Rogue cell-like chromosomal aberrations in peripheral blood lymphocytes of interventional radiologists: A case study.

We report two cases of interventional radiologists who had been exposed to radiation while performing fluoroscopically-guided interventional procedures (FGIPs), mainly transcatheter arterial chemoembolization, percutaneous catheter drainage, and percutaneous transhepatic biliary drainage procedures, for over 10 years. They had a unique multi-aberrant cell type with not only high numbers of dicentrics and/or centric rings but also excess acentric double minutes, similar to a rogue cell. As revealed in a self-administered questionnaire, they wore personal dosimeters and protective equipment at all times and used shielding devices during interventional fluoroscopy procedures. However, the exposed dose levels derived from cytogenetic dosimetry were much higher than the doses recorded on their personal dosimeters. A large number of unstable and stable chromosomal aberrations that were found in the peripheral blood lymphocytes of these interventional radiologists might be due to repeated and long-term exposure to ionizing radiation while performing FGIPs. Further investigations of chromosomal aberrations in interventional radiologists may improve the understanding of the long-term effects of radiation exposure on medical personnel.

Radiotherapy dosimetry audits carried out in Ireland at the request of the National Radiation Safety Committee in 2014 & 2017.

PURPOSE: Two requests were issued by Ireland's National Radiation Safety Committee (NRSC) to radiotherapy centres in Ireland to participate in external dosimetry audits in order to demonstrate compliance with the requirement for clinical audit in medical radiological procedures. METHODS: Centres were requested to carry out the phantom irradiation offered by the MD Anderson Dosimetry Laboratory (MDADL) for prostate IMRT in 2014 and were subsequently requested to irradiate the same organisation's head and neck phantom in 2017. RESULTS: A total of 22 audits were performed across 11 radiotherapy centres, capturing the full range of planning and c-arm linear accelerator combinations in use in Ireland at the time of the audits. The mean MDADL vs. institution measured dose for Planning Target Volume (PTV) points was 0.999 ±â€¯0.026 (1SD). The mean PTV gamma pass rate (and lower 95% confidence interval) at 7%/4 mm was 97% (90%). A significant difference was observed between prostate and head and neck irradiations but for no other subdivisions of data e.g. fixed gantry angle IMRT and VMAT. CONCLUSION: Radiotherapy centres in Ireland participated in a co-ordinated set of external audits with all centres satisfying the phantom irradiation component of the MDADL credentialing process.

Fabric Phase Sorptive Extraction-A Metabolomic Preprocessing Approach for Ionizing Radiation Exposure Assessment.

The modern application of mass spectrometry-based metabolomics to the field of radiation assessment and biodosimetry has allowed for the development of prompt biomarker screenings for radiation exposure. Our previous work on radiation assessment, in easily accessible biofluids (such as urine, blood, saliva), has revealed unique metabolic perturbations in response to radiation quality, dose, and dose rate. Nevertheless, the employment of swift injury assessment in the case of a radiological disaster still remains a challenge as current sample processing can be time consuming and cause sample degradation. To address these concerns, we report a metabolomics workflow using a mass spectrometry-compatible fabric phase sorptive extraction (FPSE) technique. FPSE employs a matrix coated with sol-gel poly(caprolactone-b-dimethylsiloxane-b-caprolactone) that binds both polar and nonpolar metabolites in whole blood, eliminating serum processing steps. We confirm that the FPSE preparation technique combined with liquid chromatography-mass spectrometry can distinguish radiation exposure markers such as taurine, carnitine, arachidonic acid, α-linolenic acid, and oleic acid found 24 h after 8 Gy irradiation. We also note the effect of different membrane fibers on both metabolite extraction efficiency and the temporal stabilization of metabolites in whole blood at room temperature. These findings suggest that the FPSE approach could work in future technology to triage irradiated individuals accurately, via biomarker screening, by providing a novel method to stabilize biofluids between collection and sample analysis.

Impact of inflammatory signaling on radiation biodosimetry: mouse model of inflammatory bowel disease.

BACKGROUND: Ionizing Radiation (IR) is a known pro-inflammatory agent and in the process of development of biomarkers for radiation biodosimetry, a chronic inflammatory disease condition could act as a confounding factor. Hence, it is important to develop radiation signatures that can distinguish between IR-induced inflammatory responses and pre-existing disease. In this study, we compared the gene expression response of a genetically modified mouse model of inflammatory bowel disease (Il10-/-) with that of a normal wild-type mouse to potentially develop transcriptomics-based biodosimetry markers that can predict radiation exposure in individuals regardless of pre-existing inflammatory condition. RESULTS: Wild-type (WT) and Il10-/- mice were exposed to whole body irradiation of 7 Gy X-rays. Gene expression responses were studied using high throughput whole genome microarrays in peripheral blood 24 h post-irradiation. Analysis resulted in identification of 1962 and 1844 genes differentially expressed (p < 0.001, FDR < 10%) after radiation exposure in Il10-/- and WT mice respectively. A set of 155 genes was also identified as differentially expressed between WT and Il10-/- mice at the baseline pre-irradiation level. Gene ontology analysis revealed that the 155 baseline differentially expressed genes were mainly involved in inflammatory response, glutathione metabolism and collagen deposition. Analysis of radiation responsive genes revealed that innate immune response and p53 signaling processes were strongly associated with up-regulated genes, whereas B-cell development process was found to be significant amongst downregulated genes in the two genotypes. However, specific immune response pathways like MHC based antigen presentation, interferon signaling and hepatic fibrosis were associated with radiation responsive genes in Il10-/- mice but not WT mice. Further analysis using the IPA prediction tool revealed significant differences in the predicted activation status of T-cell mediated signaling as well as regulators of inflammation between WT and Il10-/- after irradiation. CONCLUSIONS: Using a mouse model we established that an inflammatory disease condition could affect the expression of many radiation responsive genes. Nevertheless, we identified a panel of genes that, regardless of disease condition, could predict radiation exposure. Our results highlight the need for consideration of pre-existing conditions in the population in the process of development of reliable biodosimetry markers.

Uses of Effective Dose: The Good, the Bad, and the Future.

Effective dose (E) is a risk-adjusted dosimetric quantity developed by the International Commission on Radiological Protection. It is a key metric for practical management of the risk of stochastic health effects in a comprehensive radiation protection program. The International Commission on Radiological Protection and others have emphasized repeatedly that E is not intended to represent an actual radiation dose and should not be used as a risk-related metric for a specific person or population. The cancer risk uncertainties in the low-dose range and the underlying approximations, simplifications, and sex- and age-averaging used in generating E make it unsuitable for this purpose. However, in practice, medical imaging professionals and authors of peer-reviewed medical publications frequently and incorrectly use E as a surrogate for whole-body dose in order to calculate cancer risk estimates for specific patients or patient populations. This frequent misuse has popularized E for uses for which it was neither designed nor intended. Alternatives to E have been proposed that attempt to account for known age and sex differences in radiation sensitivity. E has also been proposed as a general indicator for communicating radiation risk to patients, if its limitations are kept in mind. Forthcoming guidance from the International Commission on Radiological Protection will likely clarify if, when, and how some form of E may be used as a rough indicator of the risk of a stochastic effect, possibly with some modifications for the substantial variations in risk known to exist with respect to age, sex, and population group.

Stochastic Dosimetry for the Assessment of Children Exposure to Uniform 50 Hz Magnetic Field with Uncertain Orientation.

This study focused on the evaluation of the exposure of children aging from five to fourteen years to 50 Hz homogenous magnetic field uncertain orientation using stochastic dosimetry. Surrogate models allowed assessing how the variation of the orientation of the magnetic field influenced the induced electric field in each tissue of the central nervous system (CNS) and in the peripheral nervous system (PNS) of children. Results showed that the electric field induced in CNS and PNS tissues of children were within the ICNIRP basic restrictions for general public and that no significant difference was found in the level of exposure of children of different ages when considering 10000 possible orientations of the magnetic field. A "mean stochastic model," useful to estimate the level of exposure in each tissue of a representative child in the range of age from five to fourteen years, was developed. In conclusion, this study was useful to deepen knowledge about the ELF-MF exposure, including the evaluation of variable and uncertain conditions, thus representing a step towards a more realistic characterization of the exposure to EMF.

Dosimetric verification of dose calculation algorithm in the lung during total marrow irradiation using helical tomotherapy.

INTRODUCTION: Treatment of proliferative diseases of the hematopoietic system involves, in most cases, chemotherapy combined with radiation therapy, which is intended to provide adequate immunosuppressant. Conventionally, total body irradiation (TBI) was used; however, total marrow irradiation (TMI) performed with helical tomotherapy (HT) has been proposed as an alternative, with the aim of delivering the highest dose in the target area (skeleton bone). PURPOSE: The purpose of this study is to evaluate the accuracy of the dose calculation algorithm for the lung in TMI delivered with HT. METHODS: Thermoluminescent detectors (TLD-100 Harshaw) were used to measure delivered doses. Doses were calculated for 95 selected points in the central lung (53 TLDs) and near the rib bones (42 TLDs) in the anthropomorphic phantom. A total of 12 Gy were delivered (6 fractions of 2 Gy/fraction). RESULTS: HT-TMI technique reduces the dose delivered to the lungs in a phantom model to levels that are much lower than those reported for TBI delivered by a conventional linear accelerator. The mean calculated lung dose was 5.6 Gy versus a mean measured dose of 5.7 ± 2.4 Gy. The maximum and minimum measured doses were, respectively, 11.3 Gy (chest wall) and 2.8 Gy (central lung). At most of the 95 points, the measured dose was lower than the calculated dose, with the largest differences observed in the region located between the target volume and the adjacent lung tissue. The mean measured dose was lower than the calculated dose in both primary locations: -3.7% in the 42 rib-adjacent detectors and -3.0% in the 53 central lung TLDs. CONCLUSION: Our study has shown that the measured doses may be lower than those calculated by the HT-TMI calculation algorithm. Although these differences between calculated and measured doses are not clinically relevant, this finding merits further investigation.

Dosimetric predictors of hematologic toxicity in patients undergoing concurrent gemcitabine-based chemoradiation for localized pancreatic cancer.

PURPOSE: This study was undertaken to identify parameters associated with hematologic toxicity or chemotherapy dose modification in patients undergoing concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer. METHODS AND MATERIALS: We reviewed patients with localized pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. The T11-L3 vertebrae were contoured as bone marrow region at risk. Linear and logistic regression models were used to test associations between dosimetric parameters and gemcitabine dose modification or hematologic toxicity during or within 3 months following CRT. Receiver operator curves were generated to identify threshold doses for hematologic toxicity. RESULTS: Forty-nine patients were included. During CRT, the maximum thoracolumbar dose was associated with grade 2+ neutropenia during CRT (P = .017) and the volume receiving 5 Gy (V5) was associated with grade 2+ leukopenia (P = .041). Post-CRT, thoracolumbar mean dose (P = .015), V5 (P = .01), and V10 (P = .012) were associated with increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar maximum dose (P = .045) and V5 (P = .045) were associated with grade 2+ neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean dose (P = .046), V5 (P = .019), and V10 (P = .037) were associated with increased grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post-CRT, there was a trend toward increased dose modifications with increased V5 (P = .065). CONCLUSIONS: In our dataset, the thoracolumbar mean dose, maximum dose, V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in patients with localized pancreatic cancer. Because of the high rates of distant failure and importance of systemic therapy in these patients, this may be an important consideration during treatment planning.

Radiobiology of tissue reactions.

Tissue effects of radiation exposure are observed in virtually all normal tissues, with interactions when several organs are involved. Early reactions occur in turnover tissues, where proliferative impairment results in hypoplasia; late reactions, based on combined parenchymal, vascular, and connective tissue changes, result in loss of function within the exposed volume; consequential late effects develop through interactions between early and late effects in the same organ; and very late effects are dominated by vascular sequelae. Invariably, involvement of the immune system is observed. Importantly, latent times of late effects are inversely dependent on the biologically equieffective dose. Each tissue component and--importantly--each individual symptom/endpoint displays a specific dose-effect relationship. Equieffective doses are modulated by exposure conditions: in particular, dose-rate reduction--down to chronic levels--and dose fractionation impact on late responding tissues, while overall exposure time predominantly affects early (and consequential late) reactions. Consequences of partial organ exposure are related to tissue architecture. In 'tubular' organs (gastrointestinal tract, but also vasculature), punctual exposure affects function in downstream compartments. In 'parallel' organs, such as liver or lungs, only exposure of a significant (organ-dependent) fraction of the total volume results in clinical consequences. Forthcoming studies must address biomarkers of the individual risk for tissue reactions, and strategies to prevent/mitigate tissue effects after exposure.

General tissue reactions and implications for radiation protection.

Non-cancer effects and risks at low doses from ionising radiation are controversial topics within the field of radiation protection. These issues are discussed in International Commission on Radiological Protection (ICRP) Publication 118, 'ICRP statement on tissue reactions'. Both non-cancer effects and risks are expected to become increasingly important to the system of radiation protection. Before this can happen, several factors must be considered: thorough characterisation of the relationship between dose and risk; verification of the biological mechanisms for any noted excess risk; and adjustment of noted excess risks through the use of a detriment factor. It is difficult to differentiate the relatively small risks associated with radiation from other risk factors in the low-dose region of the dose-response curve. Several recent papers have indicated the possibility of a non-linear dose-response relationship for non-cancer effects. In addition, there are still many uncertainties associated with the biological mechanisms for non-cancer effects. Finally, it is essential to consider the incorporation of detriment into a well-defined system of radiological protection. Given the recent interest in non-cancer effects, it is essential to facilitate discussions in order to define dose limits more clearly within the existing system of radiation protection for both cancer and non-cancer effects.

Intensity modulated arc therapy in bilaterally irradiated head and neck cancer: a comparative and prospective multicenter planning study.

A dosimetric comparison was made of Helical Tomotherapy (HT) and Rapid'Arc(®) (RA) in 115 patients with head and neck carcinoma included in a prospective and multicentric study. HT and RA provided highly conformal plans that easily complied with dose volume constraints for organs at risk. HT reduced high doses to the planning target volumes (PTVs) compared to RA and provided a more homogeneous dose distribution but with an increased Non Tumoral Integral Dose (NTID) than RA. However, the clinical consequences of these dosimetric advantages and disadvantages need further investigation.

ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context.

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

Monitoring of patients treated with particle therapy using positron-emission-tomography (PET): the MIRANDA study.

BACKGROUND: The purpose of this clinical study is to investigate the clinical feasibility and effectiveness of offline Positron-Emission-Tomography (PET) quality assurance for promoting the accuracy of proton and carbon ion beam therapy. METHODS/DESIGN: A total of 240 patients will be recruited, evenly sampled among different analysis groups including tumors of the brain, skull base, head and neck region, upper gastrointestinal tract including the liver, lower gastrointestinal tract, prostate and pelvic region. From the comparison of the measured activity with the planned dose and its corresponding simulated activity distribution, conclusions on the delivered treatment will be inferred and, in case of significant deviations, correction strategies will be elaborated. DISCUSSION: The investigated patients are expected to benefit from this study, since in case of detected deviations between planned and actual treatment delivery a proper intervention (e.g., correction) could be performed in a subsequent irradiation fraction. In this way, an overall better treatment could be achieved than without any in-vivo verification. Moreover, site-specific patient-population information on the precision of the ion range at HIT might enable improvement of the CT-range calibration curve as well as safe reduction of the treatment margins to promote enhanced treatment plan conformality and dose escalation for full clinical exploitation of the promises of ion beam therapy. TRIAL REGISTRATION: NCT01528670.

Repair of radiation damage and radiation injury to the spinal cord.

Radiation myelopathy is a rare but devastating injury to the spinal cord that usually results from an excessive radiation dose. In this chapter, we discuss the traditional and current understandings of the pathogenesis of this injury. A distinction is made between radiation damage, which occurs at the subcellular level, and radiation injury, which occurs at the tissue and organ level in response to radiation damage. Recent findings regarding the amelioration and treatment of both radiation damage and radiation injury are explored. These studies are promising developments but, as always, there are attendant caveats.

Dosimetria de raios X em mamografia para combinação Mo/Mo utilizando espectrometria Compton / X-ray dosimetry in mammography for Mo/Mo combination utilizing Compton spectrometry

OBJETIVO: Para comparar o benefício da mamografia e o risco de câncer induzido por raios X, devese investigar as doses absorvidas. Nesse sentido, determinaram-se espectros dos raios X de um mamógrafo clínico, para combinação alvo/filtro Mo/Mo, utilizando espectrometria Compton, e avaliou-se a dose glandular média (DGM) em um simulador de mamas de BR-12. MATERIAL E MÉTODO:Um detector de CdTe foi usado para espectrometria dos raios X espalhados a ~ 100° por um cilindrode PMMA, para diferentes profundidades de BR-12 e tensões entre 28 e 35 kV. Após a reconstrução do espectro dos feixes primários, a partir dos medidos, determinou-se a DGM. RESULTADOS:Obtiveram-se camadas semirredutoras de 0,39 a 0,45 mmAl (espectrometricamente) e de 0,38 a0,42 mmAl (com câmara de ionização) para os feixes incidentes na superfície do simulador. A DGMNnormalizada por unidade de kerma no ar incidente, na superfície de BR-12, variou de 0,156 a 0,226.CONCLUSÃO: Os valores de DGMN variaram de 1% a 3%, em relação aos obtidos com câmara. O método empregado é uma boa alternativa para a determinação de DGMN e da distribuição de dose em profundidade em simuladores mamários.

OBJECTIVE: To compare mammography benefit and X-ray induced cancer risk, one should investigate absorbed doses. For this purpose, spectra of primary X-ray beams from a clinical mammographyequipment were determined for Mo/Mo target/filter combination,using Compton spectrometry and average glandular dose (AGD) in a BR-12 breast phantom was evaluated. MATERIAL AND METHOD: A CdTe detector was used for spectrometry of X-ray beams Compton scattered around 100°, by a PMMA cylinder, for different depths inside the BR-12 phantom and voltages between 28 and 35 kV. The reconstruction of the primary beam spectra from the measured ones was followed by the determination of AGD. RESULTS: Half-value layer values determined by spectra resulted 0.39 to 0.45 mmAl, and by ionization chamber, 0.38 to 0.42 mmAl, respectively, for beams incident on the phantom surface. The AGDN normalized per unitary incident air kerma, on the BR-12 surface, ranged from 0.156 to 0.226. CONCLUSION: The percentage deviation of AGDN, relative to the chamber measurements, ranged from 1% to 3%. The utilized method is a good alternative to determineAGDN and depth-dose distributions in breast phantoms.

Comparison of dose from radiological examination for scoliosis in children among two pediatric hospitals by Monte Carlo simulation.

The radiation exposures of children undergoing full spine radiography were investigated in two pediatric hospitals in Greece. Entrance surface kerma (Ka,e) was assessed by thermoluminescence dosimetry and patient's effective dose (E) was estimated by Monte Carlo simulation. All required information regarding patient age and sex, the irradiation geometry, the x-ray spectra, and other exposure parameters (tube voltage and current) were registered as well. Values of Ka,e were measured to range from 0.22 mGy to 2.12 mGy, while E was estimated to range from 0.03 mSv to 0.47 mSv. In general, all values were greater in one of the two hospitals, as higher tube currents and exposure times were used in the examinations because of the difference in radiographers' training and practice. Moreover, dose to red bone marrow was found to be between 0.01 to 0.23 mSv and dose to breast ranged between 0.02 and 1.05 mSv depending on the age, projection, and hospital. These values are comparable with literature sources.

Nanodosimetry-based quality factors for radiation protection in space.

Evaluation and monitoring of the cancer risk from space radiation exposure is a crucial requirement for the success of long-term space missions. One important task in the risk calculation is to properly weigh the various components of space radiation dose according to their assumed contribution to the cancer risk relative to the risk associated with radiation of low ionization density. Currently, quality factors of radiation both on the ground and in space are defined by national and international commissions based on existing radiobiological data and presumed knowledge of the ionization density distribution of the radiation field at a given point of interest. This approach makes the determination of the average quality factor ofa given radiation field a rather complex task. In this contribution, we investigate the possibility to define quality factors of space radiation exposure based on nanodosimetric data. The underlying formalism of the determination of quality factors on the basis of nanodosimetric data is described, and quality factors for protons and ions (helium and carbon) of different energies based on simulated nanodosimetric data are presented. The value and limitations of this approach are discussed.

Fetal exposure to low frequency electric and magnetic fields.

To investigate the interaction of low frequency electric and magnetic fields with pregnant women and in particular with the fetus, an anatomical voxel model of an 89 kg woman at week 30 of pregnancy was developed. Intracorporal electric current density distributions due to exposure to homogeneous 50 Hz electric and magnetic fields were calculated and results were compared with basic restrictions recommended by ICNIRP guidelines. It could be shown that the basic restriction is met within the central nervous system (CNS) of the mother at exposure to reference level of either electric or magnetic fields. However, within the fetus the basic restriction is considerably exceeded. Revision of reference levels might be necessary.