Siegfried A. Schwab

DNA Double-Strand Breaks and Their Repair in Blood Lymphocytes of Patients Undergoing Angiographic Procedures

Objectives:To adapt &ggr;-H2AX immunofluorescence microscopy to assessment of induction and repair of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes in patients undergoing angiographic procedures. Materials and Methods:The study was approved by the institutional ethics committee. After written informed patient consents were obtained, venous blood samples were taken from 19 patients (age 23–88 years) undergoing different angiographic procedures before, during, and after (10 minutes–24 hours) the examination. Individual DSB yields were visualized by detecting the phosphorylated variant of the histone H2AX (&ggr;-H2AX) in lymphocytes using fluorescence microscopy. Values were correlated with dose area product. Single in vitro irradiation with 50 mGy was performed in 14 and additional fractionated irradiation with 10 × 5 mGy over a time period corresponding to the angiography duration in 4 patients. The radiation doses to the blood delivered during angiography were estimated by comparing the number of DSBs after angiography with DSB yields obtained after in vitro irradiation. Results:In all patients in vivo and in vitro irradiation increased the number of DSBs (0.03–1.50 per cell), even if very small doses were applied (minimum 338 &mgr;Gy × m2). Thereafter in both in vitro and in vivo a rapid loss of &ggr;-H2AX foci was observed. The number of DSBs showed a linear correlation to dose area product for specific examination regions (eg, R = 0.85, pelvic and leg arteries). Calculated radiation doses to blood delivered during angiography ranged from 2.2 to 99.9 mGy and increased if fractioned in vitro samples were used as calibration instead of single in vitro irradiations at the same total dose. Conclusions:&ggr;-H2AX immunofluorescence microscopy is a reliable and sensitive method for measuring the induction and repair of DNA damage caused by ionizing radiation during angiography. To estimate radiation doses delivered during procedures and to consider patients individual repair capacity, postangiography DSB-yields should be compared with DSB-yields after fractioned in vitro irradiation imitating examination conditions.

Direct MR Galactography: Feasibility Study

PURPOSE To compare T1- and T2-weighted direct magnetic resonance (MR) galactography, indirect MR galactography, and conventional galactography in women with pathologic nipple discharge. MATERIALS AND METHODS The study was approved by the institutional review board. Written informed consent was obtained from all patients. Twenty-three women (age range, 30-85 years) with pathologic nipple discharge and pathologic conventional galactographic findings underwent physical examination, ultrasonography, and MR imaging before surgery. A T2-weighted sequence of the affected breast was performed before (indirect MR galactography), and T1- and T2-weighted sequences were performed after (direct MR galactography), gadopentetate dimeglumine was injected into the discharging duct. MR galactographic findings were analyzed and compared with conventional galactographic findings. Sequences used were T2-weighted three-dimensional constructive interference in steady state (CISS), T1-weighted volumetric interpolated breath-hold examination (VIBE), and T1-weighted fast low-angle shot (FLASH). RESULTS The 23 patients had a total of 57 findings at conventional galactography. Indirect MR galactography with CISS showed pathologic findings in eight (42%) of 19 patients and showed 15 (33%) of 46 of all findings. Direct MR galactography with CISS showed pathologic findings in 23 (100%) of 23 patients and 47 (82%) of 57 of all findings, that with VIBE showed pathologic findings in 19 (83%) of 23 patients and 38 (67%) of 57 of all findings, and that with FLASH showed pathologic findings in 16 (100%) of 16 patients and 31 (80%) of 39 of all findings. There was a significant (P < .01) difference between indirect MR galactography and all direct MR galactography sequences in the detection of ductal disease. Eight (35%) of 23 women showed additional findings at direct MR galactography in comparison with standard MR imaging sequences. CONCLUSION MR galactography has the potential to be used in the diagnostic work-up of pathologic nipple discharge. Direct MR galactography shows more disease than does indirect MR galactography. The highest detection rate for ductal disease compared with that at conventional galactography was found with the direct MR galactography CISS and FLASH sequences.

Magnetic resonance image-guided biopsies with a high detection rate of prostate cancer.

Aim. To explore the potential of transrectal magnetic resonance image- (MRI-) guided biopsies of the prostate in a patient cohort with prior negative ultrasound guided biopsies. Patients and Methods. Ninety-six men with suspected prostate cancer underwent MRI-guided prostate biopsies under real-time imaging control in supine position. Results. Adenocarcinoma of the prostate was detected in 39 of 96 patients. For individual core biopsies, MRI yielded a sensitivity of 93.0% and a specificity of 94.4%. When stratifying patients according to the free-to-total prostate-specific antigen (PSA) ratio, the prostate cancer discovery rate was significantly higher in the group with ratios less than 0.15 (57.1%). Conclusion. MRI-guided biopsy of the prostate is a diagnostic option for patients with suspected prostate cancer and a history of repeatedly negative transrectal ultrasound-guided biopsies. Combined with the free-to-total PSA ratio, it is a highly effective method for detecting prostate cancer.

Peripheral Intravenous Power Injection of Iodinated Contrast Media through 22G and 20G Cannulas: Can High Flow Rates Be Achieved Safely? A Clinical Feasibility Study

PURPOSE Modern examination protocols for computed tomography (CT) often require high injection rates of iodinated contrast media (CM). The purpose of this study was to evaluate the maximum achievable flow rates and stability of different peripheral intravenous catheters (IVC) in vitro and to assess the feasibility of higher injection rates through small IVC in vivo. MATERIALS AND METHODS For in vitro experiments flow measurements followed by high pressure testing of different types of IVC (22, 20, and 18 gauge [G]) were performed. For the in vitro study 91 patients with already inserted 22 or 20G IVC who had been referred for CT received Iopamidol (300 mg iodine/ml) at flow rates between 2 and 5 ml/sec. Complications were documented. RESULTS The maximal achievable flow rate of the tested IVC in vitro ranged from 5 to 8 ml/sec. No damage was observed during in vitro testing. The initially targeted in vivo flow rate was dropped in 33 of 91 (36 %) patients because the IVC could not be flushed adequately with saline before CM injection. Extravasation of CM occurred in 2 cases. In the remaining 58 patients the standard CT protocol was performed with flow rates of 3 ml/sec through 22G IVC and 5 ml/sec through 20G IVC, respectively. In this group, the extravasation of CM was observed twice (p > 0.05). CONCLUSION Even with highly viscous CM, high flow rates can be applied in vitro in 22, 20, and 18G IVC without risking material damage. In vivo power injection of iodinated CM through 22G and 20G IVC seems to be safely achievable in the majority of patients with flow rates of up to 3 ml/sec and 5 ml/sec. Extravasation rates do not differ significantly between patients with high-flow or low-flow injections.

Radiation Induced DNA Double-Strand Breaks in Radiology

UNLABELLED Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on physical measurements or mathematical algorithms with standardized dose simulations. γ-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the prinicple of the γ-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations. KEY POINTS Radiologic examinations including CT and angiography induce DNA double-strand breaks. Even after mammography a slight but significant increase is detectable in peripheral blood lymphocytes. The number of radiation induced double-strand breaks correlates well with the radiation dose. Individual factors including radiation sensitivity, DNA repair capacity and the application of iodinated contrast media has an influence on the DNA damage level.

Does direct MR galactography have the potential to become an alternative diagnostic tool in patients with pathological nipple discharge

PURPOSE To compare direct magnetic resonance galactography (dMRG) and conventional galactography (CGal). MATERIALS AND METHODS Thirty women underwent CGal and dMRG. Duct localization and the depth of the assumed underlying pathology in CGal and dMRG were analyzed. RESULTS Comparing CGal and dMRG, there was no significant difference regarding sector localization, but for depth of pathology (P=.023). CONCLUSION Duct localization with dMRG was possible with the same reliability as with CGal. Thus, dMRG may have the potential to become an alternative method to CGal.

Can the Documented Patient Briefing Be Carried Out with an iPad App

To evaluate the feasibility of an iPad-based documented patient briefing for Magnetic Resonance Imaging (MRI) examinations. A standard briefing sheet and questionnaire for a MRI scan was converted from paper form into an iPad application. Twenty patients, who had been referred for an MRI scan, were briefed about the examination in paper form as well as via the iPad application before performing the MRI scan. Time each patient needed for the briefing and the number of questions that came up were documented. Patients’ acceptance of the electronic briefing was assessed using a questionnaire. The mean processing time was 2.36 min (range 0.58 to 09.35 min., standard deviation ±2.05 min) for the paper-based briefing and 4.15 min (range 1.56 to 13.48 min, SD ± 2.36 min) for the app-based briefing. Concerning technical aspects, patients asked two questions during the app-based briefing; no questions arose during the paper-based briefing. Six patients preferred electronic briefing and four patients, the paper-based form. No patient preferred the electronic form with additional multimedial information. Eight participants did not mind which briefing version was used; two participants did not express their preference at all. Our experiences showed that electronic briefing using an iPad is feasible and has the potential to become a user-friendly alternative to the conventional paper-based approach. Owing to the broad range of the results, a follow-up study will seek to determine the influencing factors on processing time and other potential questions.

[X-ray-induced DNA double-strand breaks after angiographic examinations of different anatomic regions].

PURPOSE The aim of this study was to investigate DNA double-strand breaks (DSBs) in blood lymphocytes as markers of the biological radiation effects in angiography patients. MATERIALS AND METHODS The method is based on the phosphorylation of the histone variant H 2AX (gamma-H2AX) after formation of DSBs. Blood samples were collected before and up to 24 hours after exposure of 31 patients undergoing angiographies of different body regions. Blood lymphocytes were isolated, fixed, and stained with a specific gamma-H2AX antibody. Distinct foci representing DSBs were enumerated using fluorescence microscopy. Additional in-vitro experiments (10 - 100 mGy) were performed for evaluation of DBS repair. RESULTS 15 minutes after the end of fluoroscopy values between 0.01 and 1.50 DSBs per cell were obtained. The DNA damage level normalized to the dose area product was 0.099 (cardiac angiographies), 0.053 (abdominal angiographies), 0.023 (pelvic/leg angiographies) and 0.004 excess foci/cell/mGym (2) (cerebrovascular angiographies). A linear correlation was found between gamma-H2AX foci levels and the dose area product (abdomen: R (2) = 0.96; pelvis/legs: R 2 = 0.71). In-vivo on average 46 % of DSBs disappeared within 1 hour and 70 % within 2.5 hours. CONCLUSION gamma-H2AX immunofluorescence microscopy is a sensitive and reliable method for the determination of X-ray-induced DSBs during angiography. The DNA damage level depends on the dose, the exposed anatomic region, and the duration/fractionation of the X-ray exposure.

X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

Purpose To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM) and to estimate foci after FFDM and digital breast-tomosynthesis (DBT) using a biological phantom model. Materials and Methods The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified. Results Median in-vivo foci level/cell was 0.086 (range 0.067–0.116) before and 0.094 (0.076–0.126) after FFDM (p = 0.0004). In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086–0.140) at skin level and 0.035 (range 0.030–0.050) at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040–0.081) at skin level and 0.015 (range 0.006–0.020) at glandular level. Conclusion In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques.

Computer-Aided Assessment of Anomalies in the Scoliotic Spine in 3-D MRI Images

The assessment of anomalies in the scoliotic spine using Magnetic Resonance Imaging (MRI) is an essential task during the planning phase of a patients treatment and operations. Due to the pathologic bending of the spine, this is an extremely time consuming process as an orthogonal view onto every vertebra is required. In this article we present a system for computer-aided assessment (CAA) of anomalies in 3-D MRI images of the spine relying on curved planar reformations (CPR). We introduce all necessary steps, from the pre-processing of the data to the visualization component. As the core part of the framework is based on a segmentation of the spinal cord we focus on this. The proposed segmentation method is an iterative process. In every iteration the segmentation is updated by an energy based scheme derived from Markov random field (MRF) theory. We evaluate the segmentation results on public available clinical relevant 3-D MRI data sets of scoliosis patients. In order to assess the quality of the segmentation we use the angle between automatically computed planes through the vertebra and planes estimated by medical experts. This results in a mean angle difference of less than six degrees.