SHAPE Society

1. Editorial Slides - VP Watch, September 12, 2001, Volume 1, Issue 26
MR Imaging of Fibrin to Detect Vulnerable Plaques

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. 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. 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.  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.  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. 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. 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