TY - JOUR A1 - Andelovic, Kristina A1 - Winter, Patrick A1 - Kampf, Thomas A1 - Xu, Anton A1 - Jakob, Peter Michael A1 - Herold, Volker A1 - Bauer, Wolfgang Rudolf A1 - Zernecke, Alma T1 - 2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis JF - Biomedicines N2 - Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe\(^{−/−}\), n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe\(^{−/−}\) mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability. KW - atherosclerosis KW - mouse KW - 4D flow MRI KW - aortic arch KW - flow dynamics KW - WSS KW - mapping KW - PWV KW - plaque characteristics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252164 SN - 2227-9059 VL - 9 IS - 12 ER - TY - JOUR A1 - Li, Xiang A1 - Samnick, Samuel A1 - Lapa, Constantin A1 - Israel, Ina A1 - Buck, Andreas K. A1 - Kreissl, Michael C. A1 - Bauer, Wolfgang T1 - 68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors N2 - Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions. KW - Medizin KW - Atherosclerotic plaque KW - 68Ga-DOTATATE KW - Somatostatin receptor KW - Cardiovascular risk factors KW - Macrophage Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76231 ER - TY - JOUR A1 - Herold, Volker A1 - Herz, Stefan A1 - Winter, Patrick A1 - Gutjahr, Fabian Tobias A1 - Andelovic, Kristina A1 - Bauer, Wolfgang Rudolf A1 - Jakob, Peter Michael T1 - Assessment of local pulse wave velocity distribution in mice using k-t BLAST PC-CMR with semi-automatic area segmentation. JF - Journal of Cardiovascular Magnetic Resonance N2 - Background: Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities. Methods: In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE\(^{(-/-)}\)-mice) at 12 adjacent locations along the abdominal aorta. Results: Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE\(^{(-/-)}\)-group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE \(^{(-/-)}\)-animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis. Conclusion: In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE\(^{(-/-)}\)-mice as a relevant model of atherosclerosis. KW - pulse wave velocity KW - ApoE\(^{(-/-)}\) KW - magnetic resonance imaging KW - phase contrast Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157696 VL - 19 IS - 77 ER - TY - JOUR A1 - Manchia, Mirko A1 - Adli, Mazda A1 - Akula, Nirmala A1 - Arda, Raffaella A1 - Aubry, Jean-Michel A1 - Backlund, Lena A1 - Banzato, Claudio E. M. A1 - Baune, Bernhard T. A1 - Bellivier, Frank A1 - Bengesser, Susanne A1 - Biernacka, Joanna M. A1 - Brichant-Petitjean, Clara A1 - Bui, Elise A1 - Calkin, Cynthia V. A1 - Cheng, Andrew Tai Ann A1 - Chillotti, Caterina A1 - Cichon, Sven A1 - Clark, Scott A1 - Czerski, Piotr M. A1 - Dantas, Clarissa A1 - Del Zompo, Maria A1 - DePaulo, J. Raymond A1 - Detera-Wadleigh, Sevilla D. A1 - Etain, Bruno A1 - Falkai, Peter A1 - Frisén, Louise A1 - Frye, Mark A. A1 - Fullerton, Jan A1 - Gard, Sébastien A1 - Garnham, Julie A1 - Goes, Fernando S. A1 - Grof, Paul A1 - Gruber, Oliver A1 - Hashimoto, Ryota A1 - Hauser, Joanna A1 - Heilbronner, Urs A1 - Hoban, Rebecca A1 - Hou, Liping A1 - Jamain, Stéphane A1 - Kahn, Jean-Pierre A1 - Kassem, Layla A1 - Kato, Tadafumi A1 - Kelsoe, John R. A1 - Kittel-Schneider, Sarah A1 - Kliwicki, Sebastian A1 - Kuo, Po-Hsiu A1 - Kusumi, Ichiro A1 - Laje, Gonzalo A1 - Lavebratt, Catharina A1 - Leboyer, Marion A1 - Leckband, Susan G. A1 - López Jaramillo, Carlos A. A1 - Maj, Mario A1 - Malafosse, Alain A1 - Martinsson, Lina A1 - Masui, Takuya A1 - Mitchell, Philip B. A1 - Mondimore, Frank A1 - Monteleone, Palmiero A1 - Nallet, Audrey A1 - Neuner, Maria A1 - Novák, Tomás A1 - O'Donovan, Claire A1 - Ösby, Urban A1 - Ozaki, Norio A1 - Perlis, Roy H. A1 - Pfennig, Andrea A1 - Potash, James B. A1 - Reich-Erkelenz, Daniela A1 - Reif, Andreas A1 - Reininghaus, Eva A1 - Richardson, Sara A1 - Rouleau, Guy A. A1 - Rybakowski, Janusz K. A1 - Schalling, Martin A1 - Schofield, Peter R. A1 - Schubert, Oliver K. A1 - Schweizer, Barbara A1 - Seemüller, Florian A1 - Grigoroiu-Serbanescu, Maria A1 - Severino, Giovanni A1 - Seymour, Lisa R. A1 - Slaney, Claire A1 - Smoller, Jordan W. A1 - Squassina, Alessio A1 - Stamm, Thomas A1 - Steele, Jo A1 - Stopkova, Pavla A1 - Tighe, Sarah K. A1 - Tortorella, Alfonso A1 - Turecki, Gustavo A1 - Wray, Naomi R. A1 - Wright, Adam A1 - Zandi, Peter P. A1 - Zilles, David A1 - Bauer, Michael A1 - Rietschel, Marcella A1 - McMahon, Francis J. A1 - Schulze, Thomas G. A1 - Alda, Martin T1 - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report JF - PLoS ONE N2 - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. KW - age KW - observer agreement KW - prophylactic lithium KW - mapping susceptibility genes KW - mood disorders KW - onset KW - association KW - reliability KW - morality KW - illness Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938 VL - 8 IS - 6 ER - TY - THES A1 - Bauer, Michael T1 - Die Unabhängigkeit des Abschlussprüfers im Zusammenhang mit dem gleichzeitigen Angebot von Beratungsleistungen beim Prüfungsmandanten - eine empirische Analyse T1 - Auditor Independence and the Provision of Non-Audit Services by Accounting Firms to their Audit Clients N2 - Zahlreiche, zum Teil sehr spektakuläre Unternehmenszusammenbrüche – national (z.B. Holzmann, Bankgesellschaft Berlin) wie international (z.B. Enron, Worldcom) – in Verbindung mit Bilanzmanipulationen, haben den Berufsstand in eine schwere Vertrauenskrise gestürzt. Vor allem der Zusammenbruch von Enron (vormals das siebtgrößte Unternehmen der USA) hat die internationale Wirtschaftsprüfung in großen Aufruhr versetzt. Nach Bekanntwerden des Enron-Skandals wurden weitere Fälle fragwürdiger Bilanzierungspraktiken aufgedeckt, was in der Öffentlichkeit den Eindruck erweckte, dass es sich hierbei um keinen Einzelfall handelte, sondern dass erhebliche strukturelle Defizite vorliegen müssen. Diese Entwicklungen lösten weltweit eine Reformdebatte aus, welche zahlreiche berufsständische und gesetzliche Regulierungseingriffe, sowohl national als auch international, zur Folge hatte. Unter besonderem Handlungsdruck stand der Gesetzgeber in den USA. Im Sommer 2002 wurde der „Sarbanes-Oxley Act“ verabschiedet, der stark regulierend in den Berufsstand eingreift. Die Kritik der Öffentlichkeit konzentriert sich dabei hauptsächlich auf das gleichzeitige Angebot von Prüfungs- und Beratungsleistungen durch den amtierenden Abschlussprüfer. Viele sehen dadurch die Unabhängigkeit des Abschlussprüfers und damit die Glaubwürdigkeit der Jahresabschlussinformationen gefährdet. Die Sicherung der Vertrauenswürdigkeit stellt für die Qualität der Abschlussprüfung eine existentielle Grundlage dar. Die Vorschriften zur Unabhängigkeit des Abschlussprüfers wurden daraufhin verschärft, zahlreiche Beratungsleistungen durch den Abschlussprüfer gelten nun als unvereinbar mit gleichzeitiger Abschlussprüfung. Auch in der Europäischen Union und in Deutschland wird heftig diskutiert, wie man das verloren gegangene Vertrauen der Öffentlichkeit wiedergewinnen kann. Vor dem Hintergrund dieser Reformdebatte muss die Frage gestellt werden, ob durch das gleichzeitige Angebot von Prüfungs- und Beratungsleistungen die Unabhängigkeit des Abschlussprüfers tatsächlich gefährdet ist, oder die eingeleiteten Maßnahmen der Öffentlichkeit lediglich Handlungsfähigkeit seitens des Gesetzgebers suggerieren sollen, um das Vertrauen in den Berufsstand schnellstmöglich wieder zurückzugewinnen. Aus wissenschaftlicher Sicht konnte eine Beeinträchtigung der Unabhängigkeit des Abschlussprüfers bisher weder theoretisch noch empirisch nachgewiesen werden. Einige Autoren kritisieren vor allem bei der amerikanischen Gesetzesinitiative, sie habe sich eher an der Meinung der Öffentlichkeit orientierte, ohne wirkliche Ursachenanalyse zu betreiben. Es ist jedoch ausdrücklich nicht das Anliegen dieser Arbeit, das Für und Wider einschlägiger gesetzlicher Regelungen bzw. interner Sicherungsmaßnahmen darzustellen und zu erörtern. Die vorliegende Arbeit leistet einen Beitrag zur aktuellen Diskussion, indem ausführlich untersucht wird, ob sich eine Gefährdung der Unabhängigkeit des Abschlussprüfers im Zusammenhang mit dem gleichzeitigen Angebot von Prüfungs- und Beratungsleistungen empirisch nachweisen lässt oder nicht. Dabei werden zwei Ziele verfolgt: Zum einen werden bereits vorliegende empirische Studien zu dieser Problematik vorgestellt und diskutiert, zum anderen werden zwei eigene empirische Untersuchungen, welche auf agencytheoretischen Grundüberlegungen basieren, in die Diskussion eingebracht. N2 - There has been a strong growth in accounting firms´ provisions of non-audit services to their audit clients. Regulators, financial statement users, and researchers are concerned that auditors compromise their independence. Recent accounting scandals at prominent companies such as ENRON or WORLDCOM have increased such concernings. In July 2002 President Bush singed the Sarbanes-Oxley Act, which aggravated the rules of joint provision of audit and non-audit services. This paper analyses if there is empirical evidence that non-audit services compromise auditor independence. The major model argues that companies that face potentially high agency costs purchase relatively smaller amounts of non-audit services from their auditor. High agency-cost companies require independent audits in order to reassure investors and creditors; the provision of joint services, which increase the economic bonding of the auditor to the client, may jeopardize independence or the appearance of independence. KW - Deutschland KW - Jahresabschlussprüfung KW - Abschlussprüfer KW - Unabhängigkeit KW - Abschlussprüfung und Beratung KW - Unabhängigkeit des Abschlussprüfers KW - Audit Services KW - Non-Audit Services KW - Auditor Independence Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-14913 ER - TY - JOUR A1 - Reiter, Theresa A1 - Gensler, Daniel A1 - Ritter, Oliver A1 - Weiss, Ingo A1 - Geistert, Wolfgang A1 - Kaufmann, Ralf A1 - Hoffmeister, Sabine A1 - Friedrich, Michael T. A1 - Wintzheimer, Stefan A1 - Düring, Markus A1 - Nordbeck, Peter A1 - Jakob, Peter M. A1 - Ladd, Mark E. A1 - Quick, Harald H. A1 - Bauer, Wolfgang R. T1 - Direct cooling of the catheter tip increases safety for CMR-guided electrophysiological procedures JF - Journal of Cardiovascular Magnetic Resonance N2 - Background: One of the safety concerns when performing electrophysiological (EP) procedures under magnetic resonance (MR) guidance is the risk of passive tissue heating due to the EP catheter being exposed to the radiofrequency (RF) field of the RF transmitting body coil. Ablation procedures that use catheters with irrigated tips are well established therapeutic options for the treatment of cardiac arrhythmias and when used in a modified mode might offer an additional system for suppressing passive catheter heating. Methods: A two-step approach was chosen. Firstly, tests on passive catheter heating were performed in a 1.5 T Avanto system (Siemens Healthcare Sector, Erlangen, Germany) using a ASTM Phantom in order to determine a possible maximum temperature rise. Secondly, a phantom was designed for simulation of the interface between blood and the vascular wall. The MR-RF induced temperature rise was simulated by catheter tip heating via a standard ablation generator. Power levels from 1 to 6 W were selected. Ablation duration was 120 s with no tip irrigation during the first 60 s and irrigation at rates from 2 ml/min to 35 ml/min for the remaining 60 s (Biotronik Qiona Pump, Berlin, Germany). The temperature was measured with fluoroscopic sensors (Luxtron, Santa Barbara, CA, USA) at a distance of 0 mm, 2 mm, 4 mm, and 6 mm from the catheter tip. Results: A maximum temperature rise of 22.4 degrees C at the catheter tip was documented in the MR scanner. This temperature rise is equivalent to the heating effect of an ablator's power output of 6 W at a contact force of the weight of 90 g (0.883 N). The catheter tip irrigation was able to limit the temperature rise to less than 2 degrees C for the majority of examined power levels, and for all examined power levels the residual temperature rise was less than 8 degrees C. Conclusion: Up to a maximum of 22.4 degrees C, the temperature rise at the tissue surface can be entirely suppressed by using the catheter's own irrigation system. The irrigated tip system can be used to increase MR safety of EP catheters by suppressing the effects of unwanted passive catheter heating due to RF exposure from the MR scanner. KW - EP Procedures KW - radiofrequency ablation KW - contact force KW - lesion size KW - MRI KW - temperature KW - tissue KW - wires KW - model KW - ablation KW - safety KW - catheter tip KW - MR guidance Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134927 VL - 14 IS - 12 ER - TY - JOUR A1 - Pfennig, Andrea A1 - Leopold, Karolina A1 - Bechdolf, Andreas A1 - Correll, Christoph U. A1 - Holtmann, Martin A1 - Lambert, Martin A1 - Marx, Carolin A1 - Meyer, Thomas D. A1 - Pfeiffer, Steffi A1 - Reif, Andreas A1 - Rottmann-Wolf, Maren A1 - Schmitt, Natalie M. A1 - Stamm, Thomas A1 - Juckel, Georg A1 - Bauer, Michael T1 - Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial JF - TRIALS N2 - Background: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. Methods/Design: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in-and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo) affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. Discussion: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. KW - cognitive-behavioural psychotherapy KW - bipolar disorders KW - early recognition KW - intervention study KW - of-the-literature KW - ultra-high risk KW - spectrum disorder KW - early intervention KW - rating scale Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116279 SN - 1468-6694 SN - 1745-6215 VL - 15 IS - 161 ER - TY - JOUR A1 - Leopold, Karolina A1 - Bauer, Michael A1 - Bechdolf, Andreas A1 - Correll, Christoph U. A1 - Holtmann, Martin A1 - Juckel, Georg A1 - Lambert, Martin A1 - Meyer, Thomas D. A1 - Pfeiffer, Steffi A1 - Kittel‐Schneider, Sarah A1 - Reif, Andreas A1 - Stamm, Thomas J. A1 - Rottmann‐Wolf, Maren A1 - Mathiebe, Josephine A1 - Kellmann, Eva L. A1 - Ritter, Philipp A1 - Krüger‐Özgürdal, Seza A1 - Karow, Anne A1 - Sondergeld, Lene‐Marie A1 - Roessner, Veit A1 - Sauer, Cathrin A1 - Pfennig, Andrea T1 - Efficacy of cognitive‐behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study JF - Bipolar Disorders N2 - Objective Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at‐risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive‐behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. Method In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15‐30 years were randomized to 14 weeks of at‐risk for BD‐specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At‐risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. Results Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between‐group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop‐outs. Conclusions Results suggest that young patients at‐risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification. KW - at‐risk KW - bipolar disorder KW - CBT KW - early intervention KW - group treatment KW - prodromal KW - serious mental illness KW - subthreshold bipolar Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215469 VL - 22 IS - 5 SP - 517 EP - 529 ER - TY - JOUR A1 - Andelovic, Kristina A1 - Winter, Patrick A1 - Jakob, Peter Michael A1 - Bauer, Wolfgang Rudolf A1 - Herold, Volker A1 - Zernecke, Alma T1 - Evaluation of plaque characteristics and inflammation using magnetic resonance imaging JF - Biomedicines N2 - Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients. KW - atherosclerosis KW - mouse models KW - wall shear stress KW - pulse wave velocity KW - arterial elasticity KW - inflammation KW - magnetic resonance imaging Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228839 SN - 2227-9059 VL - 9 IS - 2 ER - TY - JOUR A1 - Winter, Patrick A1 - Andelovic, Kristina A1 - Kampf, Thomas A1 - Gutjahr, Fabian Tobias A1 - Heidenreich, Julius A1 - Zernecke, Alma A1 - Bauer, Wolfgang Rudolf A1 - Jakob, Peter Michael A1 - Herold, Volker T1 - Fast self-navigated wall shear stress measurements in the murine aortic archusing radial 4D-phase contrast cardiovascular magnetic resonance at 17.6 T JF - Journal of Cardiovascular Magnetic Resonance N2 - Purpose 4D flow cardiovascular magnetic resonance (CMR) and the assessment of wall shear stress (WSS) are non-invasive tools to study cardiovascular risks in vivo. Major limitations of conventional triggered methods are the long measurement times needed for high-resolution data sets and the necessity of stable electrocardiographic (ECG) triggering. In this work an ECG-free retrospectively synchronized method is presented that enables accelerated high-resolution measurements of 4D flow and WSS in the aortic arch of mice. Methods 4D flow and WSS were measured in the aortic arch of 12-week-old wildtype C57BL/6 J mice (n = 7) with a radial 4D-phase-contrast (PC)-CMR sequence, which was validated in a flow phantom. Cardiac and respiratory motion signals were extracted from the radial CMR signal and were used for the reconstruction of 4D-flow data. Rigid motion correction and a first order B0 correction was used to improve the robustness of magnitude and velocity data. The aortic lumen was segmented semi-automatically. Temporally averaged and time-resolved WSS and oscillatory shear index (OSI) were calculated from the spatial velocity gradients at the lumen surface at 14 locations along the aortic arch. Reproducibility was tested in 3 animals and the influence of subsampling was investigated. Results Volume flow, cross-sectional areas, WSS and the OSI were determined in a measurement time of only 32 min. Longitudinal and circumferential WSS and radial stress were assessed at 14 analysis planes along the aortic arch. The average longitudinal, circumferential and radial stress values were 1.52 ± 0.29 N/m2, 0.28 ± 0.24 N/m2 and − 0.21 ± 0.19 N/m2, respectively. Good reproducibility of WSS values was observed. Conclusion This work presents a robust measurement of 4D flow and WSS in mice without the need of ECG trigger signals. The retrospective approach provides fast flow quantification within 35 min and a flexible reconstruction framework. KW - 4D flow KW - WSS KW - OSI KW - Self-navigation KW - Mouse KW - Aortic arch Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201120 VL - 21 ER -