[The "EVA" Trial: Evaluation of the Efficacy of Diagnostic Methods (Mammography, Ultrasound, MRI) in the secondary and tertiary prevention of familial breast cancer. Preliminary results after the first half of the study period]. / Die "EVA"-Studie: Evaluierung der Leistungsfähigkeit diagnostischer Verfahren (Mammographie, Sonographie, MRT) zur sekundären und tertiären Prävention des familiären Mammakarzinoms -- Zwischenergebnisse nach der ersten Hälfte der Förderungsperiode.

PURPOSE: To investigate the respective diagnostic accuracies of the different breast imaging modalities, i. e., mammography (Mx), high-frequency breast ultrasound (US), and dynamic contrast-enhanced breast (MRI) regarding the early diagnosis of familial (hereditary) breast cancer. MATERIALS AND METHODS: A prospective, non-randomized controlled clinical multi-center trial is performed at 4 academic tertiary care centers in Germany (Ulm, Munchen/Grosshadern, Munster and Bonn) for a total period of 4 years, sponsored by the German Cancer Aid. The protocol consists of semiannual clinical visits and breast ultrasound, and annual bilateral two-view Mx, US and MRI. Imaging studies were first analyzed independently, then Mx was read in conjunction with US, followed by Mx combined with MRI, and finally, all three imaging modalities were read in synopsis. We present the concept and first results of this trial. RESULTS: So far, 748 screening rounds are available for analysis in 613 women. A total of 12 breast cancers have been identified, with 11/12 cases in the pTis or pT1/N0 stage. The mean size of detected invasive cancers was 7 mm. A total of 19 benign lesions were biopsied due to false-positive imaging diagnoses. The breast cancer detection rates were: Mx: 5/12 (42 %), US 3/12 (25 %), MRI 10/12 (83 %), and the positive predictive values: Mx 5/17 (29 %), US 3/15 (30 %), and MRI 10/23 (43 %). CONCLUSION: The preliminary data suggest that early diagnosis of familial breast cancer is feasible by intensified surveillance, in particular with the addition of MRI.

Pharmacokinetics of 1M gadobutrol in patients with chronic renal failure.

RATIONALE AND OBJECTIVES: To investigate the pharmacokinetics of 1M gadobutrol as a new neutral MR contrast agent in patients with impaired renal function. METHODS: Twenty-one patients with impaired renal function and any indication for a contrast-enhanced MRI were enrolled into this prospective study and classified in two subgroups according to their creatinine clearance (group 1, 30-80 mL/ min; group 2, 30 mL/min or less, not requiring dialysis). Eleven patients were assigned to the lower dose of 0.1 mmol Gd/kg and 10 patients to the higher dose of 0.3 mmol Gd/kg. To calculate pharmacokinetic parameters, urine and venous blood samples were drawn at baseline and up to 72 hours for group 1 and 120 hours for group 2 after administration of gadobutrol. RESULTS: The predominant extracellular distribution of gadobutrol at steady state did not change according to the degree of renal impairment. The mean elimination half-life of gadobutrol increased to 7.4 +/- 2.6 hours (0.1 mmol/kg) and 5.4 +/- 1.5 hour (0.3 mmol/kg) in group 1 and to 17.9 +/- 6.2 hours (0.1 mmol/kg) and 20.4 +/- 16.9 hours (0.3 mmol/kg) in group 2, compared with 1.5 hours in healthy volunteers. The relation between serum (tbeta) and urine (t(elim)) elimination half-lives, as well as total serum and renal clearance, indicated renal elimination as the main pathway of elimination. The recovery of gadobutrol in the urine of group 1 was complete within 72 hours for both dosage levels. Patients with severe renal impairment showed a mean recovery of 80.1% (0.1 mmol/kg) and 85.3% (0.3 mmol/kg) within the observation period of 120 hours. CONCLUSIONS: The half-life of gadobutrol is prolonged in patients with impaired renal function, but elimination by means of the kidneys is the predominant route.

Amperometric creatinine biosensor for hemodialysis patients.

BACKGROUND: Creatinine is an important clinical laboratory parameter for the evaluation of kidney function. It is essential to determine its concentration in serum of patients suffering from renal insufficiency. During hemodialysis treatment, the measurement of creatinine in the effluent dialysate or ultrafiltrate may give additional information on the efficiency of the extracorporal procedure. Therefore, enzyme sensors with co-immobilized creatinine amidohydrolase, creatine amidinohydrolase and sarcosine oxidase have been used to determine creatinine. METHODS: Enzymatically generated hydrogen peroxide has amperometrically been detected at a platinum-working electrode. To exclude electroactive compounds of the sample matrix, which might interfere with the electrochemical measurement, the sensors have additionally been modified by a Nafion membrane. RESULTS: Such sensors showed a linear detection range of 0.06-1.7 mg/dl for creatinine. Diluting the sample with measuring buffer, it has also been possible to measure pathological creatinine concentrations up to 11 mg/dl. A good correlation between creatinine concentrations in serum, dialysate and ultrafiltrate determined by the presented enzyme sensors and those obtained by both, conventional colorimetric Jaffé and enzymatic measurements have been achieved. CONCLUSION: Further developments will aim at the integration of this measuring principle into the concept to low-cost disposable planar sensors.

[Gd-BOPTA enhanced excretory MR urography without administration of diuretics]. / Gd-BOPTA-gestützte MR-Ausscheidungsurographie ohne Diuretikagabe.

PURPOSE: To evaluate the feasibility and clinical utility of Gd-BOPTA enhanced excretory magnetic resonance urography without additional administration of diuretics in correlation with conventional urography. METHOD: 15 preoperative patients with pelvic tumors were examined at 1.5 T using a breath-hold high-resolution 3D-FLASH sequence during first-pass as well as 5, 10, 15 minutes after i.v. injection of 0.05 mmol/kg BW Gd-BOPTA (MultiHance) without administration of diuretics. Post-processed coronal and multiplanar MIP reconstructions were compared to conventional excretory urography with regard to morphologic accuracy, anatomic variability, filling defects, cause and level of obstruction or compression, tumor visibility, and time-effectiveness by two independent radiologists. RESULTS: Visualization of the urinary tract by MRU was comparable to conventional excretory urography in 14 of 15 cases. Caliceal fornices were better delineated on conventional urographies, whereas MRU was considered superior in the assessment of the inferior ureter sections, the urinary bladder and obstructive tumors, whose extents could be clearly marked out. Examination times of both techniques were comparable. CONCLUSION: These first results show that non-diuretic Gd-BOPTA enhanced MRU is comparable to conventional excretory urography for the preoperative diagnosis of pelvic tumors. Further improvements of this technique seem possible by optimization of examination intervals and injection doses.

[Automatic injectors in magnetic resonance imaging and computed tomography: pilot study on hygienic aspects]. / Injektionsautomaten in der Magnetresonanz- und Computertomographie: Pilotstudie zu hygienischen Aspekten.

PURPOSE: To evaluate hygienic conditions using automatic injectors in magnetic resonance imaging (MRI) and computed tomography (CT) during clinical routine. MATERIALS AND METHODS: The surfaces of medical devices (e. g., control console) and the palms of the technical and medical staff were microbiologically analyzed by taking imprints before and after hygienic education. In addition, the injector syringes for contrast medium (CM) and saline were checked for microbiological contamination following multiple (MRI: 14 h; CT 8 h) and single use. Furthermore, the potential of retrograde contamination from the patient along the tube was analyzed. RESULTS: A bacterial contamination with typical dermal bacteria was documented for the surfaces of the medical devices, the palms of the technical and medical staff, and the injection syringes following multiple use (MRI: 10/10 CM syringes, 6/10 saline syringes; CT: 8/10 CM syringes, 5/10 saline syringes). Correct hand disinfection in combination with single use of syringes avoided bacterial colonization. Retrograde bacterial contamination from the patient was not observed. CONCLUSION: Regular hygienic teaching sessions for technical and medical staff in MRI and CT departments using automatic injectors should be mandatory. Furthermore, the multiple use of syringes should be avoided until investigations addressing the potential of bacterial contamination are performed.

[The value of magnetic resonance imaging (MRI) for the follow-up of patients with transjugular intrahepatic portosystemic shunts (TIPS)]. / Der Stellenwert der Magnetresonanztomographie (MRT) für die Verlaufskontrolle bei Patienten mit transjugulärem intrahepatischem portosystemischem Stent-Shunt (TIPSS).

PURPOSE: To prospectively determine the value of magnetic resonance imaging (MRI) with flow quantification in the portal vein for the follow-up of patients with transjugular intrahepatic portosystemic shunt (TIPS). METHODS: Thirty-six patients with TIPS (23 m, 13 f) were evaluated with MR of the liver parenchyma and quantification of flow in the portal vein. MR examinations were correlated with Doppler sonography and conventional angiography including measurement of the portal pressure gradient (PPG). In cases of re-interventions (dilatation/stent application) additional examinations with MRI and Doppler sonography were performed. RESULTS: MR flow measurements in the portal vein correlated with Doppler sonography (r = 0.69) whereas no correlation of both methods with the PPG was found. No threshold velocity in the portal vein could be determined to predict shunt stenosis. All shunt occlusions (n = 5) were diagnosed correctly by MRA. Thirty measurements before and after successful angiographic interventions revealed a significant increase in portal flow velocity and a significant decrease of the PPG. Magnetic resonance images enabled a reliable detection of procedural complications (parenchymal bleedings, n = 31; extra and subcaspular hematomas, n = 2 each) and newly occurring hepatocellular carcinomas (n = 2) in the follow-up period. CONCLUSION: Magnetic resonance imaging in the follow-up of TIPS enables a morphological assessment of the liver and an accurate velocity mapping, but is not suited to predict shunt dysfunction as a single method.

[MRI study of left ventricular function in patients with coronary disease and myocardial dysfunction before and after coronary revascularization]. / MR-tomographische Untersuchung der linksventrikulären Funktion bei Patienten mit koronarer Herzerkrankung und myokardialer Dysfunktion vor und nach koronarchirurgischer Revaskularisation.

PURPOSE: To evaluate left ventricular (LV) myocardial function in ten patients with coronary artery disease (CAD) preoperatively and 6 months after coronary bypass grafting (CABG) by cardiac MRI. MATERIAL AND METHODS: Ten patients (mean 65.2 +/- 5.9 years) with angiographically proven CAD and an indication for elective CABG underwent prospective evaluation of global LV function and regional wall motion by Cine-MRI at rest using a multiphase FLASH-2D sequence following regions of interest (ROI)-defined diagnostics of regional myocardial wall motion by means of levocardiography. Within the ROIs a total of 613 LV myocardial segments were analyzed preceding and following surgical revascularization. Results were compared with the data of 10 healthy volunteers. RESULTS: Preoperatively, patients showed reduced stroke volume and ejection fraction compared with volunteers (p < 0.01). Enddiastolic wall thickness (EDWT) and systolic wall thickening (SWT) were significantly lower in the patients (p < 0.01). Based on preoperative levocardiography ROI-defined myocardial segments showed a significantly lower preoperative EDWT in areas with wall motion abnormalities (7.4 +/- 2.5 mm; p < 0.01) than in normal myocardium (9.2 +/- 2.1 mm). Ejection fraction (p < 0.05), endsystolic wall thickness, and SWT (p < 0.01) improved significantly after bypass surgery. On ROI-defined analysis myocardial segments with impaired preoperative wall motion (n = 243) showed a significant increase of EDWT, ESWT and SWT (p < 0.01). CONCLUSION: In patients with CAD, cardiac MRI enables the non-invasive determination of postinfarctional LV remodeling with an increased EDWT of myocardial segments with normal regional wall motion and of the improvement in global and regional myocardial function following coronary bypass surgery.

[T1-weighted dynamic MRI with new superparamagnetic iron oxide particles (Resovist): results of a phantom study as well as 25 patients]. / T1-gewichtete dynamische MRT mit neuen superparamagnetischen Eisenoxidpartikeln (Resovist): Ergebnisse einer Studie am Phantom sowie an 25 Patienten.

PURPOSE: Evaluation of the diagnostic usefulness of the T1-effect of Resovist (SPIO) for dynamic MRI of the liver. METHOD: In-vitro measurements of a dilution series with T1-weighted FLASH and SE sequences and investigation of 25 patients with known focal liver lesions with a T2-weighted TSE sequence and a dynamic T1-FLASH sequence. RESULTS: T1-weighted MRI with Resovist in vitro showed a positive enhancement at low concentrations and a negative enhancement at higher concentrations. In-vivo T1-weighted dynamic MRI liver parenchyma demonstrated a positive enhancement 30 s post contrast, followed by a continuous slope of signal intensity and a negative enhancement (> or = 60 s). Spleen, portal venous vessels and haemangiomas showed an early increase in signal intensity followed by a decreasing positive enhancement, but without negative enhancement. During the perfusion phase metastases showed a small but not significant increase in signal intensity. In 80% a positive ring enhancement could be observed around metastases. CONCLUSION: Resovist exhibits a diagnostically useful T1-effect. An evaluation of the perfusion of focal liver lesions during the distribution phase is possible with dynamic T1-weighted MRI. This approach may further improve characterisation of focal liver lesions.

Magnetic resonance angiography follow-up examinations to detect iatrogenic pseudoaneurysms following otorhinolaryngological surgery.

Endoscopic endonasal surgery on a 36-year-old man was complicated by perforation of the right internal carotid artery. The immediate, substantial haemorrhage was controlled by packing the sphenoid sinus. Intra-arterial angiography of the right internal carotid artery showed small irregularities proximal to the ophthalmic artery. A follow-up examination two weeks later documented a large pseudoaneurysm in the initially irregular arterial segment, which was successfully treated by endovascular coiling. This case report illustrates the need for angiographic follow-up examinations following traumatic intracranial vessel injury in order to identify late pseudoaneurysm development.

[Molecular and parametric imaging with iron oxides]. / Molekulare und parametrische Bildgebung mit Eisenoxiden.

Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression. This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging.

Hepatic MRI with SPIO: detection and characterization of focal liver lesions.

A variety of parenterally administered iron oxides have been developed for contrast-enhanced MRI of the liver. Two different classes of iron oxides are currently clinically approved or in phase 3 trials: superparamagnetic iron oxides (SPIO) with a high R2/R1 relaxivity ratio and short blood half-life (AMI-25 and SH U 555 A), and ultrasmall paramagnetic iron oxides (USPIO) with a lower R2/R1 relaxivity ratio and longer blood half-life (AMI-227). All iron oxides significantly increase tumor-to-liver contrast and allow detection of more lesions than unenhanced MRI on T2-weighted images at a field strength of 0.2-1.5 T. Malignant lesions without phagocytic cells exhibit constant signal on T2-weighted accumulation phase images with all three iron oxides. All iron oxides cause a signal decrease of benign lesions with either phagocytic cells or a significant blood pool on T2-weighted accumulation phase images. The signal decrease of benign lesions is proportional to the Kupffer cell activity or tumor vascularity and is useful for lesion characterization. Another enhancement feature for the differentiation of benign from malignant lesions is ring enhancement of malignant lesions (metastases) on T1-weighted enhanced images either during the perfusion phase with SH U 555 A or during the accumulation phase with AMI-227, which is attributed to the blood pool effects of the compounds. Differentiation of lesions and vessels is easier on enhanced images with angiographic effects than on unenhanced images. Iron oxides improve the quality of two-dimensional MR angiography techniques of the portal venous system by decreasing background signal (liver tissue with all iron oxides) and increasing intravascular signal (AMI-227). The use of iron oxides for hepatic MRI provides an alternative to the existing multistep diagnosis with CT, CT portography, MRI and biopsy.

Purification of human placental prostaglandin 15-hydroxydehydrogenase.

The NAD(+)-linked prostaglandin 15-hydroxydehydrogenase, which is responsible for the physiological inactivation of prostaglandins by catalysing the first step in the catabolism, was isolated and purified 995-fold from human placenta. The introduction of two new chromatographic steps in the purification procedure is responsible for an achieved specific activity of 1791 mU/mg. The molecular mass of the enzyme, as estimated by fast protein liquid chromatography, was 24,500 dalton. Sodium dodecyl sulphate discontinuous gel electrophoresis of the denatured enzyme revealed a molecular mass of 24,000 dalton. These data suggest that the enzyme consists of a single polypeptide chain.

[Tubercular spondylitis with retropharyngeal abscess]. / Tuberkulöse Spondylitis mit retropharyngealer Abszedierung.

In the industrialized countries, the last 15 years have seen an increasing rate of cases of tuberculosis. However, upper cervical spine tuberculosis involving a cold retropharyngeal abscess is extremely rare. We report on a 58 year old female from Sri Lanka presenting with unspecific neck pain and stiffness. She was diagnosed as having extensive tubercular osteodestruction of the second cervical spine body, including epidural and large retropharyngeal abscesses.

Detection of articular cartilage lesions: experimental evaluation of low- and high-field-strength MR imaging at 0.18 and 1.0 T.

The objective of this study was to compare the diagnostic performance of a dedicated orthopedic magnetic resonance (MR) imaging system (0.18 T) and a conventional MR imaging system (1.0 T) in the detection of articular cartilage lesions. Fifty knee joint specimens of pigs with artificially created articular cartilage lesions of different diameters, grades (2-3), and localizations, as well as 50 joints with intact articular cartilage, were imaged at 0. 18 and 1.0 T. Diagnostic performance was determined by means of receiver operating characteristics (ROC) analysis with three independent observers. For none of the pulse sequences used at 0.18 T or 1.0 T areas under ROC curves (A(z)) showed significant differences between the three observers. A(z) values from averaged data were as follows: a) 0.18 T: T1-weighted spin echo (SE): 0.70, proton-density-weighted SE: 0.59, T2-weighted SE: 0.61, two-dimensional (2D) gradient-echo (GRE): 0.73, 3D GRE: 0.75; and b) 1.0 T: T1-weighted SE: 0.73, fat-suppressed T2-weighted turbo-SE: 0. 79, 2D fast low-angle shot (FLASH): 0.79, fat-suppressed 3D FLASH: 0. 96, and water-excited 3D double-echo steady state (DESS): 0.96. With the use of 3D pulse sequences, the high-field system demonstrated a significantly better diagnostic performance than the low-field system in the detection of grades 2 and 3 articular cartilage lesions (P < 0.001).

Sensitivity of T2-weighted FSE sequences towards physiological iron depositions in normal brains at 1.5 and 3.0 T.

To evaluate the sensitivity of T2-weighted fast spin-echo (FSE) sequences to physiological iron depositions in normal brains at MR imaging field strengths of 1.5 and 3.0 T. T2-weighted FSE sequences acquired at 1.5 and 3.0 T clinical imaging systems (Gyroscan Intera, Philips Medical Systems, Best, The Netherlands) were compared by means of MRI in phantoms ( n=6) and healthy volunteers ( n=10). Contrast-to-noise ratios (CNRs) of tubes doped with iron oxides at different concentrations and of brain areas with physiological iron depositions (nucleus ruber, substantia nigra, globus pallidus) were calculated for either field strength. Apparent susceptibility effects of iron-containing brain structures were qualitatively analyzed by comparing the degree of visible hypointensity by a score system at either field strength. The mean CNR of iron oxide tubes and iron-containing brain areas was significantly decreased at 3.0 T. Qualitative analysis confirmed these measurements. Detection and diagnosis of brain disorders with altered iron content such as neurodegenerative parkinsonian disorders (NPD) or intracerebral hemorrhage should benefit from the increased sensitivity of T2-weighted FSE sequences to susceptibility effects at 3.0 T.

Three-dimensional contrast-enhanced MR angiography of endovascular covered stents in patients with peripheral arterial occlusive disease.

OBJECTIVE: Three-dimensional contrast-enhanced MR angiography was performed to study MR characteristics of Hemobahn devices. MATERIALS AND METHODS: Changes in endoluminal signal intensities and the precision of the endoluminal diameter measurement were investigated in phantom studies for different concentrations of gadopentetate dimeglumine. Before and after the Hemobahn devices had been implanted, 10 patients with peripheral arterial occlusive disease were examined on MR imaging and three-dimensional contrast-enhanced MR angiography. RESULTS: Phantom experiments using three-dimensional MR angiography showed stent-related signal void as a dark ring in the axial image orientation, providing a precise delineation of the stent--vessel border (mean endoluminal diameter, 8.2 mm; SD, 0.6 mm). Changes in endoluminal signal intensity were evaluated quantitatively. Stent-related artifacts did not compromise diagnostic imaging quality. All Hemobahn devices were found to be patent without migration of an implanted graft. In one patient, an extensive perigraft reaction (edema and contrast-enhanced perivascular tissue) was postinterventionally detected on MR imaging and corresponded to clinically evident postimplantation symptoms. CONCLUSION: Three-dimensional contrast-enhanced MR angiography is a suitable tool to follow up the implantation of Hemobahn devices and to detect intra- and extraluminal abnormalities.

Clearance of iopromide during haemodialysis with high- and low-flux membranes.

PURPOSE: The present clinical trial addressed the clearance of the contrast medium iopromide, a middle-sized molecule, during dialysis with high- and low-flux membranes. MATERIAL AND METHODS: Twenty chronic haemodialysis patients without residual renal function were dialysed either with low-flux haemophan or high-flux polyamide directly after application of the contrast medium. Iodine concentrations were determined by radiofluorescence methods. RESULTS: Plasma concentrations of iodine before dialysis ranged between 1.1 and 3.9 mg/ml. The mean clearance rates for both membranes were comparable (110+/-1.4 ml/min high-flux and 108+/-1.9 ml/min low-flux), the sieving-coefficient was 0.83 for both membranes. After three hours of dialysis, 58% (high-flux) and 62% (low-flux) of iopromide was removed, half time of elimination was reached after 140+/-16 min (high-flux) and 122+/-11 min (low-flux). CONCLUSION: Our results demonstrated that elimination of iopromide is not dependent on the pore size of the membrane during dialysis. Due to higher blood flow rate, we found a higher elimination rate and a reduced half-time of elimination than prior investigations.