Good Timing Matters: The Spatially Fractionated High Dose Rate Boost Should Come First.

Monoplanar microbeam irradiation (MBI) and pencilbeam irradiation (PBI) are two new concepts of high dose rate radiotherapy, combined with spatial dose fractionation at the micrometre range. In a small animal model, we have explored the concept of integrating MBI or PBI as a simultaneously integrated boost (SIB), either at the beginning or at the end of a conventional, low-dose rate schedule of 5x4 Gy broad beam (BB) whole brain radiotherapy (WBRT). MBI was administered as array of 50 µm wide, quasi-parallel microbeams.

Microbeam Irradiation as a Simultaneously Integrated Boost in a Conventional Whole-Brain Radiotherapy Protocol.

Microbeam radiotherapy (MRT), an experimental high-dose rate concept with spatial fractionation at the micrometre range, has shown a high therapeutic potential as well as good preservation of normal tissue function in pre-clinical studies. We investigated the suitability of MRT as a simultaneously integrated boost (SIB) in conventional whole-brain irradiation (WBRT). A 174 Gy MRT SIB was administered with an array of quasi-parallel, 50 µm wide microbeams spaced at a centre-to-centre distance of 400 µm either on the first or last day of a 5 × 4 Gy radiotherapy schedule in healthy adult C57 BL/6J mice and in F98 glioma cell cultures.

Tolerance of Normal Rabbit Facial Bones and Teeth to Synchrotron X-Ray Microbeam Irradiation.

Microbeam radiation therapy, an alternative radiosurgical treatment under preclinical investigation, aims to safely treat muzzle tumors in pet animals. This will require data on the largely unknown radiation toxicity of microbeam arrays for bones and teeth. To this end, the muzzle of six young adult New Zealand rabbits was irradiated by a lateral array of microplanar beamlets with peak entrance doses of 200, 330 or 500 Gy.

Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.

Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role.

Use of synchrotron medical microbeam irradiation to investigate radiation-induced bystander and abscopal effects in vivo.

The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile.

Response of the rat spinal cord to X-ray microbeams.

Background And Purpose: To quantify the late dose-related responses of the rat cervical spinal cord to X-ray irradiations by an array of microbeams or by a single millimeter beam.

Materials And Methods: Necks of anesthetized rats were irradiated transversely by an 11 mm wide array of 52 parallel, 35 μm wide, vertical X-ray microbeams, separated by 210 μm intervals between centers. Comparison was made with rats irradiated with a 1.

Proteomic changes in the rat brain induced by homogenous irradiation and by the bystander effect resulting from high energy synchrotron X-ray microbeams.

Purpose: To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue.

Methods: Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry.

[Alban Köhler (1874-1947): Inventor of grid therapy].

Grid (or sieve) therapy ("Gitter-" oder "Siebtherapie"), spatially fractionated kilo- and megavolt X-ray therapy, was invented in 1909 by Alban Köhler, a radiologist in Wiesbaden, Germany. He tested it on several patients before 1913 using approximately 60-70kV Hittorf-Crookes tubes. Köhler pushed the X-ray tube's lead-shielded housing against a stiff grid of 1 mm-square iron wires woven 3.

Microbeam radiation-induced tissue damage depends on the stage of vascular maturation.

Purpose: To explore the effects of microbeam radiation (MR) on vascular biology, we used the chick chorioallantoic membrane (CAM) model of an almost pure vascular system with immature vessels (lacking periendothelial coverage) at Day 8 and mature vessels (with coverage) at Day 12 of development.

Methods And Materials: CAMs were irradiated with microplanar beams (width, ∼25 μm; interbeam spacing, ∼200 μm) at entrance doses of 200 or 300 Gy and, for comparison, with a broad beam (seamless radiation [SLR]), with entrance doses of 5 to 40 Gy.

Results: In vivo monitoring of Day-8 CAM vasculature 6 h after 200 Gy MR revealed a near total destruction of the immature capillary plexus.

Proton spot scanning radiotherapy of spontaneous canine tumors.

Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanning technique to evaluate the safety and efficacy of the system, and to study the acute and late radiation reactions. Nasal tumors, soft tissue sarcomas, and miscellaneous tumors of the head were treated with a median total dose of 52.5 Gy given in 3.

Memory and survival after microbeam radiation therapy.

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 tumour using synchrotron-based microbeam radiation therapy (MRT) have shown a promising prolongation of survival times.

Materials And Methods: Two animal models of malignant brain tumour were used to study survival and memory development after MRT.

In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature.

Purpose: The purpose of this study was to assess the early effects of microbeam irradiation on the vascular permeability and volume in the parietal cortex of normal nude mice using two-photon microscopy and immunohistochemistry.

Methods And Materials: The upper part of the left hemisphere of 55 mice was irradiated anteroposteriorly using 18 vertically oriented beams (width 25 microm, interdistance 211 microm; peak entrance doses: 312 or 1000 Gy). At different times after microbeam exposure, the microvasculature in the cortex was analyzed using intravital two-photon microscopy after intravascular injection of fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB).

Relative biologic effectiveness determination in mouse intestine for scanning proton beam at Paul Scherrer Institute, Switzerland. Influence of motion.

Purpose: To determine the relative biologic effectiveness (RBE) of the Paul Scherrer Institute (PSI) scanning proton beam in reference conditions and to evaluate the influence of intestine motion on the proton dose homogeneity.

Methods And Materials: First, RBE was determined for crypt regeneration in mice after irradiation in a single fraction. Irradiation was performed at the middle of a 7-cm spread out Bragg peak (SOBP; reference position), as well as in the proximal part of the plateau and at the distal end of the SOBP.

Combining magnetic and optical tracking for computer aided therapy.

A fast and accurate magnetic tracking system was developed for applications in real-time tumor tracking, computer-aided surgery, and endoscopy. The tracking is based on the application of miniaturized sensors. Once implanted in the patient, the sensors receive signals from an external field generator.

Preliminary study of plasma vascular endothelial growth factor (VEGF) during low- and high-dose radiation therapy of dogs with spontaneous tumors.

High plasma vascular endothelial growth factor (VEGF) concentrations are associated with radiation resistance and poor prognosis. After an exposure to ionizing radiation in cell culture an early phase and a late phase of increased VEGF have been documented. The activation was dependent on the radiation dose.

Apoptotic response of irradiated T-lymphocytes. An epidemiologic study in canine radiotherapy patients.

Background: Evaluation of radiation-induced apoptosis in T-lymphocytes was developed for human medicine in order to predict the sensitivity of individual patients to radiation therapy and has regular use in cases of suspected hypersensitivity. A major goal of the present study was to evaluate the usefulness of the apoptosis assay in veterinary medicine for application in radiation sensitivity testing. The main goal was to examine potential changes in sensitivity of T-lymphocytes to radiation-induced apoptosis during the course of radiation treatment.

Assessment of a radiotherapy patient immobilization device using single plane port radiographs and a remote computed tomography scanner.

Radiation treatment requires a precise procedure for interfraction repositioning of the patient. The purpose of this study was to determine the accuracy of our fixation device in treatment position and to evaluate the setup accuracy with two different methods. The positioning data of 19 canine patients with tumors in the head region (oral, nasal, cerebral) treated with photon or proton irradiation were included in this study.

A comparison of normal tissue complication probability of brain for proton and photon therapy of canine nasal tumors.

This study compared the calculated normal tissue complication probability of brain in dogs with a nasal tumor, which had both photon and proton treatment planning. Nine dogs diagnosed with a variety of histologies, but all with large, caudally located nasal tumors were studied. Three-dimensional (3-D) photon dose distribution, and a proton dose distribution was calculated for each dog.

A single low dose of X-rays induces high frequencies of genetic instability (aneuploidy) and heritable damage (apoptosis), dependent on cell type and p53 status.

We harvested and analyzed cells from four different non-transformed cell lines surviving a single X-ray exposure. Evidence of radiation-induced karyotype instability was observed in 100% of C3H 10T1/2 fibroblast clones and 11.3% of V79 fibroblast clones.