Several major diseases, such as cancer and cardiovascular abnormalities, may be linked to pathological deposition of minerals or organic compounds in various tissues. Thus, the detection of such minerals or compounds and understanding the physicochemical processes associated with their formation are essential. As underlined by Schmidt et al., in Europe and the U.S., breast cancer will occur in 1 in 10 women. If clustered calcifications are one of the mammographic signs of early breast cancer, their chemical nature must be determined. More precisely, calcium phosphates (CaPs) are frequently associated with malignancy, but calcium oxalates are present in benign lesions. From a medical viewpoint, pathological calcifications refer to at least three very different families of biominerals: concretions, metastatic calcifications and dystrophic calcifications. Concretions are found in hollow organs or ducts of the body. For example, kidney stones are solid concretions of dissolved minerals in urine found in the kidney. In contrast, metastatic and dystrophic calcifications, which can be considered ectopic calcifications, are defined as unexpected biomineralization occurring in soft tissues. In the absence of a systemic mineral imbalance, dystrophic calcification is often associated with tissue alteration or necrosis. In contrast, metastatic calcifications resulting from mineral imbalance are more systemic and affect various tissues (e.g., vessels, lungs, kidneys). A fourth family can be considered physiological calcification (bone), which becomes pathological with diseases such as arthrosis or osteoporosis.

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Characterization and Some Physicochemical Aspects of Pathological Microcalcifications

High-intensity, high-quality beams originating from the electron-cooling method will be utilized for medical and other application at HIMAC. As a first step, an electron cooler with an adiabatic expansion factor of 10 has been designed and is under construction at HIMAC. So far, field measurements of the cooler have been completed. In this paper, the present status of the electron cooler under construction is described, and plans of medical and other application by using the electron-cooling method at HIMAC are presented.

Electron cooler for medical and other application at HIMAC

Radiation therapy with external beams of positron emitter light ions offers the optimal solution for simultaneously treating and in vivo monitoring the delivery of the dose in 3D with Positron Emission Tomography (PET) or PET-Computed Tomography (CT) imaging. Specifically, positron emitter light ion beams merge the main distinctive advantages of light ion therapy, namely a high conformal and biological effective dose delivery to the tumor, an optimal penumbra, and sparing of the surrounding normal tissues, with the advantage of a high β-activity signal mainly produced directly by the beam itself, and therefore not primarily dependent on the specific stoichiometry of the body tissues. The aim of this thesis is to explore a method to maximize the generally low production yield of C ion beams through in-flight fragmentation of a primary C ion beam on a dedicated decelerating target. The thesis provides a practical solution applicable to cyclotron, synchrotron and linac based hospital facilities. The study investigates the main steps from the production of the beam and the transport through the beam optics system to the purification of the beam from other potentially contaminating fragments. Analytical models of transport of ions in matter, as well as the Monte Carlo code SHIELD-HIT were used to conduct the analysis. The proposed beam line includes a composite production target made of a 20 cm thick liquid hydrogen section followed by a variable thickness section consisting of plane parallel slabs of polyethylene. The first section is selected to maximize the C ion beam intensity, whereas, the second section is used to reduce the beam energy to the desired value, maintaining the high C ion yield. To be able to minimize the energy spread of the beam, and the contamination from other fragments, a variable wedge-shaped degrader and a Time Of Flight (TOF) Radio-Frequency driven velocity filter are included in the beam line together with dipole and quadrupole magnets. A C ion beam intensity of about 4-6% of the primary C ion beam intensity with radial spot size confined to 0.5 cm in radius, and an energy and angular spread of about 1% and 1°, respectively, are achievable. The C ion beam purity is expected to be about 99%. The proposed system for production of high quality C ion beams contributes to the developments of an accurate PET-CT based dose delivery verification, ultimately aiming towards a biologically optimized adaptive radiation

Production of high quality 11C beams for radiation treatment and accurate PET-CT dose delivery verification

An electron cooler had been designed and constructed in order to provide high-quality and high-intensity beam for medical and other application, and was installed at HIMAC-synchrotron. In the initial experiment of the electron cooler, a momentum spread is reduced from 10 -3 -5 at FWHM by the longitudinal bunched beam cooling. The vertical beam-size at FWHM is reduced to one-third, and the cool stacking is successfully observed owing to the transverse cooling. The paper reports the results of the initial experiment of the electron cooling at HIMAC.

Commissioning of electron cooler for medical and other application at himac

The use of positron emitter light ion beams in combination with PET (Positron Emission Tomography) and PET–CT (Computed Tomography) imaging could significantly improve treatment verification and dose delivery imaging during radiation therapy. The present study is dedicated to the analysis of the beam quality in terms of the effective source size, as well as radial, angular and energy spread of the 11C ion beam produced by projectile fragmentation of a primary point monodirectional and monoenergetic 12C ion beam in a dedicated range shifter of different materials. This study was performed combining analytical methods describing the transport of particles in matter and the Monte Carlo code SHIELD-HIT+. A high brilliance and production yield of 11C fragments with a small effective source size and emittance is best achieved with a decelerator made of two media: a first liquid hydrogen section of about 20 cm followed by a hydrogen rich section of variable length. The calculated intensity of the produced 11C ion beam ranges from about 5% to 8% of the primary 12C beam intensity depending on the exit energy and the acceptance of the beam transport system. The angular spread is lower than 1 degree for all the materials studied, but the brilliance of the beam is the highest with the proposed mixed decelerator.

Effective source size, radial, angular and energy spread of therapeutic 11 C positron emitter beams produced by 12 C fragmentation

Since 1994 clinical trials have been performed successfully with carbon beam. To improve the clinical result further, new irradiation systems are under development such as a 3D-irradiation system and a verification system of range with positron emitter. There are also improvements on the accelerator performances. One is the wide range of ion species; the others are concerned with the machine devices and new beam monitors to get good machine operation. In this report we present current status of HIMAC.

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Present status of HIMAC at NIRS

We are designing a synchrotron light source dedicated to medical applications including an intravenous coronary angiography for practical uses at a hospital. The synchrotron light source system is required to be compact for installation in a limited space of the hospital. The system is also required to be operated easily as medical diagnostic devices. For the energy subtraction coronary angiography, required design parameters of a storage ring are circumference of about 45 m, 1.8 GeV electron energy and a stored beam currents of 400 mA. A multipole wiggler with superconducting coils is considered to be one of key devices to realize a required high photon intensity. A microtron with higher energy than that of commercially obtainable ones could be a good candidate of an injector for downsizing the whole system. Two optional beam lines are planned to be used for clinical diagnoses, and other beam lines of bending magnets are prepared for biology, physics, and other experiments to support the clinical diagnoses. We report the design of the compact system for the medical uses.

https://epaper.kek.jp/pac97/papers/pdf/6v021.pdf

A plan of synchrotron light source for medical applications at NIRS

Heavy-ion radiotherapy gives a good localized dose distribution just on a cancer tumor. In order to emphasize this advantage, the verification system of a particle range and an irradiated area in a human body has been developed for the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS). The idea comes from the fact that the stopping position of a short-lived positron emitting nuclei, such as 11 C, 15 O or 19 Ne, can be precisely detected by measuring annihilation gamma-rays.

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Radioactive beam project at himac

A synchrotron light source dedicated to medical applications for practical use at a hospital is planned at NIRS. The system was designed for medical imaging with the synchrotron radiation (SR) for diagnosis of coronary arteries, coronary angiography, with monochromatic x-rays of 33 and 50 keV. The coronary angiography requires higher photon flux than the other applications, such as monochromatic x-ray computer tomography (CT). The conceptual design of the synchrotron light source is based on an electron storage ring with maximum energy of 2.3 GeV and beam current of 420 mA. Combination of the storage ring and a superconducting multipole wiggler is necessary to produce high photon flux required for the angiography. An electron linac of C-band has high electric field gradient. So it could be a good candidate of a injector for downsizing the whole system. Two beamlines of the insertion devices are planned to be used for clinical diagnoses, and other beam lines of bending magnets are prepared for basic experiments to support and develop the medical applications. 1 BASIC IDEAS OF DESIGN Synchrotron radiation has great advantages of advancing medical diagnostic imaging. We have a plan of construction of a synchrotron light source dedicated to the medical applications at the National Institute of Radiological Sciences. Final goal of the plan is a compact light source to install in a hospital to utilize for medical diagnoses. A typical application of the SR is an intravenous coronary angiography (CAG) using energy subtraction method which has been clinically applied to examinees[1]. Monochromatic x-ray CT plays an important role in advancing heavy ion radiotherapy being done at the NIRS[2]. Advancing x-ray imaging using the SR will help us not only find out a cancer at the early stage, but know the characteristics of the tumor in vivo by obtaining more accurately diagnostic information. One of the most important factor for the design is photon flux required for the various medical applicaitons. We showed estimations of the photon flux required for a few applications as typical cases in Table 1. The photon flux for the x-ray CT and the radiography are estimated based on the entrance surface dose suggested by IAEA[3]. The estimation of the photon flux required for the CAG was reported in detail in the reference[4]. As shown in the table 1, the CAG application requires higher flux than the other applications. The CAG does not require a very small beam emittance. The small beam emittance is necessary for advanced imaging techniques, such as phase contrast imaging. But in the medical applications, most cases require rather than large radiation fields. This requirement is contrary to that of the small beam emittance. Our concepts of design are summarized as follows. The light source should provide enough photon flux for the CAG, which requires higher flux than the other. It is compact as much as possible for practical uses at a hospital. And a small beam emittance is not necessary. Table 1 Photon flux required for a few applications Applications Photon flux (ph/cm/sec) Energy(keV) X-ray CT 1.7×10 70 X-ray radiography 1.4×10 50 CAG (Iodine) 7.8×10 33 (Gadolinium) 4.3×10 50 2 DESIGN AND SYSTEM LAYOUT 3.1 Design parameters and Layout The design parameters are listed in Table 2. The system layout is shown in Figure 1. Table 2 Design parameters Items Designed values Beam energy 2.3 GeV Beam intensity 420 mA Circumference 79.7 m Bending magnet (×8) bending angle 45° radius 5.11 m maximum magnetic field 1.5 T Beam emittance 3.8×10 m⋅rad Energy loss per turn (total) 1140 keV RF frequency 508 MHz RF voltage 3.2 MV Injector (Linac) beam energy 500 MeV peak current 100 mA Multipole wiggler (×2) number of pole 9 maximum magnetic filed 7 T period length 420 mm The main ring has an electron linac operated in C-band as an injector. The ring has four free straight sections. Two of them are occupied by multipole wigglers, and the other are occupied by beam injection device and acceleration RF cavities, respectively. There are two beam lines from the wigglers and a few lines from bending magnets. Electron Linac (500 MeV) Multipole Wiggler (7T 9P) Bending Magnet (1.5T, 5.1m) RF Cavity

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M. Endo

Papers

Present status of HIMAC at NIRS

A plan of synchrotron light source for medical applications at NIRS

Radioactive beam project at himac

A plan of synchrotron light source dedicated to medical applications at NIRS