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Cardiovascular Molecular Imaging and Proteomics

1. Overview

Our group works on invasive and non-invasive treatment and characterization of atherosclerosis, guided by dedicated imaging techniques, and addressing questions relevant in clinical and basic research.

In the clinical field of research, we have a large interest in the treatment outcomes and follow up of bioresorbable vascular scaffolds. Invasive and non-invasive characterization is performed by invasive (e.g. OCT) or non-invasive (coronary MRI) imaging. In basic research, we have a large experience in molecular imaging contrast agents for MRI or other imaging modalities. Currently, transfer from bench to bedside is our main challenge. Furtermore, we explore the non-invasive characterization of cardiovascular disease progression by protoeme analysis.  

Coronary magnetic resonance imaging of vascular devices

Bioresorbable vascular scaffolds (BVS) are a rapidly evolving technique in interventional cardiology. Due to the non-metallic PLLA-backbone, BVS-therapy might also allow for noninvasive eva­luation of coronary arteries by magnetic resonance imaging (MRI), simultaneously yiel­ding information about anatomy and atherosclerotic plaque dynamics. Conventional metallic stents are known to shield off the radio-frequency (RF) fields during MRI signal excitation and data acquisition, which leads to a severely reduced MRI sensitivity inside the stent. Additionally, the closed metallic ring structures can create unwanted field distortions from susceptibility differences. In contrast, BVS might allow for an artifact-free imaging of the scaffold lumen, so that the patency of the vessel can be directly assessed in a noninvasive manner (Figure 1).


Cardiovascular molecular imaging using targeted contrast agents

Atherosclerosis and its resulting cardiovascular complications are the leading cause of morbidity and mortality in the western world. The progression, erosion and rupture of atherosclerotic plaques are regarded as the precipitating event for thrombus formation in myocardial infarction and stroke. Early non-invasive testing in symptomatic or asymptomatic patients can help to guide specific therapies or interventions, and may therefore help to reduce morbidity and mortality. Recent progress in magnetic resonance imaging (MRI) has provided the technical prerequisites to allow imaging of atherosclerotic plaques. There is currently considerable interest in developing contrast-ligand probes to enable imaging of specific molecules, cells and processes that are important to atherosclerosis. We have previously used functionalized microparticles of iron oxide (MPIO) to specifically target activated platelets. Therefore, we used a unique single-chain antibody recognizing ligand-induced binding-sites (LIBS) on activated glycoprotein IIb/IIIa-receptors. Using this technology, we were able to noninvasively detect platelet aggregation in arterial thrombosis of the carotid arteries in mice, and to observe the success of a thrombolytic therapy (Figure 2). In a different approach using the same contrast agent, we were able to detect platelet aggregation in cerebrovascular inflammation before the onset of clinical symptoms, or in thrombosis of coronary vessels in mice. Furthermore, using a dual imaging apporach, we can also non-invasively characterize the presence and extent of a myocardial ischemia/reperfusion injury after temoporary coronary ligation (Figure 3). Currently, research is ongoing to transfer this technique into human settings as well as into ultrasound contrast agent applications.

Imaging of monocytes/macrophages involved into plaque inflammation is another goal of our research. Macrophages are promoters of plaque inflammation and vulnerability, and therefore their timely detection would be of clinical interest. We have examined uptake mechanisms of iron oxide particles into monoctyes/macrophages, which could help to target such inflammatory cells with increased sensitivity.    

 
Cardiovascular Proteome analysis

Proteomic technologies emerged as sensitive, fast and robust tools for analysis of protein patterns in body fluids. Compared to conventional processes of marker definition, this approach allows inclusion of large numbers of proteins to identify diagnostically useful protein patterns. Accompanied by advanced software, proteomic analysis enables the de-novo establishment of protein patterns without any prior definition of proteins of interest. In current projects, we evaluate the possibility to non-invasively detect human and murine atherosclerosis by plasma and urine proteomics, facilitating the workup of patients with atherosclerosis or symptoms suspicious of coronary artery disease (Figure 3).

Labor
Prof. Dr. von zur Mühlen

Prof. Dr. C. von zur Mühlen
Telefon: 0761 270-70420
Telefax: 0761 270-70450
E-Mail: constantin.vonzurmuehlen@
universitaets-herzzentrum.de