Computed tomography angiographic biomarkers help identify vulnerable carotid artery plaque.

OBJECTIVE: The current risk assessment for patients with carotid atherosclerosis relies primarily on measuring the degree of stenosis. More reliable risk stratification could improve patient selection for targeted treatment. We have developed and validated a model to predict for major adverse neurologic events (MANE; stroke, transient ischemic attack, amaurosis fugax) that incorporates a combination of plaque morphology, patient demographics, and patient clinical information. METHODS: We enrolled 221 patients with asymptomatic carotid stenosis of any severity who had undergone computed tomography angiography at baseline and ≥6 months later. The images were analyzed for carotid plaque morphology (plaque geometry and tissue composition). The data were partitioned into training and validation cohorts. Of the 221 patients, 190 had complete records available and were included in the present analysis. The training cohort was used to develop the best model for predicting MANE, incorporating the patient and plaque features. First, single-variable correlation and unsupervised clustering were performed. Next, several multivariable models were implemented for the response variable of MANE. The best model was selected by optimizing the area under the receiver operating characteristic curve (AUC) and Cohen's kappa statistic. The model was validated using the sequestered data to demonstrate generalizability. RESULTS: A total of 62 patients had experienced a MANE during follow-up. Unsupervised clustering of the patient and plaque features identified single-variable predictors of MANE. Multivariable predictive modeling showed that a combination of the plaque features at baseline (matrix, intraplaque hemorrhage [IPH], wall thickness, plaque burden) with the clinical features (age, body mass index, lipid levels) best predicted for MANE (AUC, 0.79), In contrast, the percent diameter stenosis performed the worst (AUC, 0.55). The strongest single variable for discriminating between patients with and without MANE was IPH, and the most predictive model was produced when IPH was considered with wall remodeling. The selected model also performed well for the validation dataset (AUC, 0.64) and maintained superiority compared with percent diameter stenosis (AUC, 0.49). CONCLUSIONS: A composite of plaque geometry, plaque tissue composition, patient demographics, and clinical information predicted for MANE better than did the traditionally used degree of stenosis alone for those with carotid atherosclerosis. Implementing this predictive model in the clinical setting could help identify patients at high risk of MANE.

Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion.

OBJECTIVE: We have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV). METHODS: Structural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients. RESULTS: Of the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively). CONCLUSIONS: Interhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.