Interlaced x-ray microplanar beams: A radiosurgery approach with clinical potential

Abstract

Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25-to 90-m thick and spaced 100 -300 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 such 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°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 ؋ 3.4 ؋ 3.4 mm 3 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-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.

Emerging neurosurgical applications of synchrotron-generated microbeams

“…This radioresistance phenomenon was not observed in 9L glioma microvessels, confirming the presence of a differential response to between normal and tumour brain tissues in rodents, an effect that can have significant clinical applications [19]. The neoplastic vasculature appears to be unable to replicate the fast repair of the segments hit by the peak dose, facilitating the development of radionecrosis over the irradiated tumor [12,20,28].…”

“…Progressively lower doses (but still much higher than conventional radiosurgical or radiotherapeutic doses) are required to avoid tissue damage if ticker beams (100 to 600 gm) are used. Submillimetric beams (sized 0.6 to 0.7 mm) appear to retain the tissue sparing effect allowing to deliver incident doses of 400 Gy to the spinal cord of rats without inducing neurological damage: irradiation of rat spinal cord with four parallel 0.68-mm thick microbeams at 400 Gy in-depth beam dose did not induce paralysis after 7 months in three out of four rats [12]. This study showed not only that a highly radiosensitive structure such as the spinal cord can receive high dose irradiation through a microbeam array without neurologic sequelae but also that a beam width up to 0.68 mm is well tolerated, substantially maintaining the tissue sparing properties of thinner beams.…”

“…An incident dose of 4000 Gy delivered to the mouse brain by a 25 gm-thin cylindrical microbeam failed to induce radionecrosis, which instead appeared after an incident dose of 140 Gy delivered as a 1-mm thick cylindrical beam [6,7,8]. Further work performed in the late nineteen at the National Synchrotron Light Source (NSLS) of the BNL using synchrotron-generated X-ray microbeams, and, later on, at the ESRF, investigated further the tissue tolerance to microscopic beams at doses tens to hundreds time larger than those allowed by conventional macroscopic beams [9,10,11,12].…”

“…The exceptional resistance of the normal-tissue to high dose microbeam irradiation with no evidence of late tissue effects [12,22,23,24] lead to the development of a new concept in radiobiology, the tissue sparing effect, described in the next paragraph.…”

“…Unidirectional irradiation using microbeam arrays has been delivered to adult rat brain [11,13,15,16], suckling rats cerebellum [16], piglets cerebellum [1], duckling embryo brain [18], skin and muscle of the mouse leg [19,20], rat leg [21] and rat spinal cord [12]. The exceptional resistance of the normal-tissue to high dose microbeam irradiation with no evidence of late tissue effects [12,22,23,24] lead to the development of a new concept in radiobiology, the tissue sparing effect, described in the next paragraph.…”