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

Despite t he p roven ef ficacy o f ca rotid en darterectomy ( CEA), great i nterest h as b een generated i n car otid an gioplasty and s tenting ( CAS) as an al ternative t o CEA. The stretch caused b y ba lloon a ngioplasty de ployment dur ing C AS c an da mage t he baroreceptor function and therefore a lter t he no rmal cardiac output and induce severe damage t o t he c arotid artery l ayers an d p laque l eading t o an i ncreased ch ance o f 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 b e u sed i n an ex perimental mo del o f th e c arotid b ifurcation c omplete w ith baroreceptor response t o s train, s o t hat i t m ay be used to i dentify a nd qua ntify t he 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 m echanical behaviour of 23 hum an c arotid plaques was characterised in order to correlate plaque behaviour to pr e-operative classification d ata. 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 e valuates th e limita tions o f me chanically testing plaque specimens i n t he circumferential d irection d ue to th eir random geometry, a s well a s in vestigating th e 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 c urrent gold s tandard of pr e-operatively classifying pl aque b ehaviour, dupl ex ultrasound, w as analysed t o de termine whether i t i s a n a ccurate pr edictor of t he mechanical be haviour o f pl aque. R esults de monstrate t hat t he m echanical be haviour does not correlate with pre-operative classification as es timated by duplex u ltrasound. Testing th e a therosclerotic p laques u ntil f ailure id entified th e s tresses and s trains th at 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 ul trasonic c lassification w as s hown t o be a n uns uitable di agnostic pr edictor 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 e ach plaque sample prior to mechanical testing in order to globally characterise the biological composition of t he s pecimen. F TIR revealed that t he pl aques w ith a hi gh c oncentration of calcification co ntent p roduced a s tiffer m echanical r esponse compared to t hose w ith higher l ipid c ontent. T o va lidate t he F TIR data, e nergy di spersive X-ray (E DX) spectroscopy was carried out on plaque samples which reiterated the main outcome i.e. that t here i s a h igher content o f cal cification i n t he m echanically s tiffer p laques i n comparison to the softer based plaques. The s tress-stretch p lots o f t he t ested p laques were av eraged i nto t wo m echanical behaviour t ypes ba sed o n F TIR cl assification an d cu rve-fit to th e Yeoh strain en ergy function for FEA. A s tandard angioplasty balloon was compared to a novel two-stage helical pe rfusion ba lloon w hich a ims t o va ry compression t hrough t he w all of t he diseased t issue t o d ecrease risk of pl aque r upture and t o pr omote i mproved dr ug transport in to th e w all. The f irst s tage r educes t he inflation d iameter which showed decreased rupture pot ential i n c omparison t o t he s tandard b alloon. The second s tage 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.