DCE-MRI reveals more extensive vasa vasorum in patients with cardiovascular events
Huijun Chen1, Juan Wang2, Jie Sun3, Daniel S Hippe3, Xihai Zhao1, and Hongbing Liu2

1Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, People's Republic of, 2Cardiology, People’s Liberation Army General Hospital, Beijing, China, People's Republic of, 3Radiology, University of Washington, Seattle, WA, United States

Synopsis

Pharmacokinetic modeling of DCE-MRI can quantify the adventitial vasa vasorum of carotid atherosclerotic lesions using the transfer constant (Ktrans). However, the relationship between the DCE-MRI quantified carotid adventitial vasa vasorum and cardiovascular events remains unclear. In this study, we found that the adventitial Ktrans of carotid artery measured by DCE-MRI was associated with cardiovascular events (cerebral ischemic events and coronary artery events), suggesting that the carotid adventitial vasa vasorum is not merely a local risk factor but also a promising systemic marker for cardiovascular risk. DCE-MRI may be valuable for identifying high risk patients in clinical practice.

Introduction

Neovasculature arising from the vasa vasorum plays a significant role in atherosclerotic plaque progression and destabilization (1). Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) together with pharmacokinetic modeling has been validated with histology to have the ability to characterize neovascularization and adventitial vasa vasorum in atherosclerotic plaque by using the transfer constant (Ktrans) (2, 3). However, the relationship between the DCE-MRI quantified adventitial vasa vasorum of carotid atherosclerotic lesions and cardiovascular events (CVE) remains unclear. Therefore, we sought to investigate the relationship between CVE and neovasculature characteristics in human carotid atherosclerosis quantified by DCE-MRI in this retrospective study.

Methods

Population: After institutional ethics approval and informed consent were obtained, seventy patients (age: 66±12 years, 54male) with documented carotid plaque (intima-media thickness≥2 mm) at ultrasound examination were recruited. Enrolled subjects had their demographics and cardiovascular risk factors collected, including body mass index (BMI), smoking, hypertension, diabetes, hypercholesterolemia. Prior CVE were collected for each subjects, including coronary artery event (CAE) and cerebral ischemic event (CIE). CAE was defined as myocardial infarction or unstable angina pectoris with signs of myocardial ischemia. CIE was defined as ischemic stroke or TIA. Image acquisition and analysis: All subjects were scanned on a 3.0T scanner (GE Medical Systems) with a custom designed 4-channel carotid coil (University of Washington). Axial DCE images were acquired by a multi-slice 2D SGRE sequence (3) centered at carotid bifurcation with parameters: TR/TE=100/6.2ms, FA=30°, FOV=140×112mm2, matrix=256×192, slice thickness=2 mm, number of slices=6, time interval=18s. Coincident with the third phase, 0.1 mmol/kg of gadodiamide (Magnevist; Bayer Healthcare) was injected at a rate of 2 ml/s by a power injector. After bolus arrival, 10 phases were obtained. Other than DCE-MRI, a standard 2D multi-contrast MR imaging protocol was also used to obtain the morphological (maximum vessel wall thickness) and compositional features (lipid rich/necrotic core (LRNC), calcification (CA), and intraplaque hemorrhage (IPH)) of the carotid plaque (4). Blind review was performed using a custom-designed software (CASCADE, University of Washington) (5). A histology-validated post-processing and pharmacokinetic modeling approach was used to obtain the adventitial transfer constant (Ktrans) from the vasa vasorum image (Fig 1) derived from DCE-MRI time series (2,3) for each subject. Statistical analysis: Variables were presented as mean±SD or n(%), and compared using Student t-test or chi-square test as appropriate. Univariate and multivariate logistic regression were performed to identify risk factors for CVE. The odds ratio (OR) and the 95% confidence interval (CI) were reported for each factor.

Results

Of 70 patients, 6 (8.6%) were excluded because of poor image quality. Of the remaining 64 patients (age: 66±12 years, 51 male), 12 (19%) had no CVE and 52 (81%) suffered from CVE, including 32(50%) with CAE alone, 15(23%) with CIE alone, and 5 (8%) with both CAE and CIE. The characteristics of CVE group and non-CVE group were summarized in Table 1. Among all features, patients with CVE had higher carotid adventitial Ktrans (0.056±0.024 min-1) compared with subjects without CVE (0.034±0.008 min-1) (p<0.001). The univariate and multivariate logistic regression analysis further confirm that adventitial Ktrans of carotid artery was significantly and independently associated with CVE (OR: 2.8 per 0.01 min-1 increase; 95%CI: 1.3-6.2; p=0.008), as well as smoking (OR: 8.4; 95%CI: 1.1-65; p=0.042) (Table 2). When analyzing the subgroups of CIE alone, CAE alone and CAE&CIE, the carotid adventitial Ktrans in patients with both CAE and CIE (0.069±0.022 min-1), CIE (0.056±0.018min-1), and established CAE (0.054±0.027min-1) were all significantly higher than patients without CVE (0.034±0.008 min-1) (p<0.001, respectively) (Fig 2).

Discussion and Conclusion

In this study, we found that the adventitial Ktrans of carotid artery measured by DCE-MRI was associated with cardiovascular events, including cerebral ischemic event and coronary artery event, suggesting that the neovasculature characteristics in carotid artery is not merely a local vascular risk factor but also a promising systemic marker for cardiovascular risk in other vascular beds. DCE-MRI may be valuable for identifying high risk patients in clinical practice.

Acknowledgements

This work was supported by Army Medical Research Funds of China (11BJZ19) and Natural Science Foundation of China (81371540).

References

[1] Moreno PR, et al. Circulation 2006;113:2245-52. [2] Kerwin WS, et al. Radiology 2006;241:459-68. [3] Kerwin WS, et al. Magn Reson Med 2008;59:507-14. [4] Saam T, et al. Arterioscler Thromb Vasc Biol 2005;25:234-9. [5] Kerwin WS, et al. Top Magn Reson Imaging 2007;18:371-8.

Figures

Figure 1. Demonstration of vasa vasorum image generated from DCE-MRI from one patients with Ktrans shown in green and fractional plasma volume (vp) shown in red. The white dot indicate the carotid lumen. The green and blue contours outline the lumen and outer wall boundaries.

Figure 2. Comparison of carotid adventitial Ktrans among subjects without CVE and with CAE alone, CIE alone, both CAE and CIE. Two groups of patients were compared by Student t test.

Table 1. Clinical characteristics of study population

Table 2. Univariate and Multivariate analysis for cardiovascular events



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0960