Evolution of a Focal Brain Lesion 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 mm³ 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.

Key words

Radiosurgery - microradiosurgery - radiation - microbeams - microplanar - brain - therapy

References

• 1 Deinsberger R, Tidstrand J. Linac radiosurgery as a tool in neurosurgery.  Neurosurg Rev. 2005;  28 79-88
• 2 Slatkin DN, Spanne PO, Dilmanian FA, Gebbers J-O, Laissue JA. Subacute neuropathological effects on rats of microplanar beams of x-rays from a synchrotron wiggler.  Proc Natl Acad Sci USA. 1995;  92 8783-8787
• 3 Laissue JA, Geiser G, Spanne PO, Dilmanian FA, Gebbers JO, Geiser M, Wu XY, Makar MS, Micca PL, Nawrocky MM, Joel DD, Slatkin DS. Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated x rays.  Int J Cancer. 1998;  78 654-660
• 4 Laissue JA, Blattmann H, Di Michiel M, Slatkin DN, Lyubimova N, Guzman R, Zimmermann W, Birrer S, Bley T, Kircher P. et al .Penetrating Radiation Systems and Applications III. In: Barber HB, Roehrig H, Doty FP, Schirato RC, Morton EJ (Eds) SPIE Conference Proceeding. Vol. 4508 (Bellingham, WA, SPIE) 2001 pp: 65-73
• 5 Dilmanian FA, Morris GM, Le Duc G, Huang X, Ren B, Bacarian T, Allen JC, Kalef-Ezra J, Orion I, Rosen EM, Sandhu T, Sathé P, Wu XY, Zhong Z, Shivaprasad HL. Response of avian embryonic brain to spatially segmented x-ray microbeams.  Cellular and Molec Biol. 2001;  47 485-494
• 6 Dilmanian FA, Button TM, Le Duc G, Zhong N, Peña LA, Smith JAL, Martinez SR, Bacarian T, Tammam J, Ren B, Farmer PM, Kalef-Ezra J, Micca PL, Nawrocky MM, Niederer JA, Recksiek FP, Fuchs A, Rosen EM. Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy.  Neuro-Oncology. 2002;  4 26-38
• 7 Dilmanian FA, Morris GM, Zhong N, Bacarian T, Hainfeld JF, Kalef-Ezra J, Brewington LJ, Tammam J, Rosen EM. Murine EMT-6 carcinoma: high therapeutic efficacy of microbeam radiation therapy.  Radiat Res. 2003;  159 632-641
• 8 Rabinov JD, Brisman JL, Cole AJ, Lee PL, Bussiere MR, Chapman PH, Loeffler JS, Cosgrove GR, Chaves T, Gonzalez RG. MRI changes in the rat hippocampus following proton radiosurgery.  Stereotact Funct Neurosurg. 2004;  82 156-164
• 9 Solberg TD, Goetsch SJ, Selch MT, Melega W, Lacan G, DeSalles AA. Functional stereotactic radiosurgery involving a dedicated linear accelerator and gamma unit: a comparison study.  J Neurosurg. 2004;  101 373-380
• 10 Moskvin V, Timmerman R, DesRosiers C, Randall M, DesRosiers P, Dittmer P, Papiez L. Monte Carlo simulation of the Leksell Gamma Knife: II. Effects of heterogeneous versus homogeneous media for stereotactic radiosurgery.  Phys Med Biol. 2004;  49 4879-4895
• 11 Chang SD, Main W, Martin DP. et al . An analysis of the accuracy of the CyberKnife: a robotic frameless stereotactic radiosurgical system.  Neurosurgery. 2003;  52 140-147
• 12 Bräuer-Krisch E, Requardt H, Régnard P, Corde S, Siegbahn E, LeDuc G, Brochard T, Blattmann H, Laissue JA, Bravin A. New irradiation geometry for microbeam radiation therapy.  Phys Med Biol. 2005;  50 3103-3111
• 13 Bradley WG. MR appearance of hemorrhage in the brain.  Radiology. 1993;  189 15-26
• 14 Yu C, Main W, Taylor D, Kuduvalli G, Apuzzo ML, Adler Jr JR. An anthropomorphic phantom study of the accuracy of Cyberknife spinal radiosurgery.  Neurosurgery. 2004;  55 1138-1149
• 15 Ryu SI, Chang SD, Kim DH. et al . Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions.  Neurosurgery. 2001;  49 838-846
• 16 Whyte RI, Crownover R, Murphy MJ, Martin DP, Rice TW, DeCamp Jr MM, Rodebaugh R, Weinhous MS, Le QT. Stereotactic radiosurgery for lung tumors: preliminary report of a phase I trial.  Ann Thorac Surg. 2003;  75 1097-1101
• 17 Romanelli P, Chang SD, Koong A, Adler JR. Extracranial radiosurgery using the Cyberknife.  Techniques in Neurosurgery. 2003;  9 226-231
• 18 Pham CJ, Chang SD, Gibbs IC. et al . Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions.  Neurosurgery. 2004;  54 799-810 , discussion: 810-812
• 19 Schauble B, Cascino GD, Pollock BE, Gorman DA, Weigand S, Cohen-Gadol AA, McClelland RL. Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations.  Neurology. 2004;  63 683-687
• 20 Schrottner O, Unger F, Eder HG, Feichtinger M, Pendl G. Gamma-knife radiosurgery of mesiotemporal tumour epilepsy observations and long-term results.  Acta Neurochir. 2002;  84 49-55
• 21 Levegrun S, Hof H, Essig M, Schlegel W, Debus J. Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: correlation with dose distribution parameters.  Int J Radiat Oncol Biol Phys. 2004;  59 796-808

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