the safe treatment of liver tumors.

A simple algorithm for beam profile diagnostics using a thermographic camera.

A new algorithm for digital image processing apparatuses is developed to evaluate profiles of high-intensity DC beams from temperature images of irradiated thin foils. Numerical analyses are performed to examine the reliability of the algorithm. To simulate the temperature images acquired by a thermographic camera, temperature distributions are numerically calculated for 20 MeV proton beams with different parameters. Noise in the temperature images which is added by the camera sensor is also simulated to account for its effect. Using the algorithm, beam profiles are evaluated from the simulated temperature images and compared with exact solutions. We find that niobium is an appropriate material for the thin foil used in the diagnostic system. We also confirm that the algorithm is adaptable over a wide beam current range of 0.11-214 µA, even when employing a general-purpose thermographic camera with rather high noise (ΔT(NETD) ≃ 0.3 K; NETD: noise equivalent temperature difference).

(11)CH4 molecule production using a NaBH4 target for (11)C ion acceleration.

Solid-state materials suitable for use as proton irradiation targets were investigated for producing high-purity (11)CH4 molecules for heavy-ion cancer therapy. The radioactivity of gas produced by proton irradiation was measured for several target materials. Also, the radioactive molecular species of the produced gas were analyzed by radio gas chromatography. We found that 5 × 10(12) (11)C molecules could be collected by proton irradiation on a NaBH4 target. We also found that the (11)CH4 molecules were produced and collected directly from the irradiated target, owing to the hydrogen atoms bound in the solid-state NaBH4.

A novel method for experimental characterization of large-angle scattered particles in scanned carbon-ion therapy.

PURPOSE: It is essential to consider large-angle scattered particles in dose calculation models for therapeutic carbon-ion beams. However, it is difficult to measure the small dose contribution from large-angle scattered particles. In this paper, the authors present a novel method to derive the parameters describing large-angle scattered particles from the measured results. METHODS: The authors developed a new parallel-plate ionization chamber consisting of concentric electrodes. Since the sensitive volume of each channel is increased linearly with this type, it is possible to efficiently and easily detect small contributions from the large-angle scattered particles. The parameters describing the large-angle scattered particles were derived from pencil beam dose distribution in water measured with the new ionization chamber. To evaluate the validity of this method, the correction for the field-size dependence of the doses, "predicted-dose scaling factor," was calculated with the new parameters. RESULTS: The predicted-dose scaling factor calculated with the new parameters was compared with the existing one. The difference between the new correction factor and the existing one was 1.3%. For target volumes of different sizes, the calculated dose distribution with the new parameters was in good agreement with the measured one. CONCLUSIONS: Parameters describing the large-angle scattered particles can be efficiently and rapidly determined using the new ionization chamber. The authors confirmed that the field-size dependence of the doses could be compensated for by the new parameters. This method makes it possible to easily derive the parameters describing the large-angle scattered particles, while maintaining the dose calculation accuracy.