Chronic thrombus detection with in vivo magnetic resonance imaging and a fibrin-targeted contrast agent.

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Sirol M, Fuster V, Badimon JJ, Fallon JT, Moreno PR, Toussaint JF, Fayad ZA

Chronic thrombus detection with in vivo magnetic resonance imaging and a fibrin-targeted contrast agent.

Circulation. 2005 Sep 13;112(11):1594-600. Epub 2005 Sep 6.

PubMed ID
16145001 [ View in PubMed
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Abstract

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. METHODS AND 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.

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