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Non-invasive ultrasound molecular imaging of myocarditis and autoimmune myocardial inflammation

English title Non-invasive ultrasound molecular imaging of myocarditis and autoimmune myocardial inflammation
Applicant Kaufmann Beat
Number 149718
Funding scheme Project funding (Div. I-III)
Research institution Klinik für Kardiologie Bereich Medizin Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Cardiovascular Research
Start/End 01.04.2014 - 31.03.2017
Approved amount 365'687.00
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All Disciplines (2)

Discipline
Cardiovascular Research
Biomedical Engineering

Keywords (3)

Contrast Enhanced Ultrasound Molecular Imaging; Myocarditis; Inflammation

Lay Summary (German)

Lead
Nicht-invasive molekulare Ultraschall-Bildgebung von Herzmuskelentzündungen
Lay summary
Die Myokarditis ist eine entzündliche Erkrankung des Myokards welche durch verschiedene infektiöse, aber auch durch nicht-infektiöse Erkrankungen ausgelöst werden kann. In der westlichen Welt sind virale Infektionen die häufigste Ursache einer Myokarditis. Nach einem akuten, virus-induzierten Zellschaden können Autoimmunvorgänge zu eienr zusätzlichen Myokardschädigung führen. Eine Myokarditis kann verschiedenste Symptome hervorrufen, kann aber auch gänzlich asymptomatisch verlaufen. Bei chronischem Verlauf kann eine Myokarditis zu einem bleibenden Schaden des Herzmuskels und damit zu einer Herzschwäche führen. Heute verfügbare Tests zur Diagnose der Myokarditis sind unspezifisch und z.T. nicht sensitiv. Molekulare Ultraschall-Bildgebung verwendet Kontrastmittel, welche gegen molekulare Strukturen in Blutgefässen gerichtet werden können, wurde bereits im Tiermodell zur Detektion von Entzündungen im Rahmen der Atherosklerose und der Myokardischämie verwendet. Wir werden in unserem Projekt untersuchen, ob molekulare Ultraschall-Bildgebung die Entzündung im Herzmuskel nicht-invasiv detektieren kann.
Direct link to Lay Summary Last update: 15.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
NON-INVASIVE CONTRAST ENHANCED ULTRASOUND MOLECULAR IMAGING DETECTS MYOCARDIAL INFLAMMATORY RESPONSE IN AUTOIMMUNE MYOCARDITIS
David C. Steinl, Lifen Xu, Elham Khanicheh, Elin Ellertsdottir, Amanda Ochoa-Espinosa, Martina Mitterhuber, Katharina Glatz, Gabriela M. Kuster, Beat A. Kaufmann, NON-INVASIVE CONTRAST ENHANCED ULTRASOUND MOLECULAR IMAGING DETECTS MYOCARDIAL INFLAMMATORY RESPONSE IN AUTOIMMUNE MYOCARDITIS, in Circulation Cardiovascular Imaging, 9(8).

Collaboration

Group / person Country
Types of collaboration
Prof. Lindner/Oregon Health and Science University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Euroecho 2015 Talk given at a conference Gene therapy with ultrasound and microbubbles 03.12.2015 Sevilla, Spain Kaufmann Beat;
Cardiovascular & Metabolic Research Meeting 2015 Talk given at a conference Contrast enhanced ultrasound molecular imaging of the inflammatory response in autoimmune myocarditis 22.01.2015 Fribourg, Switzerland Steinl David;
Euroecho 2014 Talk given at a conference Contrast enhanced ultrasound molecular imaging of the inflammatory response in myocarditis 03.12.2014 Wien, Austria Steinl David;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Tag der Biomedizin, Departement Biomedizin Universitätsspital Basel German-speaking Switzerland 2016

Awards

Title Year
Best Free Communication Cardiovascular & Metabolic Research Meeting 2015 2015
Young Investigators Award Finalist - Euroecho 2014 2014

Associated projects

Number Title Start Funding scheme
141603 Contrast enhanced ultrasound molecular imaging of vascular inflammation in atherosclerosis: development of methods for early detection of cardiovascular risk and assessment of the effect of targeted therapies 01.04.2012 Ambizione
123819 Contrast enhanced ultrasound molecular imaging of vascular inflammation in atherosclerosis: development of methods for early detection of cardiovascular risk and assessment of the effect of targeted therapies 01.04.2009 Ambizione
169905 Non-invasive ultrasound molecular imaging of atherosclerosis: development of clinically translatable tracers for targeting of Vascular Cell Adhesion Molecule 1 01.04.2017 Project funding (Div. I-III)

Abstract

Myocarditis is an inflammatory disease of the myocardium caused by a variety of infectious and noninfectious diseases. In western countries, it is most often of viral origin. After an initial virus-induced cytotoxicity, T-cell-mediated autoimmunity plays an important role. Myocarditis can present with highly variable symptoms but can also be asymptomatic. However, even asymptomatic patients carry a risk for sudden death. In addition, viral myocarditis may later develop into dilated cardiomyopathy, which in young patients is a frequent cause for heart failure. Autopsy studies show histologic evidence of myocarditis in 1% and suggest that the disease is underdiagnosed. Routine cardiac tests for diagnosis lack sensitivity and/or specificity. Even endomyocardial biopsy, which is considered the gold standard for diagnosis suffers from low sensitivity.Noninvasive imaging has been used to detect wall motion abnormalities (echocardiography) or evidence of tissue damage (magnetic resonance, nuclear imaging). However, wall motion abnormalities may not be present, and tissue damage may occur not only due to inflammation, but also due to ischemia. Thus, there is a need for non-invasive imaging methods for the diagnosis and detailed characterization of myocarditis. Contrast enhanced ultrasound (CEU) molecular imaging has been used to target leukocytes and markers of endothelial inflammation in myocardial microvessels. We therefore propose to study the value of CEU molecular imaging for the diagnosis, sequential assessment and evaluation of prognosis of myocarditis.Preliminary data from our laboratory show that in mice with experimental autoimmune myocarditis (EAM) signal from contrast agents targeted to activated leukocytes is higher than signal from control contrast agents. In addition, preliminary in vitro experiments indicate that targeting of CD4 is feasible and may allow CEU molecular imaging of specific components of the inflammatory infiltrate in myocarditis. Thus, we propose the following three study aims:Specific Aim 1: To test whether CEU molecular imaging can detect myocardial inflammation in experimental autoimmune myocarditis independent of left ventricular function. CEU molecular imaging will be performed in mice with EAM and the results will be compared to results from high frequency ultrasound imging of the left ventricle and histology.Specific Aim 2: To test whether CEU molecular imaging can be used for serial assessment of inflammatory cell recruitment during all phases of autoimmune myocarditis. CEU molecular imaging will be performed at several timepoints during the development of EAM, and the results will be compared to histology and immunohistology. Specific Aim 3: To test whether CEU molecular imaging of tissue inflammation is predictive of late functional impairment. CEU molecular imaging will be performed during the peak inflammation of murine EAM and correlated to later functional impairment.Significance. Myocarditis is a frequent differential diagnosis especially in young patients with an important disease burden. The diagnostic tools currently available are imperfect, and there is a need for novel, noninvasive diagnostic imaging methods. The proposed studies will assess whether CEU molecular imaging can be developed into a feasible tool for detecting myocarditis and whether it can assess its prognosis.
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