1. Carotid Stenosis and Endarterectomy Neurovascular Intensive Course 24-29 March 2008

7. Atherogenesis and Stroke Development of fatty streaks, small subendothelial deposits of lipid. Plaque consisting of a central lipid core bounded on its lumen side by an endothelialized fibrous cap containing vascular smooth muscle cells (VSMC), and connective tissue As the plaque grows, due to the process of positive remodelling, the vessel may expand, so that initially lumen diameter is not compromised (large volume atherosclerotic plaques may coexist without significant luminal stenosis and not be readily apparent on purely angiographic imaging modalities) Clinical events are caused by rupture of the fibrous cap and by exposure of the highly thrombogenic lipid core to the circulation, resulting in the rapid formation of thrombus 3 Vessel expansion when the plaque grows 1 Vessel stenosis 2 Rupture of fibrous cap and Thrombus formation 4 Plaque neovascularization, intraluminal hemorrhage Fibrous cap Formation 5 6

8. Cellular Level Combination of high levels of circulating low-density lipoproteins (LDL ) and endothelial dysfunction (smoking, hypercholesterolemia, hypertension and diabetes have all been associated with endothelial dysfunction and increased permeability) Dysfunctional endothelium expresses adhesion molecules which allow recruitment of monocytes within the vessel wall (e.g. vascular cell adhesion molecule, VCAM-1) Monocytes mature into macrophages , which then ingest oxidized LDLs via scavenger receptors, becoming foam cells and contributing to atheroma expansion . Accumulation of foam cells and their subsequent death within the atheroma via oncosis and/or apoptosis lead to the development of the acellular lipid core composed of cholesterol esters and cell debris The vasa vasorum or plaque neovascularization is thought to be particularly important in the recruitment and adhesion of monocytes within the plaque, which can promote atheroma growth.

9. Cellular Level VSMC migrate from the medial layer of the vessel wall and synthesize extracellular matrix components such as elastin and collagen , which are essential to the formation and integrity of the fibrous cap The fibrous cap contains inflammatory cells , predominantly macrophages, which produce a number of proteases such as metalloproteinases and cathepsins , which break down the matrix proteins in the fibrous cap Dynamic imbalances in the enzymatic action of macrophages and the protective activity of VSCMCs may eventually lead to rupture of the fibrous cap and clinical events. The fragile immature vascular endothelium associated with angiogenic microvessels increase the likelihood of intraplaque haemorrhage and of subsequent complications

19. Normal internal carotid artery Doppler study with pulsatile flow and uniform systolic acceleration in flow creating a window under the frequency figure. Grossly abnormal high peak frequency internal carotid Doppler study with no clear window caused by a variety of frequencies recorded from a stenotic and turbulent region.

27. Coronal source image from the 3D CE MRA acquisition reveals a right carotid artery dissection (arrow) The MIP reconstruction (a) clearly demonstrates a carotid artery stenosis. However, quantification of stenosis is best performed on MPR images (b, c) perpendicular to the vessel axis (arrow in c, stenosis of internal carotid artery in the axial plane)

28. CE MRA demonstrates overlap between arterial and venous phases. Normal contrast enhanced 3D MRA. a-c Direct coronal view of the first pass 3D MRA acquired with elliptical centric phase encoding technique. Note good visualization of all of the major vessels as well as many smaller vessels within the neck. Also note good separation of arteries and veins, the latter not being visible. b and c The 3D MRA can be rotated in different projections as illustrated

32. Automatic quantification along the vessel centerline

38. MRA vs CTA There are not the critical safety concerns with CTA. Since many trauma patients may be unable to give a proper history, MR safety considerations may preclude use of MRA in the acute situation. Satefy in Trauma More rapidly available in many emergency Less rapidly available Availability Unable to detect the presence of intramural hematoma. MRA has the advantage of being more specific for traumatic vessel dissection since it detects the presence of intramural hematoma. Post-traumatic vessel injury or dissection Dense calcium deposits are present within an atherosclerotic plaque at the carotid bifurcation this may limit accurate quantitation of vessel lumen stenosis Accurate quantitation of vessel lumen stenosis Lumen stenosis CTA MRA

49. Preoperative Assessment

52. Grading of patients undergoing carotid endarterectomy

94. Thank You