Long-Term Carotid Plaque Progression and the Role of Intraplaque Hemorrhage: Analysis from Deep Learning-based Longitudinal Vessel Wall Imaging

Abstract

Background: Carotid atherosclerosis is a major etiology of stroke. Although intraplaque hemorrhage (IPH) is known to increase stroke risk and plaque burden, its long-term effects on plaque dynamics remain unclear. Objectives: This study aimed to evaluate the long-term impact of IPH on carotid plaque burden progression using deep learning-based segmentation on multi-contrast vessel wall imaging (VWI). Methods: Twenty-eight asymptomatic subjects with carotid atherosclerosis underwent an average of 4.7 ± 0.6 VWI scans over 5.8 ± 1.1 years. Deep learning pipelines segmented the carotid vessel walls and IPH. Bilateral plaque progression was analyzed using generalized estimating equations, and linear mixed-effects models evaluated long-term associations between IPH occurrence, IPH volume (%HV), and plaque burden (%WV) progression. Results: Two subjects with ipsilateral IPH developed new ischemic infarcts during follow-up. IPH was detected in 23/50 of arteries. Of arteries without IPH at baseline, 11/39 developed new IPH that persisted, while 5/11 arteries with baseline IPH exhibited it throughout the study. Bilateral plaque growth was significantly correlated (r = 0.54, p < 0.001), but this symmetry was weakened with IPH presence. The progression rate for arteries without IPH was -0.001 %/year (p = 0.895). However, IPH presence or development at any point was associated with a 2.34% absolute increase in %WV (p < 0.001), and %HV was associated with 0.73% per 2-fold increase over the mean of %HV (p = 0.005). Conclusions: IPH may persist asymptomatically for extended periods. While arteries without IPH demonstrated minimal progression under contemporary treatment, IPH significantly accelerated long-term plaque growth.