Exploring the Role of Neovascularisation in Carotid Plaque Vulnerability

Abstract

Non-invasive ultrasound imaging is a valuable tool for disease diagnosis and treatment monitoring. In cardiovascular diseases, identifying reliable clinical indicators of vulnerable carotid plaques is vital for improving outcomes. This thesis examines the mechanical behaviour and rupture risk of atherosclerotic plaques, focusing on neovascularisation as a potential marker of vulnerability, using mechanical testing, ultrasound imaging, histology, immunohistochemistry, and computational modelling.

To replicate the physiological loading conditions of plaques, polyvinyl alcohol cryogel phantoms were designed, developed, and tested using a custom-built inflation rig. This setup was complemented by the integration of ultrasound imaging and inverse finite element modelling. This study offered valuable insights into the mechanical behaviour of diseased vessels' surrogates, establishing a critical foundation framework for plaque testing. The workflow was then applied to fresh human atherosclerotic plaques obtained during endarterectomy surgeries. Controlled inflation allowed to subsequently study plaque biomechanics and assess the role of neovascularisation. Immunohistochemistry was then employed, enabling the visualisation of neovessels within the plaques. This offered valuable insights into the potential role of neovascularisation in plaque mechanical behaviour. Of note, plaques tended to show increased neovascularisation as their microstructural complexity increased. Uniaxial tensile testing further demonstrated that plaques with higher neovascularisation failed at lower ultimate tensile strains, highlighting a relationship between neovessels and reduced mechanical integrity.

These findings highlight neovascularisation as a potential marker for plaque vulnerability. This research paves the way for future studies to bridge the gap between research and clinical practice. By leveraging non-invasive imaging techniques like contrast-enhanced ultrasound, future work could explore in vivo neovascularisation, improving the identification of high-risk plaques and enhancing cardiovascular risk assessment.