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Spontaneous tumours in dogs and cats are an excellent model for clinical human research, such as in developing proton conformation radiotherapy for humans. The kinetics of tumour cells can be used effectively to predict prognosis and response to therapy in patients with tumours. Knowledge of the kinetic parameters in these tumours is therefore important. In the present study the kinetic parameters evaluated included the labelling index (LI), relative movement (RM), mitotic index (MI), and potential doubling time (Tpot). These parameters were determined using in vivo labelling with bromodeoxyuridine, flow cytometry and histological preparation. Samples were obtained and evaluated from 72 dogs and 20 cats, presenting as patients in our clinic. Within the groups of epithelial and mesenchymal tumours from dogs and cats, the kinetic parameters LI, RM and MI were compared with Tpot. Significant correlations were observed for the comparison Tpot and LI. No correlation was found between Tpot and RM

Purpose The aim of this study is to explore the effects of Microbeam Radiation (MR) on vascular biology using the chick chorio-allantoic membrane (CAM). Methods CAMs were irradiated with multiple planar synchrotron X-ray beams at doses between 100 and 300 Gy and were evaluated morphologically and in vivo at days 8 and 12. Results In vivo monitoring and morphological investigations of day 8 CAM immature vasculature 6 hr after MR revealed a near total destruction of the capillary plexus within the beams’ width. Surprisingly, arteries and veins were not affected. Conversely, at day 12, only well defined lesions in the microvasculature (mature ones, covered by pericytes) were observed. After 300 Gy MR, TEM revealed enlargement of the interendothelial cell junctions which could explain the oedema, the microvessels along the beam path showed signs of disruption and apoptosis. The remaining vasculature recovered rapidly and CAM regained its normal thickness. Between 1 hr and 6 hr no additional morphological changes were observed. Conclusions The effects of MR are most likely mediated by capillary damage. The vascular toxicity of MR depends on the stage of capillary maturation: the immature vessels are much more vulnerable than the mature ones. The physiological effects of MR appear within a short time, the most important structural alterations being present between 15 and 60 minutes after irradiation.

Background: Disturbances of memory function are frequently observed in patients with malignant brain tumours and as adverse effects after radiotherapy to the brain. Experiments in small animal models of malignant brain turnout using synchrotron-based microbeam radiation therapy (MRT) have shown a promising prolongation of survival times. Materials and methods: Two animal models of malignant brain turnout were used to Study survival and memory development after MRT. Thirteen days after implantation of tumour cells, animals were submitted to MRT either with or without adjuvant therapy (buthionine-SR-sulfoximine = BSO or glutamine). We used two orthogonal 1-cm wide arrays of 50 microplanar quasiparallel microbeams of 25 mu m width and a center-to-center distance of about 200 mu m, created by a multislit collimator, with a skin entrance dose of 350 Gy for each direction. Object recognition tests were performed at day 13 after tumour cell implantation and in monthly intervals Lip 10 1 year after tumour cell implantation. Results: In both animal models, MRT with and without adjuvant therapy significantly increased survival times. BSO had detrimental effects on memory function early after therapy, while administration of glutamine resulted in improved memory.

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.

Radiotherapy is among the most useful treatments of cancer. Penetrating radiation (ionizing particles or bremsstrahlung photons) is aimed toward the tumor-bearing target, gradually delivering as high radiation to it as is usefully suppressive of tumor growth, yet tolerated by normal vital tissues inevitably irradiated with the tumor. The high collimation and dose rate of synchrotron X-ray beams, even when monochromatized, favor radiotherapy. Photon activation therapy, tomotherapy, microbeam radiation therapy, and radiosurgery mediated by synchrotron wigglers are conceptually promising for difficult tumors. Radiotherapy of malignant brain tumors in rats has been encouraging, but suitable beam lines exist at only a few research facilities and much basic work must be done before the promise of synchrotron-based radiotherapy can be realized clinically.

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.

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.

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.