Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy

Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.

Synchrotron x ray induced axonal transections in the brain of rats assessed by high-field diffusion tensor imaging tractography

Since approximately two thirds of epileptic patients are non-eligible for surgery, local axonal fiber transections might be of particular interest for them. Micrometer to millimeter wide synchrotron-generated X-ray beamlets produced by spatial fractionation of the main beam could generate such fiber disruptions non-invasively. The aim of this work was to optimize irradiation parameters for the induction of fiber transections in the rat brain white matter by exposure to such beamlets. For this purpose, we irradiated cortex and external capsule of normal rats in the antero-posterior direction with a 4 mm×4 mm array of 25 to 1000 µm wide beamlets and entrance doses of 150 Gy to 500 Gy. Axonal fiber responses were assessed with diffusion tensor imaging and fiber tractography; myelin fibers were examined histopathologically. Our study suggests that high radiation doses (500 Gy) are required to interrupt axons and myelin sheaths. However, a radiation dose of 500 Gy delivered by wide minibeams (1000 µm) induced macroscopic brain damage, depicted by a massive loss of matter in fiber tractography maps. With the same radiation dose, the damage induced by thinner microbeams (50 to 100 µm) was limited to their paths. No macroscopic necrosis was observed in the irradiated target while overt transections of myelin were detected histopathologically. Diffusivity values were found to be significantly reduced. A radiation dose ≤ 500 Gy associated with a beamlet size of < 50 µm did not cause visible transections, neither on diffusion maps nor on sections stained for myelin. We conclude that a peak dose of 500 Gy combined with a microbeam width of 100 µm optimally induced axonal transections in the white matter of the brain.

Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: a proof of concept.

PURPOSE External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). METHODS A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. RESULTS Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. CONCLUSIONS The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

Relationship between surface topography and energy density distribution of Er, Cr:YSGG beam on irradiated dentin: an atomic force microscopy study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Assessment of cone beam CT registration for prostate radiation therapy : fiducial marker and soft tissue methods

Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM) and the soft tissue prostate (CBCTST). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST. Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM. Results CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.

Beam conditions for radiation generated by an electromagnetic J 0-correlated Schell-model source

Based on the 2 x 2 (electric field) cross-spectral density matrix, a model for an electromagnetic J(0)-correlated Schell-model beam is given that is a generalization of the scalar J(0)-correlated Schell-model beam. The conditions that the matrix for the source to generate an electromagnetic J(0)-correlated Schell-model beam are obtained. The condition for the source to generate a scalar J(0)-correlated Schell-model beam can be considered as a special case. (C) 2008 Optical Society of America

Studies on radiation pasteurisation of medium fatty fish 1. Control of radiation induced oxidative changes in white pomfret (Stromateus cinereus) by vacuum packaging

Marked differences were observed in proximate biochemical compositions of the skin and muscle of white pomfret. The skin showed comparatively higher content of extractable lipids and was more susceptible to radiation-induced oxidative changes like development of rancid odours and yellow discolouration than the muscle. Irradiation of skin samples under vacuum suppressed these changes. The present paper also reports on the efficacy of vacuum packaging in controlling oxidative rancidity and yellow discolouration in white pomfret skin subjected to irradiation and subsequent storage at 0-2°C.

Studies on radiation pasteurisation of medium fatty fish 3. Storage properties of white pomfret (Stromateus cinereus) fillets

White pomfret fillets packed under aerobic conditions had a limited shelf life of 8 days as against 10 days for samples packed under vacuum and stored at 0-2°C. Irradiation and subsequent storage of the fillets under vacuum at 0-2°C exhibited shelf lives of 30, 50 and 60 days for radiation doses of 0.1, 0.3 and 0.5 Mrad respectively in contrast to aerobically packed fillets which showed only 20, 35 and 50 days of storage life for the same levels of radiation doses and developed yellow discolouration and rancid odours.

Studies on radiation pasteurisation of medium fatty fish 2. Precursors of yellow discolouration in irradiated white pomfret (Stromateus cinereus)

Triglycerides, phospholipids and sarcoplasmic proteins fractions of white pomfret produced considerable amounts of thiobarbituric acid reactive substances (TBRS) on irradiation. Incubation of malonaldehyde with pomfret skin under aseptic conditions developed yellow pigmentation of the skin tissues, similar in spectral characteristics to those produced on irradiation of the skin.

Acoustic radiation force of a Bessel beam on a porous sphere.

The possibility of using acoustic Bessel beams to produce an axial pulling force on porous particles is examined in an exact manner. The mathematical model utilizes the appropriate partial-wave expansion method in spherical coordinates, while Biot's model is used to describe the wave motion within the poroelastic medium. Of particular interest here is to examine the feasibility of using Bessel beams for (a) acoustic manipulation of fine porous particles and (b) suppression of particle resonances. To verify the viability of the technique, the radiation force and scattering form-function are calculated for aluminum and silica foams at various porosities. Inspection of the results has shown that acoustic manipulation of low porosity (<0.3) spheres is similar to that of solid elastic spheres, but this behavior significantly changes at higher porosities. Results have also shown a strong correlation between the backscattered form-function and the regions of negative radiation force. It has also been observed that the high-order resonances of the particle can be effectively suppressed by choosing the beam conical angle such that the acoustic contribution from that particular mode vanishes. This investigation may be helpful in the development of acoustic tweezers for manipulation of micro-porous drug delivery carrier and contrast agents.

Radiation forces of a highly focused radially polarized beam on spherical particles

A radially polarized beam focused by a high-numerical-aperture (NA) objective has a strong longitudinal and nonpropagating electric field in the focal region, which implies that it is suitable for axial optical trapping. In this paper, we use the vectorial diffraction integral to represent the field distribution of the radially polarized beam focused by a high-NA objective and then employ the T-matrix method to compute the radiation forces on spherical particles. Effects of different parameters, such as the size of the sphere, the inner radius of the radially polarized beam, and the NA of the objective, on the radiation forces are presented.

High-efficiency transfer and expression of AdCMV-p53 in human cervix adenocarcinoma cells induced by subclinical-dose carbon beam radiation

Purpose The aim of this study is to evaluate the eVect of carbon-beam irradiation on adenovirus-mediated p53 transfer in human cervix adenocarcinoma.Materials and methods The HeLa cells pre-exposed to carbon-beam or -ray, were infected with replication-deficient adenovirus recombinant vectors, containing human wild-type p53 (AdCMV-p53) and green Xuorescent protein (GFP) (AdCMV–GFP), respectively. The GFP transfer and p53 expression were detected by Xow cytometric analysis.Results The GFP transfer frequency in C-beam with AdCMV-GFP groups was 38–50% more than that inγ-ray with AdCMV–GFP groups. The percentage of p53 positive cells in the C-beam with AdCMV–p53 groups was 34–55.6% more than that in γ-ray with AdCMV-p53 groups (p < 0.05), suggesting that subclinical-dose C-beam irradiation could signiWcantly promote exogenous p53 transfer and p53 expression, and extend the duration of p53 expression in the HeLa cells. The expression of p21 increased with p53 expression in HeLa cells. The survival fractions for the 0.5–1.0 Gy C-beam with AdCMV-p53 groups were 38–43% less than those for the isodose γ-ray with AdCMV-p53 groups, and 31–40% less than those for the C-beam only groups (p <0.05).Conclusions The subclinical-dose C-beam irradiation could signiWcantly promote the transfer and expression of exogenous p53, extend the duration of p53 expression, and enhance the suppression of p53 on cervix adenocarcinoma cells.

Design of synchrotron for hadron therapy

According to the operation and development of radiation therapy in the world, in order to further promote the radiation therapy of tumour in China, a design of a special synchrotron with two super-periodicity for hadron therapy is presented, including lattice, injection system, RF acceleration and slow extraction of the third order resonance. The synchrotron accelerates the proton beam to 250MeV and the carbon beam to 4000MeV/u.