Risk Marker Variability in Subclinical Carotid Plaques Based on Ultrasound is Influenced by Cardiac Phase, Echogenicity and Size

Identification of risk markers based on quantitative ultrasound texture analysis of carotid plaques has the ability to define vulnerable components that correlate with increased cardiovascular risk. However, data describing factors with the potential to influence the measurement variability of risk markers are limited. The aim of this study was to evaluate the influence of electrocardiogram-guided image selection, plaque echogenicity and area on carotid plaque risk markers and their variability in asymptomatic carotid plaques. Plaque risk markers were measured in 57 plaques during three consecutive heartbeats at two cardiac cycle time instants corresponding to the electrocardiogram R-wave (end diastole) and end of T-wave (end systole), resulting in six measurements for each plaque. Risk marker variability was quantified by computing the coefficient of variation (CV) across the three heartbeats. The CV was significantly higher for small plaques (area <15 mm2, 10%) than for large plaques (area >15 mm2, 6%) (p < 0.001) in measurements of area, and the CV for measurements of gray-scale median were higher for echolucent plaques (<40, 15%) than for echogenic plaques (>40, 9%) (p < 0.001). No significant differences were found between systole and diastole for the mean of any risk marker or the corresponding CV value. However, in a sub-analysis, the echolucent plaques were found to have a higher CV during systole compared with diastole. The variability also caused plaque type reclassification in 16% to 25% of the plaques depending on cutoff value. The results of this study indicate that echolucent and small plaques each contribute to increased risk marker variability. Based on these results, we recommend that measurements in diastole are preferred to reduce variation, although we found that it may not be possible to characterize small plaques accurately using contemporary applied risk markers.