Background: Risk of stroke was associated with ultrasonographic heterogeneity and echolucency of internal carotid artery stenosis (ICAS). We intended to evaluate the prediction for cerebrovascular events in asymptomatic ICAS with a recently established plaque heterogeneity index (HI) determined with three-dimensional ultrasonography (3D-US) using the Gray Scale Median (GSM) in comparison to the GSM of single 2D gray scale sections alone. We hypothesized that an association between HI and ipsilateral neurologic events exists. Patients and Methods: In 245 patients informed consent was given after pre-screening examinations and gray scale 2D- and 3D-US was performed at 10 MHz to receive longitudinal sections through ICAS in a prospective fashion. Stenoses were graded according to NASCET criteria by duplex ultrasonography. In addition a majority received a baseline computer tomography (CT) angiography of ICAS to confirm stenosis grades in combination with a cerebral CT scan. HI was determined in a blinded fashion using the GSM of three parallel 3D-rendered longitudinal slices through the plaque by calculating the difference between the maximum and the minimum GSM divided by the mean. Neurologic assessment was scheduled every 6 months. The composite endpoint transient ischemic attack, stroke and amaurosis fugax ipsilateral to the ICAS was evaluated by a neurologist and cerebral CT or magnetic resonance scans were used to confirm diagnosis. Results: 3D-US was performed in 160 asymptomatic ICAS at good quality to detemine GSM of whole plaque sections. Most of the ICAS ranged 40 - 60%. Patients with a heterogenous plaque, having a HI higher than the median, had a more than 4-fold increased risk (p < 0.05) of suffering an ipsilateral neurologic event. The Kaplan-Meier analysis also demonstrated that patients with a heterogenous plaque suffer more neurologic events (Log-rank p = 0.02). We did not find a significant association of the combined neurologic events and the GSM measured with 2D-US but there was a trend towards a lowered mean GSM in the symptomatic patients measured with 3D-US. Conclusion: The HI of ICAS was predictive for cerebrovascular events. The HI is probably a better predictor for cerebral events than GSM alone.
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