proton and heavy ion accelerator …asgsb.indstate.edu/bulletins/v16n2/v16n2p19-28.pdfj. miller —...

Gravitational and Space Biology Bulletin 16(2) June 2003 19

PROTON AND HEAVY ION ACCELERATOR FACILITIES FOR SPACE RADIATION RESEARCH Jack Miller Lawrence Berkeley Laboratory, Berkeley, CA ABSTRACT The particles and energies commonly used for medium energy nuclear physics and heavy charged particle radiobiology and radiotherapy at particle accelerators are in the charge and energy range of greatest interest for space radiation health. In this article we survey some of the particle accelerator facilities in the United States and around the world that are being used for space radiation health and related research, and illustrate some of their capabilities with discussions of selected accelerator experiments applicable to the human exploration of space. ____________________________________________________

INTRODUCTION

Protons emitted during solar particle events (SPE) and protons and heavier ions in the galactic cosmic radiation (GCR), present risks to the health of crewmembers in low Earth orbit and beyond (National Research Council, 1996; National Research Council, 2000). The transient but intense flux of protons in a SPE can produce acute radiation effects, whereas GCR exposures are chronic and may produce adverse health effects later in life.

High energy atomic nuclei (HZE) comprise only a small fraction of the charged particles in the GCR, but, since the radiation dose per particle is roughly proportional to the square of the particle charge, even relatively small numbers of “heavy” ions (charge, Z, greater than 1) can contribute significantly to the radiation dose and dose equivalent over time. This is especially the case outside the protective effects of Earth’s magnetic field and at the high orbital inclination of the International Space Station, where the geomagnetic field strength is relatively low.

In recent years high energy heavy charged particles have become a standard tool for radiation biologists (Blakely and Kronenberg, 1998), and radiobiology and biophysics research is being conducted or is planned at a number of proton and heavy ion accelerators around the world. The basic science is reviewed in depth elsewhere (Cucinotta et al., 2002; Nelson, 2003), but some illustrative examples of the biological and physical research being done at accelerators and its relevance for space radiation health are given below. This research is international in character, with many of the ISS partner nations represented.

Protons will be considered separately from ions with Z >1, as they are in many respects distinct from one another in both the health risks and experimental challenges they present. However it should be noted that there is also a good deal of overlap both in the experimental facilities and methods and in the science.

This review is not intended to be exhaustive; however the facilities and research presented here are representative of the role of charged particle accelerators in space radiation health research. (For a recent extensive compendium of space radiation research, see Cirio et al,. 2001.)

ADVANTAGES AND LIMITATIONS OF ACCELERATORS FOR SPACE RADIATION RESEARCH

Advantages The energy range of greatest interest for space radiation applications (roughly 100–2000 MeV/nucleon) is fortuitously comparable to what has been available for many years at proton and heavy ion accelerators, as shown in Figure 1. Until about the mid-1970’s, accelerator

Figure 1. Flux of selected nuclei in the galactic cosmic radiation as a function of kinetic energy per nucleon. The dashed lines denote the approximate energy range of present heavy ion particle accelerators. (Original plot from Simpson, 1983.)

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* Correspondence to: Jack Miller, Ph.D MS 74-197, Lawrence Berkeley National Laboratory Berkeley, CA 94720 USA Email: [email protected] Phone: 510-486-7130; Fax: 510-486-7934

J. Miller — Proton and Heavy Ion Accelerator Facilities

20 Gravitational and Space Biology Bulletin 16(2) June 2003

experiments were driven primarily by the interests of the nuclear and high energy physics communities. Heavy charged particles lose most of their energy in a short distance near the end of their range, and over the past several decades, proton and heavy ion irradiation has become an established treatment for some localized cancers and for other maladies (Chu, 1999). Existing accelerators have been adapted for radiotherapy and radiation biology, and dedicated facilities have been built, are under construction, or are planned. In at least one case, the Heavy Ion Medical Accelerator at Chiba, Japan (HIMAC), the traditional pattern has been reversed, and an accelerator designed and built specifically for hadron therapy has been increasingly used for basic science. Many of the experimental and theoretical methods and the accelerators developed for use in proton and heavy ion physics are directly applicable to radiobiology and radiotherapy, and it has become clear that research in those fields is critical to understanding health risks from space radiation.

Accelerators can produce well-characterized, almost mono-energetic beams, so that data can be gathered rapidly under controlled conditions for specific particles and energies, and well-defined materials and configurations. This is useful both for gathering basic physics and biology data and for calibrating flight instruments such as dosimeters. Ground-based experiments have many fewer constraints on size, power and complexity than do flight experiments, and, while access to accelerators is limited, it is much easier to obtain than access to space.

Limitations and the Role of Models It is not practical at an accelerator to replicate the mixed radiation fields found in space. Operational spacecraft have complex internal structures that are difficult to replicate on the ground, and new structural and shielding materials are constantly being proposed. These complications have necessitated the development of models (see, e.g., Wilson et al., 1991) to simulate the effects of the space radiation environment under realistic flight conditions. Models and accelerator-based measurements therefore complement one another, and physics measurements and models are being coupled with biology data and models to make possible comprehensive theoretical analysis of space radiation risk and risk mitigation. The goal is for the models to be used routinely to identify materials with desirable radiation transmission and radioprotective characteristics and to rapidly and inexpensively evaluate many different materials and configurations, the most promising of which can then be tested at accelerators and, ultimately, in flight.

Protons Protons have been one of the particles of choice throughout the more than 70-year history of accelerated particles as a tool of high energy physics—indeed, “high energy” has generally been defined by the energy of the most powerful proton accelerator available at a given time. The effectiveness of protons as a treatment for

cancer was recognized many years ago (Wilson, 1946), and a great deal of data on proton interactions in tissue are available. Two excellent reviews of modern proton radiobiology and radiotherapy are Raju, 1995, and Goitein et al., 2002. Protons are the most common heavy particle in the trapped radiation belts, the GCR and SPE, and the energies of greatest interest for space radiation health are from tens to hundreds of MeV, corresponding to a range of several centimeters in tissue. These were high energies in the 1930’s and 1940’s, but today they are available at accelerators that are small enough to be located in hospitals, and there are facilities in North America, Asia, Europe and Africa. Many of these facilities are suitable for biology, physics and biophysics research, and some of them are already being used for space radiation health research.1 Table 1 lists some of the principal facilities for research with protons exclusively.2 Table 1. Proton-only Accelerator Research Facilities

Facility Emax(MeV)

Brookhaven National Laboratory Linear AcceleratorBrookhaven, NY USA 200

Crocker Nuclear Laboratory Cyclotron University of California Davis, California, USA

70

Loma Linda Proton Treatment Center Loma Linda University Medical Center Loma Linda, California USA)

250

iThemba Laboratory for Accelerator-Based SciencesMedical Radiation Group Capetown, South Africa

200

Midwest Proton Radiotherapy Institute Indiana University Cyclotron Facility Bloomington, Indiana, USA

210

Northeast Proton Therapy Center Massachusetts General Hospital Boston, Massachusetts, USA

230

Paul Scherrer Institut Proton Therapy Facility Villigen, Switzerland 270

Proton Medical Research Center University of Tsukuba Tsukuba, Japan

500

1 Proton accelerators are also commonly used to investigate the

role of space radiation on single event upsets (SEU’s) in microelectronics, but we will not discuss that here.

2 The Internet is a good source of up-to-date information on this

rapidly developing field. Three good websites, among many, are http://sungr3.iss.infn.it/toptera/hadthe.htm (TERA Foundation, Italy), http://medrad.nac.ac.za (iThemba Labs, Medical Radiation Group, South Africa) and http://www.iucf.indiana.edu/MPRI/links_pt.html (Midwest Proton Radiotherapy Institute, Indiana University)



Of particular interest to NASA investigators is the Loma Linda University Proton Therapy Center (LLUPTC), with a synchrotron which accelerates protons to energies between 40 and 250 MeV, principally for the treatment of prostate cancer. When not in use for patient treatments, the synchrotron is available for radiobiology and biophysics (Nelson et al., 2001). Under an agreement between the NASA Space Radiation Health Program and LLUPTC, beam time is provided to NASA-sponsored investigators at nominal cost.

One of the principal advantages of accelerators for space radiation research is that physical and biological measurements can be made under similar, controlled conditions, making it possible to attempt to identify biological effects with physical effects. For example, Robertson and Coutrakon and collaborators (Robertson et al., 1994; Coutrakon, et al., 1997) have compared the relative biological effectiveness (RBE)3 of protons for a specific endpoint with microdosimetric spectra taken under comparable conditions, and found a correlation between increased RBE compared to photon irradiation and increased energy deposition in the sample.

Accelerators are also suitable for tests of specific materials. Recently at Loma Linda the radiation transmission properties of U.S. and Russian extravehicular activity (EVA) suits was measured, as shown in Figure 2. The U.S. EMU (Extravehicular Mobility Unit) and Russian Orlan-M suits were instrumented with a variety of passive and active radiation detectors placed at several locations in a tissue equivalent phantom, and exposed to protons and electrons with energies comparable to what is found in low earth orbit (LEO), in order to assess the suits’ radioprotective properties and to identify locations in the body that had relatively high or low radiation dose (Benton et al., 2001, Zeitlin et al., 2001). Reductions in dose and dose equivalent were observed within both helmets and in the lungs. Little or no dose reduction was observed in more lightly shielded locations.

3 RBE is a measure of effectiveness per unit dose at producing

a given biological effect of a given radiation modality compared to some reference standard, such as x-rays or gamma radiation.

Figure 2. Helmet from U.S. EMU EVA suit instrumented for irradiation in proton beam at Loma Linda University. The instrumented phantom head is inside the helmet.



Heavy Ions

Table 2 lists some of the heavy charged particle accelerators which are being used or which will soon be available for space radiation research. The NASA Space Radiation

Laboratory (NSRL) at Brookhaven National Laboratory (BNL) is noteworthy as the first heavy ion accelerator facility built specifically for space radiation research. Funded by NASA, it will be commissioned in mid-2003.

Table 2. Heavy Charged Particle Accelerator Research Facilities.

Facility Zproj Eproj Eproj (56Fe)

(MeV/nucleon) (MeV/nucleon)

Alternating Gradient Synchrotron (AGS) Brookhaven National Laboratory (BNL) Brookhaven, New York, USA

1–79 600–30000 600–1000

NASA Space Radiation Laboratory (NSRL) Brookhaven National Laboratory Brookhaven, New York, USA

1–79 100–3000 100–1000

Centro Nazionale di Adrotera Oncologica (CNAO) (planned) Italy

1,6 250 —

88" Cyclotron Lawrence Berkeley National Laboratory (LBNL) Berkeley, California, USA

1–8 55 —

Grand Accelerateur National D’Ions Lourds (GANIL) Caen, France

6–92 25–95 —

Heavy Ion Medical Accelerator at Chiba (HIMAC) National Institute for Radiological Sciences (Chiba, Japan)

1–54 100–800 500

Tandem-ALPI Laboratori Nazionali di Legnaro (LNL) Legnaro, Italy

1–8 8–20 —

Superconducting Cyclotron Laboratori Nazionali del Sud (LNS) Catania, Italy

1–6 70 —

ETOILE (2007) Lyon, France

1,6 50–400 —

National Superconducting Cyclotron Laboratory (NSCL) Michigan State University East Lansing, Michigan, USA

1–92 90 —

Nuclotron Joint Institute for Nuclear Research (JINR) Dubna, Russia

1–26 6000 6000

Ring Cyclotron Institute for Physical and Chemical Research (RIKEN) Wako Saitama, Japan (Wako Saitama, Japan)

6 137 —

SIS-18 Heavy Ion Synchrotron Gesellschaft für Schwerionenforschung (GSI) Darmstadt, Germany

1–92 50–2000 1000

Synchrophasotron Joint Institute for Nuclear Research (JINR) Dubna, Russia

1–16 4000 —

1 Not all energies are available for all ions. In general, the maximum energy varies inversely with the particle charge. For example, at the BNL AGS, the maximum energy for protons is 30 GeV; for gold ions the maximum energy is 11 GeV/nucleon.



Space radiation health research at heavy ion accelerators can be traced back to at least 1972, when experiments with high energy nitrogen ions at the Princeton-Penn Particle Accelerator and LBL Bevatron (Budinger et al., 1972) confirmed that heavy ions impinging on the retina would be perceived as light flashes, as shown in Figure 3. This effect had been predicted by Tobias (Tobias, 1952) and was observed by the Apollo astronauts. An Italian/Russian/Swedish collaboration is planning to use this phenomenon as a probe for possible damage to the central nervous system by space radiation, in an experiment on the ISS (Narici et al., 2001). Some of the apparatus to be used in the ISS experiment is being tested and calibrated with heavy ions at the BNL AGS, an application for which accelerators are well-suited. An extended study now in progress is using accelerated ions at the NIRS HIMAC to do the first systematic inter-comparison of passive and active detectors used in space.

Accelerated heavy ions are being used to probe the fundamental biological processes underlying radiation damage. Helium ions from the LBNL 88" cyclotron have been used to produce DNA double strand breaks in human fibroblasts, and the distribution of sizes of the resulting DNA fragments has been compared to calculations of a model that simulates the energy deposition of a heavy charged particle passing through a chromatin fiber (Rydberg et al., 2002). The results show promise that eventually it may be possible to model the microscopic action of GCR-like heavy ions passing through cell nuclei, and thereby give the evaluation of some space radiation health risks a mechanistic underpinning.

Heavy ions (Z >1) present some unique challenges, since nuclear fragmentation of the incident ions in materials such as spacecraft or planetary habitat walls or in crewmembers’ bodies can modify an initially well known radiation field. This complicates both spacecraft and habitat shielding design and evaluation of radiation risk.

Figure 3. Dr. Cornelius Tobias, Dr. Edwin McMillan, and Dr. Thomas Budinger act as subjects in an experiment to determine if high energy heavy ions impinging on the retina are perceived as light flashes, using a beam of high energy nitrogen ions at the LBL Bevatron.



The effects of materials and structures on the internal radiation environment will be a constraint on the design of future spacecraft and habitats—it is already a consideration on whether to add shielding material to the ISS (Miller et al., 2003). Consequently, a great deal of effort has gone into modeling and testing the radiation transport properties of materials for use in space. Reducing the uncertainties in the model predictions is critical: the greater the uncertainty, the greater the weight penalty in the form of increased shielding thickness required under the ALARA (As Low As Reasonably Achievable) principle of radiation protection practice (Wilson et al., 1993).

The shielding properties of various materials have been investigated theoretically using a transport and fragmentation model weighted according to known biological effects (Schimmerling et al., 1996). As can be seen from Figure 4, the self-shielding of an aluminum spacecraft wall alone is not effective against GCR HZE particles, but light elements and compounds, especially hydrogenous ones, are predicted to be effective in reducing biological effects as measured by both dose equivalent and cell transformation probability. The experimental results are not clear cut. For example, in a study of the induction of chromosomal aberrations by iron ions in human lymphocytes shielded by polyethylene, the

addition of up to 30 cm of polyethylene was found not to have a significant effect (Yang et al., 1998). This may be due to the offsetting effects of nuclear fragmentation, which tends to decrease average ionization (and therefore dose) and slowing of the particles, which increases dose. The effects of the interplay between fragmentation and energy loss of GCR-like ions in polyethylene have recently been studied systematically in an accelerator experiment (Miller et al., 2003). Samples of the aluminum ISS hull and internal crew quarter wall material were augmented with 1.2 cm polyethylene and placed in high energy heavy ion beams. The number of transmitted particles as a function of charge and energy was measured, and various dosimetric quantities were calculated using standard LET-dependent quality factors. The data show that for these modest thicknesses of polyethylene there is relatively little ionization energy lost by the incident ions, but enough nuclear fragmentation to reduce the average energy loss per incident particle. Since it is known that some biological effects may occur at very low doses—even as low as that produced by a single ion traversing a cell nucleus—these results suggest that it is advantageous to add relatively modest amounts of polyethylene as shielding against GCR, as has now been done in the crew sleeping quarters on the ISS.

Figure 4. Calculated attenuation of dose equivalent and biological effect as a function of depth of various materials, for one year exposure to GCR at 1977 solar minimum. Left panel: dose equivalent (using quality factor as a function of LET). Right panel: cell transformation. (From Schimmerling et al., 1996).



Physics Measurements

The GCR environment in the solar system is well known and the basic physics underlying the transport properties of high energy charged particles is well understood (see, e.g., Wilson et al., 1991). However, accurate and precise models require accurate and precise measurements of the nuclear fragmentation cross sections (Townsend, 1993), as source terms and must be tested against measurements of the final state radiation fields for given incident radiation. Similar arguments apply in the case of the self-shielding of critical organs within the human body.

Nuclear reaction products can be divided into three general classes: projectile fragments (for Z >1); target fragments and “mid-rapidity” fragments, which are intermediate in velocity between target and projectile. Projectile fragments are the fastest and therefore the most penetrating, and are concentrated in the forward direction. Mid-rapidity fragments tend to be light fragments emitted at large angles in the laboratory, and are detected using the same techniques as projectile fragments, but with the detector designed to cover angles well away from the projectile direction. Target fragments are slow and highly ionizing. Because of their short range they are a challenge to measure. From an operational standpoint, there are also distinctions between charged fragments and neutrons and between light and heavy projectiles. (The latter distinction is somewhat arbitrary.)

Projectile Fragmentation Many projectile fragmentation cross sections have been measured. (See, e.g., Webber et al. 1990; Knott et al., 1996; Zeitlin et al., 1997; Zeitlin et al., 2001 and references therein.) However, since the choice of projectiles, targets, energies and observables has been motivated for the most part by basic research in nuclear physics and astrophysics, the fragmentation cross section data are still limited in some regions of particular interest for space radiation health. Similarly, until recently most of the measurements with thick targets were driven by the needs of the charged particle radiotherapy community, and thus have been largely confined to relatively light ions and tissue-equivalent targets such as water and polyethylene.

Iron is the heaviest significantly abundant ion in the galactic cosmic radiation, and as such is the heaviest ion typically studied with regard to shielding effectiveness. Figure 5 illustrates how experiment and theory interact. It can be seen that none of the models successfully reproduce the data in every respect, indicating that further model development may be warranted if it is determined that the resulting uncertainties are unacceptably large.

For purposes of improving models, nuclear physics effects which might be obscured in the complicated final states of heavier ion collisions may be easier to sort out in light ion collisions. Carbon ions are now being used for radiotherapy at GSI and NIRS, which makes information on carbon fragmentation in tissue-like materials of interest. For shielding applications, relatively light ions such as helium, carbon, neon and silicon are worth

Figure 5. Charge changing cross sections for ∆Z = -1 to -14 for 1.05 GeV/nucleon 56Fe ions incident on H, C, Al and Cu targets. The lines represent the predictions of different nuclear fragmentation models: NUCFRG2 (Wilson et al., 1994), QMSFRG (Cucinotta et al., 1998) and OPTFRAG (Townsend et al., 1999). studying both in their own right and because they are produced as secondary fragments by interactions of heavier primary ions in spacecraft shielding and in the human body. Measurements with lighter ions are being made at SIS-18 (Schall et al., 1996a, 1996b) and HIMAC (Fukumura et al., 1996; Zeitlin et al., 2001).

Target Fragmentation Target fragmentation is difficult to measure, due to the short range of the target fragments. Fragments produced by a 1044 MeV deuteron beam in a gold target have been measured at the Nuclotron in Dubna, Russia (Malakhov, 2001). Charged fragments as heavy as nitrogen were detected. Typical fragment energies were up to 20 MeV for protons, 10 MeV for α particles and 2–5 MeV for the heavier fragments. Although these measurements were with a heavy target, the number of light ions in the GCR and produced in secondary collisions makes them relevant and argues for further measurements, perhaps with shielding and tissue equivalent targets.

An effective, albeit labor intensive method for measuring target fragments is with plastic nuclear track detectors (PNTDs). The measurements of Benton et al. (2001) of radiation inside the U.S. and Russian EVA produced by 232 MeV proton beams were made using PNTDs.

Neutrons Neutrons are not strictly within the scope of this article, but they are an important component of radiation in space and are amenable to studies at accelerators. A recent workshop on neutron production (Benton and Badhwar, 2001) concluded that high energy secondary neutrons



(>10 MeV) will contribute up to 20% of the total dose equivalent to personnel on the International Space Station. These neutrons will be produced in roughly equal measure by cascades initiated by trapped protons and GCR heavy ions and by GCR projectile fragmentation. Until fairly recently there was a paucity of measurements of neutron production at beam energies greater than tens of MeV, but that situation has been changing, with a number of recent measurements at beam energies above 100 MeV/nucleon. Heilbronn et al. (1998, 1999), Kurosawa et al. (1999a) and Kurosawa et al. (1999b) have measured neutron angular distributions with a number of different projectile/target/energy combinations and thick targets. As is the case with charged particle production, none of the models of neutron production accurately reproduce the data in all cases. Direct measurements with neutron beams are being done at Los Alamos and CERN.

CONCLUDING REMARKS

Particle accelerators have proven to be a powerful tool for space radiation research: facilitating basic research in biology and physics; making possible focused and systematic ground-based measurements that would be impractical to make in space; and serving as a proving ground for materials, radiation protection concepts and instrumentation. In recent years it has become increasingly clear that the mitigation of space radiation health risks will require collaboration among experimenters and theorists, biologists and physicists. Accelerator experiments are a critical part of these efforts.

ACKNOWLEDGEMENTS

I thank the many colleagues who contributed information and data for this review, in some cases prior to publication: E.R. Benton, B. Bonhomme, F.A. Cucinotta, L. Heilbronn, Y. Iwata, E. Krasavin, A.I. Malakhov, A. Moroni, D. Schardt, L.W. Townsend, J.W. Wilson and C. Zeitlin. Financial support for the author from the NASA Space Radiation Health Program is gratefully acknowledged.

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proton and heavy ion accelerator …asgsb.indstate.edu/bulletins/v16n2/v16n2p19-28.pdfj. miller —...

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