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Microbeam radiation therapy (MRT) is being performed by using an array of narrow rectangular x-ray beams (typical beam sizes 25 microm X 1 cm), positioned close to each other (typically 200 microm separation), to irradiate a target tissue. The ratio of peak-to-valley doses (PVDR's) in the composite dose distribution has been found to be strongly correlated with the normal tissue tolerance and the therapeutic effect of MRT. In this work a Monte Carlo (MC) study of the depth- and lateral-dose profiles in water for single x-ray microbeams of different shapes and energies has been performed with the MC code PENELOPE. The contributions to the dose deposition from different interaction types have been determined at different distances from the center of the microbeam. The dependence of the peak dose, in a water phantom, on the microbeam field size used in the preclinical trials, has been demonstrated. Composite dose distributions for an array of microbeams were obtained using superposition algorithms and PVDR's were determined and compared with literature results obtained with other Monte Carlo codes. The dependence of the PVDR's on microbeam width, x-ray energy used, and on the separation between adjacent microbeams has been studied in detail.

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 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.

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.

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 sample–detector 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.

International audience; Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600keV, produced by third generation synchrotron sources, such as the European Synchrotron Radiation Facility (ESRF), in France. The main advantages of highly brilliant synchrotron sources are an extremely high dose rate and very small beam divergence. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. The minimal beam divergence results in the advantage of steeper dose gradients delivered to a tumor target, thus achieving a higher dose deposition in the target volume in fractions of seconds, with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has yielded many results from preclinical trials based on different animal models, including mice, rats, piglets and rabbits. Typically, MRT uses arrays of narrow ( approximately 25-100 microm wide) microplanar beams separated by wider (100-400 microm centre-to-centre) microplanar spaces. The height of these microbeams typically varies from 1 to 100 mm, depending on the target and the desired preselected field size to be irradiated. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues, up to approximately 2 yr after irradiation, and at the same time show a preferential damage of malignant tumor tissues; these effects of MRT have now been extensively studied over nearly two decades. More recently, some biological in vivo effects of synchrotron X-ray beams in the millimeter range (0.68-0.95 mm, centre-to-centre distances 1.2-4 mm), which may differ to some extent from those of microscopic beams, have been followed up to approximately 7 months after irradiation. Comparisons between broad-beam irradiation and MRT indicate a higher tumor control for the same sparing of normal tissue in the latter, even if a substantial fraction of tumor cells are not receiving a radiotoxic level of radiation. The hypothesis of a selective radiovulnerability of the tumor vasculature versus normal blood vessels by MRT, and of the cellular and molecular mechanisms involved remains under investigation. The paper highlights the history of MRT including salient biological findings after microbeam irradiation with emphasis on the vascular components and the tolerance of the central nervous system. Details on experimental and theoretical dosimetry of microbeams, core issues and possible therapeutic applications of MRT are presented.

Microbeam Radiation Therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600 keV, produced by 2nd and 3rd generation synchrotron sources, such as the National Synchrotron Light Source (NSLS) in the U.S., and the European Synchrotron Radiation Facility (ESRF) in France, respectively. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. A small beam divergence and a filtered white beam spectrum in the energy range between 30 and 250 keV results in the advantage of steep dose gradients with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has allowed a vast number of results from preclinical trials on different animal models, including mice, rats, piglets and rabbits. Microbeams in the range between 10 and 100 micron width show an unprecedented sparing of normal radiosensitive tissues as well as preferential damage to malignant tumor tissues. Typically, MRT uses arrays of narrow ({approx}25-100 micron-wide) microplanar beams separated by wider (100-400 microns centre-to-centre, c-t-c) microplanar spaces. We note that thicker microbeams of 0.1-0.68 mm used by investigators at the NSLS are still called microbeams, although some invesigators inmore » the community prefer to call them minibeams. This report, however, limits it discussion to 25-100 {mu}m microbeams. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues. High resolution dosimetry has been developed over the last two decades, but typical dose ranges are adapted to dose delivery in conventional Radiation Therapy (RT). Spatial resolution in the sub-millimetric range has been achieved, which is currently required for quality assurance measurements in Gamma-knife RT. Most typical commercially available detectors are not suitable for MRT applications at a dose rate of 16000 Gy/s, micron resolution and a dose range over several orders of magnitude. This paper will give an overview of all dosimeters tested in the past at the ESRF with their advantages and drawbacks. These detectors comprise: Ionization chambers, Alanine Dosimeters, MOSFET detectors, Gafchromic registered films, Radiochromic polymers, TLDs, Polymer gels, Fluorescent Nuclear Track Detectors (Al{sub 2}O{sub 3}:C, Mg single crystal detectors), OSL detectors and Floating Gate-based dosimetry system. The aim of such a comparison shall help with a decision on which of these approaches is most suitable for high resolution dose measurements in MRT. The principle of these detectors will be presented including a comparison for some dosimeters exposed with the same irradiation geometry, namely a 1x1 cm{sup 5} field size with microbeam exposures at the surface, 0.1 cm and 1 cm in depth of a PMMA phantom. For these test exposures, the most relevant irradiation parameters for future clinical trials have been chosen: 50 micron FWHM and 400 micron c-t-c distance. The experimental data are compared with Monte Carlo calculations.« less

Various dosimeters have been tested for assessing absorbed doses with microscopic spatial resolution in targets irradiated by high-flux, synchrotron-generated, low-energy (approximately 30-300 keV) x-ray microbeams. A MOSFET detector has been used for this study since its radio sensitive element, which is extraordinarily narrow (approximately 1 microm), suits the main applications of interest, microbeam radiation biology and microbeam radiation therapy (MRT). In MRT, micrometer-wide, centimeter-high, and vertically oriented swaths of tissue are irradiated by arrays of rectangular x-ray microbeams produced by a multislit collimator (MSC). We used MOSFETs to measure the dose distribution, produced by arrays of x-ray microbeams shaped by two different MSCs, in a tissue-equivalent phantom. Doses were measured near the center of the arrays and maximum/minimum (peak/valley) dose ratios (PVDRs) were calculated to determine how variations in heights and in widths of the microbeams influenced this for the therapy, potentially important parameter. Monte Carlo (MC) simulations of the absorbed dose distribution in the phantom were also performed. The results show that when the heights of the irradiated swaths were below those applicable to clinical therapy (1 mm) the MC simulations produce estimates of PVDRs that are up to a factor of 3 higher than the measured values. For arrays of higher microbeams (i.e., 25 microm x 1 cm instead of 25 x 500 microm2), this difference between measured and simulated PVDRs becomes less than 50%. Closer agreement was observed between the measured and simulated PVDRs for the Tecomet MSC (current collimator design) than for the Archer MSC. Sources of discrepancies between measured and simulated doses are discussed, of which the energy dependent response of the MOSFET was shown to be among the most important.

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) 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.

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.