GSI-ESAC/BIO Date: 13.04.2004
Applications of Relativistic Ions in Radiobiology and Space Research Letter of Intent
Abstract
We propose the installation of an irradiation facility at the high energy beam line of the FAIR accelerator complex at GSI, dedicated to biophysical experiments related to space research. The new accelerator complex will be one of the few places worldwide, where heavy ions can be used up to highest energies in the order of 10 GeV/u. These ion beams are particularly interesting for studies of the radiobiological and physical properties of solar and galactic cosmic rays. Precise knowledge of these properties is required in order to reduce costly shielding for space missions to the minimum necessary. Furthermore, the new irradiation facility offers excellent conditions for performance tests and calibration of space flight instruments. It will be equipped with a raster scanning beam delivery system which ensures an extraordinary beam quality and precisely shaped homogeneous large-field irradiations over a wide range of particle fluences. At the highest energies, the production of homogenous irradiation fields will be based on a passive scattering system. For the handling of biological samples a robotic system which was developed and optimized by the GSI Biophysics group will be available. The installation of the new irradiation facility is supported by 14 research groups of the international radiobiology and cosmic ray communities. 1
GSI-ESAC/BIO
Date: 13.04.2004
Letter of Intent for: Applications of Relativistic Ions in Radiobiology and Space Research
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Members of the Collaboration
GSI Biophysics group:
D. Schardt, M. Scholz, S. Ritter and G. Kraft
External groups supporting this LOI:
→ see enclosed letters of support CALTECH, Space Radiation Laboratory, ACE-Project, (R. Mewaldt) Chalmers Univ. of Technology , Nuclear Science and Engineering (L. Sihver) DLR Köln, Institut für Luft- und Raumfahrtmedizin (G. Reitz) Dublin Institute for Advanced Studies, School of Cosmic Physics (D. O'Sullivan) INFN Torino (R. Cirio) JINR Dubna, Division of Radiation and Radiobiological Research (E. Krasavin) LBL Berkeley, Life Sciences Division (J. Miller) Massachusetts Institute of Technology, Laboratory for Nuclear Science, AMS-Project (Samuel C.C. Ting) NIRS Chiba, International Space Radiation Lab (R. Okayasu) PTB Braunschweíg, Neutron Radiation Department (H. Schuhmacher) University of Milano, Department of Physics, Radiobiology Lab (D. Bettega) University of Naples, Department of Physics (M. Durante) Univ. of Rome, Department of Physics, ALTEA and PAMELA-Projects (L. Narici and P. Picozza) Univ. of Turku, Space Research Laboratory, ERNE/SOHO-Project (E. Valtonen)
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Spokesperson: Prof. Dr. Marco Durante, Univ. of Naples, Dept. of Physics E-Mail: Marco.Durante@na.infn.it Dr. Jack Miller, LBL Berkeley, Life Sciences E-Mail: miller@lbl.gov 3
Deputy:
Introduction
Solar and galactic cosmic radiation (GCR) represent a major hazard in all space explorations [Cu89, Le87], but especially outside the protective effects of the Earth's magnetic field. In man, genetic alterations and cancer may already be induced by low levels of radiation. In the case of a solar flare or coronal mass ejection, a lethal dose could be incurred within only half an hour of exposure or even less. For computer chips and other electronic devices, the high charge locally deposited by energetic heavy ions can produce alterations in the semiconductors and change the status of solid state memory. In extreme cases, showers of particles can induce information loss and stopping heavy particles can permanently damage semiconductor devices. Because shielding is difficult and costly in space, the effects of the GCR should be known as accurately as possible in order to reduce shielding to the minimum necessary [Wi91]. Whereas solar particles are mainly protons and helium ions, the GCR has a significant component of heavier ions up to iron (Fig. 1) [Cu89, Le87]. (Significant, in the sense that even though the GCR is dominated numerically by protons and helium ions, the effects, as discussed below, tend to scale with energy deposition, which is proportional to the square of the ion charge, a factor of almost three orders of magnitude for iron ions compared to protons.)
10 1 0,1 10-2 C 10-3 Fe 10-4 10-5 10-6 10-7 10-8 UNILAC + SIS 10-9 10 102 103 SIS-200 104 105 106 107 He H
Particle flux [m2.s.sr] 1
Kinetic energy [MeV/nucleon]
Fig. 1: Energy spectrum of the particles in galactic cosmic radiation
Fig. 2: Calculated risk coefficient for the induction of transformations of mammalian cells as a model of the expected influence of cosmic radiation for long-term effects. This model calculation contains also the influence of nuclear fragmentation. (according to [Wi91])
For ions heavier than iron, the intensity becomes very low. For both, damage in living organisms and in electronic devices the dose is the determining factor. The dose can be viewed in two ways: macroscopically, it is the energy deposition per mass unit in macroscopic volumes, but more important is the local dose distribution inside individual particle tracks.
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1. Radiobiological aspects
The energy loss of particles is given by the Bethe-Bloch-formula and depends on the square of the atomic number. Therefore, the macroscopic dose from the heavy components of cosmic radiation like iron is not negligible compared to the dose from light ions although heavier ions are less frequent than lighter ones (Fig. 1). But more important than the macroscopic dose is the microscopic dose inside a track [Kr94]. The local dose of an individual particle reaches values of many kilo-Gray in the center of a track. In microscopic fields of such high dose levels, an increase of the efficiency out of proportion to the low dose response has been observed for many biological systems. Because multiple damages can be produced in close proximity to the track, e.g. at both DNA strands, the lesions can interact and potentiate their biological relevance producing the observed elevated Relative Biological Efficiency (RBE) [Kr87, We99]. Taking the RBE effect as well as the fragmentation into account the cross sections for cell transformation of Fe are much larger than for protons (Fig. 2) and compensate the difference in abundance. At energies significantly above 1GeV/u the cross section should level off due to the influence of fragmentation products, but these calculations have not been confirmed experimentally. For ions with energies in the range of the new GSI accelerators, there are no systematic measurements concerning biological or physical efficiency. It is also impossible to predict the effect of these ions only from an extrapolation from lower energies. At energies higher than 1 GeV/u the radiative energy loss becomes relevant in addition to the electronic energy loss. More interesting, however, might be the fragmentation process where the projectile produces lighter fragments emitted in a small cone in forward direction. This fragmentation process is the reason why shielding with thick layers of material does not necessarily reduce the dose: while low-energy ions are stopped in the shielding material, high-energy particles produce showers of lower-energy and therefore more highly ionizing particles. Moreover, the fact that these particles are correlated in space and time raises the question of proximity effects, not necessarily at DNA level but possibly at higher levels of organization such as cells or tissues. In order to test this hypothesis biological experiments on cellular level exploring genetic effects should be performed first [Ri00, Ri01] and should be completed by tissue experiments later on.
2. Calibration and radiation tests of space flight instruments
Heavy-ion beams from high-energy particle accelerators provide a powerful tool for the simulation of space radiation conditions, in particular for the heavy particle component of the galactic cosmic rays (GCR). Since 1991 the existing high-energy irradiation facility at GSI has attracted many groups of the international cosmic ray community (see table 2). These experiments can be divided in two categories: (i) performance and calibration of space research instruments designed for the exploration of the cosmic ray spectrum. Heavy-ion beams in the energy range of about 100 to 2000 MeV/u available at SIS-18 are well suited to test the performance of cosmic ray detectors, the isotope separation capability, mass and charge resolution etc. Examples include the Advanced Composition Explorer (ACE/ NASA) and the Finnish ERNEExperiment as a part of the SOHO mission, which were tested with heavy-ion beams at GSI and are operating successfully in satellite missions. The Italian ALTEA-detector, presently undergoing beam tests at GSI, is part of the ISS scientific programme and scheduled for the next space shuttle transport. Investigation of radiation effects on electronic components of space flight instruments, study of single event effects (SEE), tests of storage chips up to complex microprocessors. 5
(ii)
Such effects are caused by a single energetic particle and may result in malfunction of critical devices by single event upsets (SEU) or destructive errors like single event latchups (SEL). For critical components of space missions it is therefore indispensable to perform radiation tolerance tests and determine the SEE-rates expected in space. Numerous tests of electronic circuits were performed with SIS-18 beams at the irradiation facility 'Cave A' which is operated by the GSI Biophysics group. The state-ofthe-art magnetic raster scanning system provides precisely shaped homogeneous largefield irradiations covering a wide range of particle fluences. This offers ideal conditions for radiation tolerance tests of complete electronic boards. A recent example is the test of electronic components of the Alpha-Magnetic-Spectrometer (AMS) performed in the years 2000-2002 with Xe, Au and U-beams at GSI. The spectrometer will be kept for more than 3 years at the ISS. Electronic components for the AMS data acquisition system were selected for the space mission based on these tests.
Test of electronic boards (components of the AMS DAQ system) exposed to high-energy heavy-ion beams at GSI, Nov. 2000
4. Technical implementation: A high-energy irradiation facility
Most experiments in radiation biology or space-related radiation tests require an irradiation facility where the beam can be enlarged either by scattering foils or by the employment of a scanning system. Both systems for beam enlargement are necessary. The scanning system [Ha93] offers homogeneous particle fluences over large areas which is a big advantage for most irradiation experiments. In addition, the scanned beam is not contaminated with secondary fragments. The scanning system presently installed at Cave M (tumor therapy) and Cave A can be transferred to the new irradiation cave and can be used without modifications for ion beams up to 18 Tm magnetic rigidity. An extension to higher energies is possible but is limited by the increasing power losses due to eddy currents. Feasibility studies are in progress to find a tolerable compromise of field size, scanning speed and irradiation times. All target positioning systems presently used in Cave A and in particular the ROBOT-System for the remote handling of biological samples can be installed in the new irradiation cave. On the other hand, a scattering system allows study of moving targets such as cells in a centrifuge at elevated g-values which offers the opportunity to study the possible influence of gravitational effects on induction and repair of biological damages. These experiments require a representative set of ion beams from protons to uranium with fluxes in the order of 103 to 109 particles/cm2 per spill.
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Table 1: Particle flux requirements for the future irradiation facility Ion p He C O Ne Ar Fe Kr Xe U Flux [ions / spill cm2] 3.9x1010 9.9x109 1.1x109 6.6x108 3.9x108 1.2x108 5.7x107 3.0x107 1.4x107 4.5x106
The samples are placed into the beam position by a remote control robot in combination with linear transport systems. Various parameters during the irradiation procedure are monitored by similar techniques as in the existing Cave A. To control the position and the intensity of the beam over a wide intensity region, detectors such as ionization and multi-wire chambers are used. For the controlled application of a given fluence, a fast interrupt of the extraction from SIS-18 or SIS-100 is required. Besides the irradiation facility itself, extra space is needed for in-beam experiments requiring, e.g., separate vacuum chambers, a high-pressure cell, or a centrifuge for biological cells. To observe specific processes during or shortly after the ion passage through matter, in-situ monitors (e.g. spectrometers) are planned. In particular for radiation biology, an X-ray beam for comparative studies has to be available in or near the new cave. At the present planning stage the new irradiation cave is combined with an area for atomic physics experiments which will be equipped with a charge state spectrometer allowing for charge state separation behind a reaction target for beam energies up to about 1 GeV/u (≈ 20 Tm) and beam intensities of up to 109 ions/s.
15 m 15 m
1m charge separation
TP 1 AP
QD11 QD12
Q Q-1
1m
TP 2 BIO/MAT
Eisen
Scanner
Biophysics / Space Research Materials Research
Atomic Physics
Fig. 3: Experimental area for atomic physics, materials research, and biophysics using ion beams from SIS-18 and SIS-100. 7
Experimental set-up
Most systems developed for irradiation experiments in Cave A can be transferred to the new highenergy irradiation cave at SIS-100. This includes components of the magnetic scanning system, beam monitors, laser and TV systems and the robot for biological samples.
Irradiation experiments at Cave A
Beam monitor and robot for irradiation of biological samples
Online monitoring of the beam positions using the scanning system to produce a large-area homogeneous irradiation field
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5. Expected usage of the new irradiation facility at GSI
Presently, radiation biology and radiation biophysics experiments with high-energy heavy ions can be conducted at only few facilities world-wide: • the new NASA Space Radiation Laboratory (NSRL) at Brookhaven (USA) • the HIMAC-facility in Chiba (Japan) • the GSI irradiation facility Cave A • the NUCLOTRON-facility at Dubna (Russia) The NSRL is a dedicated facility which was recently brought into operation and will mainly serve the needs of the US radiation research community. The range of available ion beams (up to Au) and energies is similar to that of the GSI facility. NSRL will be operated in several time slots per year. The HIMAC-facility (heavy-ion medical accelerator) is limited to beams up to Xe (400 MeV/u) and energies up to 800 MeV/u (Si-beam). It is operated for physics and basic biology experiments during the times available outside the patient treatments. The NUCLOTRON-facility at Dubna delivers ions up to Fe with energies up to 2.2 GeV/u. Radiobiological studies were carried out in the past 4 years. The GSI irradiation facility offers the full range of ion beams from protons to uranium and energies up to 1 GeV/u at present. It is the only facility equipped with a rasterscan irradiation system. In the past 10 years it was frequently used for radiation research experiments in the fields of radiobiology, space research, materials research and detector tests. Tables 2 and 3 give an overview of experiments carried out by external groups over the past 10 years of operation of Cave A. Table 2. External groups using the irradiation facility at GSI (Cave A) 1993-2003 CCD-Chips Chips, CR39-Stacks Nucl. track detectors Nucl. track detectors Microdosimetry Ionis. chambers Crystals Ion acoustics Cosmic Ray Detector Microprocessors CsI-Detector Microstrip-detector Nucl. track detectors High-Temp. Supercond. Liquid Argon Detector Cosmic Ray Detector Cosmic Ray Detector Cosmic Ray Detector ACE Project VLSI-Chips Electr. components Cosmic Ray Detector Mice Diamond cells Neutron fields, δ-electrons Recoil detector test High-Temp. Supercond.
DLR, Institut für Flugmedizin, Köln Uni Siegen, FB Physik Uni Lund / Schweden Uni Frankfurt Zentrum für Umweltforschung, Dudweiler (Saarland) FH Darmstadt, FB Physik TH Darmstadt, Institut für angewandte Optik Fraunhofer Institut Dresden Univ. of Utah, Salt Lake City / USA IBM, Manassas / USA Kurchatov Institut Moskau INFN Como und Torino / Italien Dublin Institute for Advanced Studies, School of Cosmic Physics GSI Materials Science Advanced Research Center, Waseda Univ., Tokyo / Japan Space Research Lab, Univ. of Turku, Finland Institut für Kernphysik, Univ. Kiel California Institute of Technology, Pasadena , Goddard Space Flight Center & Washington Univ. INFN Frascati /Italy AMS Collaboration ALTEA Collaboration Roma / Italy MPI für Kernphysik, Heidelberg PTB Braunschweig, Neutron dosimetry HERMES Collaboration Houston University 9
Table 3.
Radiobiology groups using the irradiation facilities at GSI NIRS Chiba, JP JINR Dubna, RU JAERI Takasaki, JP Univ. Leiden, NL C. A. Lacassagne, F CEA, F NRPB Chilton, UK GSF München DKFZ Heidelberg DLR Köln TU Dresden Radiol. Klin. HD Univ. Göttingen Univ. Mainz Univ. Tübingen Univ. Homburg Univ. Homburg Univ. Giessen Univ. Frankfurt Univ. Bonn LMU München TU Darmstadt Therapy verification Chromosome aberrations Deinococcus radiodurans Stress pathways Micronucleus induction Chromosome aberrations Chromosome aberrations Mouse tumors, Megacolonies Rat spinal cord Mutation induction Skin reaction in minipigs Low dose hypersensitivity Chromosome aberrations Multicellular systems Fibrosis related parameters Strand break induction DNA damage Mutation induction Mouse tumors DNA damage Microdosimetry DNA damage / repair
The beamtime statistics for the years 2000-2003 are shown in table 4. The lower numbers for the years 2001/2002 are due to the limited availability of the rasterscan control system which was used for tests of the medical Gantry-system in Cave C during this time. Finally, the list of users for the year 2003 is shown in Table 5, demonstrating the ongoing interest of external groups in performing experiments at the GSI high-energy irradiation facility. Table 4 Beamtime used for high-energy irradiation experiments at GSI
400 350 300 hours of beamtime 250 200 150 100 50 0 2000 2001 Year 2002 2003
Main user Parastic user
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Table 5 Irradiation experiments performed in 2003 (Cave A) Date Feb. March April April April April July July Aug. Aug. Aug. Aug. Aug. Aug. Sept. Oct. Nov. Dec. Dec. Ion Beam Ni-58 Au-197 C-12 Ar-40 Ar-40 C-12 C-12 C-12 C-12 C-12 Xe-132 U-238 U-238 Ar-36 Kr-86 H-1 C-12 C-12 U-238 Experiment ALTEA Cosmic ray det. Diamond high pressure cells MICE (Rhodopsin-Irrad.) CR39-Irradiation Activation Neutron dosimetry MICE, Animal experiment OPAC Delta Electrons Neutron dosimeter HERMES-Detektor OPAC High Temp. Superconductors OPAC OPAC OPAC HERMES-Detektor ALTEA Cosmic ray det. HERMES-Detektor High-pressure cells Total Institutions involved Rome Univ./ GSI MPI Heidelberg / GSI Univ. Rome Univ. Siegen Dubna / GSI SiSt PTB / GSI Rome / Genova / GSI PTB Braunschw. GSI SiSt. DESY / Giessen PTB Houston Univ. PTB PTB PTB DESY / Giessen Rome Univ./ GSI DESY / Giessen MPI Heidelberg / GSI Used shifts main paras 5 1 3 1 4 1 8 8 1 2 1
6 3 3 1 15 6 5 2 36 48
References
[Cu89] S. B. Curtis et al., Adv. Space Res. 9, (10)293-(10)298 (1989). [Le87] J.R. Letaw et al., Nature 330, 709-710 (1987). [Mi98] J. Miller et al., Proceedings of the International Workshop on Responses to Heavy Particle Radiation, Chiba, NIRS 43 (1998). [Kr94] M. Krämer et al., Radiat. Environ. Biophys. 33, 91 (1994). [Kr87] G. Kraft, Nucl. Sci. Appl. 3, 1 (1987). [We99] W.K. Weyrather, Int. J. Radiat. Biol. 75, 11, 1357-1364 (1999). [Ri00] S. Ritter et al., Proceedings of the 2nd International Space Workshop 2000, Chiba, NIRS/NASDA, 115-117 (2000). [Ri01] S. Ritter et al., Annual Scientific Report 2000, GSI Report 2001-1 (2000). [Ha93] T. Haberer et al., NIM A 330, 296-305 (1993).
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