To analyze the effects of the microbeam width (25, 50 and 75 microm) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MRT50, MRT75), each using two orthogonally intersecting arrays of either 25, 50 or 75 microm wide microbeams, all spaced 211 microm on center, were tested. For each configuration, peak entrance doses of 860, 480 and 320 Gy, respectively, were calculated to produce an identical valley dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days after radiation treatment, 42 rats were killed to evaluate histopathologically the extent of tumor necrosis, and the presence of proliferating tumors cells and tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48 days for MRT25, 50 and 75, respectively. The combination of the highest entrance doses (860 Gy per array) with 25 microm wide beams (MRT25) resulted in a cumulative valley dose of 36 Gy and was excessively toxic, as it led to early death of all normal rats and of approximately 50% of tumor-bearing rats. The short survival times, particularly of rats in the MRT25 group, restricted adequate observance of the therapeutic effect of the method on tumor-bearing rats. However, microbeams of 50 microm width led to the best median survival time after 9L gliosarcoma MRT treatment and appeared as the better compromise between tumor control and normal brain toxicity compared with 75 microm or 25 microm widths when used with a 211 microm on-center distance. Despite very high radiation doses, the tumors were not sterilized; viable proliferating tumor cells remained present at the tumor margin. This study shows that microbeam width and peak entrance doses strongly influence tumor responses and normal brain toxicity, even if valley doses are kept constant in all groups. The use of 50 microm wide microbeams combined with moderate peak doses resulted in a higher therapeutic ratio.

Theoretical dose distributions for microbeam radiation therapy (MRT) are computed in this paper using the GEANT4 Monte Carlo (MC) simulation toolkit. MRT is an innovative experimental radiotherapy technique carried out using an array of parallel microbeams of synchrotron-wiggler-generated x rays. Although the biological mechanisms underlying the effects of microbeams are still largely unknown, the effectiveness of MRT can be traced back to the natural ability of normal tissues to rapidly repair small damages to the vasculature, and on the lack of a similar healing process in tumoral tissues. Contrary to conventional therapy, in which each beam is at least several millimeters wide, the narrowness of the microbeams allows a rapid regeneration of the blood vessels along the beams' trajectories. For this reason the calculation of the "valley" dose is of crucial importance and the correct use of MC codes for such purposes must be understood. GEANT4 offers, in addition to the standard libraries, a specialized package specifically designed to deal with electromagnetic interactions of particles with matter for energies down to 250 eV. This package implements two different approaches for electron and photon transport, one based on evaluated data libraries, the other adopting analytical models. These features are exploited to cross-check theoretical computations for MRT. The lateral and depth dose profiles are studied for the irradiation of a 20 cm diameter, 20 cm long cylindrical phantom, with cylindrical sources of different size and energy. Microbeam arrays are simulated with the aid of superposition algorithms, and the ratios of peak-to-valley doses are computed for typical cases used in preclinical assays. Dose profiles obtained using the GEANT4 evaluated data libraries and analytical models are compared with simulation results previously obtained using the PENELOPE code. The results show that dose profiles computed with GEANT4's analytical model are almost indistinguishable from those obtained with the PENELOPE code, but some noticeable differences appear when the evaluated data libraries are used.

Synchrotron-generated X-ray microplanar beams (microbeams) are characterized by the ability to deliver extremely high doses of radiation to spatially restricted volumes of tissue. Minimal dose spreading outside the beam path provides an exceptional degree of protection from radio-induced damage to the neurons and glia adjacent to the microscopic slices of tissue irradiated. The preservation of cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. Microbeams (size 100 µm/600 µm, center-to-center distance of 400 µm/1200 µm, peak entrance doses of 360-240 Gy/150-100 Gy) delivered to the sensorimotor cortex of six 2-month-old naïve rats generated histologically evident cortical transections, without modifying motor behavior and weight gain up to 7 months. Microbeam transections of the sensorimotor cortex dramatically reduced convulsive seizure duration in a further group of 12 rats receiving local infusion of kainic acid. No subsequent neurological deficit was associated with the treatment. These data provide a novel tool to study the functions of the cortex and pave the way for the development of new therapeutic strategies for epilepsy and other neurological diseases.