 Alright, so we're going to talk a little bit today about the biomechanics of the aorta, feel a little intimidated Jennifer talking about this with you running this session so jump on in if I say anything wrong by all means. Just to start. I have no disclosures that are relevant to this presentation. My objectives for this morning session are going to be to summarize the mechanical properties of the thoracic aorta, starting with healthy people, and then describing some of the changes that occur pathophysiologically that we see in thoracic aortic aneurysms. I'm going to go over some of the ways that we actually study these mechanics, and I'll keep the focus a little bit on echo, given the symposiums orientation. And then finally, I'm going to bring up a few of the clinical applications of aortic biomechanics. Let's start with aortic tissue properties which do define how the order behaves once we stress it during these cardiac cycle. Now, the macro structures familiar to pretty much everybody that's joining this symposium. So you know we have the three layers of the intimate the media and the adventitia. So I'm going to go a bit more into the microstructure, which is what really gives the mechanical properties of the tissue. The microstructure can be divided into the cellular and the non cellular components. So some of the common components I'm going to just basically focus on the main ones that you see in most of the literature, there's plenty of things that I'm going to have to admit because of time. So the cellular component that will concentrate on this morning, there's the smooth muscle cells. And those have both secretion function, as well as mechanical function. And then on the inner layer you have the endothelial cells which aren't shown on this image, and those contribute in part with communication into the media. Particularly they have cross links with some of the smooth muscle cells, and then they endothelial cells also provide that some of this go elastic properties of the order, which will become important later on. The tissue layer is fairly rich with fibroblasts. Those are also not shown in this picture. And then finally the myofibroblasts are recruited during times of tissue injury on a responsible some of the repair mechanisms. So those have become a point of focus and a lot of the path of physiology. Now the extracellular matrix is the is a large contributor to the overall mechanical properties that we see. So the elastic will be coiled in these elastic lamellae, and then what they'll do is they will stretch under low, low loading situations so they'll have a very nice smooth elastic motion in the early part and mid parts of the cardiac cycle when the stresses are low. You then have collagen. And what collagen will do is it will stay wavy or crimped during the early part of the cardiac cycle, and then only towards the end towards the higher points of loading will they become uncrimped, and they don't have the same elastic nature as the Elastin, and they're more responsible for the overall structural integrity of the aortic wall. And then you also have proteoglycans, and the proteoglycans will make links with hyaluronin as well as with the other components of the extracellular matrix and with the smooth muscle cells. And so the high proteoglycan hyaluronin complex creates basically almost like a compressible aggregate that smooths out some of the transmission of stresses through the wall, and then by their connections to smooth muscle cells also can help with the mechanical transduction. So now what do we see in a thoracic aortic aneurysm. So we'll see a constellation of changes on histopathology. So one of the things will be we start to see death of smooth muscle cells. Another thing that we'll see is fragmentation of your proteoglycans, and then these fragments will actually begin to pool around areas of Elastin injury. And then fibers themselves will start to become degraded, torn, damaged. And then finally we'll begin to see changes in the collagen. So often what happens is that the damaged Elastin is then replaced with collagen. And this collagen isn't always the same type of collagen that was there to begin with. So now when you know these changes are we're trying to study what these changes mean from a biomechanical standpoint, how do we test this or how are we studying this. So a great deal of research up to this point had been done using bench top mechanical testing so either axial where you're stretching it in one direction, or by axial as is shown here where you're stretching it in two directions at the same time. And basically this is you cut tissue out you map it put it into quadrants and then you put it on to the stretch tester and what that will do is have hooks into the tissue, and then you will apply a deformation to the tissue and that will give you the associated stress. And so that's what a lot of the publications have been focused on up till to reach to more recently. So when you buy axiol stress test by actual test a piece of aortic tissue and a normal healthy individual on the left panel what you kind of what you end up seeing is that you see the combination of the effects of the Elastin and the collagen on the shape of the curve. And so it's not a straight curve it's a non linear elastic response so what you'll have is early in the deformation. You'll have very much Elastin dominated part of the curve and then as you get towards higher deformation. The collagen which is the red dashed line will start to become engaged and then the shape of the curve will then represent over time, less and less and less Elastin function and more and more more collagen function. And so non a linear shape is one thing that we typically see. The other thing that is common on the right hand panel is this idea that a hysteresis is made. So what that means is that when we stretch or load the tissue, and then unload the tissue, the line doesn't follow itself. There's a space in between the two, and that space between them is what we call energy loss and that will bring I'll bring that up later on. The energy loss is representative of the visco elastic properties of the order. So when we do some mechanical testing, there's plenty of different metrics that have been measured and described, I've just represented a cluster of some of them. So what you can do is you can look at the straight parts of the curve so the low end of the deformation and the high end and that will give you tangential module I or the slopes of the curve at these points. As I mentioned, there's a period where Elastin function starts to give way to more collagen function in terms of the shape of the curve. And so this creates a transition zone so we can try to measure where that transition zone begins. And then, as I had earlier alluded to, we can look at that space in between the loading and unloading curve to measure energy loss. Then what you can do is you can take some points at the beginning of the curve and the end of their curve and generate some form of a slope between those two and that will give you some measure of an overall Elastin. And then finally, one of the tests that will do is fail as a some form of a failure test where you'll basically stretch it you need you need directionally or not you directly you'll just stretch load it you won't unload it. But you'll stretch it until the tissue fails and it breaks and so then that's tissue failure test. Now in the thoracic aortic aneurysm when we do the same bench top testing we've come up generally with different looking curves. And so what you'll find here are some changes in those five measures that I had just mentioned. So right here on the left I've, I've shown an aneurysm in the red and the normal would be in the green. You can generally see by having less Elastin because of the Elastin degradation and more collagen the for the shape of the curve starts to be more collagen dominated earlier in the deformation. And then you start to get into the high slope stiff type of met measures earlier on as well. What you can see from the parameters I had brought up is you'd have your low tangential modulus usually flattened down and your high tangential modulus will raise up. You might start to see an earlier transition zone as the collagen is activated earlier. You'll see an increase in energy loss. The overall slope of your curve should become steeper so you'll have less Elastin's. Elastin's collagen is a stiffer material. It's not, it's in general weaker so you usually see with this tissue is that it, it fails earlier on in the deformation curve. Now the bench top is very limited obviously you can only usually get abnormal tissue, you also can only get patients in a single slice of time so either when they're coming for the prophylactic repair or your testing tissue that's already been resected because it's dissected or ruptured. So advanced imaging has really led the way to some more imaging based biomechanics. So two really important ways is with CT and MRI. And so I've shown here on the left to CT what they can do is you can create stress maps of the order and look for points of high stress that might be more inclined for rupture or dissection. And then our to the right hand side using 40 flow you can look at wall shear stress. It's a bit more on ultrasound. So one of the dating back for 30 years people have done this where you can use M mode on an aortic structure and find a systolic and end diastolic diameter, and then use that to measure forms of stiffness of a stiffness index. So people have been looking at this actually for some time. I think one of the things that's really helped is the advent of speckle tracking and the use of it on the aorta. The speckle tracking as many of us have seen it for LV or RV. What you can do is you can actually use the same technology to track the wall motion of the aorta and generate the same measures of stretch or strain. So this is an example of sort of the approach that we've been taking. So this is a cross section of the ascending aorta. And so what we have done is we'll trace the walls and create our regions of interest. And then the walls will track and provide our measures of strain. Then what you can do is you can take your circumferential strain you see here divided by sections. And that will pair it with the pulse pressure or the pulse wave at the radial artery and then use a transfer function to generate an aortic pulse wave. And then we can pair the strain and the pulse wave to generate pressure strain loops. And as you'll see this looks very similar to what we had sort of seen with the mechanical testing where you have the systolic component here in the solid line. And then during vastly as it relaxes you have the hysteresis with energy loss in the middle. And we can also sort of we can also start to appreciate where the low tangential modulus would be, as well as where that transition zone occurs. So what are some of the clinical implications of this aortic biomechanics. So one of the probably most prominent areas would be in the use of determining risk for acute aortic events or rupture or dissection I think this is where a lot of the focus has been. This is a really cool one of the earlier papers I think I've seen using echo in this way it's done with the Montreal group. And so using tea, they did a similar strategy to what I had shown where you get strain of circumferential strain. And what they did was paired it again with pressure to create a loop their loop on the bottom left panel you can see is not that dissimilar for mine it has a nice hysteresis. And then what they used was the slope of a measure of an elastance basically, and then when that was paired with the histopathology of the tissue that they collected they found a correlation of decreasing elastance or an increasing slope with a higher proportion of collagen, ie a higher amount of pathophysiology, or should say pathology. And so what they did was they did a four D flow MRI and then we're able to do measures of the wall shear stress, and there's a few parameters that they matched this with, and I just wanted to bring out to that I wanted to focus on the one on the top. There's energy loss and so you can see the shear as the wall shear stress increases, it correlated strongly with an increase in the energy loss so again as we sort of said those are that energy loss is something we see increasing as the tissue becomes more and more abnormal. The bottom, the bottom box is a delamination measure. And so that obviously delamination would be a very strong indicator of intensity for dissection. And even though this was not significant from a p value standpoint you can see the clear relationship as well shear stress increases it reflects more propensity for delamination or dissection. So I think this really shows that linking between some of the imaging that we can do, and the ability to predict risk. Another area that's kind of interesting is we actually start to see changes in the order after we do surgical interventions. So the graft material itself can have impacts on aortic function. So this was a study where they did the similar echo based approach to measuring stream. I had shown previously what they did was they did it before and after ascending aortic resection. And so what they've been they're doing this at the level of the proximal descending thoracic urea. So as you can see post procedure on the right, compared to pre procedure on the left, you have an increased that descending thoracic uric strain. So what's happening is because the nature of the graph is actually changing how the pulse wave is transmitted and creating greater strain distal to where the graft has been done so the graft is not itself is not a benign substance. We locally we did study looking at the effects of EVAR so further down in the abdomen to see if how that might affect the aorta the order of competence and LV performance parameters, approximately. And so what we found is if you is that it really had an impact on the reflected waves. So as your pulse wave transmits down so on a normal patient so the pre EVAR on the left. Your pulse wave trans transmits down to your order and then it hits the branch points and when it hits branch, it's branch points. This creates a drop or an increase in resistance depending on which branch point you're at and these will create reflected waves either positive or negative depression reflected waves. And so normally what will happen is that the deflected the positive deflected wave will arrive in diastole. And that sort of helps augment some of the coronary blood flow and the very least it's not be required to be pushed against by the LV as it's ejecting. So what we found in our EVAR patients is that because that stiff material is now there, it alters the velocity of blood through the body and changes the timing and the size of the positive reflected wave. And what we found now after the EVAR is that it will come back as a larger positive reflective wave and occur during systole and this therefore increases the aortic competence on the LV. And so we found acute changes in diastolic function related to that. And so we found a study on young patients that had thoracic that had T bars for thoracic aortic trauma, and then they followed them five years later on. And what they found was that this group had significant changes in their LVH, as well as 50% of the patients had new onset hypertension. And then also what was interesting is they began to see remodeling where there was dilation and lengthening of the ascending aorta proximal to the stent. And then finally, as I mentioned, the stent does alter pulse wave transmission so I like this was kind of a cool case that we had found. So these are simultaneous pressure tracings on a patient from the right and left radial who'd had an endovascular total arch performed. So if you need sort of any proof that the graph material impacts how the pulse wave is transmitted. I mean this is a very nice clear, clear example. So in summary, it's the microstructure of the aorta that determines the mechanical properties that we care about. When you have aortic aneurysm formation the pathophysiologic changes in that microstructure will result in differences in the biomechanics of that tissue. So we can use those biomechanical measures to then try to ascertain how severe the pathophysiology is. Now, amazing advancements in imaging technology have opened new doors for us to be able to have better clinical applications of biomechanics. So this should allow for longitudinal studying can allow for large cohorts, we can do more studies on normal people. The future is really exciting in this area. And then finally, the abnormal layer of properties. It's more than just interesting for the people resecting it it's more than just interesting and for risk stratification. It does actually have implications on patients before and after their surgery that are applicable to all clinicians. And again, I would like to thank you all for having me this morning and always take emails at any time. Hello. Okay, great. Thank you so much Alex for your wonderful presentation. We do have a few minutes before the next speaker. So I would invite everyone to put their questions in the chat. And also, after around 1030 or so we'll also have a period of time to answer questions so please get your questions in the chat. So thanks once again Alex for your talk it was wonderful great summary of all the work that you, you and the whole Calgary group has done know for many many years now you guys have been studying this it's it's fantastic. I was actually involved in that TTE study by in Montreal when I was there where we try to have a imaging based way of assessing aortic biomechanics as that's our holy grail in our field as you know, I was wondering if you guys have had any success in translating it to the classic echo, and if you can elaborate on on that and also what may be the limitations and the challenges are with with echo based techniques for this. Yeah, those are those are the you basically asked all the answers, the questions we all need answers to. You know, it's, it's actually really great. I mean, a lot of the Canadian centers have done an amazing job right because you have their Toronto Montreal over Calgary everybody's really done a really good job of working on this and it's a little bit of a slightly different area that they might be focusing on. So I think for for ultrasound. So the, the one question about the trans thoracic so where we're at now is we're still focusing on the TTE. I think it's only because of the quality of imaging, but the trans thoracic crossover is going to be a man absolute mandatory I think down the line. I think once we have a handle on figuring out how to calculate the biomechanics from tea. My thought processes is that we really then need to try to have simultaneous measurements in other modalities where that CT and MRI and trans thoracic and figure out how these all translate with each other. There's some speckle tracking info data on just LV function where you can find out that using TTE versus TTE will give you different strain measures, just in the LV. So like, I can't imagine that the era will be any different. So I think what we'll have to do is sort out. If at least if there is a difference hopefully it's a predictable one where you can just have some sort of a fudge factor that then makes the two equal. If not, then we'll basically need to create on sets of normals for trans thoracic and trans esophageal. So trans thoracic is going to be vital. And I think that because that leads me to the second part of your question in terms of the limitations and benefits of these different methods. So ultrasound is nice because it's portable, it's cheap, pretty non invasive and it's easy to do the image quality obviously is far less than what you get from CT or MRI. So I think what will have to happen is that we'll have to figure out the rules that each of these play I don't think there's going to be one that that does everything. And so I think it'll be really important for us to look at all modalities, figure out normal reference ranges, and then from there starts to do these longitudinal studies. So I think the one real nice thing about echo, especially speckle tracking is that it's really amenable to retrospective studies, because the even if you do the sort of the older traditional approach of the beta stiffness beta stiffness index, you needed someone to do an M mode on the aorta at that time so that hadn't been done, which isn't a standard image to acquire intraoperatively or preoperatively with a trans thoracic. With the beta stiffness, but meant most speckle tracking as you know it's all done offline. So you could take thousands of images and have some speckle track and whether you wanted to do just something simple like beta stiffness, or some of these more complex measures, then I think that would be very doable and you don't have as much free operative CT imaging although I know that's changing everyone's making banks now but I think that will be something that would be very helpful going forward. For sure you there's two different directions you can go right you can go more and more complex with MRI and you can really. So I sort of really focus on MRI but and add more and more layers to that or you can say well what's most available to everyone that they can do with longitudinal studies in every single center right and so that that would be the the echo approach. And it could actually end up being very, very simple we might be over complicating the problem. So you were in pen right I think. I think it was Pittsburgh actually that presented at the double ATS just this year, where they were able to correlate stiffness in their aortic clinic with actual aortic events, you know aortic dissection so the actual clinical end point that's typically missing in our studies. Okay, so we do have a. We can fit in one more question. We also want a quick question. We've tried to get these straight images in the OR a few times but one of our problems that the tea probe is sometimes too close to the order for us to get a full view of the descending. Do you guys use any spacers or any other tricks or tricks on how to get these images to make sure we get as much of the order as possible. No, and unfortunately we have we'll have that same we'll have that same problem. So one of the things that we're going to actually try out is we want to see how happy the aortic probe works. So that maybe you can we're trying to see it like we want to compare because the resolution is clearly different. So what one of our next studies is going to be is trying to figure out how different it is so if they're comparable enough, then in areas where you have drop drop out so sometimes it's posed that posterior wall that drops out, sometimes depending where the PA comes across will get shadowing. So if there's drop out can you just use an epi aortic to substitute so that's one thing we kind of wanted to look at. And then the other thing is kind of Jennifer's point like I think that simultaneously we're going deeper into complexity, while at the same time looking to see if there's just some basic easy measures that, although the model might be perfect functions well enough to give us some useful clinical information. So what we're doing is when we divide our into our sections, what we might do is we focus on the sections that we have. So what we'll learn over time is, perhaps if you have that answer your section of an aneurysm that might provide enough information on the abnormality of it that even if you have some drop out another sections, you're still getting an assessment. So I think this is the point like, I think ultrasound inherently is going to have some mutations because of image quality I think that's always going to be a problem that we have to figure out. Is it something that can be worked around or is this, you know, is this a real serious limitation that makes us has to focus more on MRI and CT scans.