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.

New accelerator facility for carbon-ion cancer-therapy.

The first clinical trial with carbon beams generated from HIMAC was conducted in June 1994. The total number of patients treated as of December 2006 was in excess of 3,000. In view of the significant growth in the number of protocols, the Japanese government gave its approval for carbon-ion therapy at NIRS as an advanced medical technology in 2003. The impressive advances of carbon-ion therapy using HIMAC have been supported by high-reliability operation and by advanced developments of beam-delivery and accelerator technologies. Based on our ten years of experience with HIMAC, we recently proposed a new accelerator facility for cancer therapy with carbon ions for widespread use in Japan. The key technologies of the accelerator and beam-delivery systems for this proposed facility have been under development since April 2004, with the main thrust being focused on downsizing the facility for cost reduction. Based on the design and R&D studies for the proposed facility, its construction was begun at Gunma University in April 2006. In addition, our future plans for HIMAC also include the design of a new treatment facility. The design work has already been initiated, and will lead to the further development of therapy using HIMAC. The following descriptions give a summary account of the new accelerator facility for cancer therapy with carbon ions and of the new treatment facility at HIMAC.

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.

[Elucidation of the energy absorption spectra of the (11)C beam in a plastic scintillator.].

Heavy ion therapy using the energetic (12)C beam is successfully under way at HIMAC, Japan. The method is more advantageous than traditional radiation therapy in dose concentration owing to the Bragg peak and high relative biological effectiveness. A research study using the (11)C beam for heavy ion therapy in the future has been carried out in order to develop the capability of monitoring the dose distribution. Our group has examined the total energy absorption spectrum of the (11)C beam in a plastic scintillator. We could clearly observe the total absorption peak of (11)C in the energy spectrum and, in addition, we found a broad bump structure was associated with the peak. The bump area occupies 37% of the total spectrum and it probably affects the dose calculation for an accurate treatment planning. We elucidated the mechanism that leads to the structure of the total energy absorption spectra given by (11)C and (12)C in a block of plastic scintillator. This paper describes the method in detail and gives experimental analysis results which deal with the bump structure. We could explain the bump structure using the energy spectra caused by the fragmentation reactions.

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.

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.

[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.

[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.