Editor's Choice - Estimated Radiation Dose to the Operator During Endovascular Aneurysm Repair.

OBJECTIVE: To estimate operator organ doses from fluoroscopically guided infrarenal endovascular aneurysm repair (EVAR) procedures, using the detailed exposure information contained in radiation dose structured reports. METHODS: Conversion factors relating kerma area product (PKA) to primary operator organ doses were calculated using Monte Carlo methods for 91 beam angles and seven x-ray spectra typical of clinical practice. A computer program was written, which selects the appropriate conversion factor for each exposure listed in a structured report and multiplies it by the respective PKA. This system was used to estimate operator doses for 81 EVAR procedures for which structured reports were available. The impact of different shielding scenarios and variations in operator position was also investigated. RESULTS: Without any shielding, the median estimated effective dose was 113 µSv (interquartile range [IQR] 71, 252 µSv). The highest median organ doses were for the colon (154 µSv, IQR 81, 343) and stomach (133 µSv, IQR 76, 307). These dose estimates represent all exposures, including fluoroscopy and non-fluoroscopic digital acquisitions. With minimal shielding provided by 0.25 mm of Pb covering the torso and upper legs, the effective dose was reduced by a factor of around 6. With additional shielding from ceiling and table shields, a 25 to 50 fold reduction in dose is achievable. Estimated doses were highest where the primary beam was pointed directly away from the operator. CONCLUSION: The models suggest that with optimal use of shielding, operator doses can be reduced to levels equivalent to one to two days of natural background exposure and well below statutory dose limits.

Identification and quantification of ionising radiation-induced oxysterol formation in membranes of lens fibre cells.

Ionising radiation (IR) is a cause of lipid peroxidation, and epidemiological data have revealed a correlation between exposure to IR and the development of eye lens cataracts. Cataracts remain the leading cause of blindness around the world. The plasma membranes of lens fibre cells are one of the most cholesterolrich membranes in the human body, forming lipid rafts and contributing to the biophysical properties of lens fibre plasma membrane. Liquid chromatography followed by mass spectrometry was used to analyse bovine eye lens lipid membrane fractions after exposure to 5 and 50 Gy and eye lenses taken from wholebody 2 Gy-irradiated mice. Although cholesterol levels do not change significantly, IR dose-dependant formation of the oxysterols 7ß-hydroxycholesterol, 7-ketocholesterol and 5, 6-epoxycholesterol in bovine lens nucleus membrane extracts was observed. Whole-body X-ray exposure (2 Gy) of 12-week old mice resulted in an increase in 7ß-hydroxycholesterol and 7-ketocholesterol in their eye lenses. Their increase regressed over 24 h in the living lens cortex after IR exposure. This study also demonstrated that the IR-induced fold increase in oxysterols was greater in the mouse lens cortex than the nucleus. Further work is required to elucidate the mechanistic link(s) between oxysterols and IR-induced cataract, but these data evidence for the first time that IR exposure of mice results in oxysterol formation in their eye lenses.

The future of biological dosimetry in mass casualty radiation emergency response, personalized radiation risk estimation and space radiation protection.

PURPOSE: The aim of this brief personal, high level review is to consider the state of the art for biological dosimetry for radiation routine and emergency response, and the potential future progress in this fascinating and active field. Four areas in which biomarkers may contribute to scientific advancement through improved dose and exposure characterization, as well as potential contributions to personalized risk estimation, are considered: emergency dosimetry, molecular epidemiology, personalized medical dosimetry, and space travel. CONCLUSION: Ionizing radiation biodosimetry is an exciting field which will continue to benefit from active networking and collaboration with the wider fields of radiation research and radiation emergency response to ensure effective, joined up approaches to triage; radiation epidemiology to assess long term, low dose, radiation risk; radiation protection of workers, optimization and justification of radiation for diagnosis or treatment of patients in clinical uses, and protection of individuals traveling to space.

Sensitivity and latency of ionising radiation-induced cataract.

When managed with appropriate radiation protection procedures, ionising radiation is of great benefit to society. Opacification of the lens, and vision impairing cataract, have recently been recognised at potential effects of relatively low dose radiation exposure, on the order of 1 Gy or below. Within the last 10 years, understanding of the effects of low dose ionising radiation on the lens has increased, particularly in terms of DNA damage and responses, and how multiple radiation or other events in the lens might contribute to the overall risk of cataract. However, gaps remain, not least in the understanding of how radiation interacts with other risk factors such as aging, as well as the relative radiosensitivity of the lens compared to tissues of the body. This paper reviews the current literature in the field of low dose radiation cataract, with a particular focus on sensitivity and latency.

An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: a pilot study.

BACKGROUND: This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. METHODS: Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction. RESULTS: Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response. CONCLUSION: Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.

Chromosome Aberrations in a Group of People Exposed to Radioactive Releases from the Three Mile Island Nuclear Accident and Inferences for Radiation Effects.

Recently, it has been proposed that the doses received from 133Xe released during the accident in 1979 at the Three Mile Island (TMI) plant in Pennsylvania were much higher than has been conventionally assessed, due to a gross underestimation of the relative biological effectiveness of electrons from beta-particle-emitting radionuclides within the body. The central evidence cited in support of this proposal was the doses derived from cytogenetic analyses of blood sampled in the mid-1990s from people living near TMI at the time of the accident. However, the chromosome aberration data show a marked discrepancy in biodosimetric estimates evaluated from the frequencies of stable translocations and unstable dicentrics (corrected for temporal attenuation), strongly suggesting that exposures to clastogenic agents occurred long after the TMI accident. Few details have been reported on the people providing the blood samples and how they were selected for study. Crucially, this lack of information includes the distributions in the exposed and control groups of age at sampling, which is a critical factor in interpreting translocation data. Contrary to the recent claim, these cytogenetic data offer no support to the suggestion of a serious underestimation of internal doses from beta particles or from 133Xe discharged during the TMI accident.

Radiation-induced lens opacities: Epidemiological, clinical and experimental evidence, methodological issues, research gaps and strategy.

In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts. However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy. Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts. The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities. The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects.

Accidental neutron exposure in a medical setting: a case study.

In May 2016, a new linear accelerator (Linac) was installed at a hospital oncology department. A team of individuals supervised the installation, including a Radiation Oncologist who acted as an independent observer to the installation, calibration, beam data collection and shielding measurements. In order to ensure the shielding was correct, a licensed representative of the Turkish Atomic Energy Authority carried out formal measurements of the gamma and neutron dose rates at a variety of locations in and around the Linac facility. At 18 MV, the maximum neutron dose rate was 172µSv h-1and the maximum gamma dose rate was approximately 2µSv h-1(ambient dose equivalent in both cases), significantly higher than the expected and local background doses. As the neutron dose rates in particular were so high, it was concluded that the shielding was not sufficient, potentially due to an inadequate design. In order to rule out overexposure during the installation, biological dosimetry was carried out for a number of the individuals involved. The estimated doses were closely aligned with the doses measured using commercially available neutron dosemeters and were also within the tolerance dose ranges estimated using Monte Carlo simulations, which also supported the investigation. The results underline the need for careful planning before and after installation of new radiation exposure facilities, especially high MV Linac operation for which photo-neutrons might need to be mitigated. The results clearly indicate the importance of such checks, in addition to demonstrating the relevance of biological dosimetry supported by modelling strategies complex or unclear exposure scenarios.

Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation.

PURPOSE: Since the exact development of posterior subcapsular cataracts (PSCs) is poorly understood, we review various risk factors and propose a two-stage etiology for PSCs. METHODS: The biological mechanisms associated with age-related cataracts (primarily nuclear cataracts, cortical cataracts and PSCs) were reviewed in relation to selected risk factors that induce PSCs (including atopy, diabetes, hypoparathyroidism, myopia, retinitis, solar radiation, steroid use, uveitis, vitrectomy and ionizing radiation). We particularly focused on ionizing radiation, as this is known to be a risk factor specific to PSCs. Based on an analysis of the reviewed material, we propose a detailed explanation of the etiology of PSCs. CONCLUSIONS: Lens epithelial cells (LECs) and lens fiber cells are normally hypoxic and therefore very sensitive to changes in oxidative stress, as quantified by the radiation oxygen effect. We hypothesize that the development of PSC opacities is a two-stage process. Stage I, early in life, is driven by risk factors that promote oxidative stress and ion-pump disruption, harming lens fibers and causing aberrant LECs to proliferate and ectopically migrate as Wedl cells (perhaps by processes associated with an epithelial to mesenchymal transition) to the posterior pole region. After a latent period, in Stage II, the development of PSCs advances mainly due to chronic inflammation and other premature aging-related mechanisms that promote mature vacuolar or plaque PSC. This two-stage hypothesis of PSC etiology accounts for risk factors, such as aging, diabetes and ionizing radiation, which directly affects LECs and the lens. In addition, these risk factors can damage other ocular regions, such as the retina and vitreous, that also indirectly contribute to the development of PSCs. It is possible that the incidence of PSCs may be reduced by reversing the effects of Stage I through various means, including ocular antioxidants.

Patient radiation dose from x-ray guided endovascular aneurysm repair: a Monte Carlo approach using voxel phantoms and detailed exposure information.

Endovascular aneurysm repair (EVAR) is a well-established minimally invasive technique that relies on x-ray guidance to introduce a stent through the femoral artery and manipulate it into place. The aim of this study was to estimate patient organ and effective doses from EVAR procedures using anatomically realistic computational phantoms and detailed exposure information from radiation dose structured reports (RDSR). Methods: Lookup tables of conversion factors relating kerma area product (PKA) to organ doses for 49 different beam angles were produced using Monte Carlo simulations (MCNPX2.7) with International Commission on Radiological Protection (ICRP) adult male and female voxel phantoms for EVAR procedures of varying complexity (infra-renal, fenestrated/branched and thoracic EVAR). Beam angle specific correction factors were calculated to adjust doses according to x-ray energy. A MATLAB function was written to find the appropriate conversion factor in the lookup table for each exposure described in the RDSR, perform energy corrections and multiply by the respective exposure PKA. Using this approach, organ doses were estimated for 183 EVAR procedures in which RDSRs were available. A number of simplified dose estimation methodologies were also investigated for situations in which RDSR data are not available. Results: Mean estimated bone marrow doses were 57 (range: 2-247), 86 (2-328) and 54 (8-250) mGy for infra-renal, fenestrated/branched and thoracic EVAR, respectively. Respective effective doses were 27 (1-208), 54 (1-180) and 37 (5-167) mSv. Dose estimates using non-individualised, average conversion factors, along with those produced using the alternative Monte Carlo code PCXMC, yielded reasonably similar results overall, though variation for individual procedures could exceed 100% for some organs. In conclusion, radiation doses from x-ray guided endovascular aneurysm repairs are potentially high, though this must be placed in the context of the life sparing nature and high success rate for this procedure.

A statistical framework for radiation dose estimation with uncertainty quantification from the γ-H2AX assay.

Over the last decade, the γ-H2AX focus assay, which exploits the phosphorylation of the H2AX histone following DNA double-strand-breaks, has made considerable progress towards acceptance as a reliable biomarker for exposure to ionizing radiation. While the existing literature has convincingly demonstrated a dose-response effect, and also presented approaches to dose estimation based on appropriately defined calibration curves, a more widespread practical use is still hampered by a certain lack of discussion and agreement on the specific dose-response modelling and uncertainty quantification strategies, as well as by the unavailability of implementations. This manuscript intends to fill these gaps, by stating explicitly the statistical models and techniques required for calibration curve estimation and subsequent dose estimation. Accompanying this article, a web applet has been produced which implements the discussed methods.

The impact of iodinated contrast media on intravascular and extravascular absorbed doses in X-ray imaging: A microdosimetric analysis.

Studies suggest iodinated contrast media (ICM) may increase organ dose and blood cell DNA damage for a given X-ray exposure. The impact of ICM on dose/damage to extravascular cells and cancer risks is unclear. METHODS: We used Monte Carlo modelling to investigate the microscopic distribution of absorbed dose outside the lumen of arteries, capillaries and interstitial fluids containing blood and various concentrations of iodine. Models were irradiated with four X-ray spectra representing clinical procedures. RESULTS: For the artery model, The average dose enhancement factors (DEF) to blood were 1.70, 2.38, 7.38, and 12.34 for mass concentrations of iodine in blood (ρiI) of 5, 10, 50 and 100 mg/ml, respectively, compared to 0 mg/ml. Average DEFs were reduced to 1.26, 1.51, 3.48 and 5.56, respectively, in the first micrometre of the vessel wall, falling to 1.01, 1.02, 1.06 and 1.09 at 40-50 µm from the lumen edge. For the capillary models, DEF for extravascular tissues was on average 48% lower than DEF for the whole model, including capillaries. A similar situation was observed for the interstitial model, with DEF to the cell nucleus being 35% lower than DEF for the whole model. CONCLUSIONS: While ICM may modify the absorbed doses from diagnostic X-ray examinations, the effect is smaller than suggested by assays of circulating blood cells or blood dose enhancement. Conversely, the potentially large increase in dose to the endothelium of blood vessels means that macroscopic organ doses may underestimate the risk of radiation induced cardiovascular disease for ICM-enhanced exposures.

UNCERTAINTY ON RADIATION DOSES ESTIMATED BY BIOLOGICAL AND RETROSPECTIVE PHYSICAL METHODS.

Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the 'EURADOS Working Group 10-Retrospective dosimetry' members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios.

Enhanced radiation dose and DNA damage associated with iodinated contrast media in diagnostic X-ray imaging.

A review was undertaken of studies reporting increased DNA damage in circulating blood cells and increased organ doses, for X-ray exposures enhanced by iodinated contrast media (ICM), compared to unenhanced imaging. This effect may be due to ICM molecules acting as a source of secondary radiation (Auger/photoelectrons, fluorescence X-rays) following absorption of primary X-ray photons. It is unclear if the reported increase in DNA damage to blood cells necessarily implies an increased risk of developing cancer. Upon ICM-enhancement, the attenuation properties of blood differ substantially from surrounding tissues. Increased energy deposition is likely to occur within very close proximity to ICM molecules (within a few tens of micrometres). Consequently, in many situations, damage and dose enhancement may be restricted to the blood and vessel wall only. Increased cancer risks may be possible, in cases where ICM molecules are given sufficient time to reach the capillary network and interstitial fluid at the time of exposure. In all situations, the extrapolation of blood cell damage to other tissues requires caution where contrast media are involved. Future research is needed to determine the impact of ICM on dose to cells outside the blood itself and vessel walls, and to determine the concentration of ICM in blood vessels and interstitial fluid at the time of exposure.

Chromosome analysis in a case of a plutonium contaminated wound.

Chromosome analysis of peripheral blood lymphocytes was undertaken over a 10 year period following an intake of plutonium through a hand wound. Frequencies of cells with unstable complex aberrations remained high throughout this time, probably reflecting direct exposure of lymphocytes as they passed plutonium which had transferred to regional lymph nodes. Analysis at the final sampling time also revealed cells with stable aberrations at a much higher frequency relative to the number of unstable cells than expected from direct exposure, and is therefore most likely to be reflecting exposure to lymphocyte precursor cells from plutonium that has become deposited on bone surfaces.

Guidance on radiation dose limits for the lens of the eye: overview of the recommendations in NCRP Commentary No. 26.

PURPOSE: This review summarizes the conclusions and recommendations of the new National Council on Radiation Protection and Measurements (NCRP) Commentary No. 26 guidance on radiation dose limits for the lens of the eye. The NCRP addressed radiation protection principles in respect to the lens of the eye, discussed the current understanding of eye biology and lens effects, reviewed and evaluated epidemiology, and assessed exposed populations with the potential for significant radiation exposures to the lens while suggesting monitoring and protection practices. CONCLUSIONS: Radiation-induced damage to the lens of the eye can include the loss of clarity resulting in opacification or clouding several years after exposure. The impact is highly dependent on the type of radiation, how the exposure of the lens was delivered, the genetic susceptibilities of the individual exposed, and the location of the opacity relative to the visual axis of the individual. The preponderance of epidemiological evidence suggests that lens damage could occur at lower doses than previously considered and the NCRP has determined that it is prudent to reduce the recommended annual lens of the eye occupational dose limit from an equivalent dose of 150 mSv to an absorbed dose of 50 mGy. Significant additional research is still needed in the following areas: comprehensive evaluation of the overall effects of ionizing radiation on the eye, dosimetry methodology and dose-sparing optimization techniques, additional high quality epidemiology studies, and a basic understanding of the mechanisms of cataract development.

Uncertainty of fast biological radiation dose assessment for emergency response scenarios.

PURPOSE: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. MATERIALS AND METHODS: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. RESULTS: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. CONCLUSIONS: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.

Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.

Radiation protection of the eye lens in medical workers--basis and impact of the ICRP recommendations.

The aim of this article was to explore the evidence for the revised European Union basic safety standard (BSS) radiation dose limits to the lens of the eye, in the context of medical occupational radiation exposures. Publications in the open literature have been reviewed in order to draw conclusions on the exposure profiles and doses received by medical radiation workers and to bring together the limited evidence for cataract development in medical occupationally exposed populations. The current status of relevant radiation-protection and monitoring practices and procedures is also considered. In conclusion, medical radiation workers do receive high doses in some circumstances, and thus working practices will be impacted by the new BSS. However, there is strong evidence to suggest that compliance with the new lower dose limits will be possible, although education and training of staff alongside effective use of personal protective equipment will be paramount. A number of suggested actions are given with the aim of assisting medical and associated radiation-protection professionals in understanding the requirements.

Status of NCRP Scientific Committee 1-23 Commentary on Guidance on Radiation Dose Limits for the Lens of the Eye.

Previous National Council on Radiation Protection and Measurements (NCRP) publications have addressed the issues of risk and dose limitation in radiation protection and included guidance on specific organs and the lens of the eye. NCRP decided to prepare an updated commentary intended to enhance the previous recommendations provided in earlier reports. The NCRP Scientific Committee 1-23 (SC 1-23) is charged with preparing a commentary that will evaluate recent studies on the radiation dose response for the development of cataracts and also consider the type and severity of the cataracts as well as the dose rate; provide guidance on whether existing dose limits to the lens of the eye should be changed in the United States; and suggest research needs regarding radiation effects on and dose limits to the lens of the eye. A status of the ongoing work of SC 1-23 was presented at the Annual Meeting, "Changing Regulations and Radiation Guidance: What Does the Future Hold?" The following represents a synopsis of a few main points in the current draft commentary. It is likely that several changes will be forthcoming as SC 1-23 responds to subject matter expert review and develops a final document, expected by mid 2016.