Effects of X-Rays, Electron Beam, and Gamma Irradiation on Chemical and Physical Properties of EVA Multilayer Films.

Gamma-ray irradiation, using the cobalt-60 isotope, is the most common radiation modality used for medical device and biopharmaceutical products sterilization. Although X-ray and electron-beam (e-beam) sterilization technologies are mature and have been in use for decades, impediments remain to switching to these sterilization modalities because of lack of data on the resulting radiation effects for the associated polymers, as well as a lack of education for manufacturers and regulators on the viability of these sterilization alternatives. For this study, the compatibility of ethylene vinyl acetate (EVA) multilayer films with different ionizing radiation sterilization (X-ray, e-beam, and gamma irradiation) is determined by measuring chemical and physical film properties using high performance liquid chromatography, differential scanning calorimetry, Fourier-Transform InfraRed spectroscopy (FTIR), surface energy measurement, and electron spin resonance techniques. The results indicate that the three irradiation modalities induce no differences in thermal properties in the investigated dose range. Gamma and X-Ray irradiations generate the same level of reactive species in the EVA multilayer film, whereas e-beam generates a reduced quantity of reactive species.

Integrated atomic force microscopy and x-ray irradiation for in situ characterization of radiation-induced processes.

Understanding radiation-induced chemical and physical transformations at material interfaces is important across diverse fields, but experimental approaches are often limited to either ex situ observations or in situ electron microscopy or synchrotron-based methods, in which cases the radiation type and dose are inextricably tied to the imaging basis itself. In this work, we overcome this limitation by demonstrating integration of an x-ray source with an atomic force microscope to directly monitor radiolytically driven interfacial chemistry at the nanoscale. We illustrate the value of in situ observations by examining effects of radiolysis on material adhesion forces in aqueous solution as well as examining the production of alkali nitrates at the interface between an alkali halide crystal surface and air. For the examined salt-air interface, direct visualization under flexible experimental conditions greatly extends prior observations by enabling the transformation process to be followed comprehensively from source-to-sink with mass balance quantitation. Our novel rad-atomic force microscope opens doors into understanding the dynamics of radiolytically driven mass transfer and surface alteration at the nanoscale in real-time.

Direct visualization of radiation-induced transformations at alkali halide-air interfaces.

Radiation driven reactions at mineral/air interfaces are important to the chemistry of the atmosphere, but experimental constraints (e.g. simultaneous irradiation, in situ observation, and environmental control) leave process understanding incomplete. Using a custom atomic force microscope equipped with an integrated X-ray source, transformation of potassium bromide surfaces to potassium nitrate by air radiolysis species was followed directly in situ at the nanoscale. Radiolysis initiates dynamic step edge dissolution, surface composition evolution, and ultimately nucleation and heteroepitaxial growth of potassium nitrate crystallites mediated by surface diffusion at rates controlled by adsorbed water. In contrast to in situ electron microscopy and synchrotron-based imaging techniques where high radiation doses are intrinsic, our approach illustrates the value of decoupling irradiation and the basis of observation.

Deciding between an X-Ray and 137Cs Irradiator - It's not just about Energy Spectra.

Irradiators utilizing radioactive cesium-137 (137Cs) or cobalt-60 (60Co) gamma-ray sources have been used for biological applications for many decades. These applications include irradiation of much of the nation's blood supply and radiation biology research. In 2005, the U.S. Nuclear Regulatory Commission was assigned the task of preventing the misuse of radioactive materials by persons with malicious intentions; gamma-ray sources, in particular, were given high priority. This resulted in increased security requirements, including constant surveillance, controlled access and personnel background checks. As a result of such regulations being introduced, organizations considering the purchase of a gamma-ray irradiator for the first time or as a replacement to an existing one due to radioactive decay, are now looking into alternative technologies, primarily an X-ray irradiator. To make an educated decision on whether a particular type of X-ray irradiator is of sufficient equivalency to a particular type of 137Cs irradiator for specific applications, one must rely on relevant published comparison studies from other researchers, or perform the comparison studies on their own. This work focuses on the comparison of the radiation physics aspects of two 137Cs irradiator models and three X-ray irradiator models, for the purpose of determining whether the X-ray irradiator models could validly replace the 137Cs irradiator models for certain applications. Although evaluating the influence of relative biological effectiveness (RBE) differences among irradiators could be part of this study, that has been left for a related publication focused on the theoretical aspects of this topic. These evaluations were performed utilizing 47-g and 120-g tissue-equivalent rodent dosimetry phantoms. Our results indicate that, depending upon the user's dose uncertainty budget and maximum areal density of specimens to be irradiated, the RS 2000 160 kVp X-ray irradiator, X-RAD160 X-ray irradiator or X-RAD320 X-ray irradiator could successfully replace a 137Cs irradiator. Technically, any X-ray irradiator model providing similar irradiation geometry, and average energy similar to or higher than these three X-ray models, could also successfully replace a 137Cs irradiator. The results also reveal that differences in inherent source geometry, field geometry and irradiation geometry can counter some of the influence due to differences in energy spectrum. Our goal is that this publication be used as a guide for other similar studies, providing investigators with information on important details that can make the difference between strong and weak comparison conclusions.

Beyond Californium-A Neutron Generator Alternative for Dosimetry and Instrument Calibration in the U.S.

Evaluations of neutron survey instruments, area monitors, and personal dosimeters rely on reference neutron radiations, which have evolved from the heavy reliance on (α,n) sources to a shared reliance on (α,n) and the spontaneous fission neutrons of californium-252 (Cf). Capable of producing high dose equivalent rates from an almost point source geometry, the characteristics of Cf are generally more favorable when compared to the use of (α,n) and (γ,n) sources or reactor-produced reference neutron radiations. Californium-252 is typically used in two standardized configurations: unmoderated, to yield a fission energy spectrum; or with the capsule placed within a heavy-water moderating sphere to produce a softened spectrum that is generally considered more appropriate for evaluating devices used in nuclear power plant work environments. The U.S. Department of Energy Cf Loan/Lease Program, a longtime origin of affordable Cf sources for research, testing and calibration, was terminated in 2009. Since then, high-activity sources have become increasingly cost-prohibitive for laboratories that formerly benefited from that program. Neutron generators, based on the D-T and D-D fusion reactions, have become economically competitive with Cf and are recognized internationally as important calibration and test standards. Researchers from the National Institute of Standards and Technology and the Pacific Northwest National Laboratory are jointly considering the practicality and technical challenges of implementing neutron generators as calibration standards in the U.S. This article reviews the characteristics of isotope-based neutron sources, possible isotope alternatives to Cf, and the rationale behind the increasing favor of electronically generated neutron options. The evaluation of a D-T system at PNNL has revealed characteristics that must be considered in adapting generators to the task of calibration and testing where accurate determination of a dosimetric quantity is necessary. Finally, concepts are presented for modifying the generated neutron spectra to achieve particular targeted spectra, simulating Cf or workplace environments.

Detecting radiation-induced injury using rapid 3D variogram analysis of CT images of rat lungs.

RATIONALE AND OBJECTIVES: To investigate the ability of variogram analysis of octree-decomposed computed tomography (CT) images and volume change maps to detect radiation-induced damage in rat lungs. MATERIALS AND METHODS: The lungs of female Sprague-Dawley rats were exposed to one of five absorbed doses (0, 6, 9, 12, or 15 Gy) of gamma radiation from a Co-60 source. At 6 months postexposure, pulmonary function tests were performed and four-dimensional (4D) CT images were acquired using a respiratory-gated microCT scanner. Volume change maps were then calculated from the 4DCT images. Octree decomposition was performed on CT images and volume change maps, and variogram analysis was applied to the decomposed images. Correlations of measured parameters with dose were evaluated. RESULTS: The effects of irradiation were not detectable from measured parameters, indicating only mild lung damage. Additionally, there were no significant correlations of pulmonary function results or CT densitometry with radiation dose. However, the variogram analysis did detect a significant correlation with dose in both the CT images (r = -0.57, P = .003) and the volume change maps (r = -0.53, P = .008). CONCLUSION: This is the first study to use variogram analysis of lung images to assess pulmonary damage in a model of radiation injury. Results show that this approach is more sensitive to detecting radiation damage than conventional measures such as pulmonary function tests or CT densitometry.

The Importance of Dosimetry Standardization in Radiobiology.

Radiation dose is central to much of radiobiological research. Precision and accuracy of dose measurements and reporting of the measurement details should be sufficient to allow the work to be interpreted and repeated and to allow valid comparisons to be made, both in the same laboratory and by other laboratories. Despite this, a careful reading of published manuscripts suggests that measurement and reporting of radiation dosimetry and setup for radiobiology research is frequently inadequate, thus undermining the reliability and reproducibility of the findings. To address these problems and propose a course of action, the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Standards and Technology (NIST) brought together representatives of the radiobiology and radiation physics communities in a workshop in September, 2011. The workshop participants arrived at a number of specific recommendations as enumerated in this paper and they expressed the desirability of creating dosimetry standard operating procedures (SOPs) for cell culture and for small and large animal experiments. It was also felt that these SOPs would be most useful if they are made widely available through mechanism(s) such as the web, where they can provide guidance to both radiobiologists and radiation physicists, be cited in publications, and be updated as the field and needs evolve. Other broad areas covered were the need for continuing education through tutorials at national conferences, and for journals to establish standards for reporting dosimetry. This workshop did not address issues of dosimetry for studies involving radiation focused at the sub-cellular level, internally-administered radionuclides, biodosimetry based on biological markers of radiation exposure, or dose reconstruction for epidemiological studies.

A Dose-Dependent Hematological Evaluation of Whole-Body Gamma-Irradiation in the Göttingen Minipig.

There is a great deal of interest in the establishment of a standardized animal model for the acute radiation syndrome to allow development of diagnostic approaches and countermeasure treatments following radiological terrorist events. Due to physiological, anatomical, and biochemical similarities to humans, the minipig is an attractive large animal model for evaluating countermeasure efficacy. This study was conducted in order to aid in the establishment of the minipig, and the Göttingen minipig in particular, as an animal model for the hematopoietic acute radiation syndrome. Animals were exposed whole-body to Co at doses of 0 (sham control), 0.25, 0.5, 0.75, 1.0, and 2.0 Gy, and hematological parameters followed in time from pre-irradiation to post-irradiation Day 7. Following irradiation, a dose-dependent decrease in total white blood cells was observed, which was determined to be statistically different as compared to control animals at all dose levels above 0.25 Gy at 24 h post-irradiation. Similarly, a dose-dependent reduction in both absolute lymphocyte count and absolute neutrophil count occurred by the earliest time point measured for all exposed animals. A significant decrease in platelets was observed at post-irradiation Day 7 in animals exposed only at the highest (2.0 Gy) level. The platelet-to-lymphocyte ratio generated for exposures ranging from 0.25-2.0 Gy was able to differentiate response between high and low exposure levels even at 7 d post exposure. In conclusion, the present study supports the development of the Göttingen minipig as a suitable large animal model to study radiation-induced hematopoietic syndrome.

In vivo delivery of FTY720 prevents radiation-induced ovarian failure and infertility in adult female nonhuman primates.

OBJECTIVE: To determine whether sphingosine-1-phosphate (S1P), or the S1P mimetic FTY720 shields ovaries of adult female rhesus monkeys from damage caused by 15 Gy of targeted radiotherapy, allowing for the retention of long-term fertility, and to evaluate whether S1P protects human ovarian tissue (xenografted into mice) from radiation-induced damage. DESIGN: Research animal study. SETTING: Research laboratory and teaching hospital. PATIENT(S): Adult female rhesus macaques (8-14 years of age; n = 21) and two women (24 and 27 years of age) undergoing gynecologic surgery for benign reasons, after informed consent and approval. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian histologic analysis, ovarian reserve measurements, and fertility in mating trials. RESULT(S): Rapid ovarian failure was induced in female macaques by ovarian application of 15 Gy of radiation. Females given S1P or FTY720 by direct intraovarian cannulation for 1 week before ovarian irradiation rapidly resumed menstrual cycles because of maintenance of follicles, with greater beneficial effects achieved using FTY720. Monkeys given the S1P mimetic before ovarian irradiation also became pregnant in mating trials. Offspring conceived and delivered by radioprotected females developed normally and showed no evidence of genomic instability, as measured by micronucleus frequency in reticulocytes. Adult human ovarian cortical tissue xenografted into mice also exhibited a reduction in radiation-induced primordial oocyte depletion when preexposed to S1P. CONCLUSION(S): S1P and its analogs hold clinical promise as therapeutic agents to preserve ovarian function and fertility in female cancer patients exposed to cytotoxic treatments.

Application of high-resolution 1H MAS NMR spectroscopy to the analysis of intact bones from mice exposed to gamma radiation.

Herein we demonstrate that high-resolution magic angle spinning (MAS) 1H NMR can be used to profile the pathology of bone marrow rapidly and with minimal sample preparation. The spectral resolution obtained allows several metabolites to be analyzed quantitatively. The level of NMR-detectable metabolites in the epiphysis + metaphysis sections of mouse femur were significantly higher than that observed in the diaphysis of the same femur. The major metabolite damage to bone marrow resulting from either 3.0 Gy or 7.8 Gy of whole-body gamma radiation 4 days after exposure were (1) decreased total choline content, (2) increased fatty acids in bone marrow, and (3) decreased creatine content. These results suggest that the membrane choline phospholipid metabolism (MCPM) pathway and the fatty acid biosynthesis pathway were altered as a result of radiation exposure. We also found that the metabolic damage induced by radiation in the epiphysis + metaphysis sections of mouse femur was higher than that of the diaphysis of the same femur. Traditional histopathology analysis was also carried out to correlate radiation damage with changes in metabolites. Importantly, the molecular information gleaned from high-resolution MAS 1H NMR complements the pathology data.

Technical performance of the Luxel Al(2)O(3):C optically stimulated luminescence dosemeter element at radiation oncology and nuclear accident dose levels.

The dose ranges typical for radiation oncology and nuclear accident dosimetry are on the order of 2-70 Gy and 0.1-5 Gy, respectively. In terms of solid-state passive dosimetry, thermoluminescent (TL) materials historically have been used extensively for these two applications, with silver-halide, leuco-dye and BaFBr:Eu-based films being used on a more limited basis than TL for radiation oncology. This present work provides results on the performance of a film based on an aluminum oxide, Al(2)O(3):C, for these dosimetry applications, using the optically stimulated luminescence (OSL) readout method. There have been few investigations of Al(2)O(3):C performance at radiation oncology and nuclear accident dose levels, and these have included minimal dosimetric and environmental effects information. Based on investigations already published, the authors of this present study determined that overall improvements over film and TLDs for this Al(2)O(3):C OSL technology at radiation oncology and nuclear accident dose levels may include (1) a more tissue-equivalent response to photons compared to X-ray film, (2) higher sensitivity, (3) ability to reread dosemeters and (4) diagnostic capability using small-area imaging. The results of the present investigation indicate that additional favourable performance characteristics for the Al(2)O(3):C dosemeter are a wide dynamic range (0.001-100 Gy), a response insensitive to temperature and moisture over a wide range, negligible dose rate dependence, and minimal change in post-irradiation response. As a radiation detection medium, this OSL phosphor offers an assortment of dosimetry properties that will permit it to compete with current radiation detection technologies such as silver-halide, leuco-dye and photostimulable-phosphor-based films, as well as TLDs.

A variable-energy electron microbeam: a unique modality for targeted low-LET radiation.

We have designed and constructed a low-cost, variable-energy low-LET electron microbeam that uses energetic electrons to mimic radiation damage produced by gamma and X rays. The microbeam can access lower regions of the LET spectrum, similar to conventional X-ray or 60Co gamma-ray sources. The device has two operating modes, as a conventional microbeam targeting single cells or subpopulations of cells or as a pseudo broad-beam source allowing for direct comparison with conventional sources. By varying the incident electron energy, the target cells can be selectively exposed to different parts of the energetic electron tracks, including the track ends.

Evaluation of the new cesium-131 seed for use in low-energy x-ray brachytherapy.

Characterization measurements and calculations were performed on a new medical seed developed by IsoRay Inc. in Richland, Washington, that utilizes the short-lived isotope 131Cs. This model has recently received FDA 510(k) clearance. The objective of this work was to characterize the dosimetric properties of the new seed according to the AAPM Task Group 43 recommendations. Cesium-131 is a low-energy x-ray emitter, with the most prominent peaks in the 29 keV to 34 keV region. The intended application is brachytherapy for treating cancers in prostate, breast, head and neck, lung, and pancreas. The evaluations performed included air-kerma strength, radial dose function, anisotropy in phantom, half-life, energy spectra, and internal activity. The results indicate the CS-1 seeds have a dose-rate constant of 0.915 cGy hr(-1) U(-1) in water, dose penetration characteristics similar to 125I and 103Pd, anisotropy function values on the order of 0.71 at short distances and small angles, and an average anisotropy factor of 0.964. The overall dosimetric characteristics are similar to 125I and 103Pd seeds with the exception of half-life, which is 9.7 days, as compared to 17 days for 103Pd and 60 days for 125I. The shorter half-life may offer significant advantages in biological effectiveness.