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Von Knobelsdorff-Brenkenhoff F.,HELIOS Klinikum Berlin Buch | Von Knobelsdorff-Brenkenhoff F.,Medical University Berlin | Von Knobelsdorff-Brenkenhoff F.,Max Delbrück Center for Molecular Medicine | Frauenrath T.,Max Delbrück Center for Molecular Medicine | And 13 more authors.
European Radiology | Year: 2010

Objectives: Interest in cardiovascular magnetic resonance (CMR) at 7 T is motivated by the expected increase in spatial and temporal resolution, but the method is technically challenging. We examined the feasibility of cardiac chamber quantification at 7 T. Methods: A stack of short axes covering the left ventricle was obtained in nine healthy male volunteers. At 1.5 T, steady-state free precession (SSFP) and fast gradient echo (FGRE) cine imaging with 7 mm slice thickness (STH) were used. At 7 T, FGRE with 7 mm and 4 mm STH were applied. End-diastolic volume, end-systolic volume, ejection fraction and mass were calculated. Results: All 7 T examinations provided excellent blood/myocardium contrast for all slice directions. No significant difference was found regarding ejection fraction and cardiac volumes between SSFP at 1.5 T and FGRE at 7 T, while volumes obtained from FGRE at 1.5 T were underestimated. Cardiac mass derived from FGRE at 1.5 and 7 T was larger than obtained from SSFP at 1.5 T. Agreement of volumes and mass between SSFP at 1.5 T and FGRE improved for FGRE at 7 T when combined with an STH reduction to 4 mm. Conclusions: This pilot study demonstrates that cardiac chamber quantification at 7 T using FGRE is feasible and agrees closely with SSFP at 1.5 T. © 2010 European Society of Radiology.


Frauenrath T.,Max Delbrück Center for Molecular Medicine | Hezel F.,Max Delbrück Center for Molecular Medicine | Renz W.,Max Delbrück Center for Molecular Medicine | Renz W.,Siemens AG | And 12 more authors.
Journal of Cardiovascular Magnetic Resonance | Year: 2010

Background: To demonstrate the applicability of acoustic cardiac triggering (ACT) for imaging of the heart at ultrahigh magnetic fields (7.0 T) by comparing phonocardiogram, conventional vector electrocardiogram (ECG) and traditional pulse oximetry (POX) triggered 2D CINE acquisitions together with (i) a qualitative image quality analysis, (ii) an assessment of the left ventricular function parameter and (iii) an examination of trigger reliability and trigger detection variance derived from the signal waveforms. Results: ECG was susceptible to severe distortions at 7.0 T. POX and ACT provided waveforms free of interferences from electromagnetic fields or from magneto-hydrodynamic effects. Frequent R-wave mis-registration occurred in ECG-triggered acquisitions with a failure rate of up to 30% resulting in cardiac motion induced artifacts. ACT and POX triggering produced images free of cardiac motion artefacts. ECG showed a severe jitter in the R-wave detection. POX also showed a trigger jitter of approximately t = 72 ms which is equivalent to two cardiac phases. ACT showed a jitter of approximately t = 5 ms only. ECG waveforms revealed a standard deviation for the cardiac trigger offset larger than that observed for ACT or POX waveforms. Image quality assessment showed that ACT substantially improved image quality as compared to ECG (image quality score at end-diastole: ECG = 1.7 0.5, ACT = 2.4 0.5, p = 0.04) while the comparison between ECG vs. POX gated acquisitions showed no significant differences in image quality (image quality score: ECG = 1.7 0.5, POX = 2.0 0.5, p = 0.34). Conclusions: The applicability of acoustic triggering for cardiac CINE imaging at 7.0 T was demonstrated. ACT's trigger reliability and fidelity are superior to that of ECG and POX. ACT promises to be beneficial for cardiovascular magnetic resonance at ultra-high field strengths including 7.0 T. © 2010 Frauenrath et al; licensee BioMed Central Ltd.


Schmelzer E.,McGowan Institute for Regenerative Medicine | Triolo F.,ISMETT Mediterranean Institute for Transplantation and Specialized Therapies | Turner M.E.,University of Pittsburgh | Thompson R.L.,University of Pittsburgh | And 4 more authors.
Tissue Engineering - Part A | Year: 2010

The ability of human fetal liver cells to survive, expand, and form functional tissue in vitro is of high interest for the development of bioartificial extracorporeal liver support systems, liver cell transplantation therapies, and pharmacologic models. Conventional static two-dimensional culture models seem to be inadequate tools. We focus on dynamic three-dimensional perfusion technologies and developed a scaled-down bioreactor, providing decentralized mass exchange with integral oxygenation. Human fetal liver cells were embedded in a hyaluronan hydrogel within the capillary system to mimic an in vivo matrix and perfusion environment. Metabolic performance was monitored daily, including glucose consumption, lactate dehydrogenase activity, and secretion of alpha-fetoprotein and albumin. At culture termination cells were analyzed for proliferation and liver-specific lineage-dependent cytochrome P450 (CYP3A4/3A7) gene expression. Occurrence of hepatic differentiation in bioreactor cultures was demonstrated by a strong increase in CYP3A4/3A7 gene expression ratio, lower alpha-fetoprotein, and higher albumin secretion than in conventional Petri dish controls. Cells in bioreactors formed three-dimensional structures. Viability of cells was higher in bioreactors than in control cultures. In conclusion, the culture model implementing three-dimensionality, constant perfusion, and integral oxygenation in combination with a hyaluronan hydrogel provides superior conditions for liver cell survival and differentiation compared to conventional culture. © 2010 Mary Ann Liebert, Inc.


Dohmen P.M.,University of Leipzig | Dohmen P.M.,Medical University Berlin | Weymann A.,Medical University Berlin | Holinski S.,Medical University Berlin | And 3 more authors.
Surgical Infections | Year: 2011

Background: With high morbidity and potentially devastating consequences, surgical site infections (SSIs) after cardiac surgery add substantially to the healthcare burden. Inhibiting migration of skin microbes is likely to reduce contamination of the surgical incision by endogenous potential pathogens. We studied the effect of treatment with a cyanoacrylate-based antimicrobial skin sealant (INTEGUSEAL®) on the SSI rate in cardiac surgery patients. Methods: In a consecutive series of 910 prospective patients undergoing routine cardiac surgery, standard pre-operative preparation was performed on 721 patients of whom 189 also received antimicrobial skin sealant. A further 189 consecutive patients who received only standard pre-operative care were studied retrospectively. The primary study endpoint was occurrence of superficial or deep SSI according to the definitions of the U.S. Centers for Disease Control and Prevention. Results: The mean (standard deviation) SSI risk score based on combined pre-operative and intra-operative factors according to the Society of Thoracic Surgeons risk scoring system was significantly higher for the skin sealant group (9.1±1.0) than for the prospective (7.1±3.2; p<0.001) and retrospective (8.7±0.8; p<0.001) control groups. Surgical site infections occurred in two patients (1.1%) in the sealant group, 33 patients (4.6%) in the prospective control group (p<0.025), and nine patients (4.8%) in the retrospective control group (p<0.032). Conclusions: When added to existing pre-operative measures to reduce bacterial contamination of surgical incisions that are employed routinely at this cardiovascular surgery unit, use of antimicrobial skin sealant decreased the incidence of SSI in cardiac surgery patients. © 2011, Mary Ann Liebert, Inc.


Von Knobelsdorff-Brenkenhoff F.,Medical University Berlin | Rottgen R.,Charité - Medical University of Berlin | Schulz-Menger J.,Medical University Berlin
Journal of Heart Valve Disease | Year: 2012

The case is reported of a 28-year-old subject with a bioprosthesis (Shelhigh® 31) in the aortic position, with symptoms of heart failure and possible prosthetic dysfunction. As the echocardiographic interrogation remained inconclusive, the patient underwent cardiovascular magnetic resonance (CMR) imaging, which revealed an impaired movement of the non-coronary cusp. In addition, computed tomography (CT) demonstrated severe calcification of the immobile prosthetic component. Hence, in selected patients, both CMR and CT can be used as complementary tools to evaluate the dysfunction and pathology of heart valve bioprostheses. © Copyright by ICR Publishers 2012.


Weber O.,Bayer AG | Mercer A.A.,University of Otago | Friebe A.,Ruhr University Bochum | Knolle P.,University of Bonn | Volk H.-D.,Medical University Berlin
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2013

Viruses can manipulate the immune response against them by various strategies to influence immune cells, i.e. by over-activation leading to functional inactivation, bypassing antigen presentation or even suppression of effector functions. Little is known, however, about how these features of immune regulation and modulation could be used for therapeutic purposes. Reasons for this include the complexity of immune regulatory mechanisms under certain disease conditions and the risks that infections with viruses pose to human beings. The orf virus (ORFV), a member of the Parapoxvirus genus of the poxvirus family, is known as a common pathogen in sheep and goats worldwide. The inactivated ORFV, however, has been used as a preventative as well as therapeutic immunomodulator in veterinary medicine in different species. Here, we review the key results obtained in pre-clinical studies or clinical studies in veterinary medicine to characterise the therapeutic potential of inactivated ORFV. Inactivated ORFV has strong effects on cytokine secretion in mice and human immune cells, leading to an auto-regulated loop of initial up-regulation of inflammatory and Th1-related cytokines, followed by Th2-related cytokines that attenuate immunopathology. The therapeutic potential of inactivated ORFV has been recognised in several difficult-to-treat disease areas, such as chronic viral diseases, liver fibrosis or various forms of cancer. Further research will be required in order to evaluate the full beneficial potential of inactivated ORFV for therapeutic immunomodulation. © 2012 Springer-Verlag Berlin Heidelberg.


Von Knobelsdorff-Brenkenhoff F.,Medical University Berlin | Schulz-Menger J.,Medical University Berlin
International Journal of Cardiology | Year: 2011

Cardiac impairment by an intrathoracic stomach is an accepted indication for surgical repair. However, the assessment of the hemodynamic impact often remains a challenge. The present article reports on two subjects with intrathoracic stomach and chest discomfort, who underwent cardiovascular magnetic resonance (CMR) before and after food intake. CMR enabled the accurate assessment of cardiac compression in dependency from the gastric filling state, and demonstrated an association between food intake, decrease in left ventricular stroke volume and the occurrence of symptoms. Thus, CMR may become a valuable tool for clinical decision-making in patients with intrathoracic stomach. © 2010 Elsevier Ireland Ltd.


Von Knobelsdorff-Brenkenhoff F.,Medical University Berlin | Schulz-Menger J.,Medical University Berlin
Journal of Magnetic Resonance Imaging | Year: 2012

Ischemic heart disease is the most frequent etiology for cardiovascular morbidity and mortality. Early detection and accurate monitoring are essential to guide optimal patient treatment and assess the individual's prognosis. In this regard, cardiovascular magnetic resonance (CMR), which entered the arena of noninvasive cardiovascular imaging over the past two decades, became a very important imaging modality, mainly due to its unique versatility. CMR has proven accuracy and is a robust technique for the assessment of myocardial function both at rest and during stress. It also allows stress perfusion analysis with high spatial and temporal resolution, and provides a means by which to differentiate tissue such as distinguishing between reversibly and irreversibly injured myocardium. In particular, the latter aspect is a unique benefit of CMR compared with other noninvasive imaging modalities such as echocardiography and nuclear medicine, and provides novel information concerning the presence, size, transmurality, and prognosis of myocardial infarction. This article is intended to provide the reader with an overview of the various applications of CMR for the assessment of ischemic heart disease from a clinical perspective. © 2012 Wiley Periodicals, Inc.


Schmitt B.,Medical University Berlin | Steendijk P.,Leiden University | Ovroutski S.,Medical University Berlin | Lunze K.,Medical University Berlin | And 5 more authors.
Circulation: Cardiovascular Imaging | Year: 2010

Background-The role, interplay, and relative importance of the multifactorial hemodynamic and myocardial mechanisms causing dysfunction of the Fontan circulation remain incompletely understood. Methods and Results-Using an MRI catheterization technique, we performed a differential analysis of pulmonary vascular resistance and aortopulmonary collateral blood flow in conjunction with global ventricular pump function, myocontractility (end-systolic pressure-volume relation), and diastolic compliance (end-diastolic pressure-volume relation) in 10 patients with a Fontan circulation at rest and during dobutamine stress. Pulmonary and ventricular pressures were measured invasively and synchronized with velocity-encoded MRI-derived pulmonary and aortic blood flows and cine MRI-derived ventricular volumes. Pulmonary vascular resistance and end-systolic and end-diastolic pressure-volume relations were then determined. Aortopulmonary collateral flow was calculated as the difference between aortic and pulmonary flow. Compared to rest, dobutamine caused a small increase in mean pulmonary pressures (P<0.05). Collateral flow was significantly augmented (P<0.001) and contributed importantly to an increase in pulmonary flow (P<0.01). Pulmonary vascular resistance decreased significantly (P<0.01). Dobutamine did not increase stroke volumes significantly despite slightly enhanced contractility (end-systolic pressure-volume relation). Active early relaxation (τ) was inconspicuous, but the end-diastolic pressure-volume relation shifted upward, indicating reduced compliance. Conclusions-In patients with a Fontan circulation, aortopulmonary collateral flow contributes substantially to enhanced pulmonary flow during stress. Our data indicate that pulmonary vascular response to augmented cardiac output was adequate, but decreased diastolic compliance was identified as an important component of ventricular dysfunction. © 2010 American Heart Association, Inc.


Von Knobelsdorff-Brenkenhoff F.,Medical University Berlin | Rudolph A.,Medical University Berlin | Wassmuth R.,Medical University Berlin | Schulz-Menger J.,Medical University Berlin
Journal of Cardiovascular Magnetic Resonance | Year: 2010

Background. The orifice area of mitral bioprostheses provides important information regarding their hemodynamic performance. It is usually calculated by transthoracic echocardiography (TTE), however, accurate and reproducible determination may be challenging. Cardiovascular magnetic resonance (CMR) has been proven as an accurate alternative for assessing aortic bioprostheses. However, whether CMR can be similarly applied for bioprostheses in the mitral position, particularly in the presence of frequently coincident arrhythmias, is unclear. The aim of the study is to test the feasibility of CMR to evaluate the orifice area of mitral bioprostheses. Methods. CMR planimetry was performed in 18 consecutive patients with mitral bioprostheses (n = 13 Hancock, n = 4 Labcore, n = 1 Perimount; mean time since implantation 4.5 3.9 years) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5T MR system. CMR results were compared with pressure half-time derived orifice areas obtained by TTE. Results. Six subjects were in sinus rhythm, 11 in atrial fibrillation, and 1 exhibited frequent ventricular extrasystoles. CMR image quality was rated as good in 10, moderate in 6, and significantly impaired in 2 subjects. In one prosthetic type (Perimount), strong stent artifacts occurred. Orifice areas by CMR (mean 2.1 0.3 cm2) and TTE (mean 2.1 0.3 cm2) correlated significantly (r = 0.94; p < 0.001). Bland-Altman analysis showed a 95% confidence interval from -0.16 to 0.28 cm2 (mean difference 0.06 0.11 cm2; range -0.1 to 0.3 cm2). Intra- and inter-observer variabilities of CMR planimetry were 4.5 2.9% and 7.9 5.2%. Conclusions. The assessment of mitral bioprostheses using CMR is feasible even in those with arrhythmias, providing orifice areas with close agreement to echocardiography and low observer dependency. Larger samples with a greater variety of prosthetic types and more cases of prosthetic dysfunction are required to confirm these preliminary results. © 2010 von Knobelsdorff-Brenkenhoff et al; licensee BioMed Central Ltd.

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