A CT-based software tool for evaluating compensator quality in passively scattered proton therapy

We have developed a quantitative computed tomography (CT)-based quality assurance (QA) tool for evaluating the accuracy of manufactured compensators used in passively scattered proton therapy. The thickness of a manufactured compensator was measured from its CT images and compared with the planned thickness defined by the treatment planning system. The difference between the measured and planned thicknesses was calculated with use of the Euclidean distance transformation and the kd-tree search method. Compensator accuracy was evaluated by examining several parameters including mean distance, maximum distance, global thickness error and central axis shifts. Two rectangular phantoms were used to validate the performance of the QA tool. Nine patients and 20 compensators were included in this study. We found that mean distances, global thickness errors and central axis shifts were all within 1 mm for all compensators studied, with maximum distances ranging from 1.1 to 3.8 mm. Although all compensators passed manual verification at selected points, about 5% of the pixels still had maximum distances of >2 mm, most of which correlated with large depth gradients. The correlation between the mean depth gradient of the compensator and the percentage of pixels with mean distance <1 mm is -0.93 with p < 0.001, which suggests that the mean depth gradient is a good indicator of compensator complexity. These results demonstrate that the CT-based compensator QA tool can be used to quantitatively evaluate manufactured compensators.     

Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer

Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.     

A general solution to charged particle beam flattening using an optimized dual-scattering-foil technique, with application to proton therapy beams

This paper describes a dual-scattering-foil technique for flattening of radiotherapeutic charged particle beams. A theory for optimization of shapes and thicknesses of the scattering foils is presented. The result is a universal optimal secondary-scatterer profile, which can be adapted to any charged particle beam by a simple scaling procedure. The calculation of the mean square scattering angle of the beam after passing through the scattering foils is done using the generalized Fermi-Eyges model for charged particle transport. It is shown that the fluence profile in the plane of interest can be made flat to better than 1% inside a predefined beam radius provided the shaped secondary scatterer has the universal radial thickness profile. The thicknesses of the two foils are optimized to minimize the total energy loss. The theory has been tested experimentally in an 180 MeV clinical proton beam. The measured distributions agree well with the calculations.     

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy(-1). Sensitivity analysis revealed that E/D varied by +/-30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy(-1) in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy(-1) in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.     

A compact ridge filter for spread out Bragg peak production in pulsed proton clinical beams

A number of designs have been proposed for ridge filters and range modulators used in proton therapy to modify the beam in order to spread out the Bragg peak. Despite the variety of solutions, no simple design capable of providing large fields and easy variation of the spread out Bragg peak (SOBP) length in a pulsed beam has been developed. We propose a compact ridge filter that can be used in a proton beam of any time structure. It allows the production of depth dose distributions that meet the requirements of therapy dose fields.     

A beam source model for scanned proton beams

A beam source model, i.e. a model for the initial phase space of the beam, for scanned proton beams has been developed. The beam source model is based on parameterized particle sources with characteristics found by fitting towards measured data per individual beam line. A specific aim for this beam source model is to make it applicable to the majority of the various proton beam systems currently available or under development, with the overall purpose to drive dose calculations in proton beam treatment planning. The proton beam phase space is characterized by an energy spectrum, radial and angular distributions and deflections for the non-modulated elementary pencil beam. The beam propagation through the scanning magnets is modelled by applying experimentally determined focal points for each scanning dimension. The radial and angular distribution parameters are deduced from measured two-dimensional fluence distributions of the elementary beam in air. The energy spectrum is extracted from a depth dose distribution for a fixed broad beam scan pattern measured in water. The impact of a multi-slab range shifter for energy modulation is calculated with an own Monte Carlo code taking multiple scattering, energy loss and straggling, non-elastic and elastic nuclear interactions in the slab assembly into account. Measurements for characterization and verification have been performed with the scanning proton beam system at The Svedberg Laboratory in Uppsala. Both in-air fluence patterns and dose points located in a water phantom were used. For verification, dose-in-water was calculated with the Monte Carlo code GEANT 3.21 instead of using a clinical dose engine with approximations of its own. For a set of four individual pencil beams, both with the full energy and range shifted, 96.5% (99.8%) of the tested dose points satisfied the 1%/1 mm (2%/2 mm) gamma criterion.     

Monte Carlo simulations of neutron spectral fluence, radiation weighting factor and ambient dose equivalent for a passively scattered proton therapy unit

Stray neutron exposures pose a potential risk for the development of secondary cancer in patients receiving proton therapy. However, the behavior of the ambient dose equivalent is not fully understood, including dependences on neutron spectral fluence, radiation weighting factor and proton treatment beam characteristics. The objective of this work, therefore, was to estimate neutron exposures resulting from the use of a passively scattered proton treatment unit. In particular, we studied the characteristics of the neutron spectral fluence, radiation weighting factor and ambient dose equivalent with Monte Carlo simulations. The neutron spectral fluence contained two pronounced peaks, one a low-energy peak with a mode around 1 MeV and one a high-energy peak that ranged from about 10 MeV up to the proton energy. The mean radiation weighting factors varied only slightly, from 8.8 to 10.3, with proton energy and location for a closed-aperture configuration. For unmodulated proton beams stopped in a closed aperture, the ambient dose equivalent from neutrons per therapeutic absorbed dose (H*(10)/D) calculated free-in-air ranged from about 0.3 mSv/Gy for a small scattered field of 100 MeV proton energy to 19 mSv/Gy for a large scattered field of 250 MeV proton energy, revealing strong dependences on proton energy and field size. Comparisons of in-air calculations with in-phantom calculations indicated that the in-air method yielded a conservative estimation of stray neutron radiation exposure for a prostate cancer patient.     

Ridge filter design for proton therapy at Hyogo Ion Beam Medical Center

At the Hyogo Ion Beam Medical Center (HIBMC) we have developed a new design method for the bar ridge filter used in proton therapy, taking into consideration the scattering and nuclear interaction effects within the filter itself, which are introduced in the design. In our beam delivery system, the bar ridge filter is employed as the range modulator. It is combined with the wobbler system, and produces a three-dimensionally uniform spread-out Bragg peak (SOBP). The design program predicts the three-dimensional dose distribution. Ridge filters of 3-12 cm SOBP in 1 cm increments were designed in the maximum radiation field for 150 MeV and 190 MeV proton beams so that a uniform physical dose area is obtained in the SOBP region three-dimensionally. Measurements were performed with the constructed ridge filters to verify the uniformity and these were compared with the predictions of the design program. The predictions and measurements were found to be in agreement except for the 12 cm SOBP. The uniformities were better than +/- 3.0% for all SOBPs produced. The ridge filters are now clinically in use.     

CT图像重建中的一种新型滤波器

滤波反投影图像重建算法中滤波器设计是其中至关重要的一环。针对现有一次指数滤波器空域波形存在明显振荡、频域曲线截止频率附近没有明显压低的问题,引入高斯滤波器减小Gibbs效应,并设计一种用于CT重建领域的新型滤波器,即改进高斯滤波器。通过仿真实验对比说明滤波器中加权因子选择对图像质量的影响,另与RL滤波器、SL滤波器、一次指数滤波器、高斯滤波器实验对比验证了该滤波器拥有良好的抗噪性能,有效减小重建图像灰度波动以及明显提高重建图像质量。     

A phenomenological model for the relative biological effectiveness in therapeutic proton beams

To study the effects of a variable relative biological effectiveness (RBE) in inverse treatment planning for proton therapy, fast methods for three-dimensional RBE calculations are required. We therefore propose a simple phenomenological model for the RBE in therapeutic proton beams. It describes the RBE as a function of the dose, the linear energy transfer (LET) and tissue specific parameters. Published experimental results for the dependence of the parameters alpha and beta from the linear-quadratic model on the dose averaged LET were evaluated. Using a linear function for alpha(LET) in the relevant LET region below 30 keV per micrometre and a constant beta, a simple formula for the RBE could be derived. The new model was able to reproduce the basic dependences of RBE on dose and LET, and the RBE values agreed well with experimental results. The model was also applied to spread-out Bragg peaks (SOBP), where the main effects of a variable RBE are an increase of the RBE along the SOBP plateau, and a shift in depth of the distal falloff. The new method allows fast RBE estimations and has therefore potential applications in iterative treatment planning for proton therapy.     

Comparison of dosimetry recommendations for clinical proton beams

The formalism and data in the two most recent dosimetry recommendations for clinical proton beams, ICRU Report 59 and the forthcoming IAEA Code of Practice, are compared. Chamber calibrations in terms of air kerma and absorbed dose to water are considered, including five different cylindrical ionization chamber types commonly used in proton beam dosimetry. The methodology for both types of calibration for ionization chambers is described in ICRU Report 59. The procedure based on air kerma calibrations is compared with an alternative formalism based on IAEA Codes of Practice (TRS-277, TRS-381), modified for proton beams. The new IAEA Code of Practice is exclusively based on calibrations in terms of absorbed dose to water and a direct comparison with ICRU Report 59 recommendations is made. Common to the two formalisms are the fundamental quantities Wair and w(air) and their atmospheric conditions of applicability. The difference in the recommended values of the ratio w(air)/Wair (protons to 60Co) is as large as 2.3%. The use of Wair and w(air) values for dry air (IAEA) and for ambient air (ICRU) is a contribution to the discrepancy, and the ICRU usage is questioned. For air kerma based chamber calibrations, ICRU Report 59 does not take into account the effect of different compositions of the build-up cap and chamber wall on the calibration beam quality. For the chamber types included in the study, this introduces discrepancies of up to 1.1%. Combined with differences in the recommended basic data, discrepancies in absorbed dose determination in proton beams of up to 2.1% are found. For the absorbed dose to water based formalism, differences in the formalism, notably the omission of perturbation factors for 60Co in ICRU 59, and data yield discrepancies in calculated kQ factors, and in absorbed dose determinations, between -1.5% and +2.6%, depending on the chamber type and the proton beam quality.     

A small-body portable graphite calorimeter for dosimetry in low-energy clinical proton beams

Calorimetry has been recommended and performed in proton beams for some time, but never has graphite calorimetry been used as a reference dosimeter in clinical proton beams. Furthermore, only a few calorimetry measurements have been reported in ocular proton beams. In this paper we describe the construction and performance of a small-body portable graphite calorimeter for clinical low-energy proton beams. Perturbation correction factors for the gap effect, volume averaging effect, heat transfer phenomena and impurity effect are calculated and applied in a comparison with ionization chamber dosimetry following IAEA TRS-398. The ratio of absorbed dose to water obtained from the calorimeter measurements and from the ionization measurements varied between 0.983 and 1.019, depending on the beam type and the ionization chamber calibration modality. Standard uncertainties on these values varied between 1.9% and 2.5% including a substantial contribution from the kQ values in IAEA TRS-398. The (Wair/e)p values inferred from these measurements varied between 33.6 J C(-1) and 34.9 J C(-1) with similar standard uncertainties. A number of improvements for the small-body portable graphite calorimeter and the experimental set-up are suggested for potential reduction of the uncertainties.     

Parameterization of multiple Bragg curves for scanning proton beams using simultaneous fitting of multiple curves

Although Bortfeld's analytical formula is useful for describing Bragg curves, measured data can deviate from the values predicted by the model. Thus, we sought to determine the parameters of a closed analytical expression of multiple Bragg curves for scanning proton pencil beams using a simultaneous optimization algorithm and to determine the minimum number of energies that need to be measured in treatment planning so that complete Bragg curves required by the treatment planning system (TPS) can be accurately predicted. We modified Bortfeld's original analytical expression of Bragg curves to accurately describe the dose deposition resulting from secondary particles. The parameters of the modified analytical expression were expressed as the parabolic cylinder function of the ranges of the proton pencil beams in water. Thirty-nine discrete Bragg curves were measured in our center using a PTW Bragg Peak chamber during acceptance and commission of the scanning beam proton delivery system. The coefficients of parabolic function were fitted by applying a simultaneous optimization algorithm to seven measured curves. The required Bragg curves for 45 energies in the TPS were calculated using our parameterized analytical expression. Finally, the 10 cm width of spread-out Bragg peaks (SOBPs) of beams with maximum energies of 221.8 and 121.2 MeV were then calculated in the TPS and compared with measured data. Compared with Bortfeld's original formula, our modified formula improved fitting of the measured depth dose curves at depths around three-quarters of the maximum range and in the beam entrance region. The parabolic function described the relationship between the parameters of the analytic expression of different energies. The predicted Bragg curves based on the parameters fitted using the seven measured curves accurately described the Bragg curves of proton pencil beams of 45 energies configured in our TPS. When we used the calculated Bragg curves as the input to TPS, the standard deviations of the measured and calculated data points along the 10 cm SOBPs created with proton pencil beams with maximum energies of 221.8 and 121.2 MeV were 1.19% and 1.18%, respectively, using curves predicted by the algorithm generated from the seven measured curves. Our method would be a valuable tool to analyze measured Bragg curves without the need for time-consuming measurements and correctly describe multiple Bragg curves using a closed analytical expression.     

Dosimetry and spectral analysis of a radiobiological experiment using laser-driven proton beams

Laser-driven proton and ion acceleration is an area of increasing research interest given the recent development of short pulse-high intensity lasers. Several groups have reported experiments to understand whether a laser-driven beam can be applied for radiobiological purposes and in each of these, the method to obtain dose and spectral analysis was slightly different. The difficulty with these studies is that the very large instantaneous dose rate is a challenge for commonly used dosimetry techniques, so that other more sophisticated procedures need to be explored. This paper aims to explain a method for obtaining the energetic spectrum and the dose of a laser-driven proton beam irradiating a cell dish used for radiobiology studies. The procedure includes the use of a magnet to have charge and energy separation of the laser-driven beam, Gafchromic films to have information on dose and partially on energy, and a Monte Carlo code to expand the measured data in order to obtain specific details of the proton spectrum on the cells. Two specific correction factors have to be calculated: one to take into account the variation of the dose response of the films as a function of the proton energy and the other to obtain the dose to the cell layer starting from the dose measured on the films. This method, particularly suited to irradiation delivered in a single laser shot, can be applied in any other radiobiological experiment performed with laser-driven proton beams, with the only condition that the initial proton spectrum has to be at least roughly known. The method was tested in an experiment conducted at Queen’s University of Belfast using the TARANIS laser, where the mean energy of the protons crossing the cells was between 0.9 and 5 MeV, the instantaneous dose rate was estimated to be close to 109 Gy s?1 and doses between 0.8 and 5 Gy were delivered to the cells in a single laser shot. The combination of the applied corrections modified the initial estimate of dose by up to 40%.     

质子治疗的物理与生物学基础

近几十年来质子治疗在临床上取得了巨大成就,这是因为质子束在物理学和生物学上具有独特的优势。在肿瘤治疗学上质子比常规射线(^60Co、X射线、电子)有两个主要优势：(1)可根据肿瘤在体内的深度,使质子束精确地定位在肿瘤病灶处,以使肿瘤受到最大的照射剂量而不伤害健康组织,从而达到适形治疗。(2)可根据肿瘤的形状改变质子在微观尺度能量沉积的形状,实现辐射生物学效应的改变。基于此,对于形状较复杂的大实体瘤,质子治疗比常规治疗有更高的精度。质子的这些在治疗学上特异的可能性是由其剂量学和辐射生物学特性决定的。剂量学的性质与能量在宏观尺度的沉积特征有关,作为带电粒子,质子在介质中有确定的射程和相对小的散射歧离,此外在射程前端剂量相对较小,而到射程末端剂量达到最大,形成一个尖锐的Bragg峰,基于这屿特点使得肿瘤受到高剂量的照射而周围的健康组织受到很小的伤害;相对生物学效应与能量在微观尺度的沉积特征有关,与重离子相比虽然质子属于低LET射线,但就其能量在微观尺度沉积的性质与常规射线相比质子足致密电离辐射,因此目前已有实验证实质子治疗比常规射线治疗增加了相对生物学效应,然而目前对能量的微观沉积与生物学效应关系的原理仍需要进一步从理论上和实验上研究证明。文中分析了质子与介质的作用过程、以及传能线密度(LET)、相对生物学效应(RBE)、氧增比(OER)等放射治疗学的一般概念,讨论了质子用于肿瘤治疗的物理学与生物学性质。     

Optical resolution photoacoustic microscopy using novel high-repetition-rate passively Q-switched microchip and fiber lasers

Optical-resolution photoacoustic microscopy (OR-PAM) is a novel imaging technology for visualizing optically absorbing superficial structures in vivo with lateral spatial resolution determined by optical focusing rather than acoustic detection. Since scanning of the illumination spot is required, OR-PAM imaging speed is limited by both scanning speed and laser pulse repetition rate. Unfortunately, lasers with high repetition rates and suitable pulse durations and energies are not widely available and can be cost-prohibitive and bulky. We are developing compact, passively Q-switched fiber and microchip laser sources for this application. The properties of these lasers are discussed, and pulse repetition rates up to 100 kHz are demonstrated. OR-PAM imaging was conducted using a previously developed photoacoustic probe, which enabled flexible scanning of the focused output of the lasers. Phantom studies demonstrate the ability to image with lateral spatial resolution of 7±2 μm with the microchip laser system and 15±5 μm with the fiber laser system. We believe that the high pulse repetition rates and the potentially compact and fiber-coupled nature of these lasers will prove important for clinical imaging applications where real-time imaging performance is essential.