LBNL REPORT

Pilot Study on Long Term Effects of Low Dose Iron Cosmic-Particle Exposure on the Canine Brain

Kathleen M. Brennan and Thomas F. Budinger

Introduction

Proper planning of human crewed missions to destinations outside the geomagnetosphere (e.g. Mars) requires new information on the effects of long term exposure to galactic cosmic rays and in particular to high atomic number charged (HZE) particles. The fluence of these particles is such that, during an extended mission outside the geomagnetosphere, on the average every biologic cell will be traversed by a few HZE particles. Effects on central nervous system (CNS) functioning (especially when this results in behavioral or motor changes), aging, and tumor induction must be measured and understood to make risk estimates for human space exploration and these possible late effects can be assessed only in whole organisms (NCRP, 1989).

A ground-based experiment has been initiated to evaluate the long term effects on health and aging after HZE cosmic radiation of the brain. Long term studies of protons have been conducted on subhuman primates (Wood, 1991; Wood et al., 1988). To date no other long term study has been initiated on mammals other than rodents to study the long term effects of HZE particles on the brain. The whole dog brain was irradiated with an acute exposure calculated to match the number of HZE particles expected to be received by an astronaut's CNS over a two-year Mars mission. Iron was selected as the representative HZE particle due to its substantial contribution to the galactic cosmic ray dose and its high linear energy transfer (LET). Whole body HZE irradiation of the canine would have allowed us to study multiple organ systems using our non-invasive methods; however, it was not possible to spread the beam at the LBNL Bevalac heavy ion accelerator for whole body exposure. We were however able to spread the beam to deliver a uniform dose over the brain.

For a two year mission in space, we estimate that an average of 3 particles will traverse each cell nucleus (Curtis, 1992). Before the 1992 December close of the BEVALAC, our only source of high energy iron particles, we conducted a pilot experiment on 6 dogs with the objective of commencing a sequences of measurements on CNS effects which might be expected to manifest three or more years after exposure. Our experiment assumed all the particles with Z's between helium and iron were iron. The use of iron rather than the major components such as carbon, nitrogen, oxygen or silicon results in a higher deposited energy than would be actually experienced on a Mars mission because the LET of most of the iron particles is greater than that of C, N, O. Although iron ions are only one-tenth as abundant as carbon or oxygen ions, their contribution to the GCR dose, which is proportional to z2, is substantial (NCRP, 1989). End-points of this study are changes in neurochemistry and neuroanatomy as measured by repetitive, non-invasive studies using high resolution Positron Emission Tomography (PET) and high resolution Magnetic Resonance Imaging (MRI). Sequential imaging of tissue metabolism and structure characteristics over time in each dog will be performed over the lifetime of the dog. Radiation induced changes are not expected until over 3 years post irradiation based on preliminary work from 15 dog studies using hemibrain irradiation with helium and neon ions (Brennan et al., 1993).

A major strength of longitudinal non-invasive measurements is the ability to quantitate changes in gray matter and white matter volumes anatomically and to evaluate changes in CNS metabolism relative to age matched controls. Gray matter and white matter volume measurements of the living brain can be quantified by magnetic resonance imaging methods. The applications of MRI to brain volumes studies is based on the 30% or more contrast obtainable between gray matter, white matter and CSF as contrasted to the 1-5% contrast in X-Ray CT (Budinger, 1996; Clarke et al., 1993; Zijdenbos et al., 1994). Brain mediated changes in the hematopoetic, musculoskeletal and hormonal systems will be followed by clinical laboratory studies.

References
Brennan K. M., Roos M.S., Budinger T.F., Higgins R.J., Wong S.T. and Bristol K.S. (1993) A study of radiation necrosis and edema in the canine brain using positron emission tomography and magnetic resonance imaging. Rad Res .134: 43-53.

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