Could X-ray microbeams inhibit angioplasty-induced restenosis in the rat carotid artery?

Dilmanian, F.A.; Kalef-Ezra, J.; Petersen, Michael J.; Bozios, G.; Vosswinkel, James A.; Giron, Fabio; Ren, Biao; Yakupov, Renat; Antonakopoulos, G N

doi:10.1016/s1522-1865(03)00180-x

Cited by 19 publications

(17 citation statements)

References 40 publications

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“…However, the radiation dose tolerated by brain tissue decreased drastically with the increase of beam width, as a 1-mm thick cylindrical beam (entrance dose: 140 Gy) induced a macroscopic necrosis of the mouse brain tissue [8]. The effects of MB irradiation on normal brain are now well described in the literature [9], [10], [23]–[28] and our previous work showed that the use of 50-µm thick MB was a safer compromise (compared with 25 or 75 µm) between normal tissue sparing and brain tumor control for a 200 µm spacing [20]. In the present study, no damage was visualized by MRI in 4 control rats irradiated by intersecting, non-interlacing arrays which created 700Gy microplanar peak doses spaced by 200 µm on-center (valley dose of 12.5 Gy at 1 cm depth).…”

Section: Discussionmentioning

confidence: 99%

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

Serduc

Bräuer-Krisch

Siegbahn³

et al. 2010

PLoS ONE

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Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 µm wide, spaced 200 µm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm3 in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of synchrotron-generated X-rays enables delivery of high doses for destruction of small focal regions in human brains, with sharper dose fall-offs than those described in any other conventional radiation therapy.

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Section: Discussionmentioning

confidence: 99%

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

Serduc

Bräuer-Krisch

Siegbahn³

et al. 2010

PLoS ONE

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“…Synchrotron MRT has been used to ablate tumours in animal models at radiation levels that spare normal tissues [1], [2], [3], [4], [5], [6], [7], [8], with an apparent increase in the therapeutic index of up to 5-fold over conventional/broadbeam (BB) radiotherapy [1], [4]. There is no clear explanation as to why MRT gives a higher therapeutic index over BB irradiation.…”

Section: Introductionmentioning

confidence: 99%

“…MRT utilizes kilovoltage energy X-rays (50–250 keV) rather than the megavoltage energies produced by hospital linear accelerators, in order to maintain spatial fractionation deep into the tissues. In addition to the ‘peak’ and ‘valley’ dose there is also the ‘integrated’ dose which is the microbeam dose averaged over the entire irradiation area [3]. The Peak-to-Valley Dose Ratio (PVDR) is another important physical parameter in MRT dosimetry and is determined by several factors including the collimator geometry (i.e.…”

Section: Introductionmentioning

confidence: 99%

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

et al. 2014

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BackgroundHigh-dose synchrotron microbeam radiation therapy (MRT) has shown the potential to deliver improved outcomes over conventional broadbeam (BB) radiation therapy. To implement synchrotron MRT clinically for cancer treatment, it is necessary to undertake dose equivalence studies to identify MRT doses that give similar outcomes to BB treatments.AimTo develop an in vitro approach to determine biological dose equivalence between MRT and BB using two different cell-based assays.MethodsThe acute response of tumour and normal cell lines (EMT6.5, 4T1.2, NMuMG, EMT6.5ch, 4T1ch5, SaOS-2) to MRT (50–560 Gy) and BB (1.5–10 Gy) irradiation was investigated using clonogenic and real time cell impedance sensing (RT-CIS)/xCELLigence assays. MRT was performed using a lattice of 25 or 50 µm-wide planar, polychromatic kilovoltage X-ray microbeams with 200 µm peak separation. BB irradiations were performed using a Co60 teletherapy unit or a synchrotron radiation source. BB doses that would generate biological responses similar to MRT were calculated by data interpolation and verified by clonogenic and RT-CIS assays.ResultsFor a given cell line, MRT equivalent BB doses identified by RT-CIS/xCELLigence were similar to those identified by clonogenic assays. Dose equivalence between MRT and BB were verified in vitro in two cell lines; EMT6.5ch and SaOS-2 by clonogenic assays and RT-CIS/xCELLigence. We found for example, that BB doses of 3.4±0.1 Gy and 4.40±0.04 Gy were radiobiologically equivalent to a peak, microbeam dose of 112 Gy using clonogenic and RT-CIS assays respectively on EMT6.5ch cells.ConclusionOur data provides the first determination of biological dose equivalence between BB and MRT modalities for different cell lines and identifies RT-CIS/xCELLigence assays as a suitable substitute for clonogenic assays. These results will be useful for the safe selection of MRT doses for future veterinary and clinical trials.

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“…These components include the in-beam or \peak" dose, the valley dose (between adjacent microbeams) and the integrated dose. Dilmanian et al [13] defined the integrated dose as \the microbeam dose averaged over the entire irradiation area" and further \the integrated dose takes into account the volume of tissue in the low dose regions between the microbeams". Zhong et al [7] stated that the \integrated microbeam doses, (which for low valley doses) can be approximated as the in-beam dose times the ratio of the beam width to beam spacing".…”

mentioning

confidence: 99%

Biodosimetric quantification of short-term synchrotron microbeam versus broad-beam radiation damage to mouse skin using a dermatopathological scoring system

Priyadarshika

Crosbie²,

Kumar³

et al. 2011

BJR

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Objectives: Microbeam radiotherapy (MRT) with wafers of microscopically narrow, synchrotron generated X-rays is being used for pre-clinical cancer trials in animal models. It has been shown that high dose MRT can be effective at destroying tumours in animal models, while causing unexpectedly little damage to normal tissue. The aim of this study was to use a dermatopathological scoring system to quantify and compare the acute biological response of normal mouse skin with microplanar and broad-beam (BB) radiation as a basis for biological dosimetry. Method: The skin flaps of three groups of mice were irradiated with high entrance doses (200 Gy, 400 Gy and 800 Gy) of MRT and BB and low dose BB (11 Gy, 22 Gy and 44 Gy). The mice were culled at different time-points post-irradiation. Skin sections were evaluated histologically using the following parameters: epidermal cell death, nuclear enlargement, spongiosis, hair follicle damage and dermal inflammation. The fields of irradiation were identified by cH2AX-positive immunostaining. Results: The acute radiation damage in skin from high dose MRT was significantly lower than from high dose BB and, importantly, similar to low dose BB. Conclusion: The integrated MRT dose was more relevant than the peak or valley dose when comparing with BB fields. In MRT-treated skin, the apoptotic cells of epidermis and hair follicles were not confined to the microbeam paths.

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Could X-ray microbeams inhibit angioplasty-induced restenosis in the rat carotid artery?

Cited by 19 publications

References 40 publications

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

Biodosimetric quantification of short-term synchrotron microbeam versus broad-beam radiation damage to mouse skin using a dermatopathological scoring system

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