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Objective. Diffusion equation (DE) imaging processing is promising to enhance images showing lesions of bone metastasis (LBM). The Perona-Malik diffusion (PMD) model, which has been widely used and studied, is an anisotropic diffusion processing method to denoise or extract objects from an image effectively. However, the smoothing characteristics of PMD or its related method hinder extraction and enhancement of soft tissue regions of medical image such as computed tomography (CT), typically leaving an indistinct region with ambient tissues. Moreover, PMD expands the border region of the objects. A novel diffusion methodology must be used to enhance the LBM region effectively. Approach. For this study, we originally developed a DE quantification (DEQ) method that uses a filter function to selectively provide modulated diffusion according to the original locations of objects in an image. The structural similarity index measure (SSIM) and Lie derivative image analysis L -value map were used to evaluate image quality and processing. Main results. We determined superellipse function with its ordern=4as a better performing filter for the LBM region. DEQ was found to be more effective at contrasting LBM for various LBM CT images than PMD or its improved models when the filter was a positive exponential similar function. DEQ yields enhancement agreeing with the indications of positron emission tomography despite complex LBM comprising osteoblastic, osteoclastic, mixed tissues, and metal artifacts, which is innovative. Moreover, DEQ retained high quality of image (SSIM> 0.95), and achieved a low mean value of the L -value (<0.001), indicative of our intended selective diffusion compared to other PMD models. Significance. Our method improved the visibility of mixed tissue lesions, which can assist computer visional framework and can help radiologists to produce accurate diagnose of LBM regions which are frequently overlooked in radiology findings because of the various degrees of visibility in CT images., (Creative Commons Attribution license.)

Objective . The gamma index ( γ ) has been extensively investigated in the medical physics and applied in clinical practice. However, γ has a significant limitation when used to evaluate the dose-gradient region, leading to inconveniences, particularly in stereotactic radiotherapy (SRT). This study proposes a novel evaluation method combined with γ to extract clinically problematic dose-gradient regions caused by irradiation including certain errors. Approach . A flow-vector field in the dose distribution is obtained when the dose is considered a scalar potential. Using the Lie derivative from differential geometry, we defined L , S , and U to evaluate the intensity, vorticity, and flow amount of deviation between two dose distributions, respectively. These metrics multiplied by γ ( γL , γS , γU ), along with the threshold value σ , were verified in the ideal SRT case and in a clinical case of irradiation near the brainstem region using radiochromic films. Moreover, Moran's gradient index (MGI), Bakai's χ factor, and the structural similarity index (SSIM) were investigated for comparisons. Main results . A high L- metric value mainly extracted high-dose-gradient induced deviations, which was supported by high S and U metrics observed as a robust deviation and an influence of the dose-gradient, respectively. The S- metric also denotes the measured similarity between the compared dose distributions. In the γ distribution, γL sensitively detected the dose-gradient region in the film measurement, despite the presence of noise. The threshold σ successfully extracted the gradient-error region where γ > 1 analysis underestimated, and σ = 0.1 (plan) and σ = 0.001 (film measurement) were obtained according to the compared resolutions. However, the MGI, χ, and SSIM failed to detect the clinically interested region. Significance . Although further studies are required to clarify the error details, this study demonstrated that the Lie derivative method provided a novel perspective for the identifying gradient-induced error regions and enabled enhanced and clinically significant evaluations of γ ., (Creative Commons Attribution license.)

Positron emission tomography (PET) has been used for in vivo treatment verification, mainly for range verification, in proton therapy. Evaluating the direct dose from PET measurements remains challenging; however, it is highly desirable from a clinical perspective. In this study, a method for estimating the dose distribution from the positron emitter distributions was developed using the maximum likelihood expectation maximization algorithm. The 1D spatial relationship between positron emitter distributions and a dose distribution in an inhomogeneous target was inputted into the system matrix based on a filter framework. In contrast, spatial resolution of the PET system and total variation regularization (as prior knowledge for dose distribution) were considered in the 3D image-space. The dose estimation was demonstrated using Monte Carlo simulated PET activity distributions with substantial noise in a head and neck phantom. This mimicked the single field irradiation of the spread-out Bragg peak beams at clinical dose levels. Besides the simple implementation of the algorithm, this strategy achieved a high-speed calculation (30 s for a 3D dose estimation) and accurate dose and range estimations (less than 10% and 2 mm errors at 1-σ values, respectively). The proposed method could be key for using PET for in vivo dose monitoring.

Positron emission tomography (PET) has been extensively studied and clinically investigated for dose verification in proton therapy. However, the production distributions of positron emitters are not proportional to the dose distribution. Thus, direct dose evaluation is limited when using the conventional PET-based approach. We propose a method for estimating the dose distribution from the positron emitter distributions using the maximum likelihood (ML) expectation maximization (EM) algorithm combined with filtering. In experiments to verify the effectiveness of the proposed method, mono-energetic and spread-out Bragg-peak proton beams were delivered by a synchrotron, and a water target was irradiated at clinical dose levels. Planar PET measurements were performed during beam pauses and after irradiation over a total period of 200 s. In addition, we conducted a Monte Carlo simulation to obtain the required filter functions and analyze the influence of the number of algorithm iterations on estimation. We successfully estimated the 2D dose distributions even under statistical noise in the PET images. The accuracy of the 2D dose estimation was about 10% for both beams at the 1-[Formula: see text] values of relative error. This value is comparable to the deviations in the measured PET activity distributions. For the laterally integrated profile along the beam direction, a low error within 5% was obtained per irradiation value. Moreover, the difference of estimated proton ranges was within 1 mm, and 2D estimation from the PET images was completed in 21 ms. Hence, the proposed algorithm may be applied to real-time dose monitoring. Although this is the first attempt to use the ML-EM algorithm for dose estimation, the proposed method showed high accuracy and speed in the estimation of proton dose distribution from PET data. The proposed method is thus a step forward to exploit the full potential of PET for in vivo dose verification.

Range uncertainty is among the most formidable challenges associated with the treatment planning of proton therapy. Proton imaging, which includes proton radiography and proton computed tomography (pCT), is a useful verification tool. We have developed a pCT detection system that uses a thick bismuth germanium oxide (BGO) scintillator and a CCD camera. The current method is based on a previous detection system that used a plastic scintillator, and implements improved image processing techniques. In the new system, the scintillation light intensity is integrated along the proton beam path by the BGO scintillator, and acquired as a two-dimensional distribution with the CCD camera. The range of a penetrating proton is derived from the integrated light intensity using a light-to-range conversion table, and a pCT image can be reconstructed. The proton range in the BGO scintillator is shorter than in the plastic scintillator, so errors due to extended proton ranges can be reduced. To demonstrate the feasibility of the pCT system, an experiment was performed using a 70 MeV proton beam created by the AVF930 cyclotron at the National Institute of Radiological Sciences. The accuracy of the light-to-range conversion table, which is susceptible to errors due to its spatial dependence, was investigated, and the errors in the acquired pixel values were less than 0.5 mm. Images of various materials were acquired, and the pixel-value errors were within 3.1%, which represents an improvement over previous results. We also obtained a pCT image of an edible chicken piece, the first of its kind for a biological material, and internal structures approximately one millimeter in size were clearly observed. This pCT imaging system is fast and simple, and based on these findings, we anticipate that we can acquire 200 MeV pCT images using the BGO scintillator system.

A proton computed tomography (pCT) imaging system was constructed for evaluation of the error of an x-ray CT (xCT)-to-WEL (water-equivalent length) conversion in treatment planning for proton therapy. In this system, the scintillation light integrated along the beam direction is obtained by photography using the CCD camera, which enables fast and easy data acquisition. The light intensity is converted to the range of the proton beam using a light-to-range conversion table made beforehand, and a pCT image is reconstructed. An experiment for demonstration of the pCT system was performed using a 70 MeV proton beam provided by the AVF930 cyclotron at the National Institute of Radiological Sciences. Three-dimensional pCT images were reconstructed from the experimental data. A thin structure of approximately 1 mm was clearly observed, with spatial resolution of pCT images at the same level as that of xCT images. The pCT images of various substances were reconstructed to evaluate the pixel value of pCT images. The image quality was investigated with regard to deterioration including multiple Coulomb scattering.

In proton beam therapy, changes in the proton range due to lateral heterogeneity may cause serious errors in the dose distribution. In the present study, the pencilbeam redefinition algorithm (PBRA) was applied to proton beam therapy to address the problem of lateral density heterogeneity. In the calculation, the phase-space parameters were characterized for multiple range (i.e. proton energy) bins for given pencil beams. The particles that were included in each pencil beam were transported and redefined periodically until they had stopped. The redefined beams formed a detouring path that was different from that of the non-redefined pencil beams, and the path of each redefined beam was straight. The results calculated by the PBRA were compared with measured proton dose distributions in a heterogeneous slab phantom and an anthropomorphic phantom. Through the beam redefinition process, the PBRA was able to predict the measured proton-detouring effects. Therefore, the PBRA may allow improved calculation accuracy when dealing with lateral heterogeneities in proton therapy applications.

A feasibility study of a novel PET-based molecular image guided radiation therapy (m-IGRT) system was conducted by comparing PET-based digitally reconstructed planar image (PDRI) registration with radiographic registration. We selected a pair of opposing parallel-plane PET systems for the practical implementation of this system. Planar images along the in-plane and cross-plane directions were reconstructed from the parallel-plane PET data. The in-plane and cross-plane FWHM of the profile of 2 mm diameter sources was approximately 1.8 and 8.1 mm, respectively. Therefore, only the reconstructed in-plane image from the parallel-plane PET data was used in the PDRI registration. In the image registration, five different sizes of (18)F cylindrical sources (diameter: 8, 12, 16, 24, 32 mm) were used to determine setup errors. The data acquisition times were 1, 3 and 5 min. Image registration was performed by five observers to determine the setup errors from PDRI registration and radiographic registration. The majority of the mean registration errors obtained from the PDRI registration were not significantly different from those obtained from the radiographic registration. Acquisition time did not appear to result in significant differences in the mean registration error. The mean registration error for the PDRI registration was found to be 0.93 ± 0.33 mm. This is not statistically different from the radiographic registration which had a mean registration error of 0.92 ± 0.27 mm. Our results suggest that m-IGRT image registration using PET-based reconstructed planar images along the in-plane direction is feasible for clinical use if PDRI registration is performed at two orthogonal gantry angles.

Treatment planning for proton tumor therapy requires a fast and accurate dose-calculation method. We have implemented a simplified Monte Carlo (SMC) method in the treatment planning system of the National Cancer Center Hospital East for the double-scattering beam delivery scheme. The SMC method takes into account the scattering effect in materials more accurately than the pencil beam algorithm by tracking individual proton paths. We confirmed that the SMC method reproduced measured dose distributions in a heterogeneous slab phantom better than the pencil beam method. When applied to a complex anthropomorphic phantom, the SMC method reproduced the measured dose distribution well, satisfying an accuracy tolerance of 3 mm and 3% in the gamma index analysis. The SMC method required approximately 30 min to complete the calculation over a target volume of 500 cc, much less than the time required for the full Monte Carlo calculation. The SMC method is a candidate for a practical calculation technique with sufficient accuracy for clinical application.

The metal oxide semiconductor field-effect transistor (MOSFET) dosimeter has been widely studied for use as a dosimeter for patient dose verification. The major advantage of this detector is its size, which acts as a point dosimeter, and also its ease of use. The commercially available TN502RD MOSFET dosimeter manufactured by Thomson and Nielsen has never been used for proton dosimetry. Therefore we used the MOSFET dosimeter for the first time in proton dose measurements. In this study, the MOSFET dosimeter was irradiated with 190 MeV therapeutic proton beams. We experimentally evaluated dose reproducibility, linearity, fading effect, beam intensity dependence and angular dependence for the proton beam. Furthermore, the Bragg curve and spread-out Bragg peak were also measured and the linear-energy transfer (LET) dependence of the MOSFET response was investigated. Many characteristics of the MOSFET response for proton beams were the same as those for photon beams reported in previous papers. However, the angular MOSFET responses at 45, 90, 135, 225, 270 and 315 degrees for proton beams were over-responses of about 15%, and moreover the MOSFET response depended strongly on the LET of the proton beam. This study showed that the angular dependence and LET dependence of the MOSFET response must be considered very carefully for quantitative proton dose evaluations.

Proton beam therapy can concentrate the dose on a tumour. In order to offer high-precision proton beam therapy to the patient, it is important to confirm the range every day. At the National Cancer Center Hospital East (NCC), the range measurement tool consists of a water phantom and an ionization chamber. These large and heavy tools take a long time to set up. Therefore, we developed a simple and easy-to-handle range measurement tool for proton beam therapy. This tool consists of a plastic scintillator block and a CCD camera. We recorded visible scintillation light generated by proton irradiation on the scintillator, and could measure the range from the shape of light distribution by using a computer with automatic analysis software installed. We carried out proton irradiation experiments with this tool to examine its performance as a tool of daily range measurements. The precision of the range measurement is within 0.3 mm (sd). The tool can measure possible short-term range variation with 1 s sampling time during the time interval of a typical treatment in a few minutes. We conclude that this tool can measure the range with sufficient resolution in a short time, and is useful for range control in a clinical setting.

A multicentre phase II trial of stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer was initiated in Japan as the Japan Clinical Oncology Group trial (JCOG0403). Before starting the trial, a decision was made to evaluate the treatment machine and treatment planning in participating institutions to minimize the variations of the prescription dose between the institutions. We visited the 16 participating institutions and examined the absolute dose at the centre of a simulated spherical tumour of 3.0 cm diameter in the lung using the radiation treatment planning systems in each institution. A lung phantom for stereotactic body radiotherapy (SBRT) was developed and used for the treatment planning and film dosimetry. In the JCOG radiotherapy study group, the no model-based calculation algorithm or the model-based calculation algorithm with a dose kernel unscaled for heterogeneities were selected for use in the initial SBRT trials started in 2004, and the model-based calculation algorithm with a dose kernel scaled for heterogeneities was selected for the coming trial. The findings of this study suggest that the clinical results of lung SBRT trials should be carefully evaluated in comparison with the actual dose given to patients.

In proton radiotherapy with high focusing of irradiation on the tumour, it is important to obtain treatment beams with a highly uniform dose distribution. Uniform dose distribution in the clinical irradiation field can be obtained by the dual-ring double scattering method. This method is superior to the wobbler method, which uses electromagnetic deflection of the proton beams, because of the absence of the temporal structure of irradiation distribution. However, in the dual-ring double scattering method the condition of incident proton beams entering the scatter, especially the accuracy of the position of the incident proton beams with respect to the scatter, markedly affects the uniformity of the beam distribution in the irradiation field. In this study, to ensure the uniformity of dose distribution during treatment, we developed a control system equipped with an automatic fine adjustment of the beam axis and a mechanism for moving the second dual-ring scatter of the double scatters to the optimal position. Using this system, we achieved uniform dose distribution in the irradiation field during proton radiotherapy, with symmetry within +/-1% and flatness within 2%.

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.

The calibration coefficients of a parallel plate ionization chamber are examined by comparing the coefficients obtained through three methods: a calculation from a 60Co calibration coefficient, N(D, omega, 60Co), a cross-calibration of a parallel plate ionization chamber using a cylindrical ionization chamber at the plateau region of a mono-energetic beam and a cross-calibration of the chamber using a cylindrical chamber at the middle of the SOBP of the therapeutic beams. This paper also examines reference conditions for determining absorbed dose to water in the cases of therapeutic carbon and proton beams. In the dose calibration procedure recommended by IAEA, irradiation fields should be larger than 10 cm in diameter and the water phantom should extend by at least 5 cm beyond each side of the field. These recommendations are experimentally verified for proton and carbon beams. For proton beams, the calibration coefficients obtained by these three methods approximately agreed. For carbon beams, the calibration coefficients obtained by the second method were about 1.0% larger than those obtained by the third method, and the calibration coefficients obtained by cross-calibration using 290 MeV/u beams were 0.5% lower than those obtained using 400 MeV/u beams. The calibration coefficient obtained by the first method agreed roughly with the results obtained by SOBP beams.

Washout of 10C and 11C implanted by radioactive beams in brain and thigh muscle of rabbits was studied. The biological washout effect in a living body is important in the range verification system or three-dimensional volume imaging in heavy ion therapy. Positron emitter beams were implanted in the rabbit and the annihilation gamma-rays were measured by an in situ positron camera which consisted of a pair of scintillation cameras set on either side of the target. The ROI (region of interest) was set as a two-dimensional position distribution and the time-activity curve of the ROI was measured. Experiments were done under two conditions: live and dead. By comparing the two sets of measurement data, it was deduced that there are at least three components in the washout process. Time-activity curves of both brain and thigh muscle were clearly explained by the three-component model analysis. The three components ratios (and washout half-lives) were 35% (2.0 s), 30% (140 s) and 35% (10 191 s) for brain and 30% (10 s), 19% (195 s) and 52% (3175 s) for thigh muscle. The washout effect must be taken into account for the verification of treatment plans by means of positron camera measurements.