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Fibrin-targeted magnetic resonance imaging allows in vivo quantification of thrombus fibrin content and identifies thrombi amenable for thrombolysis.

ABSTRACT: Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus' fibrin content in vivo and for the identification of thrombus suitable for thrombolysis.Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 ?mol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus' histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R(2)=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre-EP-2104R and post-EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97-1.00] and 0.994 [95% confidence interval, 0.98-1.00] respectively).MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis.

SUBMITTER: Andia ME

PROVIDER: S-EPMC4195984 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Fibrin-targeted magnetic resonance imaging allows in vivo quantification of thrombus fibrin content and identifies thrombi amenable for thrombolysis.

Andia Marcelo E ME Saha Prakash P Jenkins Julia J Modarai Bijan B Wiethoff Andrea J AJ Phinikaridou Alkystis A Grover Steven P SP Patel Ashish S AS Schaeffter Tobias T Smith Alberto A Botnar Rene M RM Botnar Rene M RM

Arteriosclerosis, thrombosis, and vascular biology 20140410 6

<h4>Objective</h4>Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus' fibrin content in vivo and for the identification of thrombus suitable for thrombolysis.<h4>Approach and results</h4>Venous thrombosis was i ...[more]

PMID: 24723557

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Project description:BACKGROUND AND PURPOSE:Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the wall of the artery. METHODS:Since plaque lipid is a key determinant of plaque behaviour we used a newly validated, high-sensitivity T2-mapping MR technique for a systematic survey of the quantity and distribution of plaque lipid in patients undergoing endarterectomy. Lipid percentage was quantified in 50 carotid endarterectomy patients. Lipid distribution was tested, using two imaging indices (contribution of the largest lipid deposit towards total lipid (LLD %) and a newly-developed LAI 'lipid aggregation index'). RESULTS:The bifurcation contained maximal lipid volume. Lipid percentage was higher in symptomatic vs. asymptomatic patients with degree of stenosis (DS ? 50%) and in the total cohort (P = 0.013 and P = 0.005, respectively). Both LLD % and LAI was higher in symptomatic patients (P = 0.028 and P = 0.018, respectively), suggesting that for a given plaque lipid volume, coalesced deposits were more likely to be associated with symptomatic events. There was no correlation between plaque volume or lipid content and degree of luminal stenosis measured on ultrasound duplex (r = -0.09, P = 0.53 and r = -0.05, P = 0.75), respectively. However, there was a strong correlation in lipid between left and right carotid arteries (r = 0.5, P <0.0001, respectively). CONCLUSIONS:Plaque lipid content and distribution is associated with symptomatic status of the carotid plaque. Importantly, plaque lipid content was not related to the degree of luminal stenosis assessed by ultrasound. Determination of plaque lipid content may prove useful for stratification of asymptomatic patients, including selection of optimal invasive treatments.

Dataset Information

Fibrin-targeted magnetic resonance imaging allows in vivo quantification of thrombus fibrin content and identifies thrombi amenable for thrombolysis.

Publications

Fibrin-targeted magnetic resonance imaging allows in vivo quantification of thrombus fibrin content and identifies thrombi amenable for thrombolysis.

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