The goal of this study was to identify a set of carotid wall CT features that is significantly associated with the risk of carotid embolic stroke. We performed two similar analyses – one comparing carotid arteries of "carotid stroke patients" and "non-carotid stroke patients", and the other comparing the carotid arteries on the affected and unaffected sides in the "carotid stroke patients". These two analyses converged, revealing that a small number of carotid wall CT features are significantly associated with acute carotid stroke. Specifically, increased risk of acute carotid stroke was associated with an increased wall volume, a thinner fibrous cap, a higher number of lipid clusters, and lipid clusters closer to the lumen. The number of calcium clusters was a protective factor. The fibrous cap thickness was not significant in the multivariate model, despite being a consistent predictor of clinical events in prior work.18, 19
These observations mirror the current understanding as to how a carotid plaque might rupture and cause an embolic stroke. Carotid wall features have been suggested by others8–12
as a complement to luminal narrowing measurements for predicting the risk of stroke. Embolic phenomena have been previously reported as associated with thinning18, 19
and subsequent ulceration8, 12, 20, 22
of the fibrous cap on the surface of atherosclerotic plaque, resulting in release of necrotic lipid debris from the plaque substance into the parent vessel, especially in the case of a high lipid content.18, 19, 35–40
In contrast, plaques with high calcium content, especially when located close to the lumen, are thought to be associated with a lower risk of stroke.23 24, 25
In symptomatic patients with severe (≥50%) stenosis, for whom the risk of stroke approximates 15%1–4
, identification of carotid plaques containing numerous and large lipid cores could potentially help refine the selection of subjects most likely to benefit from endarterectomy or stenting (15%), while the remaining patients (85%) could be managed conservatively.
Further investigations are needed to determine if identification of thick carotid wall or carotid plaques containing numerous and large lipid cores and few calcium clusters in patients with <50% stenosis, usually treated conservatively, could trigger a surgical/stenting decision even in the absence of significant stenosis.
The originality of our research lies in the use of an imaging modality, CT, that has been demonstrated as accurate compared to conventional angiography in characterizing the degree of carotid stenosis, but that has been poorly explored in terms of carotid wall characterization, except for its calcium content. In order to characterize carotid wall features other than calcium from CT data24, 25
, we used an automated classifier computer algorithm that was validated using histology derived from carotid endarterectomy specimens as a gold standard.21
Our study, showing differences in the features assessed by the algorithm between stroke and non-stroke patients and the infarct and contralateral side, provides yet another type of validation. It demonstrates that CT is able to characterize the carotid wall in a clinically meaningful way.
This study using CT is not intended to detract from other imaging techniques. Ultrasound is noninvasive, can be performed at bedside, and gives accurate assessment of the carotid intima-media thickness. MRI, with appropriate sequences, affords unmatched tissue contrast between the different plaque components. However, CT presents the advantage of being obtained as part of the standard-of-care for numerous patients with cerebrovascular disease, as a result of the wide availability of CT scanners and the short duration of the CT studies. Our work shows that the interpretation of CT studies of the carotid arteries should not be limited to the evaluation of the degree of luminal narrowing, but should also include assessment of the carotid wall. The automated classifier computer algorithm approach affords a standardized, three-dimensional, volumetric assessment of the carotid artery wall.
We acknowledge several limitations to our study. Our results come from a cross-sectional analysis involving relatively few patients and will need to be confirmed in a larger longitudinal study.
Our study population was derived from patients admitted in our emergency department who underwent a CTA of their carotid arteries. This is a selected sample with a risk of stroke that is likely greater than that of the general population, which limits our ability to generalize our results. The internal validity of our study should, however, not be affected by this.
Our classification of patients as "carotid stroke patients" and "non-carotid stroke patients" was based on published criteria31, 32
and the Causative Classification System for Ischemic Stroke.33
This classification has a reported inter-examiner reliability of 0.90 in characterizing the probable cause of a stroke, presenting the advantage of a very low rate (4%) of indeterminate-unclassified results.33
Finally, our study was cross-sectional in nature. Carotid plaque features are known to change after stroke as a result of plaque rupture, intramural accumulation of blood components, and displacement of intramural contents. This study allows the assessment of differences between symptomatic and asymptomatic plaques but not the prospective, longitudinal risk or benefit associated with a particular plaque feature.
In conclusion, our newly developed CT-derived model identified carotid wall features significantly different in acute carotid stroke patients and on the infarct side vessel. This model has yet to be validated prospectively in a longitudinal, adequately powered study. Our automated classifier computer algorithm offers a standardized method for interpreting the carotid artery wall findings using a routine imaging technique (CT). The utility of our model to monitor carotid wall composition in future trials, both to select patients for treatment and to determine whether drug treatments are effective in altering the size and composition of the atheroma41–43
, will be the object of future investigation.