Mitsutaka Yamaguchi

Beam range estimation by measuring bremsstrahlung

We describe a new method for estimating the beam range in heavy-ion radiation therapy by measuring the ion beam bremsstrahlung. We experimentally confirm that the secondary electron bremsstrahlung process provides the dominant bremsstrahlung contribution. A Monte Carlo simulation shows that the number of background photons from annihilation gamma rays is about 1% of the bremsstrahlung strength in the low-energy region used in our estimation (63-68 keV). Agreement between the experimental results and the theoretical prediction for the characteristic shape of the bremsstrahlung spectrum validates the effectiveness of our new method in estimating the ion beam range.

Optimization and verification of image reconstruction for a Compton camera towards application as an on-line monitor for particle therapy

Particle therapy is an advanced cancer therapy that uses a feature known as the Bragg peak, in which particle beams suddenly lose their energy near the end of their range. The Bragg peak enables particle beams to damage tumors effectively. To achieve precise therapy, the demand for accurate and quantitative imaging of the beam irradiation region or dosage during therapy has increased. The most common method of particle range verification is imaging of annihilation gamma rays by positron emission tomography. Not only 511-keV gamma rays but also prompt gamma rays are generated during therapy; therefore, the Compton camera is expected to be used as an on-line monitor for particle therapy, as it can image these gamma rays in real time. Proton therapy, one of the most common particle therapies, uses a proton beam of approximately 200 MeV, which has a range of ~ 25 cm in water. As gamma rays are emitted along the path of the proton beam, quantitative evaluation of the reconstructed images of diffuse sources becomes crucial, but it is far from being fully developed for Compton camera imaging at present. In this study, we first quantitatively evaluated reconstructed Compton camera images of uniformly distributed diffuse sources, and then confirmed that our Compton camera obtained 3 %(1 σ) and 5 %(1 σ) uniformity for line and plane sources, respectively. Based on this quantitative study, we demonstrated on-line gamma imaging during proton irradiation. Through these studies, we show that the Compton camera is suitable for future use as an on-line monitor for particle therapy.

First demonstration of multi-color 3-D in vivo imaging using ultra-compact Compton camera

In the field of nuclear medicine, single photon emission tomography and positron emission tomography are the two most common techniques in molecular imaging, but the available radioactive tracers have been limited either by energy range or difficulties in production and delivery. Thus, the use of a Compton camera, which features gamma-ray imaging of arbitrary energies from a few hundred keV to more than MeV, is eagerly awaited along with potential new tracers which have never been used in current modalities. In this paper, we developed an ultra-compact Compton camera that weighs only 580 g. The camera consists of fine-pixelized Ce-doped Gd3Al2Ga3O12 scintillators coupled with multi-pixel photon counter arrays. We first investigated the 3-D imaging capability of our camera system for a diffuse source of a planar geometry, and then conducted small animal imaging as pre-clinical evaluation. For the first time, we successfully carried out the 3-D color imaging of a live mouse in just 2 h. By using tri-color gamma-ray fusion images, we confirmed that 131I, 85Sr, and 65Zn can be new tracers that concentrate in each target organ.

Development of a low-energy x-ray camera for the imaging of secondary electron bremsstrahlung x-ray emitted during proton irradiation for range estimation

Imaging of secondary electron bremsstrahlung x-ray emitted during proton irradiation is a possible method for measurement of the proton beam distribution in phantom. However, it is not clear that the method is used for range estimation of protons. For this purpose, we developed a low-energy x-ray camera and conducted imaging of the bremsstrahlung x-ray produced during irradiation of proton beams. We used a 20 mm  ×  20 mm  ×  1 mm finely grooved GAGG scintillator that was optically coupled to a one-inch square high quantum efficiency (HQE)-type position-sensitive photomultiplier tube to form an imaging detector. The imaging detector was encased in a 2 cm-thick tungsten container, and a pinhole collimator was attached to its camera head. After performance of the camera was evaluated, secondary electron bremsstrahlung x-ray imaging was conducted during irradiation of the proton beams for three different proton energies, and the results were compared with Monte Carlo simulation as well as calculated value. The system spatial resolution and sensitivity of the developed x-ray camera with 1.5 mm-diameter pinhole collimator were estimated to be 32 mm FWHM and 5.2  ×  10-7 for ~35 keV x-ray photons at 100 cm from the collimator surface, respectively. We could image the proton beam tracks by measuring the secondary electron bremsstrahlung x-ray during irradiation of the proton beams, and the ranges for different proton energies could be estimated from the images. The measured ranges from the images were well matched with the Monte Carlo simulation, and slightly smaller than the calculated values. We confirmed that the imaging of the secondary electron bremsstrahlung x-ray emitted during proton irradiation with the developed x-ray camera has the potential to be a new tool for proton range estimations.

Three-dimensional and Multienergy Gamma-ray Simultaneous Imaging by Using a Si/CdTe Compton Camera

PURPOSE To develop a silicon (Si) and cadmium telluride (CdTe) imaging Compton camera for biomedical application on the basis of technologies used for astrophysical observation and to test its capacity to perform three-dimensional (3D) imaging. MATERIALS AND METHODS All animal experiments were performed according to the Animal Care and Experimentation Committee (Gunma University, Maebashi, Japan). Flourine 18 fluorodeoxyglucose (FDG), iodine 131 ((131)I) methylnorcholestenol, and gallium 67 ((67)Ga) citrate, separately compacted into micro tubes, were inserted subcutaneously into a Wistar rat, and the distribution of the radioisotope compounds was determined with 3D imaging by using the Compton camera after the rat was sacrificed (ex vivo model). In a separate experiment, indium 111((111)In) chloride and (131)I-methylnorcholestenol were injected into a rat intravenously, and copper 64 ((64)Cu) chloride was administered into the stomach orally just before imaging. The isotope distributions were determined with 3D imaging after sacrifice by means of the list-mode-expectation-maximizing-maximum-likelihood method. RESULTS The Si/CdTe Compton camera demonstrated its 3D multinuclear imaging capability by separating out the distributions of FDG, (131)I-methylnorcholestenol, and (67)Ga-citrate clearly in a test-tube-implanted ex vivo model. In the more physiologic model with tail vein injection prior to sacrifice, the distributions of (131)I-methylnorcholestenol and (64)Cu-chloride were demonstrated with 3D imaging, and the difference in distribution of the two isotopes was successfully imaged although the accumulation on the image of (111)In-chloride was difficult to visualize because of blurring at the low-energy region. CONCLUSION The Si/CdTe Compton camera clearly resolved the distribution of multiple isotopes in 3D imaging and simultaneously in the ex vivo model.

Imaging of monochromatic beams by measuring secondary electron bremsstrahlung for carbon-ion therapy using a pinhole x-ray camera

A feasibility study on the imaging of monochromatic carbon-ion beams for carbon-ion therapy was performed. The evaluation was based on Monte Carlo simulations and beam-irradiation experiments, using a pinhole x-ray camera, which measured secondary electron bremsstrahlung (SEB). The simulation results indicated that the trajectories of the carbon-ion beams with injection energies of 278, 249 and 218 MeV/u in a water phantom, were clearly imaged by measuring the SEB with energies from 30 to 60 keV, using a pinhole camera. The Bragg-peak positions for these three injection energies were located at the positions where the ratios of the counts of SEB acquisitions to the maximum counts were approximately 0.23, 0.26 and 0.29, respectively. Moreover, we experimentally demonstrated that it was possible to identify the Bragg-peak positons, at the positions where the ratios coincided with the simulation results. However, the estimated Bragg-peak positions for the injection energies of 278 and 249 MeV/u were slightly deeper than the expected positions. In conclusion, for both the simulations and experiments, we found that the 25 mm shifts in the Bragg-peak positions can be observed by this method.

In vivo simultaneous imaging with 99m Tc and 18 F using a Compton camera

We have been developing a medical imaging technique using a Compton camera. This study evaluates the feasibility of clear imaging with 99mTc and 18F simultaneously, and demonstrates in vivo imaging with 99mTc and/or 18F. We used a Compton camera with silicon and cadmium telluride (Si/CdTe) semiconductors. We estimated the imaging performance of the Compton camera for 141 keV and 511 keV gamma rays from 99mTc and 22Na, respectively. Next, we simultaneously imaged 99mTc and 18F point sources to evaluate the cross-talk artifacts produced by a higher energy gamma-ray background. Then, in the in vivo experiments, three rats were injected with 99mTc-dimercaptosuccinic acid and/or 18F-fluorodeoxyglucose and imaged. The Compton images were compared with PET images. The rats were euthanized, and the activities in their organs were measured using a well counter. The energy resolution and spatial resolution were measured for the sources. No apparent cross-talk artifacts were observed in the practical-activity ratio (99mTc:18F  =  1:16). We succeeded in imaging the distributions of 99mTc and 18F simultaneously, and the results were consistent with the PET images and well counter measurements. Our Si/CdTe Compton camera can thus work as a multi-tracer imager, covering various SPECT and PET probes, with less cross-talk artifacts in comparison to the conventional Anger cameras using a collimator. Our findings suggest the possibility of human trials.

Estimation and correction of produced light from prompt gamma photons on luminescence imaging of water for proton therapy dosimetry

Although the luminescence images of water during proton-beam irradiation using a cooled charge-coupled device camera showed almost the same ranges of proton beams as those measured by an ionization chamber, the depth profiles showed lower Bragg peak intensities than those measured by an ionization chamber. In addition, a broad optical baseline signal was observed in depths that exceed the depth of the Bragg peak. We hypothesize that this broad baseline signal originates from the interaction of proton-induced prompt gamma photons with water. These prompt gamma photons interact with water to form high-energy Compton electrons, which may cause luminescence or Cherenkov emission from depths exceeding the location of the Bragg peak. To clarify this idea, we measured the luminescence images of water during the irradiations of protons in water with minimized parallax errors, and also simulated the produced light by the interactions of prompt gamma photons with water. We corrected the measured depth profiles of the luminescence images by subtracting the simulated distributions of the produced light by the interactions of prompt gamma photons in water. Corrections were also conducted using the estimated depth profiles of the light of the prompt gamma photons, as obtained from the off-beam areas of the luminescence images of water. With these corrections, we successfully obtained depth profiles that have almost identical distributions as the simulated dose distributions for protons. The percentage relative height of the Bragg peak with corrections to that of the simulation data increased to 94% from 80% without correction. Also, the percentage relative offset heights of the deeper part of the Bragg peak with corrections decreased to 0.2%-0.4% from 4% without correction. These results indicate that the luminescence imaging of water has potential for the dose distribution measurements for proton therapy dosimetry.

Astatine-211 imaging by a Compton camera for targeted radiotherapy

Astatine-211 is a promising radionuclide for targeted radiotherapy. It is required to image the distribution of targeted radiotherapeutic agents in a patients body for optimization of treatment strategies. We proposed to image 211At with high-energy photons to overcome some problems in conventional planar or single-photon emission computed tomography imaging. We performed an imaging experiment of a point-like 211At source using a Compton camera, and demonstrated the capability of imaging 211At with the high-energy photons for the first time.

Monte Carlo simulation of photon emission below a few hundred kiloelectronvolts for beam monitoring in carbon ion therapy

The purpose of this study is to determine whether the main component of the low-energy (63-68 keV) particles emitted perpendicularly to the 12C beam from the 12C-irradiated region in a water phantom is secondary electron bremsstrahlung (SEB). Monte Carlo simulations of a 12C-beam (290 MeV/u) irradiated on a water phantom were performed. A detector was placed beside the water phantom with a lead collimator between the phantom and the detector. To move the Bragg-peak position, a binary filter was placed in an upper stream of the phantom. The energy distributions of the particles incident on the detector and those deposited in the detector were analyzed. The simulation was also performed with suppressed delta-ray and/or bremsstrahlung generation to identify the SEB components. It was found that the particles incident on the detector were predominantly photons and neutrons. The yields of the photons and energy deposition decreased with the suppression of SEB generation. It is concluded that one of the predominant components of the yields in the regions shallower than the Bragg-peak position is due to SEB generation, and these components become significantly smaller in regions deeper than the Bragg-peak position.