Editorial Slides - VP Watch, September 12, 2001, Volume 1, Issue 26

MR Imaging of Fibrin to Detect Vulnerable Plaques

NormalRupture-prone

Fissured w/ mural thrombi ErodedCritical Stenosis Hemorrhage

Naghavi et al, Cur Ath Rep 2001

Different Types of Vulnerable Plaque As Underlying Cause of Acute Coronary Events

Anti-fibrin-antibody conjugated paramagnetic nanoparticles MR Imaging of fibrin-rich clots

Flacke et al. Circulation. 2001;104:1280

Scanning electron micrographs (x30 000) of control fibrin clot (A) and fibrin-targeted paramagnetic nanoparticles bound to clot surface (B). Arrows indicate (A) fibrin fibril; (B) fibrin-specific nanoparticle-bound fibrin epitopes.

A, Thrombi in dog external jugular vein targeted with antifibrin-Ab Gadolinium demonstrating dramatic T1-weighted contrast enhancement in gradient-echo image (arrow).

On left with flow deficit (arrow) of thrombus in corresponding phase-contrast image on right (3D phase-contrast angiogram). B, Control thrombus in contralateral external jugular vein imaged as in A.

Flacke et al. Circulation. 2001;104:1280

Gregory Lanza and Samuel Wickline ’s laboratory has developed a novel anti-fibrin-Ab Gadolinium contrast agent that allows enhanced sensitive detection and quantification of occult microthrombi overlaying the intimal surface of atherosclerotic vessels.

This unique agent is a ligand-directed, lipid-encapsulated liquid perfluorocarbon nanoparticle (250 nm nominal diameter) that has high avidity and prolonged systemic half-life, and can carry high Gd-DTPA

payloads for high detection sensitivity. (G Lanza Circulation. 1997; 95 (suppl I): I-457 )

MR imaging of plaque using paramegnetic (Gadolinium) and super paramagnetic iron oxide (SPIO) contrast media is opening a new pathway for non-invasive imaging of vulnerable plaques / patients. ( Rheum et al, Schmitz et al, Naghavi et al)

As highlighted in VP Watch this week, Sebastian Flacke, Gorge Lanza, Samuel Wickline, and colleagues extended their previous works and showed invivo in dogs the feasibility of a fibrin-targeted, Gadolinium bound contrast agent to specifically image fibrin deposits on plaque with a 1.5 T clinical magnet.

This agent was previously shown to detect fibrin clots in vitro with sizes from 0.5 to 7.0 mm with high-resolution MRI at 4.7 T. These ligand-targeted paramagnetic nanoparticles can be administered systemically in animal models. (X Yu Magn Reson Med. 2000; 44: 867–872)

Conclusion:Developing plaque targeted MR contrast agents lends substantial hope for accurate detection of vulnerable plaques / patients with magnetic resonance imaging.

Much more studies are needed to develop highly sensitive and specific vulnerable plaque targeted contrast media for all available imaging modalities including MRI, CT, PET, etc.

Fibrin-targeted Gd contrast agent has shown high sensitivity for detection of injured plaques with mural thrombi, a subset of the vulnerable plaque family that bears high risk for further thrombosis and acute clinical syndrome.

Question:

If with reasonable temporal resolution, either MRI, EBT, or CT is able to image plaque with ~ 100 micron resolution, would we be capable enough to detect all / majority of vulnerable plaques?

Do you believe that besides imaging the structure of plaque, if we ever need to image the activity of plaques (inflammation, platelet aggregation, etc)? If no, how would you imagine detection of eroded plaques from equally thick non-eroded ones? Keep in mind thickness of endothelium