Abstract 18706: Multi-Sequence Non-Contrast MRI Characterisation of Experimental Venous Thrombi Predicts Susceptibility to Lysis and is Feasible in Man

Introduction: We have previously demonstrated that non-contrast MRI using magnetisation transfer rate (MTR), apparent diffusion coefficient (ADC) and T1 mapping can characterise different aspects of organisation in a resolving venous thrombus. We now investigate whether the combination of these non-contrast agent MRI sequences can be used to identify thrombi suitable for lysis in an experimental model, and whether multi-sequence thrombus imaging (MSTI) can be translated to man. Methods: Magnetisation transfer, diffusion weighted images and T1 relaxation times were measured at days 2, 4, 7, 10, 14, 21 and 28 after venous thrombus induction in 8-10wk old male BALB/C mice (n=8/gp). Tissue plasminogen activator (10mg/kg) was administered through tail vein injection immediately after imaging at each time point and mice scanned 24hrs later to evaluate the effect of lysis. This was considered successful if more than 50% of the vein recanalised. Murine imaging sequences were combined and optimised to image the pelvic veins in man using healthy volunteers in order to produce a clinically useable imaging card. MSTI sequences were validated using phantoms before application to patients with iliofemoral deep vein thrombosis (DVT) undergoing lysis. Results: ROC curve analysis shows that the combination of MTR smaller than 2,900(%/cm3), ADC larger than 0.93(x10-3 mm2/s) and T1 shorter than 784ms has a sensitivity of 88% and specificity of 97% to identify experimental thrombi amenable to lysis. MSTI is feasible in man, with optimisation leading to successful characterisation of iliofemoral DVT in under 25mins (Figure 1). Conclusions: Non-contrast MR imaging, using a combination of MTR, ADC and T1 mapping, accurately identifies experimental venous thrombi susceptible to lysis. These MSTI sequences can also be readily translated to man where may find utility in characterising the age and structure of thrombus, and to stratify patients undergoing thrombolysis. </jats:p

Vascular Remodeling and Plaque Vulnerability in a Rabbit Model of Atherosclerosis: Comparison of Delayed-Enhancement MR Imaging with an Elastin-specific Contrast Agent and Unenhanced Black-Blood MR Imaging

PurposeTo compare delayed-enhancement (DE) magnetic resonance (MR) imaging with an elastin-specific contrast agent and unenhanced black-blood (BB) MR imaging with regard to vessel wall delineation and assessment of vascular remodeling and to test the prospective value for predicting plaque disruption in a rabbit model of atherosclerosis.Materials and MethodsAll procedures were approved by the animal ethics committee. Atherosclerosis was induced in 14 New Zealand White rabbits by means of a 1% cholesterol diet and endothelial denudation. Plaque disruption was triggered with Russell’s viper venom and histamine. Animals with atherosclerosis were imaged before triggering to identify plaques and vascular remodeling and after triggering to identify thrombus. Plaques were classified as nondisrupted (stable) or disrupted (vulnerable). Control rabbits fed a regular diet were imaged twice. Unenhanced T1-weighted BB MR imaging, DE MR imaging with an elastin-specific contrast agent, and T1 mapping were used to assess vascular remodeling and calculate the plaque area and vessel wall relaxation rate (R1 = 1/T1). Elastin was quantified by using elastica–van Gieson stain. Group comparisons were analyzed with the Mann-Whitney or paired t test. Agreement between methods was performed with Bland-Altman analysis.ResultsUnenhanced T1-weighted BB MR imaging and DE MR imaging showed that, compared with nondisrupted plaques, disrupted plaques had larger plaque area (T1-weighted BB MR imaging: 5.1 mm2 vs 5.7 mm2; DE MR imaging: 6.0 mm2 vs 7.9 mm2; P &lt; .001) and vessel area (T1-weighted BB MR imaging: 11.8 mm2 vs 14.3 mm2; DE MR imaging: 10.8 mm2 vs 13.9 mm2; P &lt; .001) and underwent positive remodeling. Assessment of positive remodeling with DE MR imaging enabled better prediction of plaque disruption compared to that with unenhanced T1-weighted BB imaging (sensitivity: 83.7% vs 58.1%). DE MR imaging showed a stronger agreement with histologic findings, whereas the vessel area was overestimated with unenhanced T1-weighted BB imaging.ConclusionCompared with unenhanced T1-weighted BB MR imaging, DE MR imaging with an elastin-specific contrast agent enables more accurate assessment of vascular remodeling in the prediction of vulnerable plaque

Fibrin-Targeted Magnetic Resonance Imaging Allows In Vivo Quantification of Thrombus Fibrin Content and Identifies Thrombi Amenable for Thrombolysis

Objective— 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. Approach and Results— 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 μmol/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 &lt;0.001). Thrombus relaxation rate ( R 1 ) 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). Conclusions— MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis. </jats:sec

The influence of pericardial fat upon left ventricular function in obese females:evidence of a site-specific effect

Background: Although increased volume of pericardial fat has been associated with decreased cardiac function, it is unclear whether this association is mediated by systemic overall obesity or direct regional fat interactions. We hypothesized that if local effects dominate, left ventricular (LV) function would be most strongly associated with pericardial fat that surrounds the left rather than the right ventricle (RV).Methods: Female obese subjects (n = 60) had cardiovascular magnetic resonance (CMR) scans to obtain measures of LV function and pericardial fat volumes. LV function was obtained using the cine steady state free precession imaging in short axis orientation. The amount of pericardial fat was determined volumetrically by the cardiac gated T1 black blood imaging and normalized to body surface area.Results: In this study cohort, LV fat correlated with several LV hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These correlations remained significant even after adjusting for the body mass index and the blood pressure. However, similar correlations became weakened or even disappeared between RV fat and LV function. LV function was not correlated with systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p &gt; 0.05).Conclusions: LV hemodynamic and diastolic function was associated more with LV fat as compared to RV or total pericardial fat, but not with systemic inflammatory markers or adipokines. The correlations between LV function and pericardial fat remained significant even after adjusting for systemic factors. These findings suggest a site-specific influence of pericardial fat on LV function, which could imply local secretion of molecules into the underlying tissue or an anatomic effect, both mechanisms meriting future evaluation.</p

Contrast-enhanced magnetic resonance imaging for the detection of ruptured coronary plaques in patients with acute myocardial infarction.

X-ray coronary angiography (XCA) is the current gold standard for the assessment of lumen encroaching coronary stenosis but XCA does not allow for early detection of rupture-prone vulnerable plaques, which are thought to be the precursor lesions of most acute myocardial infarctions (AMI) and sudden death. The aim of this study was to investigate the potential of delayed contrast-enhanced magnetic resonance coronary vessel wall imaging (CE-MRCVI) for the detection of culprit lesions in the coronary arteries.16 patients (13 male, age 61.9±8.6 years) presenting with sub-acute MI underwent CE-MRCVI within 24-72h prior to invasive XCA. CE-MRCVI was performed using a T1-weighted 3D gradient echo inversion recovery sequence (3D IR TFE) 40±4 minutes following the administration of 0.2 mmol/kg gadolinium-diethylenetriamine-pentaacetic acid (DTPA) on a 3T MRI scanner equipped with a 32-channel cardiac coil.14 patients were found to have culprit lesions (7x LAD, 1xLCX, 6xRCA) as identified by XCA. Quantitative CE-MRCVI correctly identified the culprit lesion location with a sensitivity of 79% and excluded culprit lesion formation with a specificity of 99%. The contrast to noise ratio (CNR) of culprit lesions (9.7±4.1) significantly exceeded CNR values of segments without culprit lesions (2.9±1.9, p<0.001).CE-MRCVI allows the selective visualization of culprit lesions in patients immediately after myocardial infarction (MI). The pronounced contrast uptake in ruptured plaques may represent a surrogate biomarker of plaque activity and/or vulnerability