Chronic thrombus detection with in vivo magnetic resonance imaging and a fibrin-targeted contrast agent.
BACKGROUND
Arterial thrombosis plays a critical role in acute coronary syndromes and stroke. Therefore, the ability to detect thrombus in vivo has a significant clinical implication. Magnetic resonance imaging (MRI) has shown promise in noninvasive thrombus detection. However, thrombus characterization and age definition remain difficult. We sought to evaluate the use of a fibrin-targeted peptide (EP-2104R) for MR thrombus detection and to compare this modality with non-contrast-enhanced (NCE) MRI and with Gd-DTPA injection at various ages and time points after thrombus generation.


RESULTS
Carotid artery thrombosis was induced by external injury and stasis in 18 rabbits. T1-weighted MRI was performed before and after contrast agent injection, within 6 hours of thrombus induction, at 48 hours, at 1 week, and every week up to 8 weeks after injury. Correlation with histopathology was performed. The fibrin-targeted contrast agent accurately detected all thrombi, regardless of their size, location, and age. Although thrombus signal intensity after injection decreased with thrombus age (P<0.001), enhancement at 8 weeks was still present. Gd-DTPA injection was not associated with an improvement of thrombus detection. EP-2104R was superior to both NCE and Gd-DTPA injection (P<0.001). Histopathologic examination showed thrombus organization over time. Fibrin was gradually replaced by fibrous tissue. A strong correlation was found between thrombus enhancement and collagen content of the organizing thrombus with time (R=-0.89; P<0.001).


CONCLUSIONS
In an experimental animal model of carotid thrombosis, we have demonstrated the superiority of a fibrin-targeted MR contrast agent for in vivo detection of chronic or organized thrombus, compared with NCE MRI and Gd-DTPA injection.
Sirol
Marc
M
Department of Cardiology, Hôpital Lariboisière, Paris, France.
Fuster
Valentin
V
Badimon
Juan J
JJ
Fallon
John T
JT
Moreno
Pedro R
PR
Toussaint
Jean-François
JF
Fayad
Zahi A
ZA
D000818:Animals; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000473:pathology; D002908:Chronic Disease; D003287:Contrast Media; D005682:Gadolinium; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D010455:Peptides; D011817:Rabbits; D013927:Thrombosis / Q000175:diagnosis* / Q000473:pathology
D003287:Contrast Media; C503783:EP-2104R; D010455:Peptides; D005682:Gadolinium; D019786:Gadolinium DTPA