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.

Influence of iodinated contrast media on the activities of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase in vitro.

BACKGROUND: Iodinated contrast media can cause pseudoallergic reactions associated with histamine release in significant numbers of patients. To clarify whether these adverse reactions may be aggravated by a compromised histamine catabolism we asked if radiographic contrast agents in vitro inhibit the histamine inactivating enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HMT). METHODS: Nine iodinated contrast agents were tested in vitro. Following pre-incubation of purified porcine kidney DAO and recombinant human HMT with 0.1-10mM of the respective contrast medium (H2O and specific inhibitors of DAO and HMT as controls) enzyme activities were determined by using radiometric micro assays. RESULTS: None of the contrast media irrespective of their structure showed significant inhibition of the activities of DAO and HMT. Pre-incubation of the enzymes with specific inhibitors led to complete inhibition of the respective enzymatic activity. CONCLUSIONS: The iodinated contrast media tested in vitro did not exhibit inhibition of histamine converting enzymes at physiologically relevant concentrations. However due to the in vitro character of this study these results do not directly reflect the in vivo situation.

Transvenous Renal Transplant Biopsy via a Transfemoral Approach.

Percutaneous renal biopsy (PRB) of kidney transplants might be prevented by an elevated risk of bleeding or limited access to the allograft. In the following, we describe our initial experience with 71 transvenous renal transplant biopsies in 53 consecutive patients with unexplained reduced graft function who were considered unsuitable candidates for PRB (4.2% of all renal transplant biopsies at our institution). Biopsies were performed via the ipsilateral femoral vein with a renal biopsy set designed for transjugular renal biopsy (TJRB) of native kidneys. Positioning of the biopsy system within the transplant vein was achievable in 58 of 71 (81.7%) procedures. The specimen contained a median of 10 glomeruli (range 0-38). Tissue was considered as adequate for diagnosis in 56 of 57 (98.2%) biopsies. With respect to BANFF 50.9% of the specimen were adequate (>10 glomeruli), 47.4% marginally adequate (1-9 glomeruli) and 1.8% inadequate (no glomeruli). After implementation of real-time assessment all specimen contained glomeruli. One of the fifty-eight (1.8%) procedure-related major complications occurred (hydronephrosis requiring nephrostomy due to gross hematuria). Transfemoral renal transplant biopsy (TFRTB) is feasible and appears to be safe compared to PRB. It offers a useful new alternative for histological evaluation of graft dysfunction in selected patients with contraindications to PRB.

Comparison of 128-section single-shot technique with conventional spiral multisection CT for imaging of the temporal bone.

BACKGROUND AND PURPOSE: Computed tomography is an essential modality for imaging of the temporal bone. Newest generation scanners allow the coverage of large examination volumes with a single gantry rotation. The objective of this study was to compare a 128-section SST (1 single rotation of the x-ray tube) with conventional spiral MSCT (ultra-high-resolution mode) for imaging of the temporal bone. MATERIALS AND METHODS: Fifty-four temporal bones in 27 patients were scanned with both a conventional MSCT and 128-section SST. After blinding and randomization of both examinations, 2 observers assessed the visualization of 38 anatomic structures (eg, various segments of the facial nerve canal, mallear ligaments) by using multiplanar reconstructions in the axial and coronal planes. The differences in evaluation scores obtained for the 2 techniques were analyzed by using a Wilcoxon signed rank test, with a P value of < .05 considered significant. For both methods, imaging time and radiation exposure were noted. RESULTS: Overall visualization of anatomic structures did not differ significantly between the 2 techniques (P > .05). When we compared the anatomic structures separately, there was better visualization of the lateral mallear ligament with MSCT, whereas the cochlear septa were ranked higher with SST (P < .05). Imaging time and average DLP for MSCT were 12.3 seconds and 306 mGy cm, respectively; for SST, values they were 1 second and 64 mGy cm, respectively (ie, a dose reduction of 79%). CONCLUSIONS: For imaging of the temporal bone with adequate diagnostic quality, 128-section SST can be used. The main advantages over MSCT are the dramatic reductions of imaging time and radiation exposure, which are particularly important when scanning uncooperative patients or children.

[A useful tool for routine radiological examinations : the iPhone application "KM Helper"]. / Sinnvoller Einsatz neuer elektronischer Medien bei radiologischen Untersuchungen : Die iPhone-Applikation "KM Helper"

Since Apple's iPhone revolutionized the smartphone market, numerous software application features (apps) for portable devices have been developed. Amongst many others, a broad range of medical assistance software, such as anatomic books or medical encyclopedias is now available. We developed an app which helps to identify patients who need medical treatment before intravenous or intra-arterial administration of iodinated contrast media. The purpose of this article is to show that novel techniques such as smartphone applications can be a useful tool in medicine.

Effect of CT scan protocols on x-ray-induced DNA double-strand breaks in blood lymphocytes of patients undergoing coronary CT angiography.

AIMS: To compare in vivo DNA lesions induced during helical and sequential coronary computed tomography angiography (CTA) and to evaluate the effect of CT parameters on double-strand break (DSB) levels. METHODS: Thirty-six patients were examined with various CT protocols and modes (helical scan, n = 27; sequential scan, n = 9) either using a 64-slice dual-source or a 128-slice CT system. Blood samples were obtained before and 30 min after CT. Lymphocytes were isolated, stained against the phosphorylated histone variant γ-H2AX, and DSBs were visualised by using fluorescence microscopy. RESULTS: DSB yields 30 min after CTA ranged from 0.04 to 0.71 per cell and showed a significant correlation to DLP (ρ = 0.81, p < 0.00001). Median DSB yield and median DLP were significantly lower after sequential compared to helical CT examinations (0.11 vs. 0.37 DSBs/cell and 249 vs. 958 mGy cm, p < 0.00001). Additional calcium scoring led to an increase in DLP (p = 0.15) and DSB levels (p = 0.04). DSB levels normalised to the DLP showed a significant correlation to the attenuation of the blood (ρ = 0.53, p = 0.01) and a negative correlation to the body mass index of the patients (ρ = -0.37, p = 0.06). CONCLUSION: γ-H2AX immunofluorescence microscopy allows one to determine dose-related effects on x-ray-induced DSB levels and to consider individual factors which cannot be monitored by physical dose measurements.

Ormond's disease or secondary retroperitoneal fibrosis? An overview of retroperitoneal fibrosis.

Retroperitoneal fibrosis represents a rare inflammatory disease. About two thirds of all cases seem to be idiopathic (= Ormond's disease). The remaining one third is secondary and may be ascribed to infections, trauma, radiation therapy, malignant diseases, and the use of certain drugs. Up to 15 % of patients have additional fibrotic processes outside the retroperitoneum. The clinical symptoms of retroperitoneal fibrosis are non-specific. In sonography retroperitoneal fibrosis appears as a retroperitoneal hypoechoic mass which can involve the ureters and thus cause hydronephrosis. Intravenous urography and MR urography can demonstrate the typical triad of medial deviation and extrinsic compression of the ureters and hydronephrosis. CT and MRI are the modalities of choice for the diagnosis and follow-up of this disease. The lesion typically begins at the level of the fourth or fifth lumbar vertebra and appears as a plaque, encasing the aorta and the inferior vena cava and often enveloping and medially displacing the ureters. In unenhanced CT, retroperitoneal fibrosis appears as a mass that is isodense with muscle. When using MRI, the mass is hypointense in T 1-weighted images and of variable intensity in T 2-weighted images according to its stage: it may be hyperintense in early stages, while the tissue may have a low signal in late stages. After the administration of contrast media, enhancement is greatest in the early inflammatory phase and minimal in the late fibrotic phase. Dynamic gadolinium enhancement can be useful for assessing disease activity, monitoring response to treatment, and detecting relapse. To differentiate retroperitoneal masses, diffusion-weighted MRI may provide useful information.

[Initial experience with prospectively triggered, sequential CT coronary angiography on a 128-slice scanner]. / Erste Erfahrungen mit der sequenziellen, prospektiv getriggerten CT-Koronarangiografie an einem 128-Schicht-Computertomografen.

PURPOSE: Spiral CT angiography (CTA) of the coronaries using low-pitch scanning and ECG-gated image reconstruction is a robust method for detecting or excluding relevant coronary plaque. However, the resulting dose exposure is considerable. The aim of the present study was to evaluate image quality and artifacts as well as to record dose values for sequential coronary CTA using a 128-slice scanner with a temporal resolution of 150 ms. MATERIALS AND METHODS: 20 patients with a regular heart rate and without contraindications for oral/I.V. beta blockers, who were referred for CTA of the coronaries for exclusion or detection of relevant plaques, were examined by sequential CTA with the following parameters: 120 kV, 200 ref mAs, collimation 2 x 64 x 0.6, table feed of 34.5 mm at a detector width of 38.4 mm. A total acquisition time of 380 ms per table position allowed for mild shifting of the reconstruction window within the cardiac cycle of +/- 5 %. 50 ml of contrast agent were injected at 5 ml/s followed by a 50 ml split bolus (20 % contrast). The individual start delay was determined by a test bolus scan (10 ml contrast + 50 ml saline flush at 5 ml/s). The image quality for each segment, coronary artery, and patient was determined on a 4-point scale. Dose values were estimated based on the individual dose length product as provided by the scanner's patient protocol. Artifacts were evaluated to determine the cause (calcium vs. motion). RESULTS: All patients received beta blocker pretreatment. The mean heart rate was 62 +/- 5 beats/min. 5 % (13 / 286) of all segments in 5 / 20 patients were rated as non-diagnostic. The mean dose length product was 213 mGy x cm, and the mean effective dose was 3.6 mSv. Calcifications were the major cause of non-diagnostic images. However breathing or other motion artifacts occurred as well. CONCLUSION: In select patients with effective heart rate control and thorough instruction for breath hold compliance, sequential CTA of the coronaries using a 128-slice scanner with a temporal resolution of 150 ms is technically feasible. The resulting effective dose values are clearly below those of spiral coronary CT scans.

Iodixanol induces apoptotic and antiproliferative effects but no necrotic cell death in renal proximal tubular cells in vitro.

PURPOSE: To evaluate the cytotoxic effects of the iso-osmolar contrast medium iodixanol on renal tubular cell cultures. MATERIALS AND METHODS: LLC-PK1 cells were incubated with iodixanol and isotonic NaCl (18.75 - 75 mg I/ml, 1 - 24 hours). Cell death was assessed by the trypan blue exclusion test. To assess apoptosis, mononucleosomes and oligonucleosomes of cell lysates were determined. Measurement of BrdU (5-bromo-2'-deoxyuridine) incorporation into the DNA was used for the quantification of cell proliferation. RESULTS: Iodixanol did not induce any significant increase in the number of necrotic cells (8 % and 9 % at 37.5 and 75 mg I/ml vs. 8 % for control, p > 0.05). In contrast, iodixanol significantly increased the number of oligonucleosomes indicating induction of apoptosis (125 +/- 4 % of control, p < 0.05). Iodixanol induced a significant, dose- and time-dependent inhibition of BrdU incorporation indicating the inhibition of cell proliferation (92 +/- 2 % and 79 +/- 2 % of control at 18.75 and 37.5 mg I/ml, p < 0.001). CONCLUSION: Apoptosis plus an antiproliferative effect of iodixanol without cell necrosis contribute to the renal tubular toxicity of iodixanol.

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.

[X-ray-induced DNA double-strand breaks after angiographic examinations of different anatomic regions]. / Strahleninduzierte DNA-Doppelstrangbrüche nach Angiografien verschiedener Körperregionen.

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.

Unusual subcutaneous localisation of a dermatofibrosarcoma protuberans of the female breast: a case report.

Dermatofibrosarcoma protuberans (DFSP) is a slow growing soft tissue neoplasm of dermal fibroblastic origin characterised by local invasion and a high propensity for local recurrence. We report a 31-year-old woman with subcutaneous DFSP of the breast, which is an unusual localisation. Diagnostic work-up comprised clinical examination, mammography and ultrasound. Definitive diagnosis was not possible prior to histological analysis of the lesion. Wide excision of the tumour was performed, which is the therapy of choice in DFSP. Ultrasound played an important role in histological diagnosis before definitive surgery and might be helpful in follow-up of patients with DFSP of the breast.

[How to cope with the demands of the new "Approbation Regulation" (AR) by radiology-related interdisciplinary courses. The Erlangen model]. / Wie wir die Herausforderungen der neuen Approbationsordnung (AO) durch neue computergestützte radiologisch-interdisziplinäre Programme bewältigen können. Das Erlanger Modell.

BACKGROUND: To create radiology-related interdisciplinary programs for the undergraduate education in terms of the new "Approbation Regulation". MATERIAL AND METHODS: Medical students developed in collaboration with radiologists and clinical partners virtual, radiology-related interdisciplinary training courses for different fields. Students and teachers evaluated the acceptance of the programs' structure and content as well as the possibility to replace the radiologist partly during interdisciplinary lessons. RESULTS: Six target group oriented virtual, radiology-related interdisciplinary training courses were developed which will relieve the implementation of the new AR's demands for more interdisciplinary education in small groups and the dreaded shortage of personnel. CONCLUSION: By the use of web- and CDRom-based interdisciplinary course models different fields of medicine and diagnostic radiology can be bridged in the sense of the new AR's demands as well as manpower in radiology can be saved.