Introducing the concept of spiral microbeam radiation therapy (spiralMRT).

Motivation With interlaced microbeam radiation therapy (MRT) a first kilovoltage radiotherapy (RT) concept combining spatially fractionated entrance beams and homogeneous dose distribution at the target exists. However, this technique suffers from its high sensitivity to positioning errors of the target relative to the radiation source. With spiral microbeam radiation therapy (spiralMRT), this publication introduces a new irradiation geometry, offering similar spatial fractionation properties as interlaced MRT, while being less vulnerable to target positioning uncertainties.Methods The dose distributions achievable with spiralMRT in a simplified human head geometry were calculated with Monte Carlo simulations based on Geant4 and the dependence of the result on the microbeam pitch, total field size, and photon energy were analysed. A comparison with interlaced MRT and conventional megavoltage tomotherapy was carried out.Results SpiralMRT can deliver homogeneous dose distributions, while using spatially fractionated entrance beams. The valley dose of spiralMRT entrance beams is by up to 40% lower than the corresponding tomotherapy dose, thus indicating a better normal tissue sparing. The optimum photon energy is found to be around [Formula: see text].Conclusions SpiralMRT is a promising approach to delivering homogeneous dose distributions with spatially fractionated entrance beams, possibly decreasing normal tissue side effects in hypofractionated RT

Assessment of optical CT as a future QA tool for synchrotron x-ray microbeam therapy.

Synchrotron microbeam radiation therapy (MRT) is an advanced form of radiotherapy for which it is extremely difficult to provide adequate quality assurance. This may delay or limit its clinical uptake, particularly in the paediatric patient populations for whom it could be especially suitable. This study investigates the extent to which new developments in 3D dosimetry using optical computed tomography (CT) can visualise MRT dose distributions, and assesses what further developments are necessary before fully quantitative 3D measurements can be achieved. Two experiments are reported. In the first cylindrical samples of the radiochromic polymer PRESAGE(®) were irradiated with different complex MRT geometries including multiport treatments of collimated 'pencil' beams, interlaced microplanar arrays and a multiport treatment using an anthropomorphic head phantom. Samples were scanned using transmission optical CT. In the second experiment, optical CT measurements of the biologically important peak-to-valley dose ratio (PVDR) were compared with expected values from Monte Carlo simulations. The depth-of-field (DOF) of the optical CT system was characterised using a knife-edge method and the possibility of spatial resolution improvement through deconvolution of a measured point spread function (PSF) was investigated. 3D datasets from the first experiment revealed excellent visualisation of the 50 μm beams and various discrepancies from the planned delivery dose were found. The optical CT PVDR measurements were found to be consistently 30% of the expected Monte Carlo values and deconvolution of the microbeam profiles was found to lead to increased noise. The reason for the underestimation of the PVDR by optical CT was attributed to lack of spatial resolution, supported by the results of the DOF characterisation. Solutions are suggested for the outstanding challenges and the data are shown already to be useful in identifying potential treatment anomalies

A new gas attenuator system for the ID17 biomedical beamline at the ESRF

Volume: 425Non peer reviewe

MOSFET dosimetry for microbeam radiation therapy at the European Synchrotron Radiation Facility

Preclinical experiments are carried out with ~20–30 μm wide, ~10 mm high parallel microbeams of hard, broad-‘‘white’’-spectrum x rays (~50–600 keV) to investigate microbeam radiation therapy (MRT) of brain tumors in infants for whom other kinds of radiotherapy are inadequate and/or unsafe. Novel physical microdosimetry (implemented with MOSFET chips in the ‘‘edge-on’’ mode) and Monte Carlo computer-simulated dosimetry are described here for selected points in the peak and valley regions of a microbeam-irradiated tissue-equivalent phantom. Such microbeam irradiation causes minimal damage to normal tissues, possible because of rapid repair of their microscopic lesions. Radiation damage from an array of parallel microbeams tends to correlate with the range of peak-valley dose ratios (PVDR). This paper summarizes comparisons of our dosimetric MOSFET measurements with Monte Carlo calculations. Peak doses at depths \u3c22 mm are 18% less than Monte Carlo values, whereas those depths \u3e22 mm and valley doses at all depths investigated (2 mm–62 mm) are within 2–13% of the Monte Carlo values. These results lend credence to the use of MOSFET detector systems in edge-on mode for microplanar irradiation dosimetry

In situ Biological Dose Mapping Estimates the Radiation Burden Delivered to ‘Spared’ Tissue between Synchrotron X-Ray Microbeam Radiotherapy Tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to ‘spared’ tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30–40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies

The minipig experiment: a last major milestone prior clinical trials in MRT?

International audienceMicrobeam Radiation Therapy (MRT) has made considerable advances in all domains over the last 2 decades. By now, we have a better understanding of the underlying biological processes and in particular solid proof by scientists from different laboratories of the extraordinary normal tissue sparing of MRT as well as its differential effect between the tumour vasculature and the normal tissue vasculature, inducing hypoxia in preclinical tumour models when high-dose, spatially fractionated microbeams are applied in preclinical research[1]. Further milestones include the development of a dosimetry protocol, benchmarking of Monte Carlo dose calculations using several high resolution dosimeters, the development of a treatment planning system and the development of a MRT Patient Safety system to control dose delivery at high dose rates around 8000 Gy/sec.Prior a successful translation of the biological findings into an optimized treatment plan for humans, larger animals than rodents should be treated in MRT, which is one of the aims of the veterinary trials. A realistic scenario for a clinical trial phase I could be an MRT treatment delivered as a boost in order to delay tumor growth and increase the lifespan. The plan to irradiate landrace pigs in such a regim using 3 x 11Gy as in conventional RT in 1 week compared to 2 x 11Gy plus 1 MRT irradiation at 11Gy in the valley at the tumour site is being proposed. This project represents one of the last steps towards clinical application of MRT where microbeam radiation therapy would be applied as a relevant and efficient therapeutic boost for brain tumor management. A phase I clinical trial should first demonstrate the normal tissue tolerance in humans applying a simple cross-fired microbeam array from a maximum of 3 ports prior moving to more sophisticated irradiation geometries. Such potentially interesting irradiation geometries could keep the normal tissue at very low dose values applying a large centre to centre distance of 1200 μm, and in combination with a horizontal microbeam dose delivery from several ports, tumor control could be improved using intersperced beams to deliver a radiotherapeutic relevant valley dose only at the tumour site at tighter ctc spacing.References[1] – A. Bouchet et al., “Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not inthe normal brain“ Radiotherapy and Oncology 108 (2013) 143-1

High resolution radiochromic film dosimetry: Comparison of a microdensitometer and an optical microscope

Purpose: Microbeam radiation therapy is a developing technique that promises superior tumour control and better normal tissue tolerance using spatially fractionated X-ray beams only tens of micrometres wide.Radiochromic film dosimetry at micrometric scale was performed using a microdensitometer, but this instrument presents limitations in accuracy and precision, therefore the use of a microscope is suggested as alternative. The detailed procedures developed to use the two devices are reported allowing a comparison.Methods: Films were irradiated with single microbeams and with arrays of 50 mu m wide microbeams spaced by a 400 mu m pitch, using a polychromatic beam with mean energy of 100 keV. The film dose measurements were performed using two independent instruments: a microdensitometer (MDM) and an optical microscope (OM).Results: The mean values of the absolute dose measured with the two instruments differ by less than 5% but the OM provides reproducibility with a standard deviation of 1.2% compared to up to 7% for the MDM. The resolution of the OM was determined to be similar to 1 to 2 mu m in both planar directions able to resolve pencil beams irradiation, while the MDM reaches at the best 20 mu m resolution along scanning direction. The uncertainties related to the data acquisition are 2.5-3% for the OM and 9-15% for the MDM.Conclusion: The comparison between the two devices validates that the OM provides equivalent results to the MDM with better precision, reproducibility and resolution. In addition, the possibility to study dose distributions in two-dimensions over wider areas definitely sanctions the OM as substitute of the MDM

Microbeam radiation therapy: clinical perspectives

Microbeam radiation therapy (MRT), a novel form of spatially fractionated radiotherapy (RT), uses arrays of synchrotron-generated X-ray microbeams (MB). MRT has been identified as a promising treatment concept that might be applied to patients with malignant central nervous system (CNS) tumours for whom, at the current stage of development, no satisfactory therapy is available yet. Preclinical experimental studies have shown that the CNS of healthy rodents and piglets can tolerate much higher radiation doses delivered by spatially separated MBs than those delivered by a single, uninterrupted, macroscopically wide beam. High-dose, high-precision radiotherapies such as MRT with reduced probabilities of normal tissue complications offer prospects of improved therapeutic ratios, as extensively demonstrated by results of experiments published by many international groups in the last two decades. The significance of developing MRT as a new RT approach cannot be understated. Up to 50% of cancer patients receive conventional RT, and any new treatment that provides better tumour control whilst preserving healthy tissue is likely to significantly improve patient outcomes