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Universitäts-Herzzentrum Freiburg - Bad KrozingenUniversitäts-Herzzentrum Freiburg - Bad Krozingen

Experimental Interventional Cardiology


1. Overview

Multiple non-invasive approaches are well established for diagnosis of coronary artery disease, and invasive coronary angiography is the gold standard for treatment of coronary stenoses. However, we are still limited in individualized evaluation of vascular inflammation or plaque progression resulting in coronary artery disease. Furthermore, routine coronary angiography does not provide us with information on plaque characteristics, and involves ionizing radiation – which is potentially harmful to the operator over the course of time.

We are interested in completely new approaches for individualized diagnostics and interventions in coronary artery disease. Our main interest is focused on interventional magnetic resonance imaging including plaque characterization and its specific interventional treatment (SFB), as well as robotic-assisted coronary interventions in the cath lab.

Furthermore, we are interested in the application of current interventional technologies in the clinical routine, its clinical outcomes in large nationwide cohorts, and economical aspects of these interventional approaches (CeBac).

2. Robotics in interventional cardiology



Introduction of robotics in interventional cardiology will result in completely new diagnostic and therapeutic approaches. The roboter is a device of the size of a small travel bag, which is fixed on the catheterization table, and contains all necessary motors and sensors for moving catheters and guidewires. Consequently, the interventionalist only performs the puncture of the access vessel, and then takes a seat in front of a remote control either located next to patient or in a remote area. Necessary changes in guidewires or catheters will be performed by an assistance nearby the table. This strategy has different advantages: 1.) the precision of an intervention is increased, since motors and sensors of the roboter allow careful and exact movements; 2.) the medical personnel is not directly exposed to radiation any longer- which potentially induces tumors after decades of radiation exposure; 3.) motor movements and sensor information can be saved for the individual intervention, and are available in a cloud as anonymized information, so that it can be applied worldwide in a similar coronary anatomy, also allowing a continuous improvement of the individual intervention itself – a perfect example for application of artificial intelligence in medicine; 4.) coronary interventions can also be guided by telemedicine over large distances; 5.) in the era of pandemics, it also offers a protection against potential infections to the medical personnel.  We plan to connect robotics with most recent state of the art technologies in interventional cardiology- starting in Q2/2021.

3. 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.

This project is funded by the DFG within the SFB 1425.

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

Movie 1

4. 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.    

5. 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).

6.  Center for Big Data Analysis in Cardiology (CeBAC)

The Center of Big Data Analysis in Cardiology is an association of interventional cardiologists and statisticians in order to analyze interventional procedures. Together we analyze big data sets to evaluate the clinical and economic value of modern interventional therapies. This may help to identify the ideal therapeutic options for individual patients. Beyond that we support health care policy by the evaluation of emerging therapy concepts in clinical practice.

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Prof. Dr. von zur Mühlen

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