X-ray microbeam irradiation of the contusion-injured rat spinal cord temporarily improves hind-limb function.

Spinal cord injury is a devastating condition with no effective treatment. The physiological processes that impede recovery include potentially detrimental immune responses and the production of reactive astrocytes. Previous work suggested that radiation treatment might be beneficial in spinal cord injury, although the method carries risk of radiation-induced damage. To overcome this obstacle we used arrays of parallel, synchrotron-generated X-ray microbeams (230 µm with 150 µm gaps between them) to irradiate an established model of rat spinal cord contusion injury. This technique is known to have a remarkable sparing effect in tissue, including the central nervous system. Injury was induced in adult female Long-Evans rats at the level of the thoracic vertebrae T9-T10 using 25 mm rod drop on an NYU Impactor. Microbeam irradiation was given to groups of 6-8 rats each, at either Day 10 (50 or 60 Gy in-beam entrance doses) or Day 14 (50, 60 or 70 Gy). The control group was comprised of two subgroups: one studied three months before the irradiation experiment (n = 9) and one at the time of the irradiations (n = 7). Hind-limb function was blindly scored with the Basso, Beattie and Bresnahan (BBB) rating scale on a nearly weekly basis. The scores for the rats irradiated at Day 14 post-injury, when using t test with 7-day data-averaging time bins, showed statistically significant improvement at 28-42 days post-injury (P < 0.038). H&E staining, tissue volume measurements and immunohistochemistry at day ≈ 110 post-injury did not reveal obvious differences between the irradiated and nonirradiated injured rats. The same microbeam irradiation of normal rats at 70 Gy in-beam entrance dose caused no behavioral deficits and no histological effects other than minor microglia activation at 110 days. Functional improvement in the 14-day irradiated group might be due to a reduction in populations of immune cells and/or reactive astrocytes, while the Day 10/Day 14 differences may indicate time-sensitive changes in these cells and their populations. With optimizations, including those of the irradiation time(s), microbeam pattern, dose, and perhaps concomitant treatments such as immunological intervention this method may ultimately reach clinical use.

Interleaved carbon minibeams: an experimental radiosurgery method with clinical potential.

PURPOSE: To evaluate the efficacy of "interleaved carbon minibeams" for ablating a 6.5-mm target in a rabbit brain with little damage to the surrounding brain. The method is based on the well-established tissue-sparing effect of arrays of thin planes of radiation. METHODS AND MATERIALS: Broad carbon beams from the National Aeronautics and Space Agency Space Radiation Facility at Brookhaven National Laboratory were segmented into arrays of parallel, horizontal, 0.3-mm-thick planar beams (minibeams). The minibeams' gradual broadening in tissues resulted in 0.525-mm beam thickness at the target's proximal side in the spread-out Bragg peak. Interleaving was therefore implemented by choosing a 1.05 mm beam spacing on-center. The anesthetized rabbit, positioned vertically on a stage capable of rotating about a vertical axis, was exposed to arrays from four 90° angles, with the stage moving up by 0.525 mm in between. This produced a solid radiation field at the target while exposing the nontargeted tissues to single minibeam arrays. The target "physical" absorbed dose was 40.2 Gy. RESULTS: The rabbit behaved normally during the 6-month observation period. Contrast magnetic resonance imaging and hematoxylin and eosin histology at 6 months showed substantial focal target damage with little damage to the surrounding brain. CONCLUSION: We plan to evaluate the method's therapeutic efficacy by comparing it with broad-beam carbon therapy in animal models. The method's merits would combine those of carbon therapy (i.e., tight target dose because of the carbon's Bragg-peak, sharp dose falloff, and high relative biological effectiveness at the target), together with the method's low impact on the nontargeted tissues. The method's smaller impact on the nontargeted brain might allow carbon therapy at higher target doses and/or lower normal tissue impact, thus leading to a more effective treatment of radioresistant tumors. It should also make the method more amenable to administration in either a single dose fraction or in a small number of fractions.

Polysulfone-graft-poly(ethylene glycol) graft copolymers for surface modification of polysulfone membranes.

Amphiphilic graft copolymers having polysulfone (PSf) backbones and poly(ethylene glycol) (PEG) side chains were synthesized via reaction of an alkoxide formed from PEG and a base (sodium hydride) with chloromethylated polysulfone. The resulting polysulfone-graft-poly(ethylene glycol), PSf-g-PEG, materials were hydrophilic but water insoluble, rendering them potentially useful as biomaterial coatings. PSf-g-PEG films exhibited high resistance to protein adsorption and cell attachment. When used as an additive in PSf membranes prepared by immersion precipitation, the graft copolymer preferentially segregates to the membrane surface, delivering enhanced wettability, porosity and protein resistance compared to unmodified PSf membranes. The surface properties of PSf-g-PEG modified membranes render them desirable candidates for hemodialysis.