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Preclinical Microbeam Radiation Therapy (MRT) research programs are carried out at the European Synchrotron Radiation Facility (ESRF) and at a few other synchrotron facilities. MRT needs an accurate evaluation of the doses delivered to biological tissues for carrying out pre-clinical studies. This point is crucial for determining the effect induced by changing any of the physical irradiation parameters. The doses of interest in MRT are normally calculated using Monte Carlo (MC) methods. A few MC packages have been used in the last decade for MRT dose evaluations in independent studies. The aim of this investigation is to provide a preliminary basis to perform a systematic comparison of the dose results obtained, under identical irradiation conditions and for the same scoring geometries with the following five MC codes: EGS4, PENELOPE, GEANT4, EGSnrc, and MCNPX. Dose profiles have been calculated in an in-depth region of cylindrical phantoms made of water or PMMA. Beams in both cylindrical and planar geometry have been considered. This comparison shows an overall agreement among the different codes although minor differences occur, which need further investigations. © 2008 IOP Publishing Ltd.

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 indistinguish

Clinical microbeam radiation therapy (MRT) will require a multislit collimator with adjustable uniform slit widths to enable reliable Monte Carlo-based treatment planning. Such a collimator has been designed, fabricated of >99% tungsten [W] by Tecomet/Viasys (Woburn, Massachusetts, USA) and installed at the 6 GeV electron-wiggler-generated hard x-ray ID17 beamline of the European Synchrotron Radiation Facility. Its pair of 125 parallel, 8 mm deep, 0.100 mm wide radiolucent slits, 0.400 mm on center, are perfused with nitrogen gas [N2] to dissipate heat during irradiation. Major improvements in uniformity of microbeam widths and good peak/valley dose ratios combined with a very high dose rate in targeted tissues have been achieved.

Microbeam radiation therapy (MRT) has the potential to treat infantile brain tumours when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of x-rays but provides unusual resistance to radioneurotoxicity, presumably from the migration of endothelial cells from 'valleys' into 'peaks', i.e., into directly irradiated microslices of tissues. We present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumour area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumouricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumour in the paths of the arrays.

Formation of gamma H2AX foci (a marker of DNA double-strand breaks), rates of foci clearance and apoptosis were investigated in cultured normal human fibroblasts and p53 wild-type malignant glioma cells after exposure to high-dose synchrotron-generated microbeams. Doses up to 283 Gy were delivered using beam geometries that included a microbeam array (50 mu m wide, 400 mu m spacing), single microbeams (60-570 mu m wide) and a broad beam (32 mm wide). The two cell types exhibited similar trends with respect to the initial formation and time-dependent clearance of gamma H2AX foci after irradiation. High levels of gamma H2AX foci persisted as late as 72 h post-irradiation in the majority of cells within cultures of both cell types. Levels of persistent foci after irradiation via the 570 mu m microbeam or broad beam were higher when compared with those observed after exposure to the 60 mu m microbeam or microbeam array. Despite persistence of gamma H2AX foci, these irradiation conditions triggered apoptosis in only a small proportion (<5%) of cells within cultures of both cell types. These results contribute to the understanding of the fundamental biological consequences of high-dose microbeam irradiations, and implicate the importance of non-apoptotic responses such as p53-mediated growth arrest (premature senescence)., AuthorCount:6

We report results from a pilot study in which the in-line propagation-based phase-contrast imaging technique is combined with the stereoscopic method. Two phantoms were imaged at several sampledetector distances using monochromatic, 30 keV, X-rays. High contrast- and spatial-resolution phase-contrast stereoscopic pairs of X-ray images were constructed using the anaglyph approach and a vivid stereoscopic effect was demonstrated. On the other hand, images of the same phantoms obtained with a shorter sample-to-detector distance, but otherwise the same experimental conditions (i.e. the same X-ray energy and absorbed radiation dose), corresponding to the conventional attenuation-based imaging mode, hardly revealed stereoscopic effects because of the lower image contrast produced. These results have confirmed our hypothesis that stereoscopic X-ray images of samples with objects composed of low-atomic-number elements are considerably improved if phase-contrast imaging is used. It is our belief that the high-resolution phase-contrast stereoscopic method will be a valuable new medical imaging tool for radiologists and that it will be of help to enhance the diagnostic capability in the examination of patients in future clinical practice, even though further efforts will be needed to optimize the system performance.

Microbeam Radiation Therapy (MRT) is a preclinical synchrotron radiation based therapy technique in its preclinical stage with the potential to treat brain tumours in children when other kinds of radiotherapy would be excessively toxic to the developing normal brain. The most promising feature of MRT lies in its unusual resistance of MRT irradiated tissues to radioneurotoxicity even for peak doses of several hundreds of Gray. Results obtained with the spatially fractionated beams indicate a superior therapeutic effect compared to conventional radiotherapy. MRT, solely possible at SR sources with negligible beam divergence, is profiting from the dose volume effect and most probably from some differences in the tumour and the normal tissue responses, yet to be fully understood. This paper demonstrates that dosimetric measurements requiring a spatial resolution of a few microns is feasible with the use of GafChromic® films together with a high resolution scanner system. The data so obtained can be used to benchmark Monte Carlo calculations. © 2009 Springer-Verlag.

Radiation therapy is one of the techniques most commonly used in the treatment of various types of tumors. The microbeam radiation therapy (MRT) is a very promising variant, which exploits the property that tissues can tolerate high doses of radiation in small volumes. The effectiveness of MRT is well represented by the peak-to-valley dose ratios (PVDRs), which are one of the crucial parameters associated with the outcome of the treatment. In this study, we investigate on the factors that influence PVDRs, such as different beam energies and geometries. MRT experiments typically employ rectangular (planar) microbeams of different sizes, but, for convenience of analysis, preliminary computations have been performed also using arrays of cylindrical microbeams. This work shows that the shape of the impinging irradiation field largely influences the dose distribution. It highlights that a bundle of larger microbeams, with a small separation, produces more scattered radiation and therefore lower PVDRs. The study of how dose distributions vary with different setups and irradiation parameters is an essential step in enhancing the comparability of experimental data and simulation results.

Radiation therapy is widely used in the treatment of very different types of cancer. Recent developments in this field are aiming at delivering high doses to the target volume while sparing the surrounding healthy tissues. The Microbeam Radiation Therapy (MRT) is a new kind of radiotherapy which could be used for treating infantile brain tumors, as other kinds of radiotherapy would be extremely dangerous to the normal brain development. MRT is carried out using an array of parallel microbeams of synchrotron-wiggler-generated X-rays. In this work, Monte Carlo simulations using the Geant4 toolkit are carried out to estimate the dose deposition on a 20-cm-diameter, 20-cm-long cylindrical PMMA phantom, mimicking an infantile head. A set of physics processes is implemented in Geant4 to extend the range of validity of electromagnetic interactions down to 250 eV. The dose distribution in MRT is computed to prepare the treatment planning of preclinical trials. Primary photon histories are simulated for the different experimental setups, scoring the dose in cylindrical shells. We used cylindrical monoenergetic microbeams of 50, 100 and 150 keV and one microbeam with energies sampled from the measured spectrum at the ESRF ID17 beamline. The depth- and lateral-dose profiles have been studied, and for a few typical cases, the simulation results have been compared with those obtained with other codes.

Microbeam radiation therapy (MRT) has the potential to treat infantile brain tumours when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of x-rays but provides unusual resistance to radioneurotoxicity, presumably from the migration of endothelial cells from 'valleys' into 'peaks', i.e., into directly irradiated microslices of tissues. We present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumour area by applying an innovative cross-firing technique. We propose anMRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumouricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumour in the paths of the arrays.

Microbeam Radiation Therapy (MRT) has the potential to treat infantile brain tumors when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of X-rays but provides unusual resistance to radioneurotoxicity, presumably from the rapid migration of regenerative endothelial cells from dose ''valleys'' into dose ''peaks'', i.e., into directly irradiated micro-slices of tissues. We will present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumor area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumoricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumor in the paths of the arrays.

The dosimetry of X-ray microbeams using MOSFETs results in an asymmetrical beam profile due to a lack of lateral charged particle equilibrium. Monte Carlo simulations were carried out using PENELOPE and GEANT4 codes to study this effect and a MOSFET on a micropositioner was scanned in the microbeam. Based on the simulations a new method of microbeam dosimetry is proposed. The proposed edge-on face-to-face (EOFF) MOSFET detector, a die arrangement proposed here for the first time, should alleviate the asymmetry. Further improvement is possible by thinning the silicon body of the MOSFET.

Microbeam Radiation Therapy (MRT) is a technique utilizing the fact that normal tissue can sustain high doses of radiation in small volumes without significant damage. The synchrotron generated X-ray beam, used for the treatment, is collimated and delivered in an array of narrow micrometer-sized planar rectangular fields. In this work, the Monte Carlo code PENELOPE was used for simulating the dose deposition. This code provides an accurate treatment of low-energy electron transport which is important when performing dose calculations in micron-sized ranges. A comparison with earlier results was done for a few typical cases. The buildup of dose near the phantom surface and the lateral variation of dose around the microbeams were also studied. It was confirmed that the dose in the valley region mainly depends on Compton scattered electrons and that the electron scattering model used in the MC code is a key point. Finally a comparison between MC simulations and experimental microdosimetry, with radiochromic films and MOSFET detectors, gave important indications on possible refinements of the MC simulations for future investigations.

The dosimetry of X-ray microbeams using MOSFETs results in an asymmetrical beam profile due to a lack of lateral charged particle equilibrium. Monte Carlo simulations were carried out using PENELOPE and GEANT4 codes to study this effect and a MOSFET on a micropositioner was scanned in the microbeam. Based on the simulations a new method of microbeam dosimetry is proposed. The proposed edge-on face-to-face (EOFF) MOSFET detector, a die arrangement proposed here for the first time, should alleviate the asymmetry. Further improvement is possible by thinning the silicon body of the MOSFET.

Microbeam Radiation Therapy (MRT) has the potential to treat infantile brain tumors when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of X-rays but provides unusual resistance to radioneurotoxicity, presumably from the rapid migration of regenerative endothelial cells from dose "valleys" into dose "peaks", i.e., into directly irradiated micro-slices of tissues. We will present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumor area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumoricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumor in the paths of the arrays.