Ultrasound Localization Microscopy in Identifying High-Risk Carotid Plaque Using Low-Frame-Rate Ultrasound Imaging

Intra-plaque neovascularization (IPN) is associated with carotid plaque progression and instability, increasing the risk of ischemic stroke due to hemorrhage and rupture. This study investigated the feasibility of ultrasound localization microscopy (ULM) to extract microvascular features from carotid plaque using standard low-frame-rate clinical contrast-enhanced ultrasound (CEUS), aiming to differentiate between symptomatic and asymptomatic plaques.

Between August 2020 and October 2022, 65 consecutive patients with 78 carotid atherosclerotic plaques, evaluated by clinical CEUS, were prospectively included. These plaques were assessed for ischemic symptoms. ULM involved localizing individual microbubbles at a subwavelength scale, which were then tracked to assess anatomical (microvessel density, length and tortuosity) and functional (blood velocity) features for characterization of the carotid plaque and classification of symptomatic versus asymptomatic plaques.

The study found that ULM could successfully visualize IPN in carotid plaques at a significantly higher resolution than conventional CEUS images. IPN density in symptomatic plaques (30 of 78) was significantly higher than in asymptomatic ones, with median microbubble counts of 37.93 (26.16-61.78) versus 23.55 (12.53-37.58), track counts of 2.65 (1.41-5.18) versus 1.30 (0.74-2.43) and microbubble paths of 4.08 (2.03-6.09) mm versus 1.86 (1.17-3.16) mm (all p < 0.05). Additionally, symptomatic plaques showed higher velocities, with a median of 3.64 (2.61-5.24) mm/s, compared to 3.55 (2.52-4.97) mm/s in asymptomatic plaques (p = 0.004).

These quantitative imaging biomarkers by ULM with clinical CEUS show promise for the development of a diagnostic tool aiding in patient stratification and therapeutic decision-making.