Term Radiation Damage Research Articles

Medipix3 proton and carbon ion measurements across full energy ranges and at clinical flux rates in MedAustron IR1

The Medipix3, a hybrid pixel detector with a silicon sensor, has been evaluated as a beam instrumentation device with proton and carbon ion measurements in the non-clinical research room (IR1) of MedAustron Ion Therapy Center. Protons energies are varied from 62.4 to 800 MeV with 104 to 108 protons per second impinging on the detector surface. For carbon ions, energies are varied from 120 to 400 MeV/amu with 107 to 108 carbon ions per second. Measurements include simultaneous high resolution, beam profile and beam intensity with various beam parameters at up to 1000 FPS (frames per second), count rate linearity and an assessment of radiation damage after the measurement day using an x-ray tube to provide a homogeneous radiation measurement. The count rate linearity is found to be linear within the uncertainties (dominated by accelerator related sources due to special setup) for the measurements without degraders. Various frequency components are identified within the beam intensity over time firstly including 49.98 Hz with standard deviation, σ = 0.29, secondly 30.55 Hz σ = 0.55 and thirdly 252.51 Hz σ = 0.83. A direct correlation between the number of zero counting and noisy pixels is observed in the measurements with the highest flux. No conclusive evidence of long term radiation damage was found as a result of these measurements over one day.

Adenovirus-Mediated Bcl-Xl Gene Therapy Combined with Pronase Treatment Protects the Small Intestine from Radiation-Induced Enteritis in Mouse Model

Intestinal injury is a major side effect of radiation treatment for many malignancies. The present study investigated whether transducing Bcl-xL, a potent anti-apoptotic gene, into intestinal epithelial cells would exert protective effects against radiation-induced acute injuries. Methods: Adenoviral vectors containing the human Bcl-xL gene (AxCABclxL) or β-galactosidase gene (AxCAlacZ) driven by the CAG promoter were generated. To increase transduction efficiency into the mucosal epithelium, the intraluminal space of the small intestine of mice was washed with buffered-saline and mucus components were digested with Pronase MS®. Gene transduction was performed by injecting 2×108 pfu adenoviral vector into the pre-treated small intestine. Transduction efficiency was examined by X-gal staining 24 hours after AxCAlacZ infection. Radiation-induced acute injury of the small intestine was induced by whole body irradiation (15 Gy) performed 24 hours after adenoviral vector infection. Apoptotic epithelial cells were visualized by TUNEL assay. Morphological analysis was assessed by histological examination. Results: Successful transduction after Pronase MS® treatment was achieved in the basal crypt epithelial cells in the ileum, thought to be the location of stem cells, as determined by X-gal staining. The AxCABclxL group demonstrated significantly fewer radiation-induced apoptotic mucosal epithelial cells when compared with the other two groups at 6 hours after irradiation (p<0.05). At 72 hours after irradiation, the morphological appearance of the small intestine in the AxCABclxL group showed significantly less radiation damage in terms of mucosal thickness (p<0.001). Conclusions: The present study indicates that Bcl-xL gene expression using adenoviral vector-mediated transduction is a valuable approach to prevent intestinal injury caused by radiation exposure.

SU‐EE‐A3‐03: Radiation Induced Effects in An 8.5 MHz Magnetic Resonance Imaging Coil

Purpose: Few research groups are involved in integrating magnetic resonance imaging (MRI) with a linear accelerator in order to obtain real‐time MRI images during the treatment beam‐on. Therefore, the radio frequency (RF) coils used in MRI will be irradiated during this real‐time image guided radiotherapy. The radiation effects on RF coils include instantaneous induced currents and long term radiation damage to components. These effects are potential obstacles facing linac‐MRI integration. This work measures and characterizes the instantaneous effect of pulsed radiation on MRI coils. Method and Materials: A CAT Solenoid coil was placed inside an RF cage, to remove RF noise, and connected to a current amplifier. The amplifier output was sent through RF filters to the RF cage exterior and then to an oscilloscope. The cage was placed in the pulsed beam of a linac and the current induced by pulsed radiation was measured by the oscilloscope; the waveforms were then transferred to a PC and power spectral density was calculated. Results: The RF cage was very effective in eliminating the extraneous RF noise from the radiation induced signal. The induced signal is only present when the radiation beam is on and incident upon the coil. The power spectrum of the induced current indicates that most of the power is contained below 1 MHz, but there is signal is present at the coil resonance frequency (8.5 MHz). The induced current a) occurs mainly in the copper winding, b) is reduced if buildup material is placed on the coil and c) increases linearly with the dose rate. Conclusion: Radiation induced current is present in MRI coils, but its impact on imaging is yet to be determined. This, along with magnetic field impact on induced current will be examined using the functioning 0.2 Tesla linac‐MR prototype.

Long-Term Impact of Radiation on the Stem Cell and Oligodendrocyte Precursors in the Brain

BackgroundThe cellular basis of long term radiation damage in the brain is not fully understood.Methods and FindingsWe administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries.ConclusionsThis study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursors and the inability of the stem cell compartment to compensate for this loss.

Influence of the Multigroup Approximation on VVER-1000 RPV Neutron/Gamma Flux Calculation

Abstract One-dimensional calculations of neutron and gamma group fluxes and radiation damage in terms of DPA have been carried out for VVER-1000 mock-up realized at LR-0 critical assembly, Rez, Czech Republic in order to evaluate the influence of energy dependence multigroup approximation on VVER-1000 RPV Neutron/Gamma flux calculation. Two calculational methods have been applied: Monte Carlo method (MC) with continuous energy dependence description and discrete ordinates (DO) method with multigroup energy dependence approximation. Two different multigroup neutron/gamma cross section libraries have been used: BGL1000—created especially for VVER-1000 application and BUGLE96—created for PWR application. A good consistency between the results for both methods and different cross section libraries is obtained for neutrons with energy above 0.1 MeV. The worst consistency is obtained for the thermal neutrons. For gammas a better consistency between DO and MC results is obtained when BGL1000 library is applied.

Biological effects of anhydrobiosis in an African chironomid, Polypedilum vanderplanki on radiation tolerance

Purpose: Anhydrobiotic organisms are known to have an extremely high tolerance against a range of stresses. However, the functional role of anhydrobiosis in radiation tolerance is poorly understood, especially in development following irradiation. The present study aims to evaluate effects of anhydrobiosis on radiation tolerance in an anhydrobiotic insect, Polypedilum vanderplanki.Materials and methods: Larval survival (48 h), anhydrobiotic ability, metamorphosis and reproduction after exposure to 1 – 9000 Gy of gamma-rays at the larval stage were compared between anhydrobiotic (dry) and normal (wet) phases.Results: Wet larvae were killed in a dose-dependent manner at doses higher than 2000 Gy, and all died within 8 h after 4000 Gy exposure. In contrast, dry larvae survived even 5000 Gy, and some of them still tolerated 7000 Gy and were alive at 48 h after rehydration. Moreover, greater radiotolerance of dry larva, compared to wet ones, was demonstrated in terms of metamorphoses. However, anhydrobiosis did not protect against radiation damage in terms of producing viable offspring.Conclusion: These results indicate that anhydrobiosis enhances radiotolerance, resulting in increases of successful metamorphoses.

Probing biomolecules: Gas phase experiments and biological relevance

After the discovery of X-rays, radioactivity and ultimately .i1. nuclear fission-leading to the release ofatomic bombs over Hiroshima and Nagasaki-it became clear that the exposure of living beings to high energy radiation (particles and photons) can result in fatal effects for the concerned individual. The result of such effects is subsumed under the all embracing term radiation damage. It includes damage of biological material on a short time scale, Le. the .. it became clear that immediate collapse of living cells eventually resulting in the death of the individual within hours or days but also describes effects appearing on much longer time scales since, instead of complete destruction ofcells, radiation can also change the genetic expression of DNA. This may ultimately result in cancer and the appearance of tumours; but for prolonged periods after initial exposure the individual amy appear to have no obvious problems, however such dormant effects may appear as mutations in the individuals descendants (e.g the number of deformities in babies born in the Ukraine in the years after the ChernobyI accident),

Atomic resolution structures of trypsin provide insight into structural radiation damage

Radiation damage is an inherent problem in protein X-ray crystallography and the process has recently been shown to be highly specific, exhibiting features such as cleavage of disulfide bonds, decarboxylation of acidic residues, increase in atomic B factors and increase in unit-cell volume. Reported here are two trypsin structures at atomic resolution (1.00 and 0.95 A), the data for which were collected at a third-generation synchrotron (ESRF) at two different beamlines. Both trypsin structures exhibit broken disulfide bonds; in particular, the bond from Cys191 to Cys220 is very sensitive to synchrotron radiation. The data set collected at the most intense beamline (ID14-EH4) shows increased structural radiation damage in terms of lower occupancies for cysteine residues, more breakage in the six disulfide bonds and more alternate conformations. It appears that high intensity and not only the total X-ray dose is most harmful to protein crystals.

Mechanisms and implications of genomic instability and other delayed effects of ionizing radiation exposure.

Recently there has been considerable interest in various delayed effects of radiation. These have the common property of showing a high and, in some instances, non-clonal transmission of 'damage' to distant progeny which derive from apparently normal surviving cells and their descendants. This means that conventional analysis and interpretation of long-term radiation damage in terms of mutations induced in DNA at the time of radiation exposure may be incorrect. Several reviews of this area have appeared in recent years which have described the historical development of this field. The aim of this commentary is to highlight areas of discussion, particularly concerning links between the various end-points, and to discuss some of the possible implications of genomic instability for radiation carcinogenesis in general and for the setting of radiation protection action limits in particular.

Intracranial ependymoma in the adult patient: successful treatment with surgery and radiotherapy.

Ependymoma is an uncommon intracerebral tumor in adults. Since the site of origin frequently prevents complete surgical removal, adjunctive radiotherapy is used to destroy residual disease. We present our experience in treating 10 adults with intracranial ependymoma. Five men and 5 women were treated in the past 16 years. The median age was 38 (range 24-69). All had contrast enhanced CT or MRI showing the extent of the tumor. One patient had total excision while the remainder had subtotal removal. Radiation therapy was delivered to the tumor bed with a 1-2 cm margin of normal tissue generally at 180-200 centiGray (cGy) per treatment once a day. Total dose ranged from 5400 to 7200 cGy. Two patients received experimental treatment with 100 cGy delivered twice a day for total of 6800 and 7200 cGy respectively. Four patients received initial treatment to a large field with a subsequent boost to the tumor bed. One patient received his entire course of treatment via this large field. With a median follow-up of 64 months, 7 patients are alive and free of disease while 2 died of intercurrent disease, without evidence of tumor, at 7 and 9 years following treatment. Another patient died 1 1/2 years after treatment of unknown causes. We conclude that postoperative radiotherapy is effective in preventing regrowth of intracranial ependymoma following subtotal resection in adults. Treatment fields should cover the initial tumor bed with a 1-2 cm margin to avoid long term radiation damage.

N and Ar ion-implantation effects in SiO2 films on Si single-crystal substrates

The chemistry of an argon-ion-irradiated interface between an amorphous silicon dioxide film and a silicon single-crystal substrate was studied by determining the kind and depth distribution of compounds formed after nitrogen implantation at a depth more shallow than the SiO2 film thickness. With this study we intended to obtain some insight into the chemical and physical processes involved in the formation of silicon oxynitrides in silica as a consequence of nitrogen ion implantations. Samples were mainly characterized by x-ray photoelectron and Fourier-transform infrared spectroscopies. Scanning electron microscopy, Rutherford backscattering spectrometry, nuclear reaction analysis, and secondary-ion mass spectrometry techniques were also used to complete the set of results. The experimental evidences are consistent with a picture of an argon-induced radiation damage in terms of Si—O and Si—Si bond breaking in the SiO2 and in the silicon substrate regions, respectively. The subsequently implanted nitrogen atoms are drawn toward the interface by a chemical driving force, and there interact with unsaturated silicon bonds to produce SiOxNy or SiNz compounds. The formation of a large amount of these compounds at the interface is responsible for very rough surface morphological features.

Sequential radiation damage in protein crystallography.

Radiation damage in protein crystals is described in terms of a sequential process of protein disordering. A new radiation-damage model has been tested against data from several protein crystals and can describe radiation damage corresponding to loss of the original intensity in excess of 80%. The model is an extension of previous models which characterize radiation damage in terms of successive conformational transitions of the protein from an undamaged to a spatially disordered to finally an amorphous state. The proposed model provides a more-general positional characterization of the disordered protein and includes, prior to the disordered state, a new dose-dependent state in which the protein conformation resembles the undamaged protein. Comparison of this model with the best previous model shows that the proposed model provides an improved fit to radiation-damage data.

The metamict state: Implications for radiation damage in crystalline waste forms

The long term effect of radiation damage on waste disposal mediums, either crystalline or glass, is a factor in the evaluation of the “integrity” of the waste disposal mediums. Metamict minerals are a special class of amorphous materials which were initially crystalline. Although the mechanism for the loss of crystallinity in these minerals (mostly actinide containing oxides and silicates) is not clearly understood, damage caused by alpha particles and recoil nuclei is certainly critical to the metamictization process. Comparison of metamict and non-metamict polymorphs, such as thorite and huttonite (ThSiO 4), provides a basis for the evaluation of the susceptibility of different structure types to radiation damage. Short term radiation damage experiments of these phases can be validated by comparing the results to long term radiation damage observed in minerals, such as huttonite, thorite and zircon. This paper summarizes the pertinent literature on metamictization and proposes experiments to elucidate structural controls on radiation damage in crystalline phases.