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Cardiovascular Molecular Imaging and Interventions

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1. Overview

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.

2. Interventional Magnetic Resonance Imaging

An important step towards individualized therapy in cardiovascular medicine is the specific characterization of disease followed by selective treatment. Interventional Magnetic resonance imaging (MRI) of cardiovascular disease has a high diagnostic potential due to the absence of ionizing radiation, its excellent 3D imaging capabilities, and superior soft tissue contrast compared to x-ray fluoroscopy. Recent technical developments of imaging hard- and software enable us to perform MRI-guided coronary interventions with stents or scaffolds in large animals (Figure 1, Movie 1), without any use of radiation. In addition, specific disease detection is possible by molecular MRI. Molecular imaging allows to image cells or cellular receptors on a molecular level – by dedicated contrast agents, e.g. consisting of target-specific antibodies and contrast-giving moieties.

As a perspective, MRI may constitute an ideal imaging technique for the detection and assessment of pathophysiological changes in atherosclerotic plaques, providing cell-type specificity when using molecular imaging contrast agents, and allowing a step towards an individualized interventional therapy.

Movie 1: Real-time MRI of intubation of the left coronary artery with a guiding catheter suitable for coronary interventions. From Heidt T et al. Sci Rep 2019

3. 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.    

4. Coronary magnetic resonance imaging of vascular devices

Bioresorbable vascular scaffolds (BVS) are an 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 4).

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