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Avraham Dilmanian, Ph.D.
Scientist, Medical Department, Brookhaven National
Laboratory (BNL), Upton, New York; Associate Professor of Radiology and
Biomedical Engineering, SUNY Stony Brook.
Funding through the National Institute of Neurological Disorders and Stroke.
Our research program is focused on the study of the effects of very thin
(less than 300 micrometer in width) planes of x rays (microplanar beams,
microbeams) on the central nervous system (CNS). It has been shown that
single microbeams, and arrays of parallel microbeams, are very well tolerated
by the CNS at doses reaching several hundred Grays. This effect has been
attributed in part to the survival of the endothelial cells (the cells
that line capillary blood vessels) and progenitor glial cells residing
outside the direct microbeam paths, which then replace their lethally
injured neighbors through different mechanisms. As a result, the capillary
blood vessels repair themselves from the resulting damage, and the glial
system (oligodendrocytes and astrocytes) is also regenerated. Another
remarkable effect of microbeams is that they preferentially damage malignant
tumors, even when administered from a single direction, at doses that
are tolerated by the surrounding normal tissue. This effect has been attributed
to the failure of the capillary blood vessels to recover from the microbeams’
assault because of their abnormal endothelial cells and vessel walls.
Figure 1. Loss of oligodendrocytes
(APC+), Astrocytes (GFAP+), and other cells (Hoechst+) in white
matter of the rat brain one week after exposure to a 270-µm
wide, 650 Gy microbeam. Later time points showed repopulation
of both the oligodendrocytes and astrocytes (work in collaboration
with Dr. John W. McDonald of Departments of Neurology, Neurological
Surgery, and Anatomy and Neurobiology, Washington University,
St. Louis, Missouri). |
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Besides the potential of microbeams to develop as a new method of radiation
therapy, the above-mentioned effects of microbeams on the normal CNS make
them a powerful tool to study the recovery of the system form death of
glial cells and destruction of myelin cause by single microbeams of very
high dose. The methods that have been used in the past to kill oligodendrocytes
and destroy myelin severely damage the CNS. However, rat brain and spinal
cord irradiated with up to 750 Gy microbeams recover with no apparent
vascular damage (i.e., the tissue’s infrastructure does not collapse),
and very little damage to axons. Fig. 1 shows response of a rat brain
to microbeams two weeks after irradiation.
The animal models currently used are the rat brain tumor 9LGS for the
cancer research, and the rat brain and the spinal cord for the study of
the glial system and the demyelination/remyelination processes. Several
undergraduate students are currently participating in the microbeam project.
The tasks include a) tumor inoculation, b) assistance with animal irradiations
at the X17B1 superconducting wiggler beamline of the National Synchrotron
Light Source, BNL, c) follow up of the irradiated rats using weighing
and the behavioral test “Rotor-rod” that measures the rat’s
sensorimotor competency, d) tissue perfusion and dissection, and e) data
analysis. The technical task is to master the Monte Carlo simulation code
EGS4, and use it to calculate the spatial distribution of the radiation
absorbed dose in the tissues from the microbeam(s).
Contact Information
email: dilmanian@bnl.gov
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