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PURPOSE The aim of this study was to evaluate in vitro and in vivo the enhancement properties of experimental gadolinium (Gd)-based contrast agents (GBCAs) with different molecular weights and hydration numbers (P846 and gadopiclenol) compared with clinically approved low-molecular, extracellular agents (gadopentetate and gadoterate) at 9.4 T and to discuss influencing factors on r1 relaxivities. METHODS AND MATERIALS All experiments were performed with a 9.4 T animal scanner (Bruker, Germany). We performed relaxometry measurements for all contrast agents in human plasma at 37°C using an IR-RARE sequence. In addition, we compared P846 with gadopentetate and gadopiclenol with gadoterate intraindividually in rats with hepatic colorectal cancer metastases (n = 10 each) acquiring T1-weighted FLASH sequences before and at 10 consecutive time points during 20 minutes. After intravenous contrast agent application, signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and lesion enhancement (LE) for liver parenchyma and tumors were calculated based on region of interest measurements. RESULTS Longitudinal relaxivities (r1) of the low-molecular agents were lower as compared with the experimental compounds. However, r1 of gadopentetate and gadoterate demonstrated only a moderate decrease of r1 at 9.4 T as compared with known data at lower field strengths (gadopentetate: r1 [at 9.4 T], 3.4 mM s/r1 [at 1.5 T], 4.1 mM s/gadoterate: r1 [at 9.4 T], 3.1 mM s/r1 [at 1.5 T], 3.6 mM s). In contrast, r1 of P846 showed a marked reduction at 9.4 T compared with 1.5 T (P846: r1 [at 9.4 T], 6.4 mM s/r1 [at 1.5 T], 32 mM s). Gadopiclenol provided the highest r1 in this study at 9.4 T and the drop of r1 as compared with lower field strength is less apparent (gadopiclenol: r1 [at 9.4 T], 8.7 mM s/r1 [at 1.5 T], 12.7 mM s).In vivo, P846 and gadopiclenol showed significantly higher SNR, CNR, and LE as compared with the low-molecular control agents (mean ± SD; SNRliver [gadopentetate, 18.1 ± 1.2; P846, 27.2 ± 1.5; P < 0.001]; SNRtumor [gadopentetate, 22.6 ± 1.9; P846, 40.1 ± 1.9; P < 0.001]; CNR [gadopentetate, 4.6 ± 1.0; P846, 12.9 ± 0.9; P < 0.001]; LE [gadopentetate, 7.2 ± 1.9; P846, 14.9 ± 1.9; P < 0.001]/SNRliver [gadoterate, 8.8 ± 0.5; gadopiclenol, 12.6 ± 1.3; P < 0.001]; SNRtumor [gadoterate, 11.3 ± 1.2; gadopiclenol, 20.9 ± 2.9; P < 0.001]; CNR [gadoterate, 2.5 ± 0.7; gadopiclenol, 8.3 ± 1.7; P < 0.001]; LE [gadoterate, 4.4 ± 1.2; gadopiclenol, 13.0 ± 2.9; P < 0.001]). Thus, for equal Gd doses, gadopiclenol and P846 increase the CNR of liver metastases by a factor of 2.5 to 3 at 9.4 T compared with gadoterate and gadopentetate. CONCLUSIONS P846 and gadopiclenol provide superior enhancement at 9.4 T as compared with gadopentetate and gadoterate. However, the macromolecular agent P846 shows a marked decrease of r1 from 1.5 T to 9.4 T. This effect is less apparent for the low-molecular agents gadopiclenol, gadopentetate, and gadoterate. Yet, based on the higher hydration number, r1 of P846 and gadopiclenol are markedly higher as compared with the reference contrast agents. Thus, building compounds with moderately increased molecular size and hydration number, as implemented in gadopiclenol, seems to be a promising way to develop highly effective GBCAs.Advantages for gadopiclenol include a strong enhancement regardless of the external magnetic field strength, pharmacokinetics comparable to those of clinically approved extracellular GBCAs, and the potential to either improve sensitivity in diagnostic magnetic resonance imaging by improving lesion conspicuity or to perform studies with significantly reduced Gd-dose while at the same time providing comparable diagnostic accuracy. However, all this needs to be proven in clinical studies.

Epidemiological and clinical studies have shown a relevant association between heart rate and cardiovascular mortality. Experimental studies identified vascular effects of heart rate reduction with the If channel inhibitor ivabradine. Therefore, the effects of heart rate reduction on endothelial function and indices of arterial stiffness were examined in patients with stable coronary artery disease in a prospective, placebo-controlled clinical crossover study.Twenty-three patients (18 men and 5 women) with a resting heart rate (HR) of at least 70 beats per minute (bpm) and stable coronary artery disease were enrolled in this study. In a cross-over design, all patients were treated with ivabradine (Iva, 7.5 mg b.i.d.) and placebo for 6 months each. Iva reduced heart rate by 11.4 bpm (Iva 58.8 ± 8.2 bpm vs. placebo 70.2 ± 8.3 bpm, P 0.0001). Augmentation index (AIx75), carotid-femoral pulse wave velocity (cfPWV) and central aortic blood pressure were measured using applanation tonometry (SphygmoCor). HRR by Iva increased AIx75 by 12.4% (Iva 24.3 ± 10.5% vs. placebo 21.3 ± 10.1%, P 0.05) and reduced cfPWV by 14.1% (Iva 6.3 ± 1.7 m/s vs. placebo 7.3 ± 1.4 m/s, P 0.01). Iva increased mean central blood pressure by 7.8% (Iva 107.5 ± 15.4 mmHg vs. placebo 99.1 ± 12.2 mmHg, P 0.001). Endothelial function was determined measuring the flow-mediated vasodilation (FMD) of the brachial artery. HRR by Iva increased FMD by 18.5% (Iva 7.3 ± 2.2% vs. placebo 6.0 ± 2.0%, P 0.001). Aortic distensibility was characterized by MRI. HRR by Iva increased aortic distensibility by 33.3% (Iva 0.003 ± 0.001/mmHg vs. placebo 0.002 ± 0.010/mmHg, P 0.01) and circumferential cyclic strain by 37.1% (Iva 0.062 ± 0.027 vs. placebo 0.039 ± 0.018, P 0.0001).Heart rate reduction with Iva increased endothelium-dependent vasodilation and reduced arterial stiffness in patients with stable CAD. These findings corroborate and expand the results collected in experimental studies and indicate the importance of heart rate as a determinant of vascular function.

Background Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC. Methods Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT. Results There was no significant difference regarding LD and tumor volume between MRI and CT (p≥ 0.6221, respectively p≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 (r = 0.8750) and 12 months (r = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders. Conclusions DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.

Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC.Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT.There was no significant difference regarding LD and tumor volume between MRI and CT (p ≥ 0.6221, respectively p ≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 (r = 0.8750) and 12 months (r = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders.DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.

To evaluate technical feasibility and safety of endovascular tumor specimen sampling using an escalating endovascular biopsy strategy using a directional atherectomy device compared with forceps biopsy and catheter aspiration. Between 2013 and 2017, a cohort of ten consecutive patients (6 male; median age 56, range 39–73 years) was referred for sampling of endovascular masses. Localizations included the abdominal aorta (n = 4), left brachiocephalic vein (n = 2), inferior vena cava (n = 1), and left pulmonary artery (n = 3). For each individual mass, all three endovascular tissue sampling approaches were applied including catheter-based aspiration, straight two-jaw biopsy forceps, and directional atherectomy during a single session. Aspiration and forceps biopsy did not provide sufficient material for histological analyses. In contrast, technical success for endovascular tumor sampling using directional atherectomy was 100%. After two atherectomy passages, sufficient material was available for each vessel region allowing histologic diagnosis, which revealed sarcoma and chronic inflammation for masses in the aorta, angiosarcoma for brachiocephalic vein, hepatocellular carcinoma for inferior vena cava, and angiosarcoma for pulmonary artery. In case of a histologically benign diagnosis, no malignant tumor proliferation was obvious on follow-up imaging studies after 3 months and 1 year. Thus, the rate of false-negative results was considered 0%. No procedure-associated complications, e.g., vessel perforation, were recorded. Preliminary results in a limited number of patients proved directional atherectomy beneficial as a safe and feasible technique for endoluminal tissue sampling of vascular masses. Additional large-scale studies are necessary and worthy for further evaluation in clinical practice. • Endovascular masses pose a challenge to appropriate clinical management. • Off-label directional atherectomy proved to be a safe and feasible technique for endoluminal tissue sampling of vascular masses. Furthermore, directional atherectomy was superior to aspiration or forceps biopsy in our small study cohort. • Directional atherectomy may represent the last or only option for tissue probing as a prerequisite for further treatment decisions.

Objective To retrospectively evaluate the technical feasibility and midterm results of uncovered thoracoabdominal stent placement in complicated acute aortic dissection Stanford type B (cAADB). Patients and Methods Fourteen consecutive patients (3 females; range, 44-71 years) with cAADB who had symptomatic gastrointestinal malperfusion and claudication underwent immediate uncovered stent implantation (diameter, 7-28 mm; length, 40-100 mm) into the true lumen of the thoracoabdominal aorta (n = 23) and visceral arteries (n = 5). Results Stenting resulted in elimination of gastrointestinal ischemia and symptoms in 13 of 14 patients; persisting symptoms led to secondary surgical revascularization in only 1 patient. More than 1 stent (≤4) was placed in 7 patients (2 celiac, 1 mesenteric, 2 renal, 8 aorto-iliac). Follow-up computed tomographic angiography (CTA) revealed collapse of 4 aortic stents (diameter, 9-25 mm; length, 100 mm) at 1 week in the absence of symptoms. Balloon reexpansion was possible in all 4 stents, but recollapse occurred within 1 month. Despite stent collapse, the patients remained asymptomatic; ultrasonography and CTA documented sufficient perfusion of the visceral arteries in all patients. Follow-up ranged from 6 months to 5 years (average, 2.5 years). Except for the patient who underwent iliacomesenteric bypass for unspecific abdominal pain, no other patient required additional interventional or surgical therapy. Conclusions Acute aortic dissection with suspicion of visceral ischemia should prompt for immediate intervention. Thoracoabdominal uncovered stent implantation is a technically feasible and effective minimally invasive approach that provided successful relief of acute visceral ischemia and claudication in cAADB. Stent size should be less than the normal aortic diameter to avoid possible stent collapse.

Magnetic resonance imaging (MRI) performed at ultra-high field strengths beyond 3 Tesla (T) has become increasingly prevalent in research and preclinical applications. As such, the inevitable clinical implementation of such systems lies on the horizon. The major benefit of ultra-high field MRI is the markedly increased signal-to-noise ratios achievable, enabling acquisition of MR images with simultaneously greater spatial and temporal resolution. However, at field strengths higher than 3 T, the efficacy of Gd(III)-based contrast agents is diminished due to decreased r1 relaxivity, somewhat limiting imaging of the vasculature and contrast-enhanced imaging of tumors. There have been extensive efforts to design new contrast agents with high r1 relaxivities based on macromolecular compounds or nanoparticles; however, the efficacy of these agents at ultra-high field strengths has not yet been proven. The aim of this review article is to provide an overview of the basic principles of MR contrast enhancement processes and to highlight the main factors influencing relaxivity. In addition, challenges and opportunities for contrast-enhanced MRI at ultra-high field strengths will be explored. Various approaches for the development of effective contrast agent molecules that are suitable for a broad spectrum of applied field strengths will be discussed in the context of the current literature.

Background/Aims: Dry weight estimation in hemodialysis patients is still a substantial problem. Despite meticulous clinical assessment, fluid overload is common, leading to hypertension and left ventricular hypertrophy (LVH). Segmental calf bioimpedance spectroscopy (cBIS) is a novel tool for dry weight assessment. Here we tested the hypothesis, that its clinical routine use reduces arterial hypertension and left ventricular mass. Methods: Left ventricular mass (determined by magnetic resonance imaging), blood pressure and antihypertensive medication (defined daily doses, ddd) were assessed at baseline (BL). Thereafter post-dialytic target weight was reduced until cBIS-defined dry weight was reached (DW). During a 6-month follow up, DW was re-evaluated monthly by cBIS and end-dialytic weight was adjusted correspondingly. At the end, left ventricular mass, blood pressure and antihypertensive medication were determined a 3rd time (follow-up, FU). Results: Eleven out of 15 patients were available for analysis after 6 months. Left ventricular mass showed a declining trend during the study period (Mean±SD; BL 145±54g; DW 142±55g; FU 137±52g; p=0.61, linear mixed model). Comparable results were obtained for systolic blood pressure (BL 158±18mmHg; DW 144±19mmHg; FU 149±21mmHg; p=0.07), and antihypertensive medication (BL 3.28±2.82ddd; DW 2.86±2.81ddd; FU 3.36±3.05ddd; p=0.37). Conclusions: We conclude that attainment of dry weight assessed by cBIS tends to reduce left ventricular mass and blood pressure while antihypertensive medication remains unchanged. While the study was underpowered, its results provide an important hypothesis generating data basis for the design of larger studies.

Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 andT2⁎may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 andT2⁎in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination ofT2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout(Abcb4 -/-)mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 andT2⁎correlate differently to disease severity and etiology of liver fibrosis.T2⁎shows significant decrease correlating with fibrosis in CCl4treated animals, while demonstrating significant increase with disease severity inAbcb4 -/-mice. Measurements of T1 andT2⁎may therefore facilitate discrimination between different stages and causes of liver fibrosis.

A 33-year-old female patient underwent diagnostic gynecologic laparoscopy for assessment of a cystic ovarian mass and moderate amounts of ascites. Operative exploration, unexpectedly, uncovered a coarsely multinodular liver surface suspicious of cirrhosis, and surgery was terminated by resection of the left adnexa. Histopathology of the surgical specimen and ascitic fluid analysis yielded no indication of underlying malignancy, and the patient was referred for hepatology work-up. Liver function tests were unremarkable; however, ultrasound revealed an inhomogeneous, nodular liver parenchyma with portal vein dilation and reduced portal venous flow suggestive of portal hypertension. Furthermore, the hepatic veins appeared compressed and duplex sonography failed to trace an unequivocal hepatic venous Doppler flow signal. Upper gastrointestinal endoscopy identified small esophageal varices. Comprehensive serological work-up was negative with respect to viral, metabolic, hereditary, or autoimmune liver disease. Given the insufficient visualization of hepatic veins on ultrasound, the patient underwent magnetic resonance imaging (MRI) indicating inhomogeneous hepatomegaly with regenerative nodules. Furthermore, hepatic vein and, in part, inferior vena cava (IVC) obstruction by a calcified mass extending up towards the right heart was detected. To better characterize the cardiac mass, transthoracic and transesophageal echocardiogram as well as cardiac MRI were performed. Echocardiography depicted a tumor-like right atrial (RA) structure spreading alongside the tricuspid valve (Fig. 1a, Supplemental Videos 1–2). Continuous-wave Doppler across the structure and along the right ventricular inflow tract demonstrated a pressure gradient of 8 mmHg, comparable to a relevant tricuspid stenosis. Likewise, cardiac MRI and CT reinforced the suspicion of a large calcified thrombus arising from the basal RA with appositional growth into the IVC and the hepatic veins (Fig. 1b–d, Supplemental Video 3). No signs of pulmonary embolism were found. Given the clinical diagnosis of subacute Budd–Chiari syndrome (BCS), a comprehensive laboratory assessment for potential prothrombotic conditions including JAK2 V617F testing remained without pathological finding [1]. However, a thorough review of medical history revealed that the Electronic supplementary material The online version of this article (doi:10.1007/s00392-012-0510-9) contains supplementary material, which is available to authorized users.

OBJECTIVE: A critical problem in cardiovascular MRI in small rodents is adjusting the sequence acquisition to the high heart and respiratory rates. The aim of this study was to compare a retrospectively self-gated fast low angle shot navigator (RSG-FLASH) sequence with a conventional prospectively triggered (PT-FLASH) sequence for cine imaging of the ascending aorta in mice at 9.4 T. MATERIAL AND METHODS: Ten C57/BL6 mice were examined with a horizontal bore 9.4 Tesla MRI animal scanner using a dedicated 2 × 2 phased-array surface coil. We acquired a RSG-FLASH sequence (RSG-FLASH sequences (repetition time (TR) / echo time (TE) = 6.5/2.5 ms, flip angle (FA) = 10 degrees, field of view (FOV) = 2 × 2 cm, matrix = 384 × 384, slice thickness = 1 mm, 25 movie frames) perpendicular to the ascending aorta using the IntraGate technique. At the same position, we performed a PT-FLASH sequence (TR/TE = 6.5/2.1 ms, FA = 10 degrees, FOV = 2 × 2 cm, matrix = 384 × 384, slice thickness = 1 mm) in which the maximum number of movie frames had to be adjusted to the interval between two R-peaks (RR interval) of the electrocardiogram (ECG) with: number of frames = RR interval / TR." Cross-sectional vessel areas at end-systole (AES) and end-diastole (AED) were measured to determine the aortic strain (ΔA = (AES-AED)/AED). Two blinded readers rated the sequences for presence of flow and trigger artifacts and their influence on the depiction of the blood/vessel-wall interface. Irregularities in displaying the cardiac cycle and the overall suitability of the sequence for aortic strain evaluation were assessed using a 5-level ordinal scale. Statistical differences were analyzed using Student t test and Wilcoxon signed rank test (P < 0.05). Intra- and interobserver variability was evaluated using Bland-Altman analyses. RESULTS: No significant differences were noted between techniques regarding the measured vessel areas (AED: P = 0.07, AES: P = 0.34), ΔA: P = 0.1). Similarly, there were no significant differences in heart (P = 0.06) and respiratory (P = 0.24) rates. The acquisition time for RSG-FLASH sequence was significantly shorter (P = 0.04). Significantly fewer flow and trigger artifacts were noted by both readers with the RSG-FLASH sequence. Likewise, both readers considered the RSG-FLASH sequence to be superior for depiction of the blood/vessel-wall interface. The RSG-FLASH sequence was also rated superior regarding irregularities in displaying the cardiac cycle and in terms of overall suitability for evaluation of AED, AES, and aortic strain (P < 0.05 each). CONCLUSION: RSG-FLASH is preferable for cine imaging of the aorta. It provides the same quantitative data as PT-FLASH cine imaging but is less prone to flow and trigger artifacts. RSG-FLASH permits more homogeneous depiction of the cardiac cycle and is faster than the PT-FLASH sequence. PT-FLASH is more prone to misregistration of the respiratory cycle or the ECG by the external monitoring device used for acquisition. This effect may be even more pronounced in animals with disease models that are less stable in terms of heart and respiration rate during anesthesia.

Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency predisposes to severe invasive bacterial infections in infancy and early childhood, often with a fatal course caused by a defect in Toll-like receptor and interleukin-1 receptor signaling. Despite severe invasive infections, acute phase responses are often diminished. We report the successful treatment of a child with multiple liver abscesses, diaphragm perforation and pleural empyema, accompanied by strong acute phase responses as a unique presentation of IRAK-4 deficiency.

Right ventricular (RV) pathologic hypertrophy and cardiomyopathy have been reported to be related to ventricular arrhythmias and sudden cardiac death in athletes. However, it is unclear which echocardiographic measurements reflect RV dimensions in athlete's heart (AH) correctly. We aimed to compare two-dimensional echocardiography of the RV in AH and normal hearts to magnetic resonance imaging (MRI), and derive recommendations for RV echocardiography in athletes. Twenty-three healthy male endurance athletes with AH (A; 28+/-4 yrs) and 26 healthy untrained males (C; 26+/-4 yrs) matched for body-dimensions were examined. In recommended echocardiographic parasternal and 4-chamber views, three enddiastolic RV free wall-thicknesses (T1,T5,T9) and RV diameters were determined (M-mode enddiastolic diameter [RV-EDD]; longitudinal [RV-LAX], sagittal, outflow-tract and tricuspid valve anulus diameters). MRI determined RV enddiastolic volumes (RV-EDV) and masses (RVM) in A and C were: 162+/-29 vs. 136+/-15 ml and 76+/-10 vs. 59+/-13 g (p

IntroductionCongenital malformations of the aortic arch are animportant group of pediatric pathologies. Depending on thetype of the vascular anomaly, patients may be completelyasymptomatic not requiring any therapy or may manifestwith hazardous or even life threatening situations such asrecurrent pneumonia, respiratory distress or apnea [1]. Dueto the complexity of pathologic anatomy, the clinicalsymptoms and the resulting therapeutic consequences thesemalformations require detailed diagnostic imaging.MRI is nowadays considered the imaging modality ofchoice for the work-up of vascular malformations in thepediatric age group. The application of Cine SSFP (steadystate free precession) sequences and flow sensitive phase-contrast sequences allow for depiction of vascular struc-tures and qualitative as well as quantitative assessment ofblood flow. In addition, contrast enhanced magnetic reso-nance angiography (CE-MRA) provides high-resolutionthree-dimensional (3D) datasets providing excellent imagesof even small vascular structures based on maximumintensity projection (MIP), volume rendering technique(VRT), and multiplanar reconstructions (MPR). Recentstudies have shown that CE-MRA in the pediatric agegroup may clarify uncertain diagnoses in one-third of thepatients and reveal additional unsuspected pathologicstructures in another third of cases [2, 3]. Furthermore, CE-MRA has been shown to be superior to echocardiographyfor evaluation of the pulmonary vasculature in pediatricpatients [3], [4].The value of unenhanced MRI and CE-MRA in imagingof vascular anomalies in pediatric subjects is highlighted inthis case of a congenital malformation of the aortic archwith aberrant left subclavian artery.CaseA 14-year old male patient presented with dysphagia,globus, and temporary malaise without vomiting. Physicalexamination of the patient was normal and there were nosigns of dyspnea, dizziness, or chest pain. ECG and bloodanalysis did not reveal any abnormality. A frontal viewX-ray examination of the chest demonstrated a right-sidedaortic arch (Fig. 1). Barium esophagography, performedfor further evaluation of dysphagia, revealed a right-sidedand posterior compression of the proximal esophagus at thelevel of the aortic arch (Fig. 2). The echocardiographicexamination showed regular intracardiac structures andfunction; there was a right aortic arch with origin of the leftand right carotid artery as the first two supra-aortic vessels.Based on these findings the patient was referred for MRIexamination.MRI was performed on a 1.5 T Siemens MagnetomSonata system (Siemens Medical Systems, Erlangen,Germany) using a phased-array body coil. The unenhancedMRI sequences utilized comprised T2w HASTE sequenceand retrospectively ECG-gated Cine SSFP sequences. Con-trast enhanced magnetic resonance angiography (CE-MRA)

To compare diffusion-weighted imaging (DWI) based on a fast spin echo (FSE) sequence using BLADE (PROPELLER) with conventional DWI-echoplanar imaging (EPI) techniques at 3 T and to demonstrate the influence of hardware developments on signal-to-noise ratio (SNR) with these techniques using 12- and 32-channel head coils.Fourteen patients with brain ischemia were evaluated with DWI using EPI and FSE BLADE sequences, with a 12-channel head coil, in the axial plane and 1 additional plane (either sagittal or coronal). SNR and CNR were calculated from region-of-interest measurements. Scans were evaluated in a blinded fashion by 2 experienced neuroradiologists. SNR of both DWI techniques was evaluated in 12 healthy volunteers using different parallel imaging (PI) factors (for the EPI sequence) and both the 12- and 32-channel coils.DWI-BLADE sequences acquired with the 12-channel coil revealed a significant reduction in SNR (mean +/- SD) of ischemic lesions (SNR(lesion) [5.0 +/- 2.5]), normal brain (SNR(brain) [3.0 +/- 1.9]), and subsequently in CNR (3.0 +/- 1.8) as compared with the DWI-EPI sequence (SNR(lesion) [9.3 +/- 5.2], SNR(brain) [7.7 +/- 3.5], CNR [6.1 +/- 2.8], P0.001). Despite this reduction in SNR and CNR, the blinded read revealed a marked preference for the DWI-BLADE sequence, or equality between the sequences, in the majority of patients because lesion detection was degraded by susceptibility artifacts on axial DWI-EPI scans in 14% to 43% of cases (but in no instance with the DWI-BLADE sequence). In particular, preference for the DWI-BLADE sequence or equality between the 2 techniques for lesion detection in the brainstem and cerebellum was observed. On some DWI-BLADE scans, in the additional plane, radial-like artifacts degraded lesion detection.In volunteers, SNR was significantly improved using the 32-channel coil, irrespective of scan technique. Comparing DWI-EPI acquired with the 12-channel coil (iPAT = 2) to DWI-BLADE acquired with the 32-channel coil, comparable SNR values were obtained. The 32-channel coil also makes feasible, with DWI-EPI, an increase in the PI factor to 4, which allows for a further reduction of bulk susceptibility artifacts. However, still DWI-BLADE sequences performed better because of absence of bulk susceptibility artifacts at comparable SNR values.Despite lower SNR at comparable PI factors, DWI-BLADE sequences acquired using the 12-channel coil are preferable in most instances, as compared with DWI-EPI sequences, because of the absence of susceptibility artifacts and subsequently improved depiction of ischemic lesions in the brainstem and cerebellum. With the 32-channel coil, recently FDA approved, DWI-BLADE acquired with an iPAT = 2 provides comparable SNR without bulk susceptibility artifacts as compared with the DWI-EPI sequences acquired for clinical routine to date and has the potential to replace the standard DWI technique for special indications like DWI of the cerebellum and the brainstem or in presence of metallic implants or hemorrhage.

Background— It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. Methods and Results— Thirty-three healthy white competitive elite male master endurance athletes (age range, 30–60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m 2 ; P 2 ; P 2 ; P 2 ; P P =0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. Conclusions— Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned.

The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results.

OBJECTIVES This study aims to compare the enhancement properties of an experimental high-relaxivity extracellular gadolinium chelate (P03277) with a standard extracellular contrast agent (gadobutrol) in vivo in a rat model of hepatic colorectal cancer metastases and in vitro by relaxometry measurements. MATERIALS AND METHODS Ten rats with hepatic colorectal cancer metastases were examined using a 9.4 T animal scanner (Bruker, Germany). Each animal was subjected to 2 contrast-enhanced magnetic resonance imaging experiments separated by 2 days receiving 0.1 mmol/kg body weight gadobutrol and 0.1 mmol/kg body weight P03277 intravenously in a random manner. T1-weighted self-gated fast low-angle shot sequences (time to repetition/time to echo, 45/2.5 milliseconds; flip angle, 45 degrees; acquisition time, 1:23 minutes; voxel size, 0.2 × 0.2 × 1.0 mm) were acquired before and at 10 consecutive time points after contrast injection. We assessed signal-to-noise ratio (SNR) of tumor (SNRtumor) and normal liver tissue (SNRliver), contrast-to-noise ratio, and lesion enhancement (LE). In addition, relaxation rates of P03277 and gadobutrol were assessed in vitro in human plasma at 37°C at a field strength of 9.4 T.Statistical analyses included paired t tests and Wilcoxon matched pairs signed rank tests. RESULTS SNRliver, SNRtumor, contrast-to-noise ratio, and LE were significantly higher (P < 0.05) using P03277 for all time points as compared with gadobutrol. Both agents demonstrated comparable contrast kinetics with an early peak enhancement immediately after application (initial percent LE: gadobutrol, 84%; P03277, 156%) and an early and continuous washout during the examination period (final percent LE: gadobutrol, 36%; P03277, 63%). In vitro evaluation of relaxivities demonstrated markedly higher R1 for P03277 (8.6 mM s) as compared with gadobutrol (4.2 mM s). CONCLUSIONS This study provides the first in vivo and in vitro data of P03277, an experimental extracellular MR contrast agent. P03277 demonstrates significantly better enhancement properties as compared with gadobutrol in experimental hepatic colorectal cancer metastases. In addition, in vitro data demonstrate superior relaxivities of P03277 at a broad spectrum of different field strengths. Hence, this new agent has the potential to improve lesion conspicuity and subsequently sensitivity in diagnostic imaging for both clinical magnetic resonance imaging at 1.5 or 3 T and ultra-high field applications between 4.7 and 9.4 T.

Objective: In patients with hereditary hemorrhagic telangiectasia (HHT), pulmonary arteriovenous malformations (PAVMs) can cause serious neurological complications. Our aim was to evaluate the potential of contrast-enhanced Doppler ultrasound (CE-US) of the common carotid artery as a screening test for detection of PAVMs. Methods: A total of 124 consecutive patients with HHT or a positive family history underwent screening for PAVMs with CE-US and thoracic contrast-enhanced magnetic resonance angiography (CE-MRA). CE-US was performed after receiving (D)-galactose microparticulate, and CE-MRA with gadobenate dimeglumine. Twenty-five patients with confirmed PAVMs were referred to conventional pulmonary catheter angiography (PA). Findings on CE-US and CE-MRA were evaluated using contingency tables and McNemar’s test. Results: Using CE-MRA as the reference test, CE-US had a sensitivity of 100%, a specificity of 87%, and a negative predictive value of 100%. In 25 patients who underwent PA, PAVMs that had been diagnosed on CE-US and CE-MRA were confirmed. Of the PAVMs detected by CE-MRA, 24% were not identified on PA. Conclusion: CE-US is a simple, minimally invasive screening method that can easily be performed in different settings. CE-US can predict PAVMs with high probability of success. CE-US may be a simple alternative to transthoracic echocardiography in the assessment of PAVMs in certain HHT-patients.

The aim of this study was to investigate hepatic macrophage activation and hepatocellular function after hemorrhagic shock in the rat using contrast-enhanced magnetic resonance imaging (MRI). In comparison to techniques requiring open surgery, such as intravital microscopy, MRI is a non-invasive tool; the experimental subject therefore remains intact, enabling the investigator to conduct additional follow-up procedures that may have important clinical implications. At 3 and 24 h following standardized hemorrhagic shock (40 mmHg for 90 min), MRI (2.4 T Magnet, Biospec, Bruker Karlsruhe, Germany) was performed. After application of a liver-specific contrast dye (Gd-EOB-DTPA; 50 μmol/kg BW), which is absorbed from hepatocytes and secreted into the gall fluid, the signal intensity (SI) was measured. For determination of hepatic macrophage activation, superparamagnetic ferrumoxid particles (ENDOREM® 10 μmol/kg BW) were injected and the SI was measured again. These data were compared with the findings of in vivo microscopy and bile flow performed in the animals after MRI. The sham groups received 2 ml/h Ringers Lactate for 24 h without initial hemorrhagic shock and reperfusion. In the shock group, a significantly smaller increase of SI enhancement after application of Gd-EOB-DTPA (shock group: 126.1%±10.4; sham group 159.3±3.5; p < 0.05) was found compared to the sham group 24 h after shock, which correlated with the bile flow measured. Application of ENDOREM® resulted in a decrease of SI in T2-weighted images after 3 h compared to 24 h after shock; however, no differences between the shock and sham animals could be observed (shock group -69.8%±2.8; sham group -75.8±1.6; p < 0.05). Intravital microscopy revealed a significant increase of latex beads in hepatic macrophages 3 h after shock compared to sham animals, thereby indicating enhanced macrophage activation. Intravital microscopy showed a significant increase of temporary and permanent adherent leukocytes 3 and 24 h after shock. Contrast-enhanced MRI is a useful, noninvasive method for long-term investigations of the liver after hemorrhagic shock, specifically with respect to monitoring alterations of hepatocellular function. However, a significant hepatic macrophage activation after shock was only observed by direct measurement of latex beads using intravital microscopy and not with contrast-enhanced MRI.

Cardiac troponins I and T and brain natriuretic peptide are the accepted standards to serologically identify myocardial necrosis and elevated wall stress. In addition, they allow risk stratification in cardiovascular patients. The clinical significance of increases in cardiac markers after strenuous endurance exercise in obviously healthy athletes is unclear.We therefore examined the reproducibility and clinical significance of exercise-induced increases in cardiac troponins I and T and N-terminal pro brain natriuretic peptide after two standardized endurance exercise trials in healthy endurance athletes with prior competition-induced elevations of cardiac troponins (I, 0.08-1.93 mug/l; T, 0.01-0.56 mug/l).Twenty male athletes (36+/-7 years; VO2max: 60+/-5 ml/min per kg) completed a 1-h and a 3-h exercise study (exercise intensities 100 and 75%, respectively, of the individual anaerobic threshold) on two different days in randomized order to determine cardiac markers before, 30 min and 3 h after exercise. In addition to pre- and post-exercise echocardiography including tissue Doppler imaging, delayed enhancement magnetic-resonance-imaging was performed after a 3-h exercise study to detect myocardial necrosis.A marginal increase in cardiac troponin I was documented after both exercise trials (from 0.02 to 0.03 mug/l; P0.001). Cardiac troponin T remained without significant changes. N-terminal pro brain natriuretic peptide increased by 9 and 30 ng/l after 1-h and 3-h exercise studies, respectively (P0.001). In contrast to cardiac troponins, increases in N-terminal pro brain natriuretic peptide after competition correlated with those after 1-h exercise study (rho = 0.88) and 3-h exercise-study (rho = 0.82). No pathologies were demonstrated by echocardiography or delayed-enhancement magnetic resonance imaging.Due to the missing reproducibilty and evidence of myocardial damage, exercise-induced increases in cardiac troponins may represent a physiologic reaction under special conditions and seem to be without pathological significance in healthy athletes.

Contrast enhanced magnetic resonance angiography (CE-MRA) is an established diagnostic method for evaluating vascular disease in adults. However, the use of MRA techniques has spread more slowly in children owing to significant technical challenges in the paediatric population. This article discusses the indications for CE-MRA in paediatric patients, the techniques employed and the imaging findings expected from MRA of children with vascular disease. In particular, the application of "time-resolved" CE-MRA is discussed and clinical case examples are provided to highlight the broad clinical application of this technique in paediatric vascular disease.

To prospectively determine the accuracy of differentiating benign focal nodular hyperplasia (FNH) from hepatic adenoma (HA) and liver adenomatosis (LA) by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging.The ethics committee at each center approved the study, and all patients provided informed consent. Seventy-three patients with confirmed FNH and 35 patients with confirmed HA (n = 27) or LA (n = 8) underwent MR imaging before (T2-weighted half-Fourier rapid acquisition with relaxation enhancement or T2-weighted fast spin-echo and T1-weighted gradient-echo [GRE] sequences) and at 25-30 seconds (arterial phase), 70-90 seconds (portal venous phase), 3-5 minutes (equilibrium phase), and 1-3 hours (delayed phase) after (T1-weighted GRE sequences only, with or without fat suppression) bolus administration of 0.1 mmol per kilogram of body weight gadobenate dimeglumine. The enhancement of 235 lesions (128 FNH, 32 HA, and 75 LA lesions) relative to the normal liver parenchyma was assessed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy for the differentiation of FNH from HA and LA were determined.Hyper- and isointensity on T2-weighted and iso- and hypointensity on T1-weighted GRE images were noted for 177 (88.9%) of 199 lesions visible on unenhanced images. On dynamic phase images after contrast material administration, 231 (98.3%) of 235 lesions showed rapid strong enhancement during the arterial phase and appeared hyper- to isointense during portal venous and equilibrium phases. Accurate differentiation of FNH from HA and LA was not possible on the basis of precontrast or dynamic phase images alone. At 1-3 hours after contrast material enhancement, 124 (96.9%) of 128 FNHs appeared hyper- or isointense, while 107 (100%) HA and LA lesions appeared hypointense. The sensitivity, specificity, PPV, NPV, and overall accuracy for the differentiation of FNH from HA and LA were 96.9%, 100%, 100%, 96.4%, and 98.3%, respectively.Accurate differentiation of FNH from HA and LA is achievable on delayed T1-weighted GRE images after administration of gadobenate dimeglumine.

Diffuse neonatal hemangiomatosis (DNH) is a rare, frequently fatal disorder characterized by multiple cutaneous and visceral hemangiomas. Complications include high-output cardiac failure, hemorrhage, hepatic failure, and consumption coagulopathy. We present two cases of neonates with DNH. We prescribed cyclophosphamide after failure of corticosteroids. Cyclophosphamide induced a fast regression of the lesions with no side effects in both infants. We were able to stop treatment after 3–4 courses of cyclophosphamide in both infants because of the excellent response. Cyclophosphamide seems to be a safe and effective treatment in patients suffering from life-threatening DNH unresponsive to corticosteroids. Pediatr Blood Cancer 2006;46:239–242. © 2005 Wiley-Liss, Inc.

Hepatic metastases are common in the clinical course of breast cancer and typically appear as mass lesions. This report describes the case of a 70-year-old woman with a history of breast cancer and no previously known liver disease presenting with the first episode of variceal bleeding and subacute hepatic failure. Imaging studies indicated liver cirrhosis without signs of malignant focal lesions. Comprehensive diagnostic work-up was negative for specific causes of liver disease and provided no evidence for tumor recurrence. Finally transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of metastatic tumor, spread representing a rare but important differential diagnosis of progressive liver failure. Liver biopsy is the key procedure to establish the diagnosis as imaging studies may mimic cirrhosis.

Osteonecrosis of the knee can present as a spontaneous and primary or a secondary clinical entity. The natural history of osteonecrosis follows a course of several sequential stages, and the later stages of both entities seem to be irreversible. Early diagnosis of osteonecrosis is crucial: the earlier the stage of the lesion at the time of diagnosis, the better the prognosis.Clinically, early diagnosis and treatment of osteonecrosis might prevent unnecessary surgery in cases with a concomitant degenerative meniscal tear. Early-stage osteonecrosis should be ruled out before surgery, because arthroscopy has lately been associated with osteonecrosis. Not every imaging method is equally suitable for detecting pathognomonic changes in each stage of osteonecrosis. Early-stage osteonecrosis is difficult to diagnose,because various differential diagnoses must be kept in mind. Moreover, there is a diagnostic window between the onset of symptoms and the appearance of pathognomonic changes on plain radiographs and MRI.

Since its introduction in the early 1990s, contrast-enhanced (CE) cardiac magnetic resonance imaging (MRI) has evolved rapidly for the assessment of cardiac pathologies, including in particular ischemic heart disease and inflammatory conditions. Likewise, CE-magnetic resonance angiography (MRA) is now used routinely to evaluate the thoracic vasculature. This article reviews the current use of extracellular gadolinium-based agents in CE cardiovascular imaging, focusing on ischemic heart disease, inflammatory myocardial conditions, and the use of CE-MRA in imaging of the pulmonary and aortic vasculature. Recent advances in fast and ultrafast MRI combined with the use of extracellular contrast media allow noninvasive measurements of multiple parameters of the cardiovascular system in less than 40 minutes. Beyond the assessment of left ventricular wall motion and morphology, CE cardiac MRI allows depiction of myocardial perfusion and thereby provides information regarding microvascular integrity and myocardial viability. The excellent spatial resolution of MRI, especially for the distinction of nontransmural versus transmural extent of pathology, has been shown to be superior to other modalities that are often nonlocalizing, nonspecific, or more invasive. Additional advantages of CE-MRA, particularly for the thoracic vasculature, include safety, its noninvasive character, large field of view, and the ability to demonstrate complicated three-dimensional relationships without the need for iodinated, nephrotoxic contrast media.

Bei einer 53-jahrigen, kardial bislang beschwerdefreien Patientin, die erfolgreich wegen Kammerflimmerns reanimiert worden war, zeigte sich trotz unauffalligem zweidimensionalem Echokardiogramm in einer unter Ruhebedingungen durchgefuhrten Gewebe-Doppler-Studie der longitudinalen Wandbewegung der pathologische Befund von postsystolischen Kontraktionen im Versorgungsgebiet der linken Kranzarterie. Der Verdacht auf eine Koronarischamie als mutmasliche Ursache der Arrhythmie bestatigte sich in der Koronarangiographie, die eine isolierte, hochgradige ostiale Hauptstammstenose ergab. Nach operativer Myokardrevaskularisation normalisierte sich auch der Gewebe-Doppler-Befund. Fazit: Gerade bei unauffalligem konventionellen Echokardiogramm kann die zusatzliche Analyse des longitudinalen Kontraktionsmusters mittels Gewebe-Doppler-Echokardiographie eine weitergehende Aussage erlauben.

Die echokardiographische Bestimmung linksventrikularer Muskelmassen (LVM) und Volumina ist zur Beurteilung kardialer Adaptationsmechanismen und Risikostratifizierung von wesentlicher Bedeutung. Allerdings neigen die ublicherweise angewandten ein- und zweidimensionalen Verfahren bei krankhaft hypertrophierten Herzen zur Uberschatzung der LVM. Fur physiologisch hypertrophierte Herzen liegt bisher noch keine vergleichende Untersuchung der unterschiedlichen echokardiographischen Bestimmungsmethoden mit der Referenzmethode Magnetresonanztomographie (MRT) vor. An 23 gesunden mannlichen Ausdauerathleten mit Sportherz (A; 28±4 Jahre) sowie 26 gesunden mannlichen Untrainierten (U; 26±4 Jahre) wurde die LVM mittels MRT und folgenden echokardiographischen Methoden bestimmt: ASE-Cube (ASE), Devereux (DEV), Troy (TRO) Teichholz (TEI), Reichek (REI) und Dickhuth (DIC). Die auf die Korperoberflache bezogenen LVM betrugen: MRT: 107±6g/m2 (A), 79±7g/m2 (U); ASE: 170±20g/m2 (A), 119±14g/m2 (U); DEV: 134±16g/m2 (A), 95±11g/m2 (U); TRO: 134±16g/m2 (A), 92±12g/m2 (U); TEI: 115±10 g/m2 (A), 91±8g/m2 (U); REI: 114±14g/m2 (A), 89±11g/m2 (U); DIC: 110±14g/m2 (A); 80±9g/m2 (U). Bei A und U wird die kernspintomographische LVM durch ASE, DEV, TRO, TEI und REI im Gegensatz zu DIC signifikant uberschatzt (p

The Brugada syndrome is characterized by a distinct ECG pattern consisting of ST segment elevation in the right precordial leads and right bundle branch block, a propensity for life-threatening arrhythmias, and an apparently structurally normal heart. The authors describe the case of a patient with an aborted sudden cardiac death and the typical ECG signs of Brugada syndrome. Nevertheless, magnetic resonance imaging displayed signal enhancement in the left ventricular myocardium. Additionally, histologic examination, in-situ hybridization, and PCR revealed evidence of a locally restricted inflammation due to parvovirus B19. Brugada syndrome is regarded as a primary electrical disease due to dysfunction of distinctive ion channels, but focal myocarditis may serve as a trigger for ventricular arrhythmias in this patient. Further morphologic studies will be helpful to establish the possible role of structural changes in the pathophysiology of this syndrome.

Background To determine the optimal single-dose radiotherapy schedule for pain from bone metastases in a multi-centre, international, randomised trial. Patients and methods 651 patients were randomised to either 8Gy ( n =325) or 4Gy ( n =326) radiotherapy. Pain at 4, 8, 12, 24 and 52weeks was assessed using a Categorical Scale (CS) and a Visual Analogue Scale (VAS). The primary endpoint was response at 4weeks. Results There was no significant difference in patient demographics and other co-variates. The complete response (CR) rate and ORR (complete or partial response) for all follow-up times were higher after 8Gy ( p =0.02). The Kaplan–Meier actuarial rate (categorical scale) at 4weeks for ORR was 80% after 8Gy compared to 68% after 4Gy ( p =0.0015). 117 re-treatments were given of which 72 were in the 4Gy group and 45 in 8Gy arm ( p =0.01). Conclusions There was a marked consistent difference in pain relief at all time points in favour of 8Gy. These data reinforce the case for single dose 8Gy radiotherapy to be recommended for metastatic bone pain in all healthcare settings.