Search

The stopping power ratio (SPR) of body tissues relative to water depends on the particle energy. For simplicity, however, most analytical dose planning systems do not account for SPR variation with particle energy along the beam's path, but rather assume a constant energy for SPR estimation. The range error due to this simplification could be indispensable depending on the particle species and the assumed energy. This error can be minimized by assuming a suitable energy referred to as an 'effective energy' in SPR estimation. To date, however, the effective energy has never been investigated for realistic patient geometries. We investigated the effective energies for proton, helium-, carbon-, and oxygen-ion radiotherapy using volumetric models of the reference male and female phantoms provided by the International Commission on Radiological Protection (ICRP). The range errors were estimated by comparing the particle ranges calculated when particle energy variations were and were not considered. The effective energies per nucleon for protons and helium, carbon, and oxygen ions were 70 MeV, 70 MeV, 131 MeV, and 156 MeV, respectively. Using the determined effective energies, the range errors were reduced to ⩽0.3 mm for respective particle species. For SPR estimation of multiple particle species, an effective energy of 100 MeV is recommended, with which the range error is ⩽0.5 mm for all particle species.

A simple and efficient approach is needed for robustness evaluation and optimization of treatment planning in routine clinical particle therapy. Here we propose a robustness analysis method using dose standard deviation (SD) in possible scenarios such as the robustness indicator and a fast dose warping method, i.e. deformation of dose distributions, taking into account the setup and range errors in carbon-ion therapy. The dose warping method is based on the nominal dose distribution and the water-equivalent path length obtained from planning computed tomography data with a clinically commissioned treatment planning system (TPS). We compared, in a limited number of scenarios at the extreme boundaries of the assumed error, the dose SD distributions obtained by the warping method with those obtained using the TPS dose recalculations. The accuracy of the warping method was examined by the standard-deviation-volume histograms (SDVHs) for varying degrees of setup and range errors for three different tumor sites. Furthermore, the influence of dose fractionation on the combined dose uncertainty, taking into consideration the correlation of setup and range errors between fractions, was evaluated with simple equations using the SDVHs and the mean value of SDs in the defined volume of interest. The results of the proposed method agreed well with those obtained with the dose recalculations in these comparisons, and the effectiveness of dose SD evaluations at the extreme boundaries of given errors was confirmed from the responsivity and DVH analysis of relative SD values for each error. The combined dose uncertainties depended heavily on the number of fractions, assumed errors and tumor sites. The typical computation time of the warping method is approximately 60 times less than that of the full dose calculation method using the TPS. The dose SD distributions and SDVHs with the fractionation effect will be useful indicators for robustness analysis in treatment planning, and the results of our comparative study show that the proposed analysis method would be beneficial in routine clinical use.

The single-ring OpenPET (SROP), for which the detector arrangement has a cylinder shape cut by two parallel planes at a slant angle to form an open space, is our original proposal for in-beam PET. In this study, we developed a small prototype of an axial-shift type SROP (AS-SROP) with a novel transformable architecture for a proof-of-concept. In the AS-SROP, detectors originally forming a cylindrical PET are axially shifted little by little. We designed the small AS-SROP prototype for 4-layer depth-of-interaction detectors arranged in a ring diameter of 250 mm. The prototype had two modes: open and closed. The open mode formed the SROP with the open space of 139 mm and the closed mode formed a conventional cylindrical PET. The detectors were simultaneously moved by a rotation handle allowing them to be transformed between the two modes. We evaluated the basic performance of the developed prototype and carried out in-beam imaging tests in the HIMAC using (11)C radioactive beam irradiation. As a result, we found the open mode enabled in-beam PET imaging at a slight cost of imaging performance; the spatial resolution and sensitivity were 2.6 mm and 5.1% for the open mode and 2.1 mm and 7.3% for the closed mode. We concluded that the AS-SROP can minimize the decrease of resolution and sensitivity, for example, by transforming into the closed mode immediately after the irradiation while maintaining the open space only for the in-beam PET measurement.

Our institute has constructed a new treatment facility for carbon ion scanning beam therapy. The first clinical trials were successfully completed at the end of November 2011. To evaluate patient setup accuracy, positional errors between the reference Computed Tomography (CT) scan and final patient setup images were calculated using 2D-3D registration software. Eleven patients with tumors of the head and neck, prostate and pelvis receiving carbon ion scanning beam treatment participated. The patient setup process takes orthogonal X-ray flat panel detector (FPD) images and the therapists adjust the patient table position in six degrees of freedom to register the reference position by manual or auto- (or both) registration functions. We calculated residual positional errors with the 2D-3D auto-registration function using the final patient setup orthogonal FPD images and treatment planning CT data. Residual error averaged over all patients in each fraction decreased from the initial to the last treatment fraction [1.09 mm/0.76° (averaged in the 1st and 2nd fractions) to 0.77 mm/0.61° (averaged in the 15th and 16th fractions)]. 2D-3D registration calculation time was 8.0 s on average throughout the treatment course. Residual errors in translation and rotation averaged over all patients as a function of date decreased with the passage of time (1.6 mm/1.2° in May 2011 to 0.4 mm/0.2° in December 2011). This retrospective residual positional error analysis shows that the accuracy of patient setup during the first clinical trials of carbon ion beam scanning therapy was good and improved with increasing therapist experience.

To increase the accuracy of carbon ion beam scanning therapy, we have developed a GUI (graphical user interface)-based digitally-reconstructed radiograph (DRR) software system for use in routine clinical practice at our center. The DRR software is used in particular scenarios in the new treatment facility to achieve the same level of geometrical accuracy at the treatment as at the imaging session. DRR calculation is implemented simply as the summation of CT image voxel values along the x-ray projection ray. Since we implemented GPU (graphics processing unit)-based computation, the DRR images are calculated with a speed sufficient for the particular clinical practice requirements. Since high spatial resolution flat panel detector (FPD) images should be registered to the reference DRR images in patient setup process in any scenarios, the DRR images also needs higher spatial resolution close to that of FPD images. To overcome the limitation of the CT spatial resolution imposed by the CT voxel size, we applied image processing to improve the calculated DRR spatial resolution. The DRR software introduced here enabled patient positioning with sufficient accuracy for the implementation of carbon-ion beam scanning therapy at our center.

Purpose: In radiotherapy with a scanned carbon-ion beam, its Bragg peak is shifted along the depth direction either by inserting the range shifter plates or by changing the beam-extraction energy of a synchrotron. In the former technique (range shifter scanning: RS), the range shifter plates broaden the beam size and produce secondary fragments through nuclear reactions. In the latter technique (active-energy scanning: ES), it may take several seconds to change the beam energy depending on the synchrotron operation cycle, leading to a long treatment time. The authors propose a hybrid depth scan technique (hybrid scanning: HS), where several beam energies are used in conjunction with the range shifter plates for finer range shift. In this study, HS is evaluated from the viewpoints of dose distribution and treatment time. Methods: Assuming realistic accelerator and beam-delivery systems, the authors performed computer simulations using GEANT4 Monte Carlo code for beam modeling and a treatment planning system to evaluate HS. Three target volumes with the same dimensions of 60 x 60 x 60 mm{sup 3} were generated at depths of 45, 85, and 125 mm in water phantom, and uniform clinical dose was planned for these targets. The sizes of lateral dose falloff andmore » the peak to plateau ratio defined as the ratio of the clinical dose averaged over the target to the clinical dose at the entrance as well as the treatment time were compared among the three depth scan techniques. Results: The sizes of lateral dose falloffs at the center of SOBP are 11.4, 8.5, and 5.9 mm for the three targets in RS, while they are 5.7, 4.8, and 4.6 mm in ES and 6.6, 5.7, and 5.0 mm in HS, respectively. The peak to plateau ratios are 1.39, 1.96, and 2.15 in RS, while they are 1.48, 2.04, and 2.19 in ES and 1.47, 2.03, and 2.18 in HS, respectively. The treatment times are 128.7, 128.6, and 128.6 s in ES, while they are 61.2, 54.6, and 47.8 s in RS and 43.2, 44.1, and 44.7 s in HS, respectively. The multiple scattering and the nuclear reaction by range shifter degraded the beam qualities such as lateral dose falloff and peak to plateau ratio, which was especially pronounced for the shallow target in RS. The depth scan timing was limited by accelerator cycle in ES. That increased the treatment time by a few times. Conclusions: This study revealed that HS can provide dose distributions with steeper lateral dose falloffs and higher peak to plateau ratio comparing to RS and comparable to ES. In addition, the treatment time can be considerably reduced in HS compared to ES.« less

Purpose: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction. Methods: The authors calculated the electron densities and effective densities for stopping power,multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction. Results: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone. Conclusions: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user’s specific system.

On the basis of more than 10 years of experience with HIMAC, we proposed and designed a new treatment research facility, as an extension of the existing facility, for the further development of radiotherapy with HIMAC. The new facility employs a 3D rescanning technique developed at NIRS. Its building construction was completed in March 2010 and the devices are being installed. A beam commissioning and a pre-clinical study will be initiated from this October. Here, we report recent progress for this new treatment facility project at HIMAC.

A fluorescent screen + a charge coupled device (CCD) system were developed to verify the performance of scanned ion beams at the HIMAC. The fluorescent light from the screen is observed by the CCD camera. Two-dimensional fields, produced by the scanning process, i.e., the position and the size of the beam for each scan, represent of the important issues in scanning irradiation. In the developed system, the two-dimensional relative fluence and the flatness of the irradiation field were measured in a straightforward technique from the luminance distribution on the screen. The position and the size of the beams were obtained from centroid computation results of the brightness. By the good sensitivity and spatial resolution of the fluorescent screen + CCD system, the scanned ion beams were verified as the measurements at the HIMAC prototype scanning system.

The OpenPET geometry is our new idea to visualize a physically opened space between two detector rings. In this paper, we developed the first small prototype to show a proof-of-concept of OpenPET imaging. Two detector rings of 110 mm diameter and 42 mm axial length were placed with a gap of 42 mm. The basic imaging performance was confirmed through phantom studies; the open imaging was realized at the cost of slight loss of axial resolution and 24% loss of sensitivity. For a proof-of-concept of PET image-guided radiation therapy, we carried out the in-beam tests with (11)C radioactive beam irradiation in the heavy ion medical accelerator in Chiba to visualize in situ distribution of primary particles stopped in a phantom. We showed that PET images corresponding to dose distribution were obtained. For an initial proof-of-concept of real-time multimodal imaging, we measured a tumor-inoculated mouse with (18)F-FDG, and an optical image of the mouse body surface was taken during the PET measurement by inserting a digital camera in the ring gap. We confirmed that the tumor in the gap was clearly visualized. The result also showed the extension effect of an axial field-of-view (FOV); a large axial FOV of 126 mm was obtained with the detectors that originally covered only an 84 mm axial FOV. In conclusion, our initial imaging studies showed promising performance of the OpenPET.

A 'patch-field' strategy is often used for tumors with large volumes exceeding the available field size in passive irradiations with ion beams. Range and setup errors can cause hot and cold spots at the field junction within the target. Such errors will also displace the field to miss the target periphery. With scanned ion beams with fluence modulation, the two junctional fields can be overlapped rather than patched, which may potentially reduce the sensitivity to these uncertainties. In this study, we have developed such a robust optimization algorithm. This algorithm is composed of the following two steps: (1) expanding the target volume with margins against the uncertainties, and (2) solving the inverse problem where the terms suppressing the dose gradient of individual fields are added into the objective function. The validity of this algorithm is demonstrated through simulation studies for two extreme cases of two fields with unidirectional and opposing geometries and for a prostate-cancer case. With the proposed algorithm, we can obtain a more robust plan with minimized influence of range and setup uncertainties than the conventional plan. Compared to conventional optimization, the calculation time for the robust optimization increased by a factor of approximately 3.

Purpose: In moving target irradiation with pencil beam scanning, the interplay effect between the target motion and the scanned beam is a problem because this effect causes over or under dosage in the target volume. To overcome this, we have studied rescanning using a gating technique. Methods: A simulation and experimental study was carried out. In the experiment, we used the fast scanning system developed at the HIMAC to verify the validity of phase controlled rescanning method, in which the time for rescanning irradiation of each slice is matched to the gating duration. Results: Simulation and experimental results showed that controlling the scan speed to match the respiration cycle with rescans can deliver the blurred dose distribution. In the comparison between the static measurements and the moving measurements with the phase controlled rescanning method, the dose difference was less than 2% for pinpoint chambers in the target volume. Conclusions: The simulation and experimental results demonstrated that the phase controlled rescanning method makes it possible to deliver the dose distribution close to the expected one. As an experimental result for 3D irradiation, it was estimated that blurring by the probability density function was not only for a lateral distribution, but alsomore » for a distal distribution, even in the lateral rescanning.« less

The microdosimetric kinetic (MK) model underestimates the cell-survival fractions for high linear energy transfer (LET) and high dose irradiations. To address the issue, some researchers previously extended the MK model to the stochastic microdosimetric kinetic (SMK) model. In the SMK model, the radiation induced cell-survival fractions were estimated from the specific energies z d and z n absorbed by a microscopic subnuclear structure domain and a cell nucleus, respectively. By taking the stochastic nature of z n as well as that of z d into account, the SMK model could reproduce the measured cell-survival fractions for radiations with wide LET and dose ranges. However, treatment planning based on the SMK model was unrealistic in clinical practice due to its long computation time and huge memory space required for the computation. In this study, we modified the SMK model to shorten the computation time and to reduce the memory space required for the computation. By using the dose-averaged cell-nucleus specific energy per event [Formula: see text] in the SMK formalism, the stochastic nature of z n was reflected onto the estimated cell-survival fractions. The accuracy of the modified SMK model was examined through the comparison between the estimated and the measured survival fractions of human salivary gland tumor cells and V79 cells. We then implemented the modified SMK model into the in-house treatment planning software for scanned charged-particle therapy to validate its applicability in clinical practice. As examples, treatment plans of helium-, carbon-, and neon-ion beams were made for an orbital tumor case. The modified SMK model could reproduce the measured cell-survival fractions more accurately compared to the MK model especially for high-LET and high-dose irradiations. In summary, the modified SMK model offers the accuracy and simplicity required in treatment planning of scanned charged-particle therapy for wide LET and dose ranges.

The original version of this article unfortunately contained a mistake. Figure 2 was published with fake signals in panels (a) and (b) which are corrected in this Erratum. The authors are not responsible for this procedural lapse.

Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed. The model has been benchmarked with published in vitro data, HSG, V79 and CHO cells in aerobic and hypoxic conditions, for different ion irradiation. The model has been included in the simulation of treatments for a clinical case (brain tumour) using proton, lithium, helium, carbon and oxygen ion beams. A study of the tumour control probability (TCP) as a function of oxygen partial pressure, dose per fraction and primary ion type has been performed. The modelled OER depends on both the LET and ion type, also showing a decrease for an increased dose per fraction with a slope that depends on the LET and ion type, in good agreement with the experimental data. In the investigated clinical case, a significant increase in TCP has been found upon increasing the ion charge. Higher OER variations as a function of dose per fraction have also been found for low-LET ions (up to 15% varying from 2 to 8 Gy(RBE) for protons). This model could be exploited in the identification of treatment condition optimality in the presence of hypoxia, including fractionation and primary particle selection.

In the last few years, hospital-based facilities for carbon-ion radiotherapy are being constructed and proposed in Europe and Asia. During the next few years, several new facilities will be opened for carbon-ion radiotherapy in the world. These facilities in operation or under construction are categorized in two types by the beam shaping method used. One is the passive beam shaping method that is mainly improved and systematized for routine clinical use at HIMAC, Japan. The other method is active beam shaping which is also known as beam scanning adopted at GSI/HIT, Germany. In this paper an overview of some technical aspects for beam shaping is reported. The technique of passive beam shaping is established for stable clinical application and has clinical result of over 4000 patients in HIMAC. In contrast, clinical experience of active beam shaping is about 400 patients, and there is no clinical experience to respiratory moving target. A great advantage of the active beam shaping method is patient-specific collimator-less and compensator-less treatment. This may be an interesting potential for adaptive radiotherapy.

A field-size effect of physical doses was studied in scanning irradiation with carbon ions. For the target volumes of 60 × 60 × 80 , 40 × 40 × 80 , and 20 × 20 × 80 mm 3 , the doses along the beam axis within the spread-out Bragg peaks reduced to 99.4%, 98.2%, and 96.0% of the dose for the target of 80 × 80 × 80 mm 3 , respectively. The present study revealed that the observed reductions can be compensated for by adopting the three-Gaussian form of lateral dose distributions for the pencil beam model used in the treatment planning system. The parameters describing the form were determined through the irradiation experiments making flat concentric squared frames with a scanned carbon beam. Since utilizing the three-Gaussian model in the doseoptimization loop is at present time consuming, the correction for the field-size effect should be implemented as a “predicted-dose scaling factor.” The validity of this correction method was confirmed through the irradiation of a target of 20 × 20 × 80 mm 3 .

Heavy-ion therapy is one of the important methods for the cancer treatment. More than 3400 patients were treated between 1994 and 2007 at Heavy Ion Medical Accelerator in Chiba (HIMAC). For the promotion of carbon-ion therapy, a compact carbon-therapy facility was developed. The size of the new facility is three times smaller, while the accelerator can supply the beams similar to those used at HIMAC. The new irradiation system was developed in order to obtain a precise dose distribution for moving and/or deforming organs.

The authors have developed a method to reconstruct the 3D dose distribution in a particle beam scanning irradiation system. In this scheme, 3D dose distribution is reconstructed by using the measured images of fluence distribution, which are taken for each iso-energy slice (i.e., the unit of the depth scanning). A fluorescent screen with a CCD camera is used to measure the fluence distribution. This system was installed at the HIMAC experimental port and tested by using carbon ion beams. Since a maximum difference between the reconstructed dose and the ionization chamber measurement was around 5% in the target volume, this system can be useful for quick verification of 3D dose distribution.

Based on more than 10 years of experience with HIMAC, we have proposed a new treatment facility for the further development of therapy with HIMAC. The new facility, as an extension of the existing one, has been designed and the related R&D work has been carried out. The following descriptions give a summary account of the design study and the related R&D work for this new treatment facility at HIMAC.

In order to utilize an intensity-controlled raster scan method at the new treatment facility in HIMAC, we have developed, as a first step, a research version of a treatment planning tool. In this tool, treatment plans are produced according to the following steps: (a) import a planned target volume (PTV) delineated on a CT data set, (b) determine the primary treatment parameters, (c) convert the PTV in the CT system to the one in the water equivalent system, (d) choose beam positions within the PTV, (e) optimize the scan trajectory, (f) determine the particle numbers for each pencil beam and (g) produce the beam steering file. As an example, a treatment plan was produced for the data of a patient treated at HIMAC in this paper. The reliability of the tool was confirmed with irradiation experiments according to the obtained beam steering file.

A project to construct a new treatment facility as an extension of the existing HIMAC facility has been initiated for the further development of carbon-ion therapy. In the new facility, one of the treatment rooms will be equipped with an iso-centric gantry system employing a 3D pencil beam scanning irradiation method. In order to realize a compact design, the final 90 deg bending magnet is divided into two bending magnets of 60 deg and 30 deg. The scanning magnets are set between these two bending magnets, although the aperture of the 30 deg. magnet increases. Finally, we achieved 350 tons of total weight for 400 MeV/u carbon beams with a 150 mm square field.

The long patient port of a PET scanner tends to put stress on patients, especially patients with claustrophobia. It also prevents doctors and technicians from taking care of patients during scanning. In this paper, we proposed an 'open PET' geometry, which consists of two axially separated detector rings. A long and continuous field-of-view (FOV) including a 360 degrees opened gap between two detector rings can be imaged enabling a fully 3D image reconstruction of all the possible lines-of-response. The open PET will become practical if iterative image reconstruction methods are applied even though image reconstruction of the open PET is analytically an incomplete problem. First we implemented a 'masked' 3D ordered subset expectation maximization (OS-EM) in which the system matrix was obtained from a long 'gapless' scanner by applying a mask to detectors corresponding to the open space. Next, in order to evaluate imaging performance of the proposed open PET geometry, we simulated a dual HR+ scanner (ring diameter of D = 827 mm, axial length of W = 154 mm x 2) separated by a variable gap. The gap W was the maximum limit to have axially continuous FOV of 3W though the maximum diameter of FOV at the central slice was limited to D/2. Artifacts, observed on both sides of the open space when the gap exceeded W, were effectively reduced by inserting detectors partially into unnecessary open spaces. We also tested the open PET geometry using experimental data obtained by the jPET-D4. The jPET-D4 is a prototype brain scanner, which has 5 rings of 24 detector blocks. We simulated the open jPET-D4 with a gap of 66 mm by eliminating 1 block-ring from experimental data. Although some artifacts were seen at both ends of the opened gap, very similar images were obtained with and without the gap. The proposed open PET geometry is expected to lead to realization of in-beam PET, which is a method for an in situ monitoring of charged particle therapy, by letting the beams pass through the gap. The proposed open PET geometry will also allow simultaneous PET/CT measurements of the same PET FOV as the CT FOV, in contrast to the conventional PET/CT where each FOV is separated by several tens of centimeters.

The utility of positron emitter nuclei generated by photonuclear reactions was verified for X-ray beam monitoring in a phantom.Positron emission tomography-computed tomography (PET-CT) images of a gelatinous water phantom (H(2)O target) and a polyethylene phantom (CH(2) target) were acquired 5 min after delivering a dose of 17 Gy with an X-ray beam energy of 21 MV. Reconstructed PET images and the calculated half-life showed that the positron emitters of (15)O (half-life 122.2 s) in the H(2)O target and (11)C (half-life 20.4 min) in the CH(2) target were generated by photonuclear reactions.A comparison was made between measured activity and dose distributions for each target. The measured times of annihilation gamma rays from the positron emitter nucleus were 10 and 30 min for the (15)O nucleus in the H(2)O target and the (11)C nucleus in the CH(2) target, respectively. The activity distributions of the (15)O and (11)C positron emitter nuclei were similar to the measured dose distributions for both depth and lateral directions except for dose buildup and collimator edge regions. It was confirmed that no activity was detected at an X-ray energy of 14 MV, which was far below the energy threshold for both photonuclear reactions.It was estimated that the PET-CT image acquired from the activity of the (15)O and (11)C positron emitter nuclei might provide the area of X-ray beam irradiation in a phantom.

The aim of this work is to define a simplified semi-analytical beam transportation code that can calculate the spatial distribution of projectile fragments which are widely distributed in a patient's body during heavy-ion beam radiotherapy. In this code, we employed an elemental pencil beam model where the spatial distribution of radiation quality for an elemental beam is calculated and superposed according to the emittance ellipse of the narrow heavy-ion beam determined at the entrance of the target. The radiation quality for an elemental beam was calculated using Goldhaber's model of fragment distribution. The calculation results were compared with the experimental observations for a mono-energetic narrow (12)C beam measured at the secondary beam line in HIMAC. Despite its simplicity, the developed code could reproduce the experimental results well.

For the effective utilization of the favorable properties of heavy-ion beams in cancer treatment, it is important to evaluate the range of incident ions and the deposited dose distribution in a patient's body. For this purpose, the utilization of positron emitters induced in therapeutic irradiation is, at present, the only feasible method for in situ and non-invasive monitoring of heavy-ion therapy. In this study, we performed irradiation experiments with three species of ions to a water target, and the annihilation gamma-ray distributions were obtained with a positron camera. We applied the maximum likelihood estimation (MLE) method for the detected distributions to derive the range of incident ions and the deposited dose distribution in the target. As a result, the ranges were determined with a difference between the MLE range R MLE and the experimental range R exp less than 1.1 mm. The good agreement between the estimated dose distribution with the MLE method and the measured one implies that a deposited dose distribution in a target could be estimated from a detected annihilation gamma-ray distribution.

In three-dimensional irradiation with pencil beam scanning, an extra dose is inevitably delivered to the irradiated site due to the finite reaction times of the beam delivery system, and it causes a severe distortion of the dose distribution in the target region. Since the amount of the extra dose is proportional to the beam intensity, the dose uniformity deteriorates as the beam intensity is increased in order to shorten the treatment time. In order to overcome this problem and shorten the treatment time, we have developed an optimization method in which the extra dose is integrated into the optimization process of the best weighting matrix. The effectiveness and applicability of the optimization method for spot and raster scanning irradiation were confirmed with computer simulations and also confirmed using irradiation experiments for spot scanning irradiation. The treatment time could be shortened to about one sixth of the time needed without taking the extra dose into account while obtaining the same degree of dose homogeneity in the target volume. A typical treatment time with the proposed method is about 15 s for the irradiation of a spherical target with an 80 mm diameter at 3 GyE.

In proton therapy, it is important to evaluate the field irradiated with protons and the deposited dose distribution in a patient's body. Positron emitters generated through fragmentation reactions of target nuclei can be used for this purpose. By detecting the annihilation gamma rays from the positron emitters, the annihilation gamma ray distribution can be obtained which has information about the quantities essential to proton therapy. In this study, we performed irradiation experiments with mono-energetic proton beams of 160 MeV and the spread-out Bragg peak beams to three kinds of targets. The annihilation events were detected with a positron camera for 500 s after the irradiation and the annihilation gamma ray distributions were obtained. In order to evaluate the range and the position of distal and proximal edges of the SOBP, the maximum likelihood estimation (MLE) method was applied to the detected distributions. The evaluated values with the MLE method were compared with those estimated from the measured dose distributions. As a result, the ranges were determined with the difference between the MLE range and the experimental range less than 1.0 mm for all targets. For the SOBP beams, the positions of distal edges were determined with the difference less thanmore » 1.0 mm. On the other hand, the difference amounted to 7.9 mm for proximal edges.« less

A project to construct a new treatment facility as an extension of the existing heavy-ion medical accelerator in chiba (HIMAC) facility has been initiated for further development of carbon-ion therapy. The greatest challenge of this project is to realize treatment of a moving target by scanning irradiation. For this purpose, we decided to combine the rescanning technique and the gated irradiation method. To determine how to avoid hot and/or cold spots by the relatively large number of rescannings within an acceptable irradiation time, we have studied the scanning strategy, scanning magnets and their control, and beam intensity dynamic control. We have designed a raster scanning system and carried out a simulation of irradiating moving targets. The result shows the possibility of practical realization of moving target irradiation with pencil beam scanning. We describe the present status of our design study of the raster scanning system for the HIMAC new treatment facility.

One of the challenging applications of PET is implementing it for in-beam PET, which is an in situ monitoring method for charged particle therapy. For this purpose, we have previously proposed two geometries for our original open-type PET scanners named OpenPET. Following our initial proposal of the dual-ring OpenPET (DROP) in 2008, we developed a whole-body prototype of DROP (WBDROP) in 2014 to show a proof-of-concept. On the other hand, in 2011, we also proposed the single-ring OpenPET (SROP), which is more efficient than DROP in terms of manufacturing cost, width of open gap. In this paper, we developed the whole-body prototype of SROP (WBSROP). The WBSROP prototype was designed with 4 axial shifted detector rings of 40 depth-of-interaction (DOI) detectors. The detector rings were each 66 cm in diameter. The rings were slanted by 45 deg from the axial direction to obtain large open gap of 43-cm width. The DOI detectors consist of 1024 Zr-doped GSO crystals which are arranged in 4 layers of 16 χ 16 arrays, coupled to a 64-ch flat panel position sensitive PMT with a super-bialkali photocathode, which had a 30% higher quantum efficiency. Each crystal element is 2.8 × 2.8 × 7.5 mm3. In order to enable stable in-beam PET measurement even under high background radiations, voltage divider circuits were designed so as to have 5 times higher linearity. Front-end circuit equipped only resister chain and amplifier and the data acquisition system was separated from the gantry by 7-m coaxial cables for protecting electronics circuits from radiation damage by secondary particles. For sensitivity comparison between WBSROP and WBDROP prototypes, both scanners were simulated using Monte-Carlo simulation. Predicted sensitivity of the WBSROP prototype was 3.1%. The WBSROP prototype promises high sensitivity although wide open gap.

We assessed the impact of changes in patient position on carbon-ion scanning beam distribution during treatment for prostate cancer.68 patients were selected. Carbon-ion scanning dose was calculated. Two different planning target volumes (PTVs) were defined: PTV1 was the clinical target volume plus a set-up margin for the anterior/lateral sides and posterior side, while PTV2 was the same as PTV1 minus the posterior side. Total prescribed doses of 34.4 Gy [relative biological effectiveness (RBE)] and 17.2 Gy (RBE) were given to PTV1 and PTV2, respectively. To estimate the influence of geometric variations on dose distribution, the dose was recalculated on the rigidly shifted single planning CT based on two dimensional-three dimensional rigid registration of the orthogonal radiographs before and after treatment for the fraction of maximum positional changes.Intrafractional patient positional change values averaged over all patients throughout the treatment course were less than the target registration error = 2.00 mm and angular error = 1.27°. However, these maximum positional errors did not occur in all 12 treatment fractions. Even though large positional changes occurred during irradiation in all treatment fractions, lowest dose encompassing 95% of the target (D95)-PTV1 was98% of the prescribed dose.Intrafractional patient positional changes occurred during treatment beam irradiation and degraded carbon-ion beam dose distribution. Our evaluation did not consider non-rigid deformations, however, dose distribution was still within clinically acceptable levels.Inter- and intrafractional changes did not affect carbon-ion beam prostate treatment accuracy.

Carbon-ion radiotherapy treatment plans are designed on the assumption that the beams are delivered instantaneously, irrespective of actual dose-delivery time structure in a treatment session. As the beam lines are fixed in the vertical and horizontal directions at our facility, beam delivery is interrupted in multi-field treatment due to the necessity of patient repositioning within the fields. Single-fractionated treatment for non-small cell lung cancer (NSCLC) is such a case, in which four treatment fields in multiple directions are delivered in one session with patient repositioning during the session. The purpose of this study was to investigate the effects of the period of dose delivery, including interruptions due to patient repositioning, on tumor control probability (TCP) of NSCLC. All clinical doses were weighted by relative biological effectiveness (RBE) evaluated for instantaneous irradiation. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions induced in DNA were applied to the single-fractionated treatment of NSCLC. Treatment plans were made for an NSCLC case for various prescribed doses ranging from 25 to 50 Gy (RBE), on the assumption of instantaneous beam delivery. These plans were recalculated by varying the interruption time τ ranging from 0 to 120 min between the second and third fields for continuous irradiations of 3 min per field based on the MKM. The curative doses that would result in a TCP of 90% were deduced for the respective interruption times. The curative dose was 34.5 Gy (RBE) for instantaneous irradiation and 36.6 Gy (RBE), 39.2 Gy (RBE), 41.2 Gy (RBE), 43.3 Gy (RBE) and 44.4 Gy (RBE) for τ = 0 min, 15 min, 30 min, 60 min and 120 min, respectively. The realistic biological effectiveness of therapeutic carbon-ion beam decreased with increasing interruption time. These data suggest that the curative dose can increase by 20% or more compared to the planned dose if the interruption time extends to 30 min or longer. These effects should be considered in carbon-ion radiotherapy treatment planning if a longer dose-delivery procedure time is anticipated.

In treatment planning of charged-particle therapy, tissue heterogeneity is conventionally modeled as water with various densities, i.e. stopping effective densities [Formula: see text] and the integrated depth dose measured in water (IDD) is applied accordingly for the patient dose calculation. Since the chemical composition of body tissues is different from that of water, this approximation causes dose calculation errors, especially due to difference in nuclear interactions. Here, we propose and validate an IDD correction method for these errors in patient dose calculations.For accurate handling of nuclear interactions, [Formula: see text] of the patient is converted to nuclear effective density [Formula: see text] defined as the ratio of the probability of nuclear interactions in the tissue to that in water using a recently formulated semi-empirical relationship between the two. The attenuation correction factor [Formula: see text] defined as the ratio of the attenuation of primary carbon ions in a patient to that in water, is calculated from a linear integration of [Formula: see text] along the beam path. In our treatment planning system, a carbon-ion beam is modeled to be composed of three components according to their transverse beam sizes: primary carbon ions, heavier fragments, and lighter fragments. We corrected the dose contribution from primary carbon ions to IDD as proportional to [Formula: see text] and corrected that from lighter fragments as inversely proportional to [Formula: see text] We tested the correction method for some non-water materials, e.g. milk, lard, ethanol and water solution of potassium phosphate (K2HPO4), with un-scanned and scanned carbon-ion beams.In un-scanned beams, the difference in IDD between a beam penetrating a 150 mm-thick layer of lard and a beam penetrating water of the corresponding thickness amounted to-4%, while it was +6% for a 150 mm-thick layer of 40% K2HPO4. The observed differences were accurately predicted by the correction method. The corrected IDDs agreed with the measurements within±1% for all materials and combinations of them. In scanned beams, the dose estimation error in target dose amounted to 4% for a 150 mm-thick layer of 40% K2HPO4. The error is significantly reduced with the correction method. The planned dose distributions with the method agreed with the measurements within±1.5% of target dose for all materials not only in the target region but also in the plateau and fragment-tail regions.We tested the correction method of IDD in some non-water materials to verify that this method would offer the accuracy and simplicity required in carbon-ion radiotherapy treatment planning.

For spot-scanning irradiation, we have developed a new control system in the experiments involving secondary beams of short half-lives. Fast beam switching and spot-by-spot dose monitoring were incorporated into this system. The control system can interface with various instruments, perform sequencing of measurements, control the motion of instruments and data acquisition. Synchronized communications with the period of beam spills in the LAN are introduced in the system to avoid the conflicts among computer communications. As an example of measurement, the results of dose distribution in 3D spot-scanning irradiation are presented.

The latest heavy ion therapy tends to require information about the spatial distribution of the quality of radiation in a patient's body in order to make the best use of any potential advantage of swift heavy ions for the therapeutic treatment of a tumour. The deflection of incident particles is described well by Molière's multiple-scattering theory of primary particles; however, the deflection of projectile fragments is not yet thoroughly understood. This paper reports on our investigation of the spatial distribution of fragments produced from a therapeutic carbon beam through nuclear reactions in thick water. A DeltaE-E counter telescope system, composed of a plastic scintillator, a gas-flow proportional counter and a BGO scintillator, was rotated around a water target in order to measure the spatial distribution of the radiation quality. The results revealed that the observed deflection of fragment particles exceeded the multiple scattering effect estimated by Molière's theory. However, the difference can be sufficiently accounted for by considering one term involved in the multiple-scattering formula; this term corresponds to a lateral 'kick' at the point of production of the fragment. This kick is successfully explained as a transfer of the intra-nucleus Fermi momentum of a projectile to the fragment; the extent of the kick obeys the expectation derived from the Goldhaber model.

In radiation therapy with hadron beams, conformal irradiation to a tumour can be achieved by using the properties of incident ions such as the high dose concentration around the Bragg peak. For the effective utilization of such properties, it is necessary to evaluate the volume irradiated with hadron beams and the deposited dose distribution in a patient's body. Several methods have been proposed for this purpose, one of which uses the positron emitters generated through fragmentation reactions between incident ions and target nuclei. In the previous papaer, we showed that the maximum likelihood estimation (MLE) method could be applicable to the estimation of beam end-point from the measured positron emitting activity distribution for mono-energetic beam irradiations. In a practical treatment, a spread-out Bragg peak (SOBP) beam is used to achieve a uniform biological dose distribution in the whole target volume. Therefore, in the present paper, we proposed to extend the MLE method to estimations of the position of the distal and proximal edges of the SOBP from the detected annihilation gamma ray distribution. We confirmed the effectiveness of the method by means of simulations. Although polyethylene was adopted as a substitute for a soft tissue target in validating the method, the proposed method is equally applicable to general cases, provided that the reaction cross sections between the incident ions and the target nuclei are known. The relative advantage of incident beam species to determine the position of the distal and the proximal edges was compared. Furthermore, we ascertained the validity of applying the MLE mehtod to determinations of the position of the distal and the proximal edges of an SOBP by simulations and we gave a physical explanation of the distal and the proximal information.

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

The OpenPET is our original idea that realizes the world's first open-type 3D PET scanner for PET-image guided particle therapy such as in situ dose verification and direct tumor tracking. Even with a full-ring geometry, the OpenPET has an open gap between its 2 detector rings through which the treatment beam passes. Following our initial 2008 proposal, we developed a small prototype in 2010 to show a proof-of-concept. Now, we report the development of a prototype whole-body OpenPET. The key technology which enabled the OpenPET realization is our original, 4-layered depth-of-interaction detector. In order to measure a radiation from the limited activity produced though fragmentation reactions, Zr-doped GSO (GSOZ), which contains less natural radioactivity, was chosen for the scintillators instead of Lu-based scintillators although timing performance was compromised. In order to compensate for the limited light yield, on the other hand, we used 64-channel flat-panel PMTs with a super-bialkali photocathode, which had a 30% higher quantum efficiency. In order to enable stable in-beam PET measurement even under high background radiations, voltage divider circuits were designed to provide 5 times higher linearity. Additionally, to avoid severe radiation damage, we did not use gain control ASICs in the front-end circuits, and position analyzer circuits were placed with a 15-m cable extension. The prototype consists of 2 detector rings, and each detector ring has 2 sub-rings of 40 detectors. Each detector consists of 16 × 16 × 4 array of GSOZ (2.8 × 2.8 × 7.5mm3). The portable gantry has a compact design; each detector ring has a 940 mm outer diameter and 171 mm thickness for the detector inner bore of 640 mm diameter and 113 mm thickness. The system was tested with a carbon beam irradiation at a clinical intensity. Phantom images were obtained by applying a GPGPU-based, list mode iterative reconstruction algorithm with geometrical detector response modeling.

For the purpose of in situ visualization of an irradiation field in particle therapy, it is ideal to use radioactive beams for in-beam positron emission tomography (PET) imaging. In the Heavy Ion Medical Accelerator in Chiba (HIMAC), there is a beam course to produce 11C and 10C as secondary beams, but generation of 15O has never been investigated. This study was devoted to analysis of the feasibility of secondary 15O production for in-beam PET by 16O primary beam in different absorbing materials (targets) with various thicknesses in order to find out the optimum target material and its thickness. The study was performed using analytical method, LISE++ code, and the Monte Carlo method, PHITS code. The calculation results showed that the highest intensity of the secondary 15O beam observed for primary 16O beam decelerating in liquid hydrogen but practically almost impossible to apply. The final optimum target was considered to be polyethylene with thickness of 11 cm. The 15O beam was produced in the HIMAC secondary beam line using the optimum target and the in-beam PET imaging was presented for a PMMA phantom irradiated with the produced beam.

Relationships based on the microdosimetric-kinetic model are presented that calculate the average number of lethal lesions, and the associated cell survival, produced in mammalian cells by exposure to protracted continuous irradiation by temporary and permanent implantation of radioactive sources. The influence of cell parameters of linear-quadratic survival, repair function and proliferation rate, as well as the influence of dose rate, isotopic decay rate and linear energy transfer (LET) quality on cell killing are displayed and discussed. An expression for biologic effective dose (BED) is presented that facilitates comparison of the effects of protracted low-dose-rate irradiation and with a course of multiple instantaneously administered radiation treatments (fractions).

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.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.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.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.

To evaluate a patient-specific QA program and system for constancy checking of a scanning delivery system developed at the National Institute of Radiological Sciences.For the patient-specific QA, all the planned beams are recalculated on a water phantom with treatment planning software (TPS). The recalculated dose distributions are compared with the measured distributions using a 2D ionization chamber array at several depths, and evaluated using gamma index analysis with criteria of 3% and 3 mm and a pass rate of 90%. For the constancy check, the authors developed the multiwire proportional chamber (MWPC), which can record the delivered 2D fluence images in a slice-by-slice manner. During irradiation for dosimetric QA with the 2D ionization chamber array and an accordion-type water phantom, the 2D fluence images are recorded using the MWPC in the delivery system. These recorded images are then compared to those taken in the treatment session to check the constancy check. This analysis also employs gamma index analysis using the same criteria as in the patient-specific QA. These patient-specific QA and constancy check evaluations were performed using the data of 122 patients.In the patient-specific QA, the measured dose distributions agreed well with those calculated by the TPS, and the QA criteria were satisfied in all measurements. The additional check of the fluence comparison ensured the constancy of the delivered field during each treatment irradiation.The authors established a patient-specific QA program and additional check of delivery constancy in every treatment session. Fluence comparison is a strong tool for constancy checking of the delivery system.

We proposed to apply the MLE method for determining the range of heavy ions and demonstrated the effectiveness of this method by experiments with 12 C beams. We performed irradiation experiments with stable 12 C ions of mono-energetic 290 MeV/u to a water, a polyethylene and a PMMA target. The theoretical ranges for 12 C ions of 290 MeV/u in these targets are 160.5, 157.9 and 139.8 mm, respectively. The annihilation events from positron emitters generated by 12 C ions were detected with a positron camera for 500 s just after the irradiation. To evaluate the range of 12 C ions, the MLE method was applied to the annihilation gamma ray distribution. The derived ranges for the three targets were 160.6, 158.9 and 140.4 mm, respectively. Therefore, we can conclude that the range of 12 C ions was determined within an accuracy of 1.0 mm for all targets.

Treatment planning of carbon-ion radiotherapy (C-ion RT) should best use the physical and biological advantages of the radiation, which is heavily coupled to the beam delivery system. In this section, overview of conventional system for broad-beam delivery, which has been used for many years, and a state-of-the-art system for pencil-beam scanning are described in addition to general aspects to plan a treatment of carbon-ion radiotherapy. Finally, we demonstrate the comparison between broad- and scanning-beam plans for a few cases.

Relations based on the microdosimetric-kinetic (MK) model are presented that describe killing of mammalian cells by protracted continuous exposure to ionizing radiation of varying linear energy transfer quality (LET) at constant dose rate. The consequences of continuous irradiation exposure actually consisting of a discontinuous sequence of events corresponding to passage of each high-energy particle through or near the cell are incorporated into the model. The derived relations are applied to protracted irradiation experiments of Amdur and Bedford to determine the rate of repair of potentially lethal lesions. It is found that as the dose rate becomes less than about 5 Gy per hour the repair rate decreases significantly with decreasing dose rate. This suggests that repair function in these cells is induced and maintained in response to the intensity of irradiation. Clinical and radiation protection implications of this finding are noted.

In ion beam radiotherapy, secondary neutrons contribute to an undesired dose outside the target volume, and consequently the increase of secondary cancer risk is a growing concern. In this study, neutron ambient dose equivalents in carbon-ion radiotherapy (CIRT) with an active beam delivery system were measured with a rem meter, WENDI-II, at National Institute of Radiological Sciences. When the same irradiation target was assumed, the measured neutron dose with an active beam was at most ∼15 % of that with a passive beam. This percentage became smaller as larger distances from the iso-centre. Also, when using an active beam delivery system, the neutron dose per treatment dose in CIRT was comparable with that in proton radiotherapy. Finally, it was experimentally demonstrated that the use of an active scanned beam in CIRT can greatly reduce the secondary neutron dose.

In situ visualization of deposited dose distribution is necessary to exploit the advantages of Carbon-ion therapy. Therefore we are developing the world's first, open-type PET “OpenPET” to verify the field irradiated. In addition, a method of utilizing activity measurement in the target irradiated with the beam with positron-emitting radioisotopes (RI) such as 11C and 10C has been proposed. This method has advantage in the amount of activity as well as direct visualization of primary particles themselves, compared with the irradiation with stable nuclei 12C beam. With the RI beam, however, the profile of the dose was still different from that of the activity. Therefore interpretation from activity distribution to dose distribution is necessary to confirm the irradiation field precisely. In this paper, we developed a method of estimating the dose distribution from PET measurements. To utilize the activity measurement of the target, we used the code which calculated the activation distribution and dose distribution taking initial beam energy as a free parameter. Then the maximum likelihood parameter of the initial energy was determined by comparing the measured and the calculated distributions. By using the parameter determined, the dose distribution in the target was calculated as the estimated distribution for the actual one. The uniform PMMA target was irradiated with 11C beam for 10 s. The target was measured from the time beam irradiation started and to 60 s after finishing the irradiation by using a small single-ring OpenPET prototype developed for a proof-of-concept of the in-beam monitoring for charged particle therapy. As a result, the dose distribution, which was originally different from primary particles distribution, was successfully estimated. The peak depth of the estimated dose distribution was in good agreement with the measured dose peak.