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140 mr imaging of fibrin

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140 mr imaging of fibrin

  1. 1. Editorial Slides - VP Watch, September 12, 2001, Volume 1, Issue 26 MR Imaging of Fibrin to Detect Vulnerable Plaques
  2. 2. Normal Rupture-prone Fissured w/ mural thrombi Eroded Critical Stenosis Hemorrhage Naghavi et al, Cur Ath Rep 2001 Different Types of Vulnerable Plaque As Underlying Cause of Acute Coronary Events
  3. 3. 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.
  4. 4. 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
  5. 5.  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)
  6. 6.  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)
  7. 7. 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.
  8. 8. 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

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