Experimental benchmarking of Monte Carlo simulations for radiotherapy dosimetry using monochromatic X-ray beams in the presence of metal-based compounds.

The local dose deposition obtained in X-ray radiotherapy can be increased by the presence of metal-based compounds in the irradiated tissues. This finding is strongly enhanced if the radiation energy is chosen in the kiloelectronvolt energy range, due to the proximity to the absorption edge. In this study, we present a MC application developed with the toolkit Geant4 to investigate the dosimetric distribution of a uniform monochromatic X-ray beam, and benchmark it against experimental measurements. Two validation studies were performed, using a commercial PTW RW3 water-equivalent slab phantom for radiotherapy, and a custom-made PMMA phantom conceived to assess the influence of high atomic number compounds on the dose profile, such as iodine and gadolinium at different concentrations. An agreement within 9% among simulations and experimental data was found for the monochromatic energies considered, which were in the range of 30-140 keV; the agreement was better than 5% for depths <60 mm. A dose enhancement was observed in the calculations, corresponding to the regions containing the contrast agents. Dose enhancement factors (DEFs) were calculated, and the highest values were found for energies higher than the corresponding K-edges of iodine and gadolinium. The in-silico results are in line with the empirical findings, which suggest that Geant4 can be satisfactorily used as a tool for the calculation of the percentage depth dose (PDD) at the energies considered in this study in the presence of contrast agents.

Synchrotron-generated microbeam sensorimotor cortex transections induce seizure control without disruption of neurological functions.

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.

Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence of the microbeam width at constant valley dose.

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.