Inflammation in Carotid Atherosclerotic Plaque: A Dynamic Contrast-enhanced MR Imaging Study

Abstract

Purpose-To prospectively evaluate if there is an association between plaque enhancement at magnetic resonance (MR) imaging and proinflammatory cardiovascular risk factors and plaque content.Materials and Methods-This study was performed with informed consent, HIPAA compliance, and institutional review board approval. Contrast agent dynamics within carotid plaques were measured in 30 patients (29 men, one woman; mean age, 67.7 years ± 10.7 [standard deviation]) who were scheduled to undergo carotid endarterectomy. Measurements were based on kinetic modeling of images obtained at 15-second intervals during which a gadolinium-based contrast agent was injected. The time-varying signal intensities within the plaques were used to estimate the fractional plasma volume (v p ) and transfer constant (K trans ) of contrast material into the extracellular space. Pearson correlation coefficients were computed between blinded MR measurements and histologic measurements of plaque composition, including macrophages, neovasculature, necrotic core, calcification, loose matrix, and dense fibrous tissue. Correlation coefficients or mean differences were computed regarding clinical markers of cardiovascular risk.Results-Analyzable MR images and histologic results were obtained in 27 patients. Measurements of K trans correlated with macrophage (r = 0.75, P < .001), neovasculature (r = 0.71, P <.001), and loose matrix (r = 0.50, P = .01) content. Measurements of v p correlated with macrophage (r = 0.54, P = .004), neovasculature (r = 0.68, P <.001), and loose matrix (r = 0.42, P = .03) content. For clinical parameters, significant associations were correlated with K trans only, with decreased high-density lipoprotein levels (r = −0.66, P <.001) and elevated K trans measurements in smokers compared with nonsmokers (mean, 0.134 min −1 vs 0.074 min −1 , respectively; P = .01). Conclusion-The correlations between K trans and histologic markers of inflammation suggest thatK trans is a quantitative and non-invasive marker of plaque inflammation, which is further supported by the correlation of K trans with proinflammatory cardiovascular risk factors, decreased high-density lipoprotein levels, and smoking.Address correspondence to W.S.K. (e-mail: bkerwin@u.washington.edu).. Author contributions: Guarantor of integrity of entire study, W.S.K.; study concepts/study design or data acquisition or data analysis/ interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, W. Contrast material enhancement in carotid atherosclerotic plaques has been observed in several recent investigations with magnetic resonance (MR) imaging after the injection of clinically available gadolinium-based contrast agents (1-5). Strong contrast enhancement suggests the presence of a vascular supply to the plaque and increased endothelial permeability that facilitates the entry of the contrast agent from the blood plasma. Because neov...

Imaging of the Carotid Artery Vulnerable Plaque

“…Moreover, they showed that early plaque enhancement is due to the presence of internal neovessels, while late enhancement is related neovasculature supply and endothelial permeability [94]. The correlation between the degree of plaque enhancement and the degree of neovascularization, which is itself linked to the degree of plaque inflammation, also was confirmed at histology in a recent study by Millon et al [96].…”

“…Different contrast agents are currently used to characterize carotid plaque. Gadolinium-chelates contrast agents are most commonly used for MRA examinations; for the assessment of unstable plaques, the vascular enhancement of the carotid plaques themselves has been demonstrated to hallmark the presence of an increased endothelial permeability due to plaque inflammation that facilitates the entry of contrast agents [83,[91][92][93][94][95].…”

Quantifying Intracranial Aneurysm Wall Permeability for Risk Assessment Using Dynamic Contrast-Enhanced MRI: A Pilot Study

“…and biologic changes in the wall. 25 A future correlation of K trans IA wall permeability with computational fluid dynamics or 4D-flow MR imaging may assist in identifying focal aneurysm regions of high risk or stress.…”

Molecular Imaging in Cardiovascular Diseases

“…Using gadolinium-based liposomes that bond specifically with α vβ3 integrin, local angioneogenesis has been successfully demonstrated on a rabbit model with atherosclerosis [37]. Alternatively, the increased blood flow resulting from neovascularization can be directly visualized and quantified through the utilization of dynamic contrast-enhanced MRI sequences [66]. In this case, clinically-approved contrast agents such as Gd-DTPA are suitable, as they effect a change in signal intensity in the target region across a wide dosage range as a function of their concentration.…”