Intravascular MRI for the Evaluation of Lipid-Rich Vulnerable Plaques in Coronary and Peripheral Vessels
- Volume 4 - Issue 5 - Sept/Oct 2007
- Posted on: 9/5/08
- 0 Comments
- 5511 reads
1Robert L. Wilensky, MD and 2Jacob Schneiderman, MD
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.
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.
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.
1. Virmani R, Burke AP, Farb A, et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006;47:C13–18.
2. Goldschmidt-Clermont PJ, Creager MA, Lorsordo DW, et al. Atherosclerosis 2005: Recent discoveries and novel hypotheses. Circulation 2005;112:3348–3353.
3. Botnar RM, Perez AS, Witte S, et al. In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation 2004;109:2023–2029.
4. Winter PM, Caruthers SD, Yu X, et al. Improved molecular imaging contrast agent for detection of human thrombus. Magn Reson Med 2003;50:411–416.
5. Kooi ME, Cappendijk VC, Cleutjens KB, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 2003;107:2453–2458.
6. Morawski AM, Winter PM, Crowder KC, et al. Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 2004;51:480–486.
7. Toussaint JF, LaMuraglia GM, Southern JF, et al. Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation 1996;94:932–938.
8. Cai JM, Hatsukami TS, Ferguson MS, et al. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 2002;106:1368–1373.
9. Hatsukami TS, Ross R, Polissar NL, et al. Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation 2000;102:959–964.
10. Trivedi RA, U-King-Im JM, Graves MJ, et al. MRI-derived measurements of fibrous-cap and lipid-core thickness: The potential for identifying vulnerable carotid plaques in vivo. Neuroradiology 2004;46:738–743.
11. Yuan C, Zhang SX, Polissar NL, et al. Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke. Circulation 2002;105:181–185.
12. Schneiderman J, Wilensky RL, Weiss A, et al. Diagnosis of thin cap fibroatheromas by a self-contained intravascular magnetic resonance imaging probe in ex vivo human aorta and in-situ coronary arteries. J Am Coll Cardiol 2005;45:1961–1969.
13. Regar E, Hennen B, Grube E, et al. First in men application of a miniature self-contained intracoronary magnetic resonance imaging probe: A multi-center safety and feasibility trial. Euro Intervent 2006;2:77–83.
14. Dunmore BJ, McCarthy MJ, Naylor AR, et al. Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques. J Vasc Surg 2007;45:155–159.
15. Clark DJ, Lessio S, O’Donoghue M, et al. Safety and utility of intravascular-guided carotid artery stenting. Catheter Cardiovasc Interv 2004;63:355–362.