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Title: Evolution of a Focal Brain Lesin Produced by Interlaced Microplanar X-rays

Abstract

Stereotactic radiosurgery has led to advances in the treatment of central nervous system disease. It relies upon the principle of delivering relatively high dose irradiation to a precise target, while exposing surrounding tissues to extremely low doses. We describe a novel radiosurgical approach using interlaced microplanar X-rays which we have termed 'microradiosurgery.' The use of microbeams allows for 1000-times greater precision than current clinically employed techniques. As a demonstration of this new method, we produced a -3.8 mm{sup 3} lesion in the rat brain. The lesion was followed over a period of 216 days using 9.4 Tesla magnetic resonance imaging. Our results show a gradually developing lesion at the site of the interlaced beams. The lesion began as a high T2 signal only, but advanced to include a central area of low T1 and mixed T2 signal within 2 months. No lesion was observed in the other side of the brain which was exposed to non-interlaced microbeams only. Interlaced microbeams is an effective method to create focal brain microlesions. This technique may allow the future treatment of pathology not accessible by surgical or more traditional radiosurgical means.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929981
Report Number(s):
BNL-80588-2008-JA
TRN: US0806679
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Minimally Invasive Neurosurgery; Journal Volume: 50
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; BEAMS; BRAIN; CENTRAL NERVOUS SYSTEM; CURRENTS; DOSES; IRRADIATION; MAGNETIC RESONANCE; PATHOLOGY; RADIOTHERAPY; RATS; SIGNALS; SURGERY; X RADIATION; national synchrotron light source

Citation Formats

Anschell,D., Romanelli, P., Benveniste, H., Foerster, B., Kalef-Ezra, J., Zhong, Z., and Dilmanian, F. Evolution of a Focal Brain Lesin Produced by Interlaced Microplanar X-rays. United States: N. p., 2007. Web. doi:10.1055/s-2007-976514.
Anschell,D., Romanelli, P., Benveniste, H., Foerster, B., Kalef-Ezra, J., Zhong, Z., & Dilmanian, F. Evolution of a Focal Brain Lesin Produced by Interlaced Microplanar X-rays. United States. doi:10.1055/s-2007-976514.
Anschell,D., Romanelli, P., Benveniste, H., Foerster, B., Kalef-Ezra, J., Zhong, Z., and Dilmanian, F. Mon . "Evolution of a Focal Brain Lesin Produced by Interlaced Microplanar X-rays". United States. doi:10.1055/s-2007-976514.
@article{osti_929981,
title = {Evolution of a Focal Brain Lesin Produced by Interlaced Microplanar X-rays},
author = {Anschell,D. and Romanelli, P. and Benveniste, H. and Foerster, B. and Kalef-Ezra, J. and Zhong, Z. and Dilmanian, F.},
abstractNote = {Stereotactic radiosurgery has led to advances in the treatment of central nervous system disease. It relies upon the principle of delivering relatively high dose irradiation to a precise target, while exposing surrounding tissues to extremely low doses. We describe a novel radiosurgical approach using interlaced microplanar X-rays which we have termed 'microradiosurgery.' The use of microbeams allows for 1000-times greater precision than current clinically employed techniques. As a demonstration of this new method, we produced a -3.8 mm{sup 3} lesion in the rat brain. The lesion was followed over a period of 216 days using 9.4 Tesla magnetic resonance imaging. Our results show a gradually developing lesion at the site of the interlaced beams. The lesion began as a high T2 signal only, but advanced to include a central area of low T1 and mixed T2 signal within 2 months. No lesion was observed in the other side of the brain which was exposed to non-interlaced microbeams only. Interlaced microbeams is an effective method to create focal brain microlesions. This technique may allow the future treatment of pathology not accessible by surgical or more traditional radiosurgical means.},
doi = {10.1055/s-2007-976514},
journal = {Minimally Invasive Neurosurgery},
number = ,
volume = 50,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25- to 90-{micro}m thick and spaced 100-300 {micro}m on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of suchmore » beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90 deg angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 x 3.4 x 3.4 mm3 exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120- and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-{micro}{micro}m dose falloff (80-20%) at the edge of the target, which is much less than the 2- to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.« less
  • Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of bystander effects in these repairs.
  • A multislit collimator was designed and fabricated for basic studies on microbeam radiation therapy (MRT) with an x-ray energy of about 100 keV. It consists of 30 slits that are 25 {mu}m high, 30 mm wide, and 5 mm thick in the beam direction. The slits were made of 25 {mu}m-thick polyimide sheets that were separated by 175 {mu}m-thick tungsten sheets. The authors measured the dose distribution of a single microbeam with a mean energy of 125 keV by a scanning slit method using a phosphor coupled to a charge coupled device camera and found that the ratios of themore » dose at the center of a microbeam to that at midpositions to adjacent slits were 1050 and 760 for each side of the microbeam. This dose distribution was well reproduced by the Monte Carlo simulation code PHITS.« less
  • Purpose: The purpose is to evaluate effects of a new radiotherapy protocol, microbeam radiation therapy, on the artery wall. In previous studies on animal models, it was shown that capillaries recover well from hectogray doses of X-rays delivered in arrays of narrow ({<=}50 {mu}m) beams with a minimum spacing of 200 {mu}m. Here, short- and long-term effects of comparable microplanar beam configurations on the saphenous artery of the mouse hind leg were analyzed in situ by use of nonlinear optics and compared with histopathologic findings. Methods and Materials: The left hind leg of normal mice including the saphenous artery wasmore » irradiated by an array of 26 microbeams of synchrotron X-rays (50 {mu}m wide, spaced 400 {mu}m on center) with peak entrance doses of 312 Gy and 2,000 Gy. Results: The artery remained patent, but narrow arterial smooth muscle cell layer segments that were in the microplanar beam paths became atrophic and fibrotic in a dose-dependent pattern. The wide tunica media segments between those paths hypertrophied, as observed in situ by two-photon microscopy and histopathologically. Conclusions: Clinical risks of long-delayed disruption or occlusion of nontargeted arteries from microbeam radiation therapy will prove less than corresponding risks from broad-beam radiosurgery, especially if peak doses are kept below 3 hectograys.« less