Dynamic contrast-enhanced MR imaging of carotid vasa vasorum in relation to coronary and cerebrovascular events
Introduction
The tunica adventitia of large- and medium-sized arteries contains a microvascular network referred to as vasa vasorum [1]. Proliferation of adventitial vasa vasorum is a prominent feature in diseased arteries, making the adventitia one of the most vascularized regions in atherosclerosis [1], [2]. Concurrently, the adventitia of atherosclerotic plaque sees increased cell migration and extracellular matrix production. High-resolution ultrasound studies measuring carotid adventitial thickness suggested that carotid adventitia is amenable to noninvasive imaging with submillimeter spatial resolution [3], [4]. As such, structural changes during atherogenesis have laid the foundation for characterizing carotid adventitial vasa vasorum using clinical imaging modalities and conventional contrast media. In previous studies, distinct adventitial enhancement was observed on CT or MR images after contrast administration [5], [6], [7], [8], [9].
Biologically, the adventitia is an appealing target for imaging, not only because adventitial vasa vasorum play a role in atherosclerotic plaque progression, but also because the adventitia represents an active site of plaque inflammation [10], [11]. Dynamic contrast-enhanced MR imaging (DCE-MRI) allows quantitative characterization of the functional status of carotid adventitial vasa vasorum by providing pharmacokinetic parameters that are reflective of local angiogenesis, micro-flow regulation, and neovessel permeability [8]. However, the multifaceted, molecular-level information also means a unique challenge for the interpretation of DCE-MRI measurements. Although a significant correlation has been noted between DCE-MRI measures and histology-measured macrophages and neovessels [8], seeking further understanding of the clinical implications of such physiological measures relies on clinical cohort studies. To our knowledge, no previous studies have examined DCE-MRI measures of adventitial vasa vasorum in relation to the various clinical conditions of cardiovascular events (CVE). In a single-center study, we sought to investigate the relationship between DCE-MRI measures of carotid adventitial vasa vasorum and documented CVE including both coronary and cerebrovascular events.
Section snippets
Study population
This is a retrospective study of prospectively collected data. From March 2011 to June 2014, 70 patients underwent DCE-MRI of carotid arteries at our institution, representing a convenient study sample for this investigation. Patients were eligible for DCE-MRI if carotid plaque (maximum intima-media thickness≥2 mm) was found in at least one carotid artery during clinical ultrasound examination. Exclusion criteria included atrial fibrillation, vasculitis, recent infection, tumor, other severe
Patient characteristics
Six subjects were excluded because of poor image quality attributed to motion artifacts. Of the remaining 64 subjects, 52 (81%) had documented CVE, including 32 (50%) with coronary events alone, 15 (23%) with cerebrovascular events alone, and 5 (8%) with both coronary and cerebrovascular events (Fig. 2). Table 1 summarizes patient characteristics. The mean age was 66 ± 12 years. Fifty-one (80%) subjects were male. The CVE group had a lower level of HDL-C (1.1 ± 0.4 vs. 1.4 ± 0.5 mmol/L, p
Discussion
We found that adventitial Ktrans of carotid plaques, a physiological parameter related to the density and permeability of vasa vasorum, was independently associated with CVE. Compared to carotid plaques in patients without CVE, higher adventitial Ktrans was seen not only in patients with documented cerebrovascular events but also in patients with documented coronary events. Furthermore, there was an inverse correlation between adventitial Ktrans and time since clinical event. These novel
Conflict of interest
HC received grants from Natural Science Foundation of China and Philips Healthcare. DSH received grants from GE Healthcare, Philips Healthcare, and Toshiba America Medical Systems. HL received grants from Army Medical Research Funds of China. All other authors have no conflict of interest to disclose.
Financial support
This work was supported by Army Medical Research Funds of China (11BJZ19), the Natural Science Foundation of China (81371540), and the National Institutes of Health (R01 HL103609).
Author contributions
JW performed literature review, participated in data collection and data analysis, and drafted the manuscript. HC and JS designed the study, participated in literature review, study coordination, data analysis and interpretation, and revised the manuscript. DSH participated in statistical analysis and manuscript revision. HZ, SY, and LX participated in data collection, data interpretation, and manuscript revision. JC and BC implemented the MRI protocol and participated in manuscript revision.
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These authors contributed equally to this work.