Tumour characteristics of screen-detected and interval cancers in the Flemish Breast Cancer Screening Programme: A mammographic breast density study.

OBJECTIVE: The objective is to investigate tumour prognostic factors versus breast density in screen-detected cancers and interval cancers. The results may highlight the need for more personalised screening protocols based on breast density in organized screening programmes. STUDY DESIGN: A retrospective study was performed of tumour characteristics of screen-detected cancers (n=468) and interval cancers (n=515) of 983 women who participated in the Flemish Breast Cancer Screening Programme in 2009-2010. Breast density was obtained from the screening programme data. Information on nodal invasion and histological grading was taken from the Belgian Cancer Registry. Tumour size and proliferation and receptor expression status were retrieved from pathology reports. The differences in tumour characteristics between screen-detected and interval cancers as well as the variation in these variables with breast density in both groups were studied by logistic regression. RESULTS: A comparison of tumour characteristics between screen-detected cancers and interval cancers systematically showed features of more aggressive tumours in interval cancers: larger tumour size, nodal invasion, grade 3 tumours, and hormone receptor negative phenotype (p<0.05). The analysis of tumour characteristics versus breast density in screen-detected cancers showed higher numbers of aggressive grade 3 tumours in low-density breasts and of the luminal A subtype with good prognosis in high-density breasts (p<0.05). This analysis for interval cancers highlights a high proportion of the difficult-to-treat triple-negative subtype in low-density breasts compared with high-density breasts. In conclusion, the study data support arguments against changes in breast cancer screening programmes with prolongation of screening intervals in low-density breasts.

DNA double strand breaks induced by low dose mammography X-rays in breast tissue: A pilot study.

Breast tissue is very sensitive to ionizing radiation due to the presence of reproductive hormones, including estrogen. In the present pilot study, the efficiency of mammography X-rays to induce DNA double strand breaks (DSB) in mammary epithelial cells was investigated. For this, freshly resected healthy breast tissue was irradiated with 30 kV mammography X-rays in the dose range 0-500 mGy (2, 4, 10, 20, 40, 100 and 500 mGy). Breast specimens were also irradiated with identical doses of 60Co γ-rays as a radiation quality standard. With the γH2AX-foci assay, the number of DNA DSB induced by radiation were quantified in the mammary epithelial cells present in breast tissue. Results indicated that foci induced by 30 kV X-rays and γ-rays followed a biphasic linear dose-response. For 30 kV X-rays, the slope in the low dose region (0-20 mGy) was 8.71 times steeper compared with the slope in the higher dose region (20-500 mGy). Furthermore, compared with γ-rays, 30 kV X-rays were also more effective in inducing γH2AX-foci. This resulted in a relative biological effectiveness (RBE) value of 1.82 in the low dose range. In the higher dose range, an RBE close to 1 was obtained. In conclusion, the results indicated the existence of a low dose hypersensitive response for DSB induction in the dose range representative for mammography screening, which is probably caused by the bystander effect. This could affect the radiation risk calculations for women participating in mammography screening.

A new approach for modeling patient overall radiosensitivity and predicting multiple toxicity endpoints for breast cancer patients.

INTRODUCTION: Evaluation of patient characteristics inducing toxicity in breast radiotherapy, using simultaneous modeling of multiple endpoints. METHODS AND MATERIALS: In 269 early-stage breast cancer patients treated with whole-breast irradiation (WBI) after breast-conserving surgery, toxicity was scored, based on five dichotomized endpoints. Five logistic regression models were fitted, one for each endpoint and the effect sizes of all variables were estimated using maximum likelihood (MLE). The MLEs are improved with James-Stein estimates (JSEs). The method combines all the MLEs, obtained for the same variable but from different endpoints. Misclassification errors were computed using MLE- and JSE-based prediction models. For associations, p-values from the sum of squares of MLEs were compared with p-values from the Standardized Total Average Toxicity (STAT) Score. RESULTS: With JSEs, 19 highest ranked variables were predictive of the five different endpoints. Important variables increasing radiation-induced toxicity were chemotherapy, age, SATB2 rs2881208 SNP and nodal irradiation. Treatment position (prone position) was most protective and ranked eighth. Overall, the misclassification errors were 45% and 34% for the MLE- and JSE-based models, respectively. p-Values from the sum of squares of MLEs and p-values from STAT score led to very similar conclusions, except for the variables nodal irradiation and treatment position, for which STAT p-values suggested an association with radiosensitivity, whereas p-values from the sum of squares indicated no association. Breast volume was ranked as the most significant variable in both strategies. DISCUSSION: The James-Stein estimator was used for selecting variables that are predictive for multiple toxicity endpoints. With this estimator, 19 variables were predictive for all toxicities of which four were significantly associated with overall radiosensitivity. JSEs led to almost 25% reduction in the misclassification error rate compared to conventional MLEs. Finally, patient characteristics that are associated with radiosensitivity were identified without explicitly quantifying radiosensitivity.

Data-Based Radiation Oncology: Design of Clinical Trials in the Toxicity Biomarkers Era.

The ability to stratify patients using a set of biomarkers, which predict that toxicity risk would allow for radiotherapy (RT) modulation and serve as a valuable tool for precision medicine and personalized RT. For patients presenting with tumors with a low risk of recurrence, modifying RT schedules to avoid toxicity would be clinically advantageous. Indeed, for the patient at low risk of developing radiation-associated toxicity, use of a hypofractionated protocol could be proposed leading to treatment time reduction and a cost-utility advantage. Conversely, for patients predicted to be at high risk for toxicity, either a more conformal form or a new technique of RT, or a multidisciplinary approach employing surgery could be included in the trial design to avoid or mitigate RT when the potential toxicity risk may be higher than the risk of disease recurrence. In addition, for patients at high risk of recurrence and low risk of toxicity, dose escalation, such as a greater boost dose, or irradiation field extensions could be considered to improve local control without severe toxicities, providing enhanced clinical benefit. In cases of high risk of toxicity, tumor control should be prioritized. In this review, toxicity biomarkers with sufficient evidence for clinical testing are presented. In addition, clinical trial designs and predictive models are described for different clinical situations.

Screen-detected versus interval cancers: Effect of imaging modality and breast density in the Flemish Breast Cancer Screening Programme.

OBJECTIVES: To investigate if direct radiography (DR) performs better than screen-film mammography (SF) and computed radiography (CR) in dense breasts in a decentralized organised Breast Cancer Screening Programme. To this end, screen-detected versus interval cancers were studied in different BI-RADS density classes for these imaging modalities. METHODS: The study cohort consisted of 351,532 women who participated in the Flemish Breast Cancer Screening Programme in 2009 and 2010. Information on screen-detected and interval cancers, breast density scores of radiologist second readers, and imaging modality was obtained by linkage of the databases of the Centre of Cancer Detection and the Belgian Cancer Registry. RESULTS: Overall, 67% of occurring breast cancers are screen detected and 33% are interval cancers, with DR performing better than SF and CR. The interval cancer rate increases gradually with breast density, regardless of modality. In the high-density class, the interval cancer rate exceeds the cancer detection rate for SF and CR, but not for DR. CONCLUSIONS: DR is superior to SF and CR with respect to cancer detection rates for high-density breasts. To reduce the high interval cancer rate in dense breasts, use of an additional imaging technique in screening can be taken into consideration. KEY POINTS: • Interval cancer rate increases gradually with breast density, regardless of modality. • Cancer detection rate in high-density breasts is superior in DR. • IC rate exceeds CDR for SF and CR in high-density breasts. • DR performs better in high-density breasts for third readings and false-positives.

Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation.

PURPOSE: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network. MATERIALS AND METHODS: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices. RESULTS: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances. CONCLUSIONS: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation.

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.

RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay).

PURPOSE: In the framework of the 'Realizing the European Network of Biodosimetry' (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. MATERIALS AND METHODS: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. RESULTS: The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (≤ 0.94 Gy). For higher dose points (≥ 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. CONCLUSION: The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories.

RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

PURPOSE: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. RESULTS: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

In vitro cellular radiosensitivity in relationship to late normal tissue reactions in breast cancer patients: a multi-endpoint case-control study.

PURPOSE: A minority of patients exhibits severe late normal tissue toxicity after radiotherapy (RT), possibly related to their inherent individual radiation sensitivity. This study aimed to evaluate four different candidate in vitro cellular radiosensitivity assays for prediction of late normal tissue reactions, in a retrospective matched case-control set-up of breast cancer patients. METHODS: The study population consists of breast cancer patients expressing severe radiation toxicity (12 cases) and no or minimal reactions (12 controls), with a follow-up for at least 3 years. Late adverse reactions were evaluated by comparing standardized photographs pre- and post-RT resulting in an overall cosmetic score and by clinical examination using the LENT-SOMA scale. Four cellular assays on peripheral blood lymphocytes reported to be associated with normal tissue reactions were performed after in vitro irradiation of patient blood samples to compare case and control radiation responses: radiation-induced CD8+ late apoptosis, residual DNA double-strand breaks, G0 and G2 micronucleus assay. RESULTS: A significant difference was observed for all cellular endpoints when matched cases and controls were compared both pairwise and grouped. However, it is important to point out that most case-control pairs showed a substantial overlap in standard deviations, which questions the predictive value of the individual assays. The apoptosis assay performed best, with less apoptosis seen in CD8+ lymphocytes of the cases (average: 14.45%) than in their matched controls (average: 30.64%) for 11 out of 12 patient pairs (p < .01). The number of residual DNA DSB was higher in cases (average: 9.92 foci/cell) compared to their matched control patients (average: 9.17 foci/cell) (p < .01). The average dose response curve of the G0 MN assay for cases lies above the average dose response curve of the controls. Finally, a pairwise comparison of the G2 MN results showed a higher MN yield for cases (average: 351 MN/1000BN) compared to controls (average: 219 MN/1000BN) in 9 out of 10 pairs (p < .01). CONCLUSION: This matched case-control study in breast cancer patients, using different endpoints for in vitro cellular radiosensitivity related to DNA repair and apoptosis, suggests that patients' intrinsic radiosensitivity is involved in the development of late normal tissue reactions after RT. Larger prospective studies are warranted to validate the retrospective findings and to use in vitro cellular assays in the future to predict late normal tissue radiosensitivity and discriminate individuals with marked RT responses.

Pitfalls in Prediction Modeling for Normal Tissue Toxicity in Radiation Therapy: An Illustration With the Individual Radiation Sensitivity and Mammary Carcinoma Risk Factor Investigation Cohorts.

PURPOSE: To identify the main causes underlying the failure of prediction models for radiation therapy toxicity to replicate. METHODS AND MATERIALS: Data were used from two German cohorts, Individual Radiation Sensitivity (ISE) (n=418) and Mammary Carcinoma Risk Factor Investigation (MARIE) (n=409), of breast cancer patients with similar characteristics and radiation therapy treatments. The toxicity endpoint chosen was telangiectasia. The LASSO (least absolute shrinkage and selection operator) logistic regression method was used to build a predictive model for a dichotomized endpoint (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer score 0, 1, or ≥2). Internal areas under the receiver operating characteristic curve (inAUCs) were calculated by a naïve approach whereby the training data (ISE) were also used for calculating the AUC. Cross-validation was also applied to calculate the AUC within the same cohort, a second type of inAUC. Internal AUCs from cross-validation were calculated within ISE and MARIE separately. Models trained on one dataset (ISE) were applied to a test dataset (MARIE) and AUCs calculated (exAUCs). RESULTS: Internal AUCs from the naïve approach were generally larger than inAUCs from cross-validation owing to overfitting the training data. Internal AUCs from cross-validation were also generally larger than the exAUCs, reflecting heterogeneity in the predictors between cohorts. The best models with largest inAUCs from cross-validation within both cohorts had a number of common predictors: hypertension, normalized total boost, and presence of estrogen receptors. Surprisingly, the effect (coefficient in the prediction model) of hypertension on telangiectasia incidence was positive in ISE and negative in MARIE. Other predictors were also not common between the 2 cohorts, illustrating that overcoming overfitting does not solve the problem of replication failure of prediction models completely. CONCLUSIONS: Overfitting and cohort heterogeneity are the 2 main causes of replication failure of prediction models across cohorts. Cross-validation and similar techniques (eg, bootstrapping) cope with overfitting, but the development of validated predictive models for radiation therapy toxicity requires strategies that deal with cohort heterogeneity.

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients.

PURPOSE: Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. MATERIALS AND METHODS: The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. RESULTS: For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. CONCLUSION: This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

A semi­automated FISH­based micronucleus­centromere assay for biomonitoring of hospital workers exposed to low doses of ionizing radiation.

The aim of the present study was to perform cytogenetic analysis by means of a semi­automated micronucleus­centromere assay in lymphocytes from medical radiation workers. Two groups of workers receiving the highest occupational doses were selected: 10 nuclear medicine technicians and 10 interventional radiologists/cardiologists. Centromere­negative micronucleus (MNCM­) data, obtained from these two groups of medical radiation workers were compared with those obtained in matched controls. The blood samples of the matched controls were additionally used to construct a 'low­dose' (0­100 mGy) MNCM­ dose­response curve to evaluate the sensitivity and suitability of the micronucleus­centromere assay as an 'effect' biomarker in medical surveillance programs. The physical dosimetry data of the 3 years preceding the blood sampling, based on single or double dosimetry practices, were collected for the interpretation of the micronucleus data. The in vitro radiation results showed that for small sized groups, semi­automated scoring of MNCM­ enables the detection of a dose of 50 mGy. The comparison of MNCM­ yields in medical radiation workers and control individuals showed enhanced MNCM­ scores in the medical radiation workers group (P=0.15). The highest MNCM­ scores were obtained in the interventional radiologists/cardiologists group, and these scores were significantly higher compared with those obtained from the matched control group (P=0.05). The higher MNCM­ scores observed in interventional radiologists/cardiologists compared with nuclear medicine technicians were not in agreement with the personal dosimetry records in both groups, which may point to the limitation of 'double dosimetry' procedures used in interventional radiology/cardiology. In conclusion, the data obtained in the present study supports the importance of cytogenetic analysis, in addition to physical dosimetry, as a routine biomonitoring method in medical radiation workers receiving the highest occupational radiation burdens.

The role of Size-Specific Dose Estimate (SSDE) in patient-specific organ dose and cancer risk estimation in paediatric chest and abdominopelvic CT examinations.

OBJECTIVES: To develop a clinically applicable method to estimate patient-specific organ and blood doses and lifetime attributable risks (LAR) from paediatric torso CT examinations. METHODS: Individualized voxel models were created from full-body CT data of 10 paediatric patients (2-18 years). Patient-specific dose distributions of chest and abdominopelvic CT scans were simulated using Monte Carlo methods. Blood dose was calculated as a weighted sum of simulated organ doses. LAR of cancer incidence and mortality were estimated, according to BEIR-VII. A second simulation and blood dose calculation was performed using only the thoracic and abdominopelvic region of the original voxel models. For each simulation, the size-specific dose estimate (SSDE) was calculated. RESULTS: SSDE showed a significant strong linear correlation with organ dose (r > 0.8) and blood dose (r > 0.9) and LAR (r > 0.9). No significant differences were found between blood dose calculations with the full-body voxel models and the thoracic or abdominopelvic models. CONCLUSION: Even though clinical CT images mostly do not cover the whole body of the patient, they can be used as a voxel model for blood dose calculation. In addition, SSDE can estimate patient-specific organ and blood doses and LAR in paediatric torso CT examinations. KEY POINTS: • Blood dose can be simulated using the patient's clinical CT images. • SSDE estimates patient-specific organ/blood dose and LAR in paediatric CAP CT-examinations. • SSDE makes on-the-spot dose and LAR estimations possible in routine clinical practice.

Correlation of clinical and physical-technical image quality in chest CT: a human cadaver study applied on iterative reconstruction.

BACKGROUND: The first aim of this study was to evaluate the correlation between clinical and physical-technical image quality applied to different strengths of iterative reconstruction in chest CT images using Thiel cadaver acquisitions and Catphan images. The second aim was to determine the potential dose reduction of iterative reconstruction compared to conventional filtered back projection based on different clinical and physical-technical image quality parameters. METHODS: Clinical image quality was assessed using three Thiel embalmed human cadavers. A Catphan phantom was used to assess physical-technical image quality parameters such as noise, contrast-detail and contrast-to-noise ratio (CNR). Both Catphan and chest Thiel CT images were acquired on a multislice CT scanner at 120 kVp and 0.9 pitch. Six different refmAs settings were applied (12, 30, 60, 90, 120 and 150refmAs) and each scan was reconstructed using filtered back projection (FBP) and iterative reconstruction (SAFIRE) algorithms (1,3 and 5 strengths) using a sharp kernel, resulting in 24 image series. Four radiologists assessed the clinical image quality, using a visual grading analysis (VGA) technique based on the European Quality Criteria for Chest CT. RESULTS: Correlation coefficients between clinical and physical-technical image quality varied from 0.88 to 0.92, depending on the selected physical-technical parameter. Depending on the strength of SAFIRE, the potential dose reduction based on noise, CNR and the inverse image quality figure (IQF(inv)) varied from 14.0 to 67.8%, 16.0 to 71.5% and 22.7 to 50.6% respectively. Potential dose reduction based on clinical image quality varied from 27 to 37.4%, depending on the strength of SAFIRE. CONCLUSION: Our results demonstrate that noise assessments in a uniform phantom overestimate the potential dose reduction for the SAFIRE IR algorithm. Since the IQF(inv) based dose reduction is quite consistent with the clinical based dose reduction, an optimised contrast-detail phantom could improve the use of contrast-detail analysis for image quality assessment in chest CT imaging. In conclusion, one should be cautious to evaluate the performance of CT equipment taking into account only physical-technical parameters as noise and CNR, as this might give an incomplete representation of the actual clinical image quality performance.

Organ Doses and Radiation Risk of Computed Tomographic Coronary Angiography in a Clinical Patient Population: How Do Low-Dose Acquisition Modes Compare?

OBJECTIVE: To compare the organ doses and lifetime-attributable risk of cancer for electrocardiogram-triggered sequential and high-pitch helical scanning in a clinical patient population. METHODS: Phantom thermoluminiscence dosimeter measurements were used as a model for the organ dose assessment of 314 individual patients who underwent coronary computed tomographic angiography. Patient-specific lifetime-attributable cancer risks were calculated. RESULTS: Phantom measurements showed that heart rate had a significant influence on the delivered radiation exposure in sequential mode, and calcium scoring and contrast bolus tracking scans make a nonnegligible contribution to patients' dose. Therefore, they should be taken into account for patients' organ dose estimations. Median cancer induction risks are low, with 0.008% (0.0016%) and 0.022% (0.056%) for high-pitch and sequential scanning for men (women), respectively. CONCLUSIONS: The use of high-pitch helical scanning leads to 65% and 72% lower lifetime-attributable risk values for men and women, respectively, compared with sequential scanning.

Analysis of metal artifact reduction tools for dental hardware in CT scans of the oral cavity: kVp, iterative reconstruction, dual-energy CT, metal artifact reduction software: does it make a difference?

INTRODUCTION: Metal artifacts may negatively affect radiologic assessment in the oral cavity. The aim of this study was to evaluate different metal artifact reduction techniques for metal artifacts induced by dental hardware in CT scans of the oral cavity. METHODS: Clinical image quality was assessed using a Thiel-embalmed cadaver. A Catphan phantom and a polymethylmethacrylate (PMMA) phantom were used to evaluate physical-technical image quality parameters such as artifact area, artifact index (AI), and contrast detail (IQFinv). Metal cylinders were inserted in each phantom to create metal artifacts. CT images of both phantoms and the Thiel-embalmed cadaver were acquired on a multislice CT scanner using 80, 100, 120, and 140 kVp; model-based iterative reconstruction (Veo); and synthesized monochromatic keV images with and without metal artifact reduction software (MARs). Four radiologists assessed the clinical image quality, using an image criteria score (ICS). RESULTS: Significant influence of increasing kVp and the use of Veo was found on clinical image quality (p = 0.007 and p = 0.014, respectively). Application of MARs resulted in a smaller artifact area (p < 0.05). However, MARs reconstructed images resulted in lower ICS. CONCLUSION: Of all investigated techniques, Veo shows to be most promising, with a significant improvement of both the clinical and physical-technical image quality without adversely affecting contrast detail. MARs reconstruction in CT images of the oral cavity to reduce dental hardware metallic artifacts is not sufficient and may even adversely influence the image quality.

EPI-CT: in vitro assessment of the applicability of the γ-H2AX-foci assay as cellular biomarker for exposure in a multicentre study of children in diagnostic radiology.

PURPOSE: To conduct a feasibility study on the application of the γ-H2AX foci assay as an exposure biomarker in a prospective multicentre paediatric radiology setting. MATERIALS AND METHODS: A set of in vitro experiments was performed to evaluate technical hurdles related to biological sample collection in a paediatric radiology setting (small blood sample volume), processing and storing of blood samples (effect of storing blood at 4°C), the reliability of foci scoring for low-doses (merge γ-H2AX/53BP1 scoring), as well as the impact of contrast agent administration as potential confounding factor. Given the exploratory nature of this study and the ethical constraints related to paediatric blood sampling, blood samples from adult volunteers were used for these experiments. In order to test the feasibility of pooling the γ-H2AX data when different centres are involved in an international multicentre study, two intercomparison studies in the low-dose range (10-500 mGy) were performed. RESULTS: Determination of the number of X-ray induced γ-H2AX foci is feasible with one 2 ml blood sample pre- and post-computed tomography (CT) scan. Lymphocyte isolation and fixation on slides is necessary within 5 h of blood sampling to guarantee reliable results. The possible enhancement effect of contrast medium on the induction of DNA DSB in a patient study can be ruled out if radiation doses and the contrast agent concentration are within diagnostic ranges. The intercomparison studies using in vitro irradiated blood samples showed that the participating laboratories, executing successfully the γ-H2AX foci assay in lymphocytes, were able to rank blind samples in order of lowest to highest radiation dose based on mean foci/cell counts. The dose response of all intercomparison data shows that a dose point of 10 mGy could be distinguished from the sham-irradiated control (p = 0.006). CONCLUSIONS: The results demonstrate that it is feasible to apply the γ-H2AX foci assay as a cellular biomarker of exposure in a multicentre prospective study in paediatric CT imaging after validating it in an in vivo international pilot study on paediatric patients.

Novel X-ray imaging technology enables significant patient dose reduction in interventional cardiology while maintaining diagnostic image quality.

OBJECTIVES: The purpose of this study was to quantify the reduction in patient radiation dose during coronary angiography (CA) by a new X-ray technology, and to assess its impact on diagnostic image quality. BACKGROUND: Recently, a novel X-ray imaging technology has become available for interventional cardiology, using advanced image processing and an optimized acquisition chain for radiation dose reduction. METHODS: 70 adult patients were randomly assigned to a reference X-ray system or the novel X-ray system. Patient demographics were registered and exposure parameters were recorded for each radiation event. Clinical image quality was assessed for both patient groups. RESULTS: With the same angiographic technique and a comparable patient population, the new imaging technology was associated with a 75% reduction in total kerma-area product (KAP) value (decrease from 47 Gycm2 to 12 Gycm2, P<0.001). Clinical image quality showed an equivalent detail and contrast for both imaging systems. On the other hand, the subjective appreciation of noise was more apparent in images of the new image processing system, acquired at lower doses, compared to the reference system. However, the higher noise content did not affect the overall image quality score, which was adequate for diagnosis in both systems. CONCLUSIONS: For the first time, we present a new X-ray imaging technology, combining advanced noise reduction algorithms and an optimized acquisition chain, which reduces patient radiation dose in CA drastically (75%), while maintaining diagnostic image quality. Use of this technology may further improve the radiation safety of cardiac angiography and interventions.

Operational guidance for radiation emergency response organisations in Europe for using biodosimetric tools developed in EU MULTIBIODOSE project.

In the event of a large-scale radiological emergency, the triage of individuals according to their degree of exposure forms an important initial step of the accident management. Although clinical signs and symptoms of a serious exposure may be used for radiological triage, they are not necessarily radiation specific and can lead to a false diagnosis. Biodosimetry is a method based on the analysis of radiation-induced changes in cells of the human body or in portable electronic devices and enables the unequivocal identification of exposed people who should receive medical treatment. The MULTIBIODOSE (MBD) consortium developed and validated several biodosimetric assays and adapted and tested them as tools for biological dose assessment in a mass-casualty event. Different biodosimetric assays were validated against the 'gold standard' of biological dosimetry-the dicentric assay. The assays were harmonised in such a way that, in an emergency situation, they can be run in parallel in a network of European laboratories. The aim of this guidance is to give a concise overview of the developed biodosimetric tools as well as how and when they can be used in an emergency situation.