Therapeutic Carbon Beams Research Articles

Comparison of linear energy transfer measurement for therapeutic carbon beam using CR-39 and TLD

The measurement of linear energy transfer (LET) is crucial for the evaluation of the radiation effect in heavy ion therapy. As two detectors which are convenient to implant into the phantom, the performance of CR-39 and thermoluminescence detector (TLD) for LET measurement was compared by experiment and simulation in this study. The results confirmed the applicability of both detectors for LET measurements, but also revealed that the CR-39 detector would lead to potential overestimation of dose-averaged LET compared with the simulation by PHITS, while the TLD would have a large uncertainty measuring ions with LET larger than 20 keV μm−1. The results of this study were expected to improve the detection method of LET for therapeutic carbon beam and would finally be benefit to the quality assurance of heavy ion radiotherapy.

OSLD nanoDot characterization for carbon radiotherapy dosimetry

Objective. This study characterized optically-stimulated luminescent dosimeter (OSLD) nanoDots for use in a therapeutic carbon beam using the Imaging and Radiation Oncology Core (IROC) framework for remote output verification. Approach. The absorbed dose correction factors for OSLD (fading, linearity, beam quality, angularity, and depletion), as defined by AAPM TG 191, were characterized for carbon beams. For the various correction factors, the effect of linear energy transfer (LET) was examined by characterizing in both a low and high LET setting. Main results. Fading was not statistically different between reference photons and carbon, nor between low and high LET beams; thus, the standard IROC-defined exponential function could be used to characterize fading. Dose linearity was characterized with a linear fit; while low and high LET carbon linearity was different, these differences were small and could be rolled into the uncertainty budget if using a single linearity correction. A linear fit between beam quality and dose-averaged LET was determined. The OSLD response at various angles of incidence was not statistically different, thus a correction factor need not be applied. There was a difference in depletion between low and high LET irradiations in a primary carbon beam, but this difference was small over the standard five readings. The largest uncertainty associated with the use of OSLDs in carbon was because of the k Q correction factor, with an uncertainty of 6.0%. The overall uncertainty budget was 6.3% for standard irradiation conditions. Significance. OSLD nanoDot response was characterized in a therapeutic carbon beam. The uncertainty was larger than for traditional photon applications. These findings enable the use of OSLDs for carbon absorbed dose measurements, but with less accuracy than conventional OSLD audit programs.

Development of a Time Projection Chamber Readout with Hybrid Pixel Sensors for Beam Monitoring.

To monitor the position and profile of therapeutic carbon beams in real-time, in this paper, we proposed a system called HiBeam-T. The HiBeam-T is a time projection chamber (TPC) with forty Topmetal-II- CMOS pixel sensors as its readout. Each Topmetal-II- has 72 × 72 pixels with the size of 83 μm × 83 μm. The detector consists of the charge drift region and the charge collection area. The readout electronics comprise three Readout Control Modules and one Clock Synchronization Module. This Hibeam-T has a sensitive area of 20 × 20 cm and can acquire the center of the incident beams. The test with a continuous 80.55 MeV/u 12C6+ beam shows that the measurement resolution to the beam center could reach 6.45 μm for unsaturated beam projections.

Evaluation of a therapeutic carbon beam using a G2000 glass scintillator

A G2000 glass scintillator (G2000-SC) was used to determine the carbon profile and range of a 290-MeV/n carbon beam used in heavy-ion therapy because it was sensitive enough to detect single-ion hits at hundreds of mega electron Volts. An electron-multiplying charge-coupled device camera was used to detect the ion luminescence generated during the irradiation of G2000-SC with the beam. The resulting image showed that the position of the Bragg peak can be determined. The beam passes through the 112-mm-thick water phantom and stops 5.73 ± 0.03 mm from the incident side to the G2000-SC. Additionally, the location of the Bragg peak was simulated when irradiating G2000-SC with the beam using the Monte Carlo code particle and heavy ion transport system (PHITS). Simulation results show that the incident beam stops at 5.60 mm after entering G2000-SC. The beam stop location obtained from images and the PHITS code is defined at 80% distal fall-off from the Bragg peak position. Consequently, G2000-SC provided effective profile measurements of therapeutic carbon beams.

Uncertainty in tissue equivalent proportional counter assessments of microdosimetry and RBE estimates in carbon radiotherapy

Microdosimetry is an important tool for assessing energy deposition distributions from ionizing radiation at cellular and cellular nucleus scales. It has served as an input parameter for multiple common mathematical models, including evaluation of relative biological effectiveness (RBE) of carbon ion therapy. The most common detector used for microdosimetry is the tissue-equivalent proportional counter (TEPC). Although it is widely applied, TEPC has various inherent uncertainties. Therefore, this work quantified the magnitude of TEPC measurement uncertainties and their impact on RBE estimates for therapeutic carbon beams. Microdosimetric spectra and frequency-, dose-, and saturation-corrected dose-mean lineal energy (****) were calculated using the Monte Carlo toolkit Geant4 for five monoenergetic and three spread-out Bragg peak carbon beams in water at every millimeter along the central beam axis. We simulated the following influences on these spectra from eight sources of uncertainty: wall effects, pulse pile-up, electronics, gas pressure, W-value, gain instability, low energy cut-off, and counting statistics. Statistic uncertainty was quantified as the standard deviation of perturbed values for each source. Bias was quantified as the difference between default lineal energy values and the mean of perturbed values for each systematic source. Uncertainties were propagated to RBE using the modified microdosimetric kinetic model (MKM). Variance introduced by statistic sources in and averaged 3.8% and 3.4%, respectively, and 1.5% in across beam depths and energies. Bias averaged 6.2% and 7.3% in and and 4.8% in These uncertainties corresponded to 1.2 ± 0.9% on average in RBEMKM. The largest contributors to variance and bias were pulse pile-up and wall effects. This study established an error budget for microdosimetric carbon measurements by quantifying uncertainty inherent to TEPC measurements. It is necessary to understand how robust the measurement of RBE model input parameters are against this uncertainty in order to verify clinical model implementation.

Measurement of therapeutic 12C beam in a water phantom using CR-39

The motivation for this study was to explore a new method to test the particle spatial distribution for a therapeutic carbon beam. CR-39 plastic nuclear track detectors were irradiated to a 276.5 MeV u−1 mono-energy carbon beam at the heavy ion facility in the Shanghai Proton and Heavy Ion Center. The spatial distribution of the primary carbon beam and secondary fragments in a water phantom were systematically analyzed both in the transverse direction (perpendicular to the projection direction of the primary beam) and at different depths in the longitudinal direction (along the projection direction of the primary beam) with measured tracks on the CR-39 detectors. Meanwhile, the theoretically spatial distribution and linear energy transfer (LET) spectra of the primary beam and secondary fragments were calculated using the Monte Carlo (MC) toolkit Geant4. The results showed that the CR-39 detectors are capable of providing high lateral resolution of carbon ion at different depths. In the range of the primary carbon beam, the beam width simulated with MC is in good agreement with that of experimental measurement. The track size registered in the CR-39 has a good correlation with the particle LET. These findings indicate that the CR-39 can be used for measuring both the particle flux and its spatial distribution of carbon ions.

Absorbed dose estimation using LET dependence in glow curve of thermoluminescent phosphor Li3B7O12:Cu in therapeutic carbon beams

ABSTRACTA high temperature ratio (HTR) method has been proposed to correct the linear energy transfer (LET) dependence of thermoluminescent (TL) efficiency. To realize the use of the slab-type thermoluminescence detector (TLD) that based on the phosphor Li3B7O12:Cu for heavy charged particle beam, the HTR method has been considered. To improve the reproducibility of HTR, the slow heating rate method is introduced in this report and the coefficient variations of HTR decreased from 10%–20% to 8%. The relation between TL-efficiency, HTR, and LET for Li3B7O12:Cu was manifested and the TL-efficiency as a function of HTR was derived in an attempt to measure the absorbed dose without LET information. The feasibility of the HTR method in therapeutic carbon beams was evaluated by comparing the dose estimated by Li3B7O12:Cu and by an ionization chamber. The accuracy of dose estimation in carbon beams was improved by using the HTR method, but there is room for further improvement. The use of Li3B7O12:Cu in heavy charged particle beams can be materialized with further improvement of HTR sensitivity.

Detection of a gas region in a human body across a therapeutic carbon beam by measuring low-energy photons

We studied feasibility of detection of a gap which is located across a beam track by measuring low-energy (63–68 keV) photons generated by beam irradiation. An experiment was performed with the Heavy Ion Medical Accelerator in Chiba (HIMAC). A 12C beam having 290 MeV/u was injected on a target consisting of two acrylic blocks. These two blocks were placed with a 10 mm gap along the beam axis. A detection system consisting of a semiconductor detector, a lead collimator having a slit, and borated polyethylene blocks was placed on a movable stage to detect low-energy photons emitted perpendicularly to the beam axis. The position of the detection system was moved at 2 mm intervals along the beam axis. It was found that the yield of 63–68 keV photons was clearly correlated with the position of the detection system. The position at which the yield curve had the lowest value agreed with the gap position. We also confirmed that the experimental result was well reproduced by a Monte Carlo simulation that includes generation of secondary electron bremsstrahlung.

Single track coincidence measurements of fluorescent and plastic nuclear track detectors in therapeutic carbon beams

In this paper we present a method for single trackcoincidence measurements using two different track detector materials. Weemployed plastic and fluorescent nuclear track detectors (PNTDs and FNTDs)in the entrance channel of a monoenergetic carbon ion beam covering thetherapeutic energy rangefrom 80 to 425 MeV/u. About 99% ofall primary particle tracks detected by both detectors were successfullymatched, while 1% of the particles were only detected by the FNTDsbecause of their superior spatial resolution. We conclude that both PNTDsand FNTDs are suitable for clinical carbon beam dosimetry with a detectionefficiency of at least 98.82% and 99.83% respectively, ifirradiations are performed with low fluence in the entrance channel of theion beam. The investigated method can be adapted to other nuclear trackdetectors and offers the possibility to characterize new track detectormaterials against well-known detectors. Further, by combining two detectorswith a restricted working range in the presented way a hybrid-detectorsystem can be created with an extended and optimized working range.

16: Measurement of charged particle yields emitted during irradiation with therapeutic proton and Carbon beams in view of the design of a new tool for the monitoring of hadrontherapy treatments

16: Measurement of charged particle yields emitted during irradiation with therapeutic proton and Carbon beams in view of the design of a new tool for the monitoring of hadrontherapy treatments

Response of a plate-type thermoluminescence dosimeter to a therapeutic carbon beam

In order to measure the three-dimensional dose distribution in X-ray radiotherapy, we developed a plate-type thermoluminescence dosimeter (TLD) using the TL phosphor Li3B7O12:Cu, which has Zeff = 7.42 and a density of 1.01 gcm−3. This detector was expected on useful application in advanced X-ray radiotherapies such as intensity-modulated ratiation therapy (IMRT) etc., because it can obtain 3D dose measurements simply and quickly with a single exposure. In this paper, we report the response of this plate-type TLD to a therapeutic carbon beam at the Heavy Ion Medical Accelerator in Chiba (HIMAC). Using a plate heater and charge coupled device (CCD) camera, we captured thermoluminescence images of plate-type TLDs irradiated by a therapeutic carbon beam. The TL intensity was measured at each water equivalent depth and compared with output of the ionization chamber. The relative TL efficiency of this TLD as 60Co gamma-ray equivalent decreased gradually with increasing dose-averaged linear-energy-transfer (LET), reaching about 20% at the Bragg peak of 290 MeV/u carbon ions.

A Model of Radiation-Induced Cell Killing: Insights into Mechanisms and Applications for Hadron Therapy

A mechanism-based, two-parameter biophysical model of cell killing was developed with the aim of elucidating the mechanisms underlying radiation-induced cell death and predicting cell killing by different radiation types, including protons and carbon ions at energies and doses of interest for cancer therapy. The model assumed that certain chromosome aberrations (dicentrics, rings and large deletions, called "lethal aberrations") lead to clonogenic inactivation, and that aberrations derive from μm-scale misrejoining of chromatin fragments, which in turn are produced by "dirty" double-strand breaks called "cluster lesions" (CLs). The average numbers of CLs per Gy per cell were left as a semi-free parameter and the threshold distance for chromatin-fragment rejoining was defined the second parameter. The model was "translated" into Monte Carlo code and provided simulated survival curves, which were compared with survival data on V79 cells exposed to protons, carbon ions and X rays. The agreement was good between simulations and survival data and supported the assumptions of the model at least for doses up to a few Gy. Dicentrics, rings and large deletions were found to be lethal not only for AG1522 cells exposed to X rays, as already reported by others, but also for V79 cells exposed to protons and carbon ions of different energies. Furthermore, the derived CL yields suggest that the critical DNA lesions leading to clonogenic inactivation are more complex than "clean" DSBs. After initial validation, the model was applied to characterize the particle and LET dependence of proton and carbon cell killing. Consistent with the proton data, the predicted fraction of inactivated cells after 2 Gy protons was 40-50% below 7.7 keV/μm, increased by a factor ∼1.6 between 7.7-30.5 keV/μm, and decreased by a factor ∼1.1 between 30.5-34.6 keV/μm. These LET values correspond to proton energies below a few MeV, which are always present in the distal region of hadron therapy spread-out Bragg peaks (SOBP). Consistent with the carbon data, the predicted fraction of inactivated cells after 2 Gy carbon was 40-50% between 13.7-32.4 keV/μm, it increased by a factor ∼1.7 between 32.4-153.5 keV/μm, and decreased by a factor ∼1.1 between 153.5-339.1 keV/μm. Finally, we applied the model to predict cell death at different depths along a carbon SOBP used for preclinical experiments at HIMAC in Chiba, Japan. The predicted fraction of inactivated cells was found to be roughly constant (less than 10%) along the SOBP, suggesting that this approach may be applied to predict cell killing of therapeutic carbon beams and that, more generally, dicentrics, rings and deletions at the first mitosis may be regarded as a biological dose for these beams. This study advanced our understanding of the mechanisms of radiation-induced cell death and characterized the particle and LET dependence of proton and carbon cell killing along a carbon SOBP. The model does not use RBE values, which can be a source of uncertainty. More generally, this model is a mechanism-based tool that in minutes can predict cell inactivation by protons or carbon ions of a given energy and dose, based on an experimental photon curve and in principle, a single (experimental) survival point for the considered ion type and energy.

Linear energy transfer and track pattern recognition of secondary radiation generated in hadron therapy beam in a PMMA target

Hadron therapy uses ion beams for irradiation of cancerous tissue taking advantage of the highly localized dose deposition in the target tumor. For a correct estimation of dose deposited in tissue surrounding the target it is necessary to consider also the contribution of energetic secondary radiation generated by primary ions. It was already experimentally demonstrated that this contribution can be measured using the semiconductor pixel detector Timepix (256 × 256 pixels with 55 μm pitch) visualizing traces of secondary particles. The resolving power of the detector enables the differentiation of traces of different types of particles. In this work we studied the possibilities of determination of different types of secondary particles in correlation with their flight direction. Such identification allows correct assignment of dose for each type of particle. The distribution of secondary particles was compared to Monte Carlo simulations. Measurements were performed with a PMMA target irradiated with a therapeutic carbon beam at the Heidelberg Ion-Beam Therapy Center (HIT).

A simulation study of a C-shaped in-beam PET system for dose verification in carbon ion therapy

The application of hadrons such as carbon ions is being developed for the treatment of cancer. The effectiveness of such a technique is due to the eligibility of charged particles in delivering most of their energy near the end of the range, called the Bragg peak. However, accurate verification of dose delivery is required since misalignment of the hadron beam can cause serious damage to normal tissue. PET scanners can be utilized to track the carbon beam to the tumor by imaging the trail of the hadron-induced positron emitters in the irradiated volume. In this study, we designed and evaluated (through Monte Carlo simulations) an in-beam PET scanner for monitoring patient dose in carbon beam therapy. A C-shaped PET and a partial-ring PET were designed to avoid interference between the PET detectors and the therapeutic carbon beam delivery. Their performance was compared with that of a full-ring PET scanner. The C-shaped, partial-ring, and full-ring scanners consisted of 14, 12, and 16 detector modules, respectively, with a 30.2cm inner diameter for brain imaging. Each detector module was composed of a 13×13 array of 4.0mm×4.0mm×20.0mm LYSO crystals and four round 25.4mm diameter PMTs. To estimate the production yield of positron emitters such as 10C, 11C, and 15O, a cylindrical PMMA phantom (diameter, 20cm; thickness, 20cm) was irradiated with 170, 290, and 350AMeV 12C beams using the GATE code. Phantom images of the three types of scanner were evaluated by comparing the longitudinal profile of the positron emitters, measured along the carbon beam as it passed a simulated positron emitter distribution. The results demonstrated that the development of a C-shaped PET scanner to characterize carbon dose distribution for therapy planning is feasible.

Field size effect of radiation quality in carbon therapy using passive method

The authors have investigated the dependency of radiation quality and absorbed dose on radiation field size in therapeutic carbon beams. The field size of the broad beam, formed using the passive technique, was controlled from 20 to 100 mm per side with a multileaf collimator. The absorbed dose and radiation quality on the beam center were evaluated at several depths in a water phantom using microdosimetric technique in experiments and Monte Carlo simulations. With an increase in the field size, the radiation quality was reduced, although the absorbed dose grew at the center of the field. This indicates that the dose and radiation quality at the center of the broad beam are influenced by particles from the off-center region via large-angle scattering and that such particles have relatively low radiation quality and mainly consist of fragment particles. Because such a tendency appeared to be more remarkable in the deeper region of the water phantom, it is likely that fragment particles that are born in a water phantom have a marked role in determining the field size effect.

Field‐size dependence of doses of therapeutic carbon beams

To estimate the physical dose at the center of spread-out Bragg peaks (SOBP) for various conditions of the irradiation system, a semiempirical approach was applied. The dose at the center of the SOBP depends on the field size because of large-angle scattering particles in the water phantom. For a small field of 5 x 5 cm2, the dose was reduced to 99.2%, 97.5%, and 96.5% of the dose used for the open field in the case of 290, 350, and 400 MeV/n carbon beams, respectively. Based on the three-Gaussian form of the lateral dose distributions of the carbon pencil beam, which has previously been shown to be effective for describing scattered carbon beams, we reconstructed the dose distributions of the SOBP beam. The reconstructed lateral dose distribution reproduced the measured lateral dose distributions very well. The field-size dependencies calculated using the reconstructed lateral dose distribution of the therapeutic carbon beam agreed with the measured dose dependency very well. The reconstructed beam was also used for irregularly shaped fields. The resultant dose distribution agreed with the measured dose distribution. The reconstructed beams were found to be applicable to the treatment-planning system.

Microdosimetric Evaluation of Secondary Particles in a Phantom Produced by Carbon 290 MeV/nucleon Ions at HIMAC

Microdosimetric single event spectra as a function of depth in a phantom for the 290 MeV/nucleon therapeutic carbon beam at HIMAC were measured by using a tissue equivalent proportional counter (TEPC). Two types of geometries were used: one is a fragment particle identification measurement (PID-mode) with time of flight (TOF) method without a backward phantom, and the other is an in-phantom measurement (IPM-mode) with a backward phantom. On the PID-mode geometry, fragments produced by carbon beam in a phantom are identified by the DeltaE-TOF distribution between two scintillation counters positioned up- and down-stream relative to the tissue equivalent proportional counter (TEPC). Lineal energy distributions for carbon and five ion fragments (proton, helium, lithium, beryllium and boron) were obtained in the lineal-energy range of 0.1-1000 keV/microm at eight depths (7.9-147.9 mm) in an acrylic phantom. In the IPM-mode geometry, the total lineal energy distributions measured at eight depths (61.9-322.9 mm) were compared with the distributions in the PID-mode. Both spectra are consistent with each other. This shows that the PID-mode measurement can be discussed as the equivalent of the phantom measurement. The dose distribution of the carbon beam and fragments were obtained separately. In the depth dose curve, the Bragg peak was observed. Relative biological effectiveness (RBE) for the carbon beam in the acrylic phantom was obtained based on a biological response function as a lineal-energy. The RBE of carbon beam had a maximum of 4.5 at the Bragg peak. Downstream of the Bragg peak, the RBE rapidly decreases. The RBE of fragments is dominated by Boron particles around the Bragg peak region.

Study of fragmentation of therapeutic carbon beams with emulsion

Study of fragmentation of therapeutic carbon beams with emulsion

Specification of Carbon Ion Dose at the National Institute of Radiological Sciences (NIRS)

The clinical dose distributions of therapeutic carbon beams, currently used at NIRS HIMAC, are based on in-vitro Human Salivary Gland (HSG) cell survival response and clinical experience from fast neutron radiotherapy. Moderate radiosensitivity of HSG cells is expected to be a typical response of tumours to carbon beams. At first, the biological dose distribution is designed so as to cause a flat biological effect on HSG cells in the spread-out Bragg peak (SOBP) region. Then, the entire biological dose distribution is evenly raised in order to attain a RBE (relative biological effectiveness) = 3.0 at a depth where dose-averaged LET (linear energy transfer) is 80 keV/mum. At that point, biological experiments have shown that carbon ions can be expected to have a biological effect identical to fast neutrons, which showed a clinical RBE of 3.0 for fast neutron radiotherapy at NIRS. The resulting clinical dose distribution in this approximation is not dependent on dose level, tumour type or fractionation scheme and thus reduces the unknown parameters in the analysis of the clinical results. The width SOBP and the clinical / physical dose at the center of SOBP specify the dose distribution. The clinical results analysed in terms of TCP were found to show good agreement with the expected RBE value at higher TCP levels. The TCP analysis method was applied for the prospective dose estimation of hypofractionation.

Dose contributions from large‐angle scattered particles in therapeutic carbon beams

In carbon therapy, doses at center of spread-out Bragg peaks depend on field size. For a small field of 5 x 5 cm2, the central dose reduces to 96% of the central dose for the open field in case of 400 MeV/n carbon beam. Assuming the broad beam injected to the water phantom is made up of many pencil beams, the transverse dose distribution can be reconstructed by summing the dose distribution of the pencil beams. We estimated dose profiles of this pencil beam through measurements of dose distributions of broad uniform beams blocked half of the irradiation fields. The dose at a distance of a few cm from the edge of the irradiation field reaches up to a few percent of the central dose. From radiation quality measurements of this penumbra, the large-angle scattered particles were found to be secondary fragments which have lower LET than primary carbon beams. Carbon ions break up in beam modifying devices or in water phantom through nuclear interaction with target nuclei. The angular distributions of these fragmented nuclei are much broader than those of primary carbon particles. The transverse dose distribution of the pencil beam can be approximated by a function of the three-Gaussian form. For a simplest case of mono-energetic beam, contributions of the Gaussian components which have large mean deviations become larger as the depth in the water phantom increases.