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Dual Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by MRI.
MedLine Citation:
PMID:  24951772     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, non-invasive imaging approach using molecular magnetic resonance imaging (MRI) in an in vivo mouse model of myocardial ischemia and reperfusion.
METHODS AND RESULTS: -Ischemia/reperfusion injury was induced in 10 week old C57BL/6N mice by temporary ligation of the "left anterior descending coronary artery"(LAD). Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein (GP)IIb/IIIa (=LIBS-MPIO). After injection and imaging of LIBS-MPIO, late gadolinium enhancement (LGE) was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y12 (-/-) mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by MRI via a significant signal effect caused by LIBS-MPIO in the area of LAD occlusion two hours after reperfusion. In parallel, LGE identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIO significantly bound to microthrombi in reperfused myocardium. Only background-binding was found in P2Y12 (-/-) mice.
CONCLUSIONS: -Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIO as well as myocardial necrosis by LGE. This non-invasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes, and highlights the potential of molecular MRI for characterizing ischemia/reperfusion injury.
Authors:
Dominik von Elverfeldt; Alexander Maier; Daniel Duerschmied; Moritz Braig; Thilo Witsch; Xiaowei Wang; Maximilian Mauler; Irene Neudorfer; Marius Menza; Marco Idzko; Andreas Zirlik; Timo Heidt; Peter Bronsert; Christoph Bode; Karlheinz Peter; Constantin von Zur Muhlen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-20
Journal Detail:
Title:  Circulation     Volume:  -     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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