Monitoring the irradiation field of 12C and 16O SOBP beams using positron emitters produced through projectile fragmentation reactions.

In order to effectively utilize the prominent properties of heavy ions in radiotherapy, it is important to evaluate both the position of the field irradiated with incident ions and the absorbed dose distribution in a patient's body. One of the methods for this purpose is the utilization of the positron emitters produced through the projectile fragmentation reactions of stable heavy ions with target nuclei. In heavy-ion therapy, spread-out Bragg peak (SOBP) beams are used to achieve uniform biological dose distributions in the whole tumor volume. Therefore, in this study, we designed SOBP beams of 30 and 50 mm water-equivalent length (mmWEL) in width for (12)C and (16)O, and carried out irradiation experiments using them. Water, polyethylene and polymethyl methacrylate were selected as targets to simulate a human body. Pairs of annihilation gamma rays were detected by means of a limited-angle positron camera for 500 s, and annihilation gamma-ray distributions were obtained. The maximum likelihood estimation (MLE) method was applied to the detected distributions for evaluating the positions of the distal and proximal edges of the SOBP in a target. The differences between the positions evaluated with the MLE method and those derived from the measured dose distributions were less than 1.7 mm and 2.5 mm for the distal and the proximal edge, respectively, in all irradiation conditions. When the positions of both edges are determined with the MLE method, the most probable shape of the dose distribution in a target can be estimated simultaneously. The close agreement between the estimated and the measured distributions implied that the shape of the dose distribution in an irradiated target could be evaluated from the detected annihilation gamma-ray distribution.

Optimization for fast-scanning irradiation in particle therapy.

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.

Design study of a raster scanning system for moving target irradiation in heavy-ion radiotherapy.

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.

Maximum likelihood estimation of proton irradiated field and deposited dose distribution.

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 than 1.0 mm. On the other hand, the difference amounted to 7.9 mm for proximal edges.

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an ionization chamber. The good agreement between the derived and the measured distributions implies that the deposited dose distribution in a target can be estimated from the detected annihilation gamma-ray distribution with a positron camera.

Enhanced efficiency in cell killing at the penetration depths around the Bragg peak of a radioactive 9C-ion beam.

PURPOSE: To evaluate the potential importance of radioactive 9C-ion beam in cancer radiotherapy. METHODS AND MATERIALS: Human salivary gland (HSG) cells were exposed to a double-radiation-source 9C beam at different depths around the Bragg peak. Cell survival fraction was determined by standard clonogenic assay. For comparison, the same experiment was conducted for a therapeutic 12C beam. To determine relative biologic effectiveness (RBE) values, HSG cells were also irradiated with 60Co gamma-rays of fractionation scheme as the reference. RESULTS: The 9C beam was more efficient in cell killing at the depths around its Bragg peak than was the 12C beam, which corresponded to the 9C-ion stopping region and where delayed low-energy particles were emitted. The RBE value at 50% survival level for the 9C beam varied from 1.38 to 4.23. Compared with the 12C beam, the RBE values for the 9C beam were always higher; an increase in RBE by a factor of up to 1.87 has been observed at the depths distal to the Bragg peak. CONCLUSION: The potential advantage of radioactive 9C-ion beam in cancer therapy has been revealed at low dose rate in comparison with a therapeutic 12C beam. This observation, however, remains to be investigated at therapeutic dose rates in the future.

Simulation for position determination of distal and proximal edges for SOBP irradiation in hadron therapy by using the maximum likelihood estimation method.

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 paper, 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 method 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.

Quantitative comparison of suitability of various beams for range monitoring with induced beta+ activity in hadron therapy.

In radiation therapy with hadron beams, it is important to evaluate the range of incident ions and the deposited dose distribution in a patient body for the effective utilization of such properties as the dose concentration and the biological effect around the Bragg peak. However, there is some ambiguity in determining this range because of a conversion error from the x-ray CT number to the charged particle range. This is because the CT number is related to x-ray absorption coefficients, while the ion range is determined by the electron density of the substance. Using positron emitters produced in the patient body through fragmentation reactions during the irradiation has been proposed to overcome this problem. The activity distribution in the patient body can be deduced by detecting pairs of annihilation gamma rays emitted from the positron emitters, and information about the range of incident ions can be obtained. In this paper, we propose a quantitative comparison method to evaluate the mean range of incident ions and monitor the activity distribution related to the deposited dose distribution. The effectiveness of the method was demonstrated by evaluating the range of incident ions using the maximum likelihood estimation (MLE) method and Fisher's information was calculated under realistic conditions for irradiations with several kinds of ions. From the calculated Fisher's information, we compared the relative advantages of initial beams to determine the range of incident ions. The (16)O irradiation gave the most information among the stable heavy ions when we measured the induced activity for 500 s and 60 s just after the irradiation. Therefore, under these conditions, we concluded that the (16)O beam was the optimum beam to monitor the activity distribution and to evaluate the range. On the other hand, if the positron emitters were injected directly as a therapeutic beam, the (15)O irradiation gave the most information. Although the relative advantages of initial beams as well as the measured activity distributions slightly varied according to the measurement conditions, comparisons could be made for different conditions by using Fisher's information.

Range verification system using positron emitting beams for heavy-ion radiotherapy.

It is desirable to reduce range ambiguities in treatment planning for making full use of the major advantage of heavy-ion radiotherapy, that is, good dose localization. A range verification system using positron emitting beams has been developed to verify the ranges in patients directly. The performance of the system was evaluated in beam experiments to confirm the designed properties. It was shown that a 10C beam could be used as a probing beam for range verification when measuring beam properties. Parametric measurements indicated the beam size and the momentum acceptance and the target volume did not influence range verification significantly. It was found that the range could be measured within an analysis uncertainty of +/-0.3 mm under the condition of 2.7 x 10(5) particle irradiation, corresponding to a peak dose of 96 mGyE (gray-equivalent dose), in a 150 mm diameter spherical polymethyl methacrylate phantom which simulated a human head.

[Feasibility study on a noninvasive measurement system for boron concentration.].

The kinematics of boron compounds in vivo is crucial to fully and safely utilize boron neutron capture therapy. In this paper, we proposed a prompt gamma-ray Compton scatter camera (PG-CSC), which can evaluate the 3-D kinematics of boron compounds without invasion. This PG-CSC combines a Compton camera with prompt gamma-ray analysis. The results of its design optimization and tests using simulations showed that one-hour-measurement was sufficient to evaluate a 3-D boron concentration distribution in a rat's brain with the resolution of 1 mm in FWHM.

[Experimental study on treatment planning verification using a positron emitting (10)C beam for heavy-ion radiotherapy.].

An advantage of heavy-ion therapy is its good dose concentration. A limit for full use of this desirable feature comes from range ambiguities in treatment planning. The treatment planning is based on X-ray CT measurements, and the range ambiguities are mainly due to an error in calibration of the CT number. The heavy-ion ranges are related to electron density of the medium while the CT numbers are defined using the X-ray attenuation coefficient. The range verification method using positron emitter beams has been developed to reduce the range ambiguities. In this verification, probing beams of positron emitters are implanted into the tumor, and pairs of annihilation gamma rays are detected with a positron camera. This paper demonstrates an application to verify treatment planning. Here the treatment planning was made on a head phantom and the ranges estimated from the CT-number were compared with the ranges measured with the positron camera. As a result, disagreements were detected between the planned ranges and the measured ones; there were 1.6 mm at maximum. The disagreements were due to an error of transformation of CT-number to range for the phantom material in the water column depth-dose measurement. The disagreements could be lowered to 0.4 mm by using the calibrated water-equivalent lengths. It was confirmed that the range verification system has a designed measurement accuracy of 1 mm and is useful for verifying irradiation fields on heavy-ion radiotherapy.

[The examination of optimal positron emitting nuclide in the estimation of attainment depth within the body of RI beams by positron camera].

The (10)C and (11)C beam stop position in a homogeneous phantom was measured using the range verification system in HIMAC. This system was developed to clear uncertainty of beam range within the patient body in heavy ion radiotherapy. In this system, a target is irradiated with RI beams ((11)C or (10)C) and the distribution of the beam end-points are measured by a positron camera. To inspect the precision of the measurement, three experiments were done, simple PMMA phantom irradiation, empirical beam stop position measurements using a range shifter and boundary irradiation using PMMA and lung phantom. Results of the first two experiments were consistent. Consequently, a 0.2 mm standard deviation of statistical error measurement was possible with 250 determinations. For the third experiment, we compared the precision using (10)C and (11)C beams. The boundary of the PMMA and lung phantom was irradiated with both beams to maximize the positron range effect in the beam range measurement. Consequently, no significant difference was observed between the two beams in spite of the different positron range. Thus, we conclude that the (10)C beam was useful for clinical application because of its good statistics owing to the short half-life.