Björn Friebe

Analysis of DNA Double-Strand Breaks and Cytotoxicity after 7 Tesla Magnetic Resonance Imaging of Isolated Human Lymphocytes

The global use of magnetic resonance imaging (MRI) is constantly growing and the field strengths increasing. Yet, only little data about harmful biological effects caused by MRI exposure are available and published research analyzing the impact of MRI on DNA integrity reported controversial results. This in vitro study aimed to investigate the genotoxic and cytotoxic potential of 7 T ultra-high-field MRI on isolated human peripheral blood mononuclear cells. Hence, unstimulated mononuclear blood cells were exposed to 7 T static magnetic field alone or in combination with maximum permissible imaging gradients and radiofrequency pulses as well as to ionizing radiation during computed tomography and γ-ray exposure. DNA double-strand breaks were quantified by flow cytometry and automated microscopy analysis of immunofluorescence stained γH2AX. Cytotoxicity was studied by CellTiter-Blue viability assay and [3H]-thymidine proliferation assay. Exposure of unstimulated mononuclear blood cells to 7 T static magnetic field alone or combined with varying gradient magnetic fields and pulsed radiofrequency fields did not induce DNA double-strand breaks, whereas irradiation with X- and γ-rays led to a dose-dependent induction of γH2AX foci. The viability assay revealed a time- and dose-dependent decrease in metabolic activity only among samples exposed to γ-radiation. Further, there was no evidence for altered proliferation response after cells were exposed to 7 T MRI or low doses of ionizing radiation (≤ 0.2 Gy). These findings confirm the acceptance of MRI as a safe non-invasive diagnostic imaging tool, but whether MRI can induce other types of DNA lesions or DNA double-strand breaks during altered conditions still needs to be investigated.

DNA double-strand breaks and micronuclei in human blood lymphocytes after repeated whole body exposures to 7T Magnetic Resonance Imaging.

PURPOSE To examine the extent of genetic damage, assessed from deoxyribonucleic acid (DNA) double-strand breaks (DSBs) and micronuclei (MN) in peripheral blood mononuclear cells obtained from individuals repeatedly exposed to 7T Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS The study protocol was approved by the local ethics committee. Informed consent was obtained from 22 healthy, non-smoking, non-alcoholic male individuals, who had never undergone radio-/chemo-therapy, scintigraphy, and had not undergone X-ray examination one year prior blood withdrawal. Eleven participants were repeatedly exposed to 7T and 3T MRI while working with/around scanners or frequently participating as 7T and lower field MRI research subjects (mean age 34±7years). The other half was never exposed to 7T or lower field MRI and served as controls (mean age 33±9years). The damage in lymphocytes was assessed using anti-γH2AX immunofluorescence staining of DNA DSBs and by quantification of MN. Isolated cells were further exposed in vitro to 7T MRI either alone or in the presence of the DNA damaging drug etoposide, to determine if there is any additional combined effect. The kinetics of DNA damage repair were examined. RESULTS The mean base-level of γH2AX foci/cell and incidence of MN between repeatedly exposed and control group were not significantly different (P=0.618 and P=0.535, respectively). The additional in vitro exposure of cells to 7T MRI had no significant impact on MN frequencies and γH2AX foci at 1, 20 and 72h after exposure. CONCLUSION Frequently repeated 7T MRI exposure did not result in a detectable increase in genotoxicity indices and alterations of DNA repair kinetics.

Sensory perceptions of individuals exposed to the static field of a 7T MRI: A controlled blinded study

To determine the subjective experience of subjects undergoing 7T magnetic resonance imaging (MRI) compared to a mock scanner with no magnetic field.

Impact of in Vivo High-Field-Strength and Ultra-High-Field-Strength MR Imaging on DNA Double-Strand-Break Formation in Human Lymphocytes

Purpose To determine the impact of different magnetic field strengths (1, 1.5, 3, and 7 T) and the effect of contrast agent on DNA double-strand-break (DSB) formation in patients undergoing magnetic resonance (MR) imaging. Materials and Methods This in vivo study was approved by the local ethics committee, and written informed consent was obtained from each patient. To analyze the level of DNA DSBs, peripheral blood mononuclear cells were isolated from blood samples drawn directly before, as well as 5 minutes and 30 minutes after MR imaging examination. After performing γH2AX immunofluorescence staining, DSBs were quantified with automated digital microscopy. MR group consisted of 43 patients (22 women, 21 men; mean age, 46.1 years; range, 20-77 years) and was further subdivided according to the applied field strength and administration of contrast agent. Additionally, 10 patients undergoing either unenhanced or contrast material-enhanced computed tomography (CT) served as positive control subjects. Statistical analysis was performed with Friedman test. Results Whereas DSBs in lymphocytes increased after CT exposure (before MR imaging: 0.14 foci per cell ± 0.05; 5 minutes after: 0.26 foci per cell ± 0.07; 30 minutes after: 0.24 foci per cell ± 0.07; P ≤ .05), no alterations were observed in patients examined with MR imaging (before MR imaging: 0.13 foci per cell ± 0.02; 5 minutes after: 0.12 foci per cell ± 0.02; 30 minutes after: 0.11 foci per cell ± 0.02; P > .05). Differentiated analysis of MR imaging subgroups again revealed no significant changes in γH2AX level. Conclusion Analysis of γH2AX foci showed no evidence of DSB induction after MR examination, independent of the applied field strength and administration of gadolinium-based contrast agent.

Initial Assessment of the Efficacy of Irreversible Electroporation in the Focal Treatment of Localized Renal Cell Carcinoma With Delayed-interval Kidney Tumor Resection (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] Trial—An Ablate-and-Resect Pilot Study)

OBJECTIVE To assess the efficacy of irreversible electroporation (IRE) ablation of pT1a renal cell carcinoma (RCC) in the first prospective, monocentric phase 2a pilot ablate-and-resect study (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] trial). It has been postulated that focal IRE can bring about complete ablation of soft-tissue tumors with protection of healthy peritumoral tissue and anatomic structures. PATIENTS AND METHODS The first 7 study patients with biopsy-proven pT1a RCC (15-39 mm) underwent IRE. Percutaneous computed tomography-guided IRE was performed with electrocardiographic triggering under general anesthesia and deep muscle paralysis with 3-6 monopolar electrodes positioned within the renal tumor. Twenty-eight days later, the tumor region was completely resected to confirm tumor destruction pathologically. Individual results for these patients are displayed, described, and discussed. RESULTS Technical feasibility was attained in all patients, but electrode placement and ablation were complex, with a mean overall procedure time of 129 minutes. There were no major complications. Partial kidney resection was performed in 5 patients, and radical nephrectomy was performed in 2 patients because of central tumor location and ablation areas. Resections revealed by tumor, node, and metastasis classification of the International Union for Cancer Control 2017 no residual tumor as complete ablation in 4 cases (ypT0V0N0Pn0R0) and microscopic residual tumor cells as incomplete ablation in the other 3 cases (ypT1aV0N0Pn0R1). CONCLUSION Renal percutaneous IRE appears to be a safe treatment for pT1a RCC but requires substantial procedural effort. Resection specimens of the ablation zone revealed a high rate of microscopic incomplete ablation 4 weeks after IRE. According to these initial study results, curative, kidney-sparing ablation of T1a RCC appears possible but needs technical improvement to ensure complete ablation.

MRI and Genetic Damage: An Update

Purpose of ReviewMagnetic resonance imaging (MRI) is generally considered to be a safe imaging technology when compared to diagnostic tools utilizing ionizing radiation. Unlike ionizing radiation, for which the detrimental biological effects, such as DNA damage, are known and well established, the potential of MRI to directly or indirectly induce genetic alterations is still not evident. This review article summarizes recent findings in MRI research related to DNA damage.Recent FindingsApplying different exposure conditions, several studies have examined the potential impact of MRI on DNA. While some authors reported increases in DNA damage, the largest studies and those with the highest field strength (up to 7 T) and highest exposure did not find a significant excess in DNA damage.SummaryThe debate about biological effects of MRI has been increasingly tackled over the last years, due to extended use of MRI systems in clinic and research. The balance of scientific evidence from available literature does not allow a final conclusion regarding any significant risk related to DNA damage induced by MRI. The risk and its impact on public health, if any, should be substantially small.

Transcatheter arterial embolization of acute bleeding as 24/7 service: predictors of outcome and mortality

OBJECTIVE To analyze times of occurrence and identify risk factors (RFs) for technical and clinical failure and mortality of transcatheter arterial embolization (TAE) of acute bleeding in a major hospital. METHODS All TAEs performed at our hospital from 2006 to 2013 (n = 327) were retrospectively analyzed. RESULTS TAEs were performed during regular weekday hours in 165 (50%) and during off-hours in 162 (50%) cases. With 40 regular and 128 off-hours/week, 3.25 times more TAEs were performed during regular hours. There was an even distribution across weekdays (Mon-Fri:16.9 ± 1.5%), while fewer TAEs were performed on weekends (Sat: 8.3%, Sun: 7.3%). Technical success of TAEs was 93.9% with a clinical success of 79.2% and a 30-day mortality of 18.4%. Shock was an RF for technical failure (p = 0.022). RFs for clinical failure were low hemoglobin (Hb) (p = 0.021) and transfusion of ≥6 units packed cells (p = 0.009). Independent RFs for mortality were clinical failure (p < 0.001), coagulopathy (p = 0.005), and shock (p < 0.001). CONCLUSION Our results provide no evidence for a subjectively perceived increase in TAEs during off-hours but rather appear to show that most TAEs are performed during regular hours. Prompt TAE to control acute bleeding is crucial to prevent a drop in Hb with shock and the need for transfusion, which may promote coagulopathy and rebleeding, all of which are risk factors for a negative outcome. ADVANCES IN KNOWLEDGE The presented analysis provides insights of occurrences and risk factors for success of transcatheter arterial embolization in acute bleeding in a large study population.

Cardiac Magnetic Resonance Imaging Using an Open 1.0T MR Platform: A Comparative Study with a 1.5T Tunnel System

Summary Background Cardiac magnetic resonance imaging (cMRI) has become the non-invasive reference standard for the evaluation of cardiac function and viability. The introduction of open, high-field, 1.0T (HFO) MR scanners offers advantages for examinations of obese, claustrophobic and paediatric patients. The aim of our study was to compare standard cMRI sequences from an HFO scanner and those from a cylindrical, 1.5T MR system. Material/Method Fifteen volunteers underwent cMRI both in an open HFO and in a cylindrical MR system. The protocol consisted of cine and unenhanced tissue sequences. The signal-to-noise ratio (SNR) for each sequence and blood-myocardium contrast for the cine sequences were assessed. Image quality and artefacts were rated. The location and number of non-diagnostic segments was determined. Volunteers’ tolerance to examinations in both scanners was investigated. Results SNR was significantly lower in the HFO scanner (all p<0.001). However, the contrast of the cine sequence was significantly higher in the HFO platform compared to the 1.5T MR scanner (0.685±0.41 vs. 0.611±0.54; p<0.001). Image quality was comparable for all sequences (all p>0.05). Overall, only few non-diagnostic myocardial segments were recorded: 6/960 (0.6%) by the HFO and 17/960 (1.8%) segments by the cylindrical system. The volunteers expressed a preference for the open MR system (p<0.01). Conclusions Standard cardiac MRI sequences in an HFO platform offer a high image quality that is comparable to the quality of images acquired in a cylindrical 1.5T MR scanner. An open scanner design may potentially improve tolerance of cardiac MRI and therefore allow to examine an even broader patient spectrum.

In-vivo-Analyse von DNA-Doppelstrangbrüchen in humanen mononukleären Zellen (MNZ) nach klinischen MRT-Untersuchungen

Material und Methodik: Bei insgesamt 43 Patienten (22 weiblich, 21 männlich, Altersspanne 20-77 Jahre, Durchschnittsalter 46,3 Jahre) wurde unmittelbar vor sowie 5 und 30 Minuten nach einer klinischen MRT-Untersuchung peripheres venöses Blut entnommen. Die klinischen MRT-Untersuchungen fanden an einem 1 Tesla-, 1,5 Tesla-, 3 Teslaoder 7 Tesla-Scanner, mit oder ohne Verabreichung von gadoliniumhaltigem Kontrastmittel statt und entsprachen klinisch üblichen MRT-Protokollen (Thorax, Abdomen, Becken, Herz, Muskuloskelettal). Als Referenz fungierten 10 Patienten mit CT-Untersuchungen (5 mit jodhaltigem Kontrastmittel, 5 nativ). Die mononukleären Zellen (MNZ) wurden mittels Dichtegradientenzentrifugation separiert und unmittelbar danach fixiert. Anschließend wurde die Anzahl von ?H2AX-Foci als Marker für DNA-Doppelstrangbrüche mittels Immunfluoreszenzfärbung und automatisierter Mikroskopie (AKLIDES-System, Medipan GmbH) zu den drei verschiedenen Zeitpunkten vor (t = -1 min) und nach der Exposition (t = 5 min und 30 min) bestimmt.

Radiological Diagnostics of Postoperative Sternal Osteomyelitis

Primary osteomyelitis of the sternum is very rare and is mainly seen in children (Narchi 1999; Upadhyayaa et al. 2005). Adults develop this disease only if certain risk factors such as i.v. drug abuse, acne fulminans, or palmoplantar pustulosis are present (Boll and Jurik 1990; Kalra et al. 1988; Vellacott 1952).