Cath Lab Digest

After stabilization of the IVMRI probe within an artery, a field of view (FOV) 2-mm in length, 60 degrees along the circumference, radial depth of penetration of 250 µ, is acquired. Several acquisitions can be obtained by rotating the catheter. The image obtained by the intravascular MRI probe is not a picture of the actual morphology of the plaque, but provides a simplified spatial representation of its lipid-rich component. In order to allow “online” interpretation of the lipid composition in each measurement zone, color-coding is used, where yellow represents the presence of lipid, while blue denotes non-lipidemic tissue, whether fibrous tissue or normal vascular smooth muscle cells. Color-coded data from each measurement sector are displayed separately with a numerical lipid-fraction index. Depending on the imaging protocol, each sector can display lipid fraction in various measurement zones, based on the zone depth.

Preclinical Data
Proof of concept studies were performed in a series of studies. An initial in vivo study made use of a patch of subcutaneous fat sewn on either the left anterior descending (LAD) coronary artery through open chest surgery or the femoral artery (Figure 1). The IVMRI catheter was introduced into the LAD via a femoral approach and MRI measurements were performed in 4 quadrants. The same animal was used for MRI examination in the noninstrumented femoral artery. The vessel was dissected and a subcutaneous fat patch was tightly wrapped around half of the vessel’s circumference. The IVMRI catheter was introduced directly into the femoral artery, and measurements were performed at wrapped and unwrapped segments of the artery. The MRI displays obtained in both arterial locations demonstrated the capability of the MRI probe to detect lipid-rich tissue within the range of its radial penetration. The thin (100µ) femoral artery allowed diagnosis of lipid at the superficial corresponding sector, whereas the rather thick (300 µ) coronary artery left the wrapped fat beyond the functional diagnostic capabilities of the IVMRI probe. Subsequent studies performed in atherosclerotic and nonatherosclerotic swine demonstrated the ability of the IVMRI catheter to locate increased intra-arterial lipid concentrations, as well as the safety of the device within coronary and peripheral vessels.

Studies were then performed to determine the efficacy of IVMRI to determine the presence of lipid-rich vulnerable plaques in human coronary arteries. In this ex vivo study, in situ coronary arteries with atherosclerosis from 14 hearts were evaluated.¹² Post-mortem coronary angiography identified moderately stenotic atherosclerotic lesions, 30–60% in severity. Circumferential IVMRI acquisition was performed and lesion composition characterized by a blinded observer. The IVMRI diagnosis of lesion characteristics correlated with histologic diagnosis in 16 out of the interrogated 18 lesions (89%), with correct assessment of all 3 thin-cap fibroatheromas. These studies demonstrated that the intravascular MRI catheter could potentially differentiate vulnerable plaques from stable atherosclerotic lesions in human coronary arteries.

Evaluation of aortic lesions was also performed in this study.¹² Interrogation of selected intimal sites, extending from macroscopically normal appearing luminal surface to complex protruding or ulcerated lesions was performed. The IVMRI was mechanically applied to the surface within a saline bath at 37°C. One sector measurement was performed, obtaining an online MRI display, showing the lipid content within the wall to a depth of 250 µ. The site undergoing MRI examination was analyzed histologically for correlative validation. The IVMRI scans correctly predicted the histologic diagnosis in 15 of 16 lesions (94%). Figure 2 depicts typical photomicrographs of relatively normal aortic segments devoid of significant lipid component, compared to lesions with high lipid content.

Clinical Data
Two studies have been completed. The First-in-Man study enrolled 29 patients in 4 European centers and was designed to demonstrate safety and feasibility of the self-contained IVMRI system during a diagnostic or therapeutic cardiac catheterization.¹³ A single nonobstructive plaque with a minimal arterial luminal diameter between 2 and 4 mm in diameter was interrogated. The study demonstrated that the IVMRI catheter was safe, as no catheter-related complications at 30-day follow-up were observed, (absent of a composite of cardiac death, MI (Q wave and non-Q wave). The IVMRI data suggested that the plaque lipid fraction in the study population showed a frequency distribution similar to that found in the ex vivo study of aortic plaques.

The subsequent Phase II study has completed the enrollment of 131 patients and was designed to evaluate the IVMRI catheter in more unstable, higher-risk patients, including patients with ACS, as well as patients undergoing percutaneous coronary interventions. The results are currently being evaluated, but no safety concerns have been raised. Correlations of lipid fraction index and clinical parameters are anticipated in the near future. Based on the safety results, the European CE mark has been obtained, and approval from the FDA is being sought. Figure 3 shows an example of results from a patient with hyperlipidemia and a family history of coronary artery disease (CAD), demonstrating heterogeneity of the atherosclerotic plaque with regard to lipid concentration. Two of the 6 interrogated sections had an increased lipid fraction index, while the other 4 segments did not.