oa Referral Pattern And 3D Visualization Of Microstructure Of Carotid Artery Plaque, Using Laser-Scanning Confocal-Microscopy (LSCM)

Background: Strokes account for over 8% of deaths in men and 12% of deaths in women in the UK and the total cost of Stroke to the National Health Service within the UK is estimated to be over £7 billion per year. Carotid artery disease can cause stroke, transient ischaemic attack (TIA) and amaurosis fugax. Surgical intervention to remove the carotid plaque is likely to be helpful in symptomatic patients with > 50% stenosis of the carotid artery. The aims of this study were to (i) investigate referral pattern of carotid artery disease for duplex vascular ultrasound in a local hospital in UK; (ii) investigate whether confocal microscopy can be used to obtain 3D images of the micro-structure of atherosclerotic carotid plaques; (iii) construct a blood flow model with a view to investigate how forces resulting from fluid flow interact with structural stability of carotid atherosclerotic plaque Methods: A one-year audit for the total number of carotid artery vascular ultrasound scans referred to the Medical Physics Department by all specialists was carried out between (January- December). Those with > 50% stenosis (using St Mary's criteria) were identified, including those with symptoms who underwent carotid endarterectomy (CEA) . Carotid plaques were collected from routine carotid endarterectomy surgery and examined using flow-modelling, bright-field and Laser-Scanning Confocal-Microscopy (LSCM) to generate 3D image datasets and visualisations of surgically removed carotid plaques. Results: Over a one-year period, the total number of carotid artery referrals by all specialists for ultrasound scanning at the Medical Physics Department was 1353; 63.3% (n=856) of whom were referred from the TIA Clinics by stroke specialists. Out of this total referral, there were 139 patients (10.3%) with > 50% carotid artery stenosis, 57 of whom were symptomatic and underwent surgical intervention (CEA). 3D imaging of carotid plaques, using LSCM showed that most specimens were predominately composed of lipid material, comprising necrotic core of amorphous debris and cholesterol clefts, with varying degrees of fibrous tissue present in all plaques. Regions of actual fibrous cap disruption and some ulceration were also seen. Fraying of the fibrous cap was notable with fibrous cap erosion and exposure of underlying necrotic core to lumen. Evidence of carotid plaque vulnerability as demonstrated by reduced fibrous cap thickness and large lipid-necrotic core with evidence of cracking was also seen in the 3D visualization. A blood flow simulation model shows how blood velocity changes could occur associated with reduction in lumen diameter caused by the plaque. The degree of carotid artery stenosis measurements obtained from these flow models were consistent with, and comparable to the degree of stenosis measurement recorded on the pre-operative vascular ultrasound reports of patients from whom these plaques were taken. Conclusions: The visualization of the internal 3-dimensional microstructure and geometry of the plaques could help in: (i) investigating key features that affect plaque structural stability; (ii) comparing 3D microstructure of the plaque with clinical imaging assessment and blood flow investigations; and (iii) developing markers to identify patients requiring clinical intervention.