Towards the development of guidelines for the surgical treatment of carotid artery disease: a tissue characterisation approach

Despite the proven efficacy of carotid endarterectomy (CEA), great interest has been generated in carotid angioplasty and stenting (CAS) as an alternative to CEA. The stretch caused by balloon angioplasty deployment during CAS can damage the baroreceptor function and therefore alter the normal cardiac output and induce severe damage to the carotid artery layers and plaque leading to an increased chance of restenosis. However, there is the potential to limit these damaging effects by improving the balloon device design and varying the balloon inflation parameters. Initially, this study focused on investigating the feasibility of developing a material that can be used in an experimental model of the carotid bifurcation complete with baroreceptor response to strain, so that it may be used to identify and quantify the effects that subjecting the baroreceptor nerves to sustained circumferential stretch has to the blood flow rate as is the case during angioplasty. An electrically conductive silicone was developed and investigated using a novel test system to highlight the qualitatively similar electrical response of the material to the baroreceptor nerves undergoing strain. The mechanical behaviour of 23 human carotid plaques was characterised in order to correlate plaque behaviour to pre-operative classification data. Plaques underwent uniaxial stretch in the circumferential direction at a physiological strain rate in order to replicate the instantaneous systolic pulse experienced by the plaque in vivo. This study also evaluates the limitations of mechanically testing plaque specimens in the circumferential direction due to their random geometry, as well as investigating the effects that changing the geometrical ratios of the specimens for uniaxial testing has on the curve-fitted strain energy function models used for finite element analysis (FEA). The current gold standard of pre-operatively classifying plaque behaviour, duplex ultrasound, was analysed to determine whether it is an accurate predictor of the mechanical behaviour of plaque. Results demonstrate that the mechanical behaviour does not correlate with pre-operative classification as estimated by duplex ultrasound. Testing the atherosclerotic plaques until failure identified the stresses and strains that plaques can withstand prior to rupture and indicated that the majority of strains applied during a typical CAS procedure could cause plaque to rupture. As ultrasonic classification was shown to be an unsuitable diagnostic predictor of plaque material properties, an improved method is developed in this study through the use of Fourier-transform infrared (FTIR). FTIR was carried out on each plaque sample prior to mechanical testing in order to globally characterise the biological composition of the specimen. FTIR revealed that the plaques with a high concentration of calcification content produced a stiffer mechanical response compared to those with higher lipid content. To validate the FTIR data, energy dispersive X-ray (EDX) spectroscopy was carried out on plaque samples which reiterated the main outcome i.e. that there is a higher content of calcification in the mechanically stiffer plaques in comparison to the softer based plaques. The stress-stretch plots of the tested plaques were averaged into two mechanical behaviour types based on FTIR classification and curve-fit to the Yeoh strain energy function for FEA. A standard angioplasty balloon was compared to a novel two-stage helical perfusion balloon which aims to vary compression through the wall of the diseased tissue to decrease risk of plaque rupture and to promote improved drug transport into the wall. The first stage reduces the inflation diameter which showed decreased rupture potential in comparison to the standard balloon. The second stage completes the deployment similar to the diameter similar to the standard balloon which shows an increased amount of peak stresses due to the geometrical difference in design. This study also demonstrates the different effects that these types of balloon have on the two plaque types based on FTIR classification and that plaques with higher calcification may not be suitable for angioplasty treatment