Patients who suffered from cerebrovascular ischemic symptoms including recent stroke or TIA and underwent MR vessel wall imaging examination with the time interval from onset of symptom to MR scan less than 3 months were consecutively recruited in this study. Patients with the following conditions were excluded:1) no confirmed side of symptom; 2) symptomatic carotid artery with >70% of stenosis; and 3) previous history of carotid endarterectomy (CEA). TIA was defined as the rapidly developing signs of a neurological deficit or monocular loss of vision, lasting less than 24 hours with no apparent cause other than that of vascular origin. Ischemic stroke was defined as the rapidly developing clinical signs of a neurological deficit, lasting more than 24 hours with no apparent cause other than that of vascular origin and without evidences of an intracranial hemorrhage on CT/MR images. The clinical information of all patients, such as age, sex, body mass index (BMI), hypertension, diabetes, hyperlipidemia, smoking, anti-hypertension medication use and statin use, was collected and reviewed. The study protocol was approved by institutional review board and all subjects provided written consent form. All methods were performed in accordance with the relevant guidelines and regulations
Carotid artery MR imaging
All MR imaging was performed on a 3.0 T MR scanner (SignaHDx, GE Medical System, Milwaukee, WI, USA) with dedicated phase-arrayed carotid coils. Multi-contrast MR protocol including following parameters: three-dimensional (3D) time-of-flight (TOF) MR angiography: repetition time (TR)/echo time (TE) 29 ms/4.9 ms, field of view (FOV)14×14 cm2,matrix size 256×256, flip angle 20°, and 2 mm slice thickness; T1-weighted (T1W) quadruple inversion recovery (QIR): TR/TE 800 ms/10 ms, FOV14×14 cm2,matrix size 256×256, flip angle 90°, and 2 mm slice thickness; and T2-weighted (T2W) multi-slice double inversion recovery (DIR): TR/TE 4800 ms/50 ms, FOV14×14 cm2,matrix size 256×256, flip angle 90°, and 2 mm slice thickness. All MR imaging was centered to the bifurcation of the symptomatic side of carotid artery with longitudinal coverage of 24 mm.
MR image analysis
Two radiologists with more than 3 years’ experience in plaque imaging interpreting reviewed the MR vessel wall images of carotid arteries using custom-designed software CASCADE (University of Washington, Seattle, USA) and were blinded to clinical information of all recruited patients. The quality of carotid MR images was graded as poor, marginal, good and excellent according to the overall signal-to-noise and images graded as poor were excluded from this study. The lumen and wall boundaries were traced manually and the lumen area, wall area, maximum wall thickness, and wall volume was measured and calculated. Measure of carotid plaque burden was expressed by the normalized wall index (NWI) which was defined as the wall area divided by the total wall area. The degree of luminal stenosis of carotid arteries was measured on the 3D TOF MR angiographic images by maximum intensity projection reconstruction according to the North American symptomatic carotid endarterectomy trials criteria. The presence or absence of plaque compositions, such as lipid-rich necrotic core, intraplaque hemorrhage and calcification was identified and the volume of each plaque component as a percentage of the wall volume was measured and calculated according to published criteria[12,13]. The wall volume was calculated by 2 mm × wall areas of slice with plaque.
Twenty patients were randomly selected from the study sample for testing the inter-observer and intra-observer agreement in measuring morphology and compositions of carotid plaque. All the patients were used for testing the inter-observer and intra-observer agreement in identifying the presence of carotid plaque compositions.
Continuous variables were summarized as mean ± standard deviation (SD) and categorical variables were presented as percentage. The clinical characteristics and carotid plaque measurements were compared between patients with TIA and stroke using independent Student t-test, Mann-Whitney U test or chi-square test. Univariate and multi-variable logistic regression models were used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) of carotid plaque features in discriminating the type of ischemic events. Two-sided p<0.05 was considered statistically significant. All the statistical analyses were performed using SPSS 22.0 (IBM, Chicago, IL).