I first want to present the Cerebrovascular Section BEST Clinical Scientific Paper. This is awarded to Dr. Hussain Mousavi. And the excavation of non-ulceration best describes the process of plaque degradation. This will be discussed by Dr. John Wilson. Congratulations. Thank you. Good morning. I want to thank you for this award and also inviting us to New Orleans. And I have to also thank Dr. Yunus for his mentorship in this project. This morning I'll be talking about the process of the plaque degradation based on the morphological analysis of 345 intact plaques. Dr. C. Miller Fisher in 1951, for the first time, identified the atherosclerotic plaque at the carotid bifurcation as a potential cause of stroke with a great man. Such plaques are responsible for 10% to 20% of strokes. They could lead to a stroke either through the distal emboli or hemodynamically significant luminal stenosis. Transformation of the plaque to a complex plaque is associated with high risk of strokes and has been demonstrated by the imaging studies. Metabolic and inflammatory process are known factors and also responsible for the formation of the complex plaques. Treatment options could include the medical management, carotid endarterectomy, and carotid stenting. So what were our questions for this study? How does a plaque turn into a complex one? Why and where does the ulceration occur in a plaque? What is the relationship between the ulceration and intraplaque hemorrhage? When does a false lumen occur with regard to the intraplaque hemorrhage? Are all these processes integrated or independent? To answer these questions, we performed a retrospective study. Between 1985 to 2005, there were 413 plaques in patients with high degree of stenosis or symptomatic plaques underwent resection. All plaques were dissected and photographed by the senior author with an operative microscope. Patients had been de-identified and multiple images were stored in sequential binders and there were a total of 345 plaques with no fracture and sufficient images that were enrolled in our study. So what was our methodology? Here I'm showing our methodology for plaque dissection and imaging obtaining. On the images A and B, we're showing a plaque from each side. On the image C, we are looking at the plaque from the proximal part and on the image D, we are looking at the plaque from the distal part. Image E, you can see the plaque is dissected transversely and on the image F, you can see the dissected plaques from the above. The image G and H is similar at the image F with 25 magnification. So what do we find out in this study? We found three different phenotype. The first phenotype that we observed and we all know is a plaque ulceration which you see the schematic view on the left side. So here I'm showing four different plaques with the ulceration and all you're looking at the plaque from the proximal portion of the plaque. On the image A, you can see this paper arrow is pointing to the vascular lumen and this paper arrow is pointing to the ulceration. The ulceration on the other images B, C, and D are pointed by black arrows. Of note, we also observed that 92% of ulcerations happen proximal to the point of maximal stenosis. The second phenotype that we observed was intraplaque hemorrhage. As you see the schematic figure on the left side. Figure A, we are looking at a plaque from below the upper paper arrow pointing to the vascular lumen and this paper arrow is pointing to the intraplaque hemorrhage through an ulceration. And the figure B in the upper image, we are seeing this black arrow is pointing to an ulceration which opens to a intraplaque hemorrhage. And plaque B, the same plaque has been dissected longitudinally and we are seeing the intraplaque hemorrhage in this plaque. Of note, there is also 92% of the intraplaque hemorrhage is a continuity of the ulceration. In some plaques with IPH, we see that due to expansion of the IPH, the lumen is severely compressed and displaced which hemodynamically could lead to dominant flow diversion into the IPH. I'm showing some examples here. In figure A, you see that the plaque is dissected longitudinally and the paper arrow here, you're seeing that is pointing to the intraplaque hemorrhage and this one point to the vascular lumen. And these are two different plaques with the intraplaque hemorrhage that severely compressed the vascular lumen. The third phenotype that we observed has not been described well in existing literature. It's a plaque with false luminal formation and that's a name that we chose for. On the image A, you can see the upper image. The upper arrow is pointing to a empty cavity and when we dissected the plaque longitudinally, you can see the inside of the lumen. On the figure B, you're seeing that this arrow is pointing to the vascular lumen and this one is pointing to an empty cavity and when you dissect the plaque, you see the difference. Actually, you see the empty lumen here. On the plaque C, you see that this intermembrane that separates the vascular lumen and the empty lumen has been severely damaged and causes formation of the second plaque. In this slide, I'm showing the incidence of each phenotype of our plaques. The blue bar is showing the plaque with a specified pathology and the yellow is showing the plaques with only a specified pathology. We had 62 plaques with no degradation. We have 283 plaques with ulceration and 50 of them had only ulceration. There are 233 plaques with intraplaque hemorrhage and only one had ulceration. Intraplaque hemorrhage and 18 with only intraplaque hemorrhage and 165 plaques with false luminal formation and there were zero with only false luminal formation. What we conclude is that 76% of our plaques have more than one pathology and you also see the incidence of the phenotype. We have more ulceration than intraplaque hemorrhage than false luminal formation. This slide is showing, like visualizing the prior slide that ulceration is more than intraplaque hemorrhage and the false luminal formation. By adding time to that equation, we actually generated an animation of how the plaque degradation occurs in this process. You know, as we see, here we have hemodynamic forces that exert their effect on the proximal part of the plaque that causes ulceration formation as you see as a stage one of plaque. The same forces causes more degeneration of the plaque content and also damage to the vasovasarum that leads to the intraplaque hemorrhage. That's a stage two. During the course of the time, the intraplaque hemorrhage and intraplaque content washed out intracranial and going to the brain and it causes a formation of the false lumen. These forces damage the plaque intermembrane and also causes the second lumen and during the course of the time, eventually the plaque intermembrane is totally washed out and we see that the continuity of the vascular lumen and the second lumen with residual plaque as you know, we see in the animation. So, what is our conclusion? How can I go to the next slide, it doesn't go? Yes. Okay, so we call this process excavation. A dynamic process that we think could be best explained the plaque degradation through the effect of hemodynamic forces. Here I have the, in the image I'm showing, that the first stage is the plaque ulceration, the second is intraplaque hemorrhage and the third would be the formation of the false lumen and so on, the rest of degradation of the plaque. What is the clinical implication of this study? I mean, is it useful? As we know, the complex plaques are more prone to the iatrogenic strokes when we place carotid stenting. We think that this process is due to catheter interactions with the intraplaque hemorrhage, you know, intraplaque contents and also entering to the false lumen. To minimize such complications, we recommend that surgical procedures should be considered for the complex plaques. Thank you. I appreciate the opportunity to discuss this paper by Dr. Mousavi, Sorte, and Jonas. It's an excellent paper. It's really a Yeoman's work that where they took over 400 specimens resulting in 345 that were available for analysis. These were contemporaneously sectioned both longitudinally and transversely and photographed with an operating microscope. There were between five and 20 images for each specimen. A number of different pathologies were characterized as well as the location of the plaque relative to the point of maximal stenosis. As you see here, 18% of the specimens had no pathology while 82% were found to have ulceration or ulceration in addition to additional pathologies. The ulceration was located at the point of maximal stenosis 92% of the time and or was proximal to that point of maximal stenosis in virtually every case. As you see here, 82% of the specimens with ulceration were also found to have intraplaque hemorrhage. 92% of the time that intraplaque hemorrhage was in continuity with the ulcer consistent with the author's hemodynamic theory of progressive plaque degradation. But in 8% of the specimens, the intraplaque hemorrhage was located at a separate location in the plaque seemingly not directly related to the ulceration. Of the 345 specimens, 82% were found to have ulceration, 68 intraplaque hemorrhage, 48 had false lumen formation with nearly 80% of those false lumens being in continuity with intraplaque hemorrhage. The sequential decline in the incidence of these progressively worsening morphologic characteristics was felt to be evidence of a sequential process. The limitations of this study, it was a retrospective review. There was a potential sampling error created by that retrospective review and the fact that they had been obtained so far in the past. There was no correlation with the degree of stenosis, no correlation with symptomatic status. The hypothesis fails to fully account for several morphologic findings that you can see here, and the technique fails to account for other pathophysiologic mechanisms implicated in plaque degradation. For example, numerous studies have implicated the renin-angiotensin system in atherosclerotic plaque vulnerability, and in 1999, we demonstrated precise localization of angiotensin-converting enzyme messenger RNA within areas of inflammation and neovascularization in human carotid plaque specimens. The pathophysiology of atherosclerotic plaque degradation is complex and multifaceted, and undoubtedly involves both biochemical as well as hemodynamic processes. It boils down really to a chicken or an egg phenomenon. I would say, rather than characterizing this as a hemodynamic excavation and not ulceration, I would characterize the process as an amalgamation, and say that it's excavation and ulceration that describes the process of plaque degradation. I congratulate the authors for adding significantly to our understanding of the processes and how hemodynamic stresses may sequentially impact that process. Thank you.

plaque degradation

phenotypes

hemodynamic forces

surgical procedures

complex plaques