Radiation exposure during angiographic interventions in interventional radiology - risk and fate of advanced procedures.

PURPOSE: Advanced angiographic procedures in interventional radiology are becoming more important and are more frequently used, especially in the treatment of several acute life-threatening diseases like stroke or aortic injury. In recent years, technical advancement has led to a broader spectrum of interventions and complex procedures with longer fluoroscopy times. This involves the risk of higher dose exposures, which, in rare cases, may cause deterministic radiation effects, e.g. erythema in patients undergoing angiographic procedures. Against this background, these procedures recently also became subject to national and international regulations regarding radiation protection. At the same time, individual risk assessment of possible stochastic radiation effects for each patient must be weighed up against the anticipated benefits of the therapy itself. Harmful effects of the administered dose are not limited to the patient but can also affect the radiologist and the medical staff. In particular, the development of cataracts in interventionalists is a rising matter of concern. Furthermore, long-term effects of repeated and prolonged x-ray exposure have long been neglected by radiologists but have come into focus in the past years. CONCLUSIONS: With all this in mind, this review discusses different efforts to reduce radiation exposition levels for patients and medical staff by means of technical, personal as well as organizational measures.

Impact of medical imaging on the epigenome - low-dose exposure in the course of computed tomography does not induce detectable changes of DNA-methylation profiles in peripheral blood cells.

BACKGROUND: Computed tomography (CT) is a main contributor to artificial low-dose exposure. Understanding the biological effects induced by CT exposure and their dependency on the characteristics of photon spectra is essential for knowledge-driven risk assessment. In a previous gene expression study, we have identified upregulation of AEN, BAX, DDB2, EDA2R and FDXR after ex vivo exposure with single-energy CT and dual-energy CT (DECT). In this study, we focused on CT-induced changes of DNA methylation. This epigenetic modification of DNA is a central regulator of gene expression and instrumental in preserving genome integrity. Previous studies reported focal hypermethylation and global hypomethylation after exposure with doses above 100 mSv, however, the effect of low dose exposure on DNA methylation is hardly explored. MATERIALS AND METHODS: DNA was isolated from peripheral blood of three healthy individuals 6 h after ex vivo exposition to single-energy (80 kV and 150 kV) and DECT (80 kV/Sn150 kV) with a calculated effective dose of 7.0 ± 0.08 mSv. The experimental setting was identical to the one used in our previous gene expression study enabling a direct comparison of gene expression results with changes of DNA methylation identified in this study. DNA methylation was analyzed by high-throughput sequencing of bisulfite-treated DNA targeted methylation sequencing. RESULTS: Unsupervised hierarchical clustering based on DNA methylation profiles of all samples created three distinct clusters. Formation of these three clusters was solely determined by the origin of samples, indicating the absence of prominent irradiation-associated changes of DNA methylation. In line with this observation, inter-individual comparison of non-irradiated samples revealed 1163, 1224 and 4550 significant differentially methylated regions (DMRs), respectively, whereas the pairwise comparison of irradiated and non-irradiated samples failed to identify irradiation-induced DMRs in any of the three probands. This even applied to the genomic regions harboring AEN, BAX, DDB2, EDA2R and FDXR, the five genes known to be upregulated by CT exposure. CONCLUSIONS: CT exposure with various photon spectra did not result in detectable changes of DNA methylation. However, minor effects in a subpopulation of irradiated cells cannot be ruled out. Thus, future studies with extended observation intervals are needed to investigate DNA methylation changes that are induced by indirect effects at later points of time or become detectable by clonal expansion of affected cells. Moreover, our data suggest that DNA methylation analysis is less sensitive in detecting immediate effects of low-dose irradiation when compared to gene expression analysis.

Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra.

Dual-energy CT provides enhanced diagnostic power with similar or even reduced radiation dose as compared to single-energy CT. Its principle is based on the distinct physical properties of low and high energetic photons, which, however, may also affect the biological effectiveness and hence the extent of CT-induced cellular damage. Therefore, a comparative analysis of biological effectiveness of dual- and single-energy CT scans with focus on early gene regulation and frequency of radiation-induced DNA double strand breaks (DSBs) was performed. Blood samples from three healthy individuals were irradiated ex vivo with single-energy (80 kV and 150 kV) and dual-energy tube voltages (80 kV/Sn150kV) employing a modern dual source CT scanner resulting in Volume Computed Tomography Dose Index (CTDIvol) of 15.79-18.26 mGy and dose length product (DLP) of 606.7-613.8 mGy*cm. Non-irradiated samples served as a control. Differential gene expression in peripheral blood mononuclear cells was analyzed 6 h after irradiation using whole transcriptome sequencing. DSB frequency was studied by 53BP1 + γH2AX co-immunostaining and microscopic evaluation of their focal accumulation at DSBs. Neither the analysis of gene expression nor DSB frequency provided any evidence for significantly increased biological effectiveness of dual-energy CT in comparison to samples irradiated with particular single-energy CT spectra. Relative to control, irradiated samples were characterized by a significantly higher rate of DSBs (p < 0.001) and the shared upregulation of five genes, AEN, BAX, DDB2, FDXR and EDA2R, which have already been suggested as radiation-induced biomarkers in previous studies. Despite steadily decreasing doses, CT diagnostics remain a genotoxic stressor with impact on gene regulation and DNA integrity. However, no evidence was found that varying X-ray spectra of CT impact the extent of cellular damage.

Genomic Adaption and Mutational Patterns in a HaCaT Subline Resistant to Alkylating Agents and Ionizing Radiation.

Sulfur mustard (SM) is a chemical warfare agent that can damage DNA via alkylation and oxidative stress. Because of its genotoxicity, SM is cancerogenic and the progenitor of many chemotherapeutics. Previously, we developed an SM-resistant cell line via chronic exposure of the popular keratinocyte cell line HaCaT to increasing doses of SM over a period of 40 months. In this study, we compared the genomic landscape of the SM-resistant cell line HaCaT/SM to its sensitive parental line HaCaT in order to gain insights into genetic changes associated with continuous alkylation and oxidative stress. We established chromosome numbers by cytogenetics, analyzed DNA copy number changes by means of array Comparative Genomic Hybridization (array CGH), employed the genome-wide chromosome conformation capture technique Hi-C to detect chromosomal translocations, and derived mutational signatures by whole-genome sequencing. We observed that chronic SM exposure eliminated the initially prevailing hypotetraploid cell population in favor of a hyperdiploid one, which contrasts with previous observations that link polyploidization to increased tolerance and adaptability toward genotoxic stress. Furthermore, we observed an accumulation of chromosomal translocations, frequently flanked by DNA copy number changes, which indicates a high rate of DNA double-strand breaks and their misrepair. HaCaT/SM-specific single-nucleotide variants showed enrichment of C > A and T > A transversions and a lower rate of deaminated cytosines in the CpG dinucleotide context. Given the frequent use of HaCaT in toxicology, this study provides a valuable data source with respect to the original genotype of HaCaT and the mutational signatures associated with chronic alkylation and oxidative stress.

Additional CTA-Subtraction Technique in Detection of Pulmonary Embolism-a Benefit for Patients or Only an Increase in Dose?

Latest advantages in computed tomography (CT) come with enhanced diagnostic imaging and also sophisticated dose reduction techniques. However, overall exposure to ionizing radiation of patients in Germany rises slightly, which is mainly based on the growing number of performed CT scans. Furthermore, new possibilities in modern imaging, including 4D scans or perfusion protocols, offer new medical insights but require additional scans.In this study, we reevaluated data sets from patients undergoing CT examinations because of suspected pulmonary embolism and compared doses and diagnostic results of the standard protocol to the additional modern CT subtraction technique. Two groups of single-blinded radiologists were provided with CT data sets from 50 patients. One group (G1) had access to full datasets including CT subtraction with perfusion map. The other group (G2) only evaluated conventional CT angiography. Results were compared to final clinical diagnosis. Dose length product (DLP) of CT angiography was compared to CT subtraction technique, which consists of an additional non-contrast-enhanced scan and perfusion map. Effective dose was calculated using a Monte Carlo simulation-based software tool (ImpactDose). Inter-rater agreement of both groups was strong in G1 with κ = .896 and minimal in G2 (κ = .307). Agreement to final diagnosis was strong in both groups (G1, κ = .848; G2, κ = .767). Doses applied using the CT subtraction technique were 34.8% higher than for CT angiography alone (G1 DLP 337.6 ± 171.3 mGy x cm; G2 DLP 220.2 ± 192.8 mGy x cm; p < .001). Calculated effective dose was therefore significantly higher for G1 (G1 4.82 ± 2.20 mSv; G2 3.04 ± 1.33 mSv; p < .001). Our results indicate a benefit of the CT subtraction technique for the detection of pulmonary embolisms in clinical routine, accompanied by an increase in the dose administered. Although CT protocols should always be applied carefully to specific clinical indications in order to maximize the potential for dose reduction and keep the administered dose as low as reasonably achievable, one should never lose sight of the diagnostic benefit, especially in vital clinical indications.

CT Irradiation-induced Changes of Gene Expression within Peripheral Blood Cells.

Computed tomography (CT) is a crucial element of medical imaging diagnostics. The widespread application of this technology has made CT one of the major contributors to medical radiation burden, despite the fact that doses per individual CT scan steadily decrease due to the advancement of technology. Epidemiological risk assessment of CT exposure is hampered by the fact that moderate adverse effects triggered by low doses of CT exposure are likely masked by statistical fluctuations. In light of these limitations, there is need of further insights into the biological processes induced by CT scans to complement the existing knowledge base of risk assessment. This prompted us to investigate the early transcriptomic response of ex vivo irradiated peripheral blood of three healthy individuals. Samples were irradiated employing a modern dual-source-CT-scanner with a tube voltage of 150 kV, resulting in an estimated effective dose of 9.6 mSv. RNA was isolated 1 h and 6 h after exposure, respectively, and subsequently analyzed by RNA deep sequencing. Differential gene expression analysis revealed shared upregulation of AEN, FDXR, and DDB2 6 h after exposure in all three probands. All three genes have previously been discussed as radiation responsive genes and have already been implicated in DNA damage response and cell cycle control after DNA damage. In summary, we substantiated the usefulness of AEN, FDXR, and DDB2 as RNA markers of low dose irradiation. Moreover, the upregulation of genes associated with DNA damage reminds one of the genotoxic nature of CT diagnostics even with the low doses currently applied.