Critical mechanical conditions within atherosclerotic lesions (BHF FS/13/33/30168)
Most stroke and heart attacks are due to the rupture of an atherosclerotic plaque. Under the physiological condition, plaque is subject to mechanical loading due to pulsatile blood pressure. Plaque structure possibly fails if this loading exceeds its material strength. Therefore, critical mechanical conditions should be integrated with plaque compositional features for a more accurate vulnerability assessment.
This study is designed to assess the mechanical stress and stretch conditions within lesions in the carotid (using MRI) and coronary (using IVUS and OCT) and the association with clinical symptoms and subsequent ischaemic events.
Material behaviour of atherosclerotic tissues (BHF PG/11/74/29100)
Material strength of atherosclerotic tissues, particularly fibrous cap, is essential for assessing the stability of a lesion and for an accurate mechanical prediction. Ex vivo material test is performed in this study to understand the non-linear material behaviour of different atherosclerotic tissues and the ultimate material strength with the local micro structure and inflammatory condition.
People specializing in this area
Research themes in the Bioengineering group
- High resolution, multi contrast magnetic resonance (MR) image
Stroke is the 3rd leading cause of death and the leading cause of disability in developed countries. Carotid atherosclerotic disease is responsible for 25-30% of all strokes. Currently, luminal stenosis is the only validated diagnostic criterion for patient risk stratification, but this criterion becomes less reliable in patients with mild to moderate stenoses. Increasing evidence suggests that the physical characteristics of atherosclerotic plaques may have better potential to define clinical progression than luminal stenosis alone. A vulnerable carotid atherosclerotic plaque is characterised by the presence of intra-plaque haemorrhage (IPH) and a large lipid-rich necrotic core; symptomatic plaques also exhibit fibrous cap (FC) rupture. These features can be quantified accurately by in vivo high-resolution, multi-contrast MRI imaging.
- Mechanical analysis for assessing the atherosclerotic plaque vulnerability
In the carotid, although ~60% symptomatic patients exhibit IPH or FC rupture at baseline, only about 10-15% will experience a recurrent event at one year. In the coronary circulation, similarly, the predicting power of identified high risk features, including large plaque burden, thin fibrous cap and tight luminal area, for future ischaemic events is low. It is therefore clear that imaging-detected morphological and compositional features cannot serve as a robust marker for prospective cerebrovascular risk, and additional biomarkers are required.
Under physiological conditions, carotid plaques are subject to mechanical loading from blood pressure and flow. FC rupture may occur when this loading exceeds its material strength. Indeed, plaques with high mechanical stress concentrations are associated with fissuring in both coronary and carotid plaques. Furthermore, we have shown that FC stress can differentiate symptomatic vs. asymptomatic patients, and it is associated with subsequent cerebrovascular ischaemic events in symptomatic patients.
- Material testing
Computing the mechanical loading within the lesion is insufficient to have a comprehensive risk assessment as the risk of rupture also depends on the material properties, including ultimate strength, of local tissues. We have therefore performed extensive experimental work to quantify the material properties of atherosclerotic tissues from human carotid plaques. We also study their anisotropic behaviour by investigating the fiber structure.
- The pathological role of high mechanical loading in the aneurysm
With a similar hypothesis as the one for the atherosclerosis that aneurysm wall may rupture when the mechanical loading exceeding its material strength. In collaboration of Dr James Rudd in the Department of Medicine, aneurysm structural stresses are calculated using finite element analysis. The relationship between maximum aneurysm 18F-FDG standardized uptake value and aneurysm structural stress, patient clinical characteristics, aneurysm morphology and compositions is explored. We are also interested in the role of mechanical stress in predicting aneurysm expansion.
- Novel aneurysm management strategy using bare metal stent
Complicated aortic aneurysm involving vital side branches has been difficult to treat endovascularly. The advanced branched/fenestrated endografts have offered a feasible way of preserving major branches, but the procedure often requires customized devices and technical expertise in visceral branches’ cannulation and stenting. Moreover, current fenestrated endografts are still not capable of preserving minor vital branches. The emerging flow-diverting strategy may provide a new perspective on side branches’ maintenance while stabilizing the aneurysm. By elevating the local resistance, the multilayer device effectively decreases the flow velocity and total blood volume flowing into the aneurysm, modulates local flow pattern, and eventually promotes thrombus formation.