[00:00:04]
>> I think that what I have today is probably a little bit. It's more clinically or unaided talk but I would try to have some basic things whenever possible in this crowded as first roses. Is closely linked with stroke. So. There has basically been established procedures that each time when you see a star doses like I showed here in this case this is a carotid artery this image is actually as M.R. image this one is.

[00:00:36]
Disease or subtraction and geography showing the same location pretty much. You can get fairly good sense of where distances and then the current clinical practice is whenever your system Gnosis like this if the stenosis is over certain level then you operate on those patients. There is a fundamental flaw of this type of imaging regardless whether it is done by M.R. always done by the so-called gold standard in this case to the image is this really measures the lesion into it indirectly this only measures the fact of the atherosclerosis that is actually growing in the wall not in the lumen itself but this simply tells you that this part is likely to have lesions.

[00:01:25]
But this does not really tell you whether lesions grow at other areas and also this does not tell you what is really in this lesion. And at this moment a lot of the research are aimed at looking at the lesion itself because fundamentally people believe the lesion especially its contents is going to have a lot impact of what is whether this lesion is stable or unstable.

[00:01:53]
This ars. Some sample would he stolid G images of a plaque this is really not coming from this one but is just example of saying. If we started looking at the wall. What do we see and this is pretty much the gold standard of things you can see in that you see a woman here that has narrowed.

[00:02:11]
This is where the plaque is you also see that the plaque itself can be fairly the tissue type within a plaque can be highly complicated especially in a carotids where this is a relatively large artery in human. So he as I have said that stenosis even though it is a fact are now used to determine whether this patient how the fifteen patients should be treated this clearly is based on major clinical trials that this basically shows it is not enough information.

[00:02:44]
So if we believe that the still Gnosis is not enough to look at us. Then what should we look at especially from imaging point of view what information do we truly need this is a more of a composite drawing of what we believe that we should be looking at this is a simplified model of what a diseased artery supposed to look like this is the remaining woman in this case is very narrowed.

[00:03:08]
This was the origin of war and then in between the you can have many different types of tissues in particular you can have look at deposits. You can have areas that is fairly hemorrhagic In other words that blood can actually get into those areas and heavily calcified areas.

[00:03:26]
I don't know in Atlanta region that in Seattle you constantly listen to this radio commercials of asking people to do. C.T. scans they're really looking primarily looking at calcium and calcium is a pretty dominant feature in plaques. In karate it's also. So as far as from imaging point of view that we sort of have a look at this pretty extensively at the beginning I must say that we really were just looking we really don't have anything fixed in mind of what we're looking at but gradually This seems to be migrating into.

[00:04:02]
The areas. One is to look at something called Fabrice cap which really is showed very nicely of this image here that this is in his stolid G What it's a blue layer of fabric is tissue that separates the lesion Bach in this case to the lumen And if you think about this intuitively you can imagine that if this cap is very strong in this case that it's fairly sick and then a plaque is likely going to be relatively stable in other words is not likely going to rupture rupture in Karate is really is the event that triggers either stroke or T.I.A. is but if you look at the right at the lesion on the right side.

[00:04:44]
This has narrowed movement just like this one but if you were to look at is there really no cap in this case and it's completely ruptured this entire region here is filled with blood. It's into plaque hemorrhage. So if we have a way from imaging point of view of knowing the differences of these two type of plaques we clearly can tell this one will have a very different future than this part here.

[00:05:11]
And then for they are tissue composition. This is a list of tissues that are very quick you will see this very frequently in carotid lesions start from fabulous tissues that may include what I just showed there's a nicely formed fibers cap and also can includes other fibers tissues Interplast hemorrhage lifted a lip it can be fairly complicated because of it could stay as a so-called the free cholesterol that actually is physically in Crystal in shape.

[00:05:44]
And can also be quite cluster Aster and usually Crestor asters can be formed in droplets this means A LOT TO M.R. because M.R. Rather M.R. signal is very sensitive to so-called liquid phase signals but it's not very sensitive to solid a crystal in phase material. So this basically tells you if you have to look at Libya in this case you can get highly variable signals depending on what kind of a class for your sea.

[00:06:10]
Also you have that issues necrotic tissue and callus hims those are two examples again coming from histology of what how messy a planet can be in the carotids. The third area that actually imaging can potentially be used for is used to look at this phenomenon. This is called expensive remodeling that was first reported in quote corner arteries by.

[00:06:38]
By a famous for solitary space in Chicago black off the idea is that when lesions started to develop in the wall. It doesn't really impact the movement at all rather than a lesion grow outwards. And then this process at a later stage will started impact the lumen size and becomes in the stuff I know States lesion was a tight stenosis was a largely symbolic.

[00:07:03]
What is really interesting. It turns out is is if we have a way of looking at the lesion at this stage we're much likely to treat them much earlier in the process and reverse the entire process. So they don't even have to go to this point to this point and with the current that gnostic tools.

[00:07:23]
If we simply are looking at movement. We're going to miss all lesions in the stage and this is this in especially in corner arteries. We're missing a lot of information by not looking at where the non-student So not a part of the artery is. So for us the motivation of doing carotid artery as I have said first is this is an area that the atherosclerosis here is directly linked was a stroke or T.I.A.'s the so-called the transit is skimming attacks.

[00:07:58]
The second one from the imaging point of view is that this art. Trees are rather superficial structures so we can actually get using surface so-called surface coil technology C M R to try to get as much higher signal as possible that can be translated into better resolution images.

[00:08:18]
And the third thing in this is this is an area that the current treatment for advanced lesions has been doing surgery. When you do surgery that the plaque actually is removed from the patients and this is what you see plaque removed from the artery and the vascular surgeons at our institution has developed this technique actually remove the lesion completely intact.

[00:08:43]
So the movement is actually ripped preserved in this case. And once you have the specimen what you can do is actually can do all the histology you want to that that is critical for the images like us because in order for us to make any statement about what we truly see in human artery.

[00:09:02]
We have to have references in this case we truly can use the specimen as the reference to say that what exactly we see in vivo is truly that what we see in this his logic studies of the specimen. This is why that we try to use corral it with the study that if you were to look at all the vasculature is in a body.

[00:09:23]
This is the truly the only art or you can get this from a live patients from other places. You cannot really get very nice specimens like this. And once we do this. We also have developed a pretty extensive way of doing looking at he stolidly. That we basically make the entire specimen.

[00:09:41]
Prepared for histology and then the sections are cut along this entire segment like this. And once they're stained they can be digitized and the digitized ones can be basically of line paper solaces of what issues and forms a three D. map like this. Ard. If you were to compare that M.R.I. images versus the other image of modalities why M.R.I. is better in this case that first of all this is completely noninvasive and then this has very good soft tissue.

[00:10:17]
Sensitivity and also M.R.I. images really if you think about. M.R. signal that M.R. signal is sensitive for to both stationary tissues the most of the brain such tissues and also that M.R. is very sensitive to flowing tissues in this case blood. So you can actually try to use M.R.I. images to highlight where the blood is in the so-called techniques of an M.R.I. and geography.

[00:10:42]
Also you can do an atomic or images to look at the structures specifically in this case that we believe we can actually we should be able to use post the so called a stationary sensitivity and also the flowing information to look at the vessel was more comprehensively. This is a picture of a human carotid M.R.I. and.

[00:11:05]
This actually shows what the lesion looks like an M.R.I. images in this case. This is the internal carotid and this is the extra No carotid if you were to look at the extra carotids it's easier to enter stand. This is the near normal woman and the sister wall.

[00:11:22]
It's a bright ring here is the wall. There's a wall. You should see similar things. If the internal crowded is is normal but rather what you see is a very narrow woman like this right here and then you see this entire region is all field was lesions that's really the plaque bug in this case.

[00:11:41]
Clearly you can see that. M.R. can see a lot by simply looking at the C. image but the M.R. does have plenty of these advantages. The first one is is the scan time tend to be fairly long especially comparing with cities or ultrasound in this case the M.R.I. as you can get images of this type in so.

[00:12:02]
In minutes rather than you can get images if you have a technique you can get images in real time they certainly would be much better. Also M.R. is relatively expensive is expensive. So if we were to. Down the road trying to use this kind of a technique as a screening tool that we certainly will need a lot of engineering input how to make this as a fast effective way of doing the screening.

[00:12:31]
The goal of our research has been into areas. One is that we're interested of distinguishing. Vulnerable plugs from stable plugs so-called vulnerable plugs other plugs that are likely to rupture. And those are usually the ones that cause symptoms. And we hope that by differentiating this two group of plaques we can identify surgical candidates from the announcers who group was a pair quite area and the current clinical standards of using stenosis as the quote here.

[00:13:09]
So we can eliminate some of the unnecessary surgeries. If a patient who has a lesion that actually is causing type stenosis but if the lesion is actually stable then those patients probably should not go through surgery rather than they should actually be treated. Otherwise. And also we're hoping that we can use this to identify those patients who may have a lesion that has not really caused severe stenosis yet but they may have they may be vulnerable to rupture and those patients.

[00:13:39]
If we can catch them early on we can treat them much more effectively. We're also hoping that we can use carotids to predict corner artery disease in some fashion especially that. There have been pretty extensive reports of using ultrasound carotid imaging as a predictor of looking at corner of disease overall that we believe that the direct measurement of carotid.

[00:14:02]
As we're doing with M.R. should have should be a better predictor in this than what our sun can provide of simply looking at the best what they can is. The second thing is in order to do this work effectively what we truly have to do is which really have to provide quantitative in the seas of what we see in a lesion this can be translated in terms of the size of the lesion the volume of the lesion thickness those type of things.

[00:14:28]
Also can be translated into. Tissue composition in the seas such as the percent of limpid and where they are and so on. So this part is heavily image processing based project because that we believe that we have to have a summer automatic way of looking at this and we have to be able to generate quantitative information of what we see in M.R.I. images such that those information can be used to follow patients over time to see that how this process actually evolves over time.

[00:15:06]
This is a series of publications coming out from from from our lab pretty much. Of looking at as this has looked at if you were to look at this that each one sort of a look at a different aspect of the development the this paper was published in the first Nature Medicine issue that was looking at the rabbit model where basically showed in this study that.

[00:15:32]
You can use. M.R. to follow patients serially and you can actually see not only follow them serially Also you can actually see the changes of the lesion was M.R.I. since then we have look at whether we can measure plaque size based on. M.R. and look at specifically fibers cap and also later on we started to look at whether that we can use.

[00:15:53]
M.R. to determine lesion types that this is an American Heart Association's lesion type definition by the we can actually use Emma. Are to also determine those types of so this is pretty as you can see that here that we have basically trying to look at different aspects based on a developed technique of using M.R. to look at this.

[00:16:16]
So I would like to do next is actually talk a little bit about the technique that we're using. First of all that. Because of the carotids are rather superficial. M.R. really is a technique that where the signal are sampled through coils in this case that we built those coil those that try to make them as close to the human subjects as possible that this are the two coils.

[00:16:42]
That is sitting on either side of the patients and you can pretty much place them on a gnat on patients in a surface of this corals are actually flexible so you can bend it slightly by looking at adjusting that to us certain shapes of patients. We also have this pretty nice design headquarters and this actually is an older model of the head holder we have the idea is that you try to place the patients had there.

[00:17:08]
Such that they can really move easily that forward in order to get good images. From patients that one thing that is really critical is that patients remain pretty much still over all this time as I mentioned M.R. tend to be fairly slow and if you have a protocol that will require patients to stay there for not only minutes but up to an hour.

[00:17:32]
You have to have some you can isms to actually control their motion and this had Holder is one of the McAdams turns out to be very useful for us and also that. Having a head holder like this we can actually if we want to scan patients repeatedly we can actually apply placing them onto the same had holder.

[00:17:50]
They pretty much would go back to the same location relative to the first time the second time sort time and so on. By doing those that we have a pretty effective way of tracking the progression of lesions by looking by. Exactly. Examine him over time. This are some of the aspects of Alex talking about a little bit.

[00:18:12]
The first thing is is the issue of flow suppression. In order to do effective imaging of the vessel wall the very first thing that we have to do effectively is to suppress signals from blood that happens to be right next to those lesions. This turns out to be not necessarily easy thing to do as shown here that.

[00:18:36]
There are two images taking. From a normal subject of on the left is the image taking with the technique we call this a double inversion recovered. This was actually introduced by Dr Adelman pretty early on as a in fact a flow suppression technique this on your right is using a standard so called the Flow suppression that usually a manufacturer will provide and if you were to look at this image without having this image around what you will see is this is the common carotid artery of the Left common carotid artery of this normal subject this material here that you see looks very much like a plaque.

[00:19:15]
So you can easily misdiagnose that this is really is pretty extensive plaque build up in this patient in this subject but the subject really is in his twenty's. It's very hard to imagine you have something and even to look at this image here that turns out with this type of flow suppression you have a very effective way of suppressing flow.

[00:19:36]
The reason why this region is so difficult to suppress is if you know a little bit about flow dynamics of the bifurcation region in carotid is this is the region where the flow tend to be circulating rather than it's a streamline flow through there's a region is specially at the carotid ball showing here that the flow becomes stagnate and is circulating within the region this in M.R. is a tremendously challenge place of getting true flow.

[00:20:02]
If suppress the images and at this moment seems to be that the effective way of doing this is. Double I.R. from suppression. The W.R. flow suppression is very good for for the for that point but it is a very slow technique that the normal way of doing this is that you have to do one slice at a time.

[00:20:28]
So if one slice it takes about one minute or so if you want to cover the cross-section areas of the carotids that requires somewhere from ten to twenty slices. That means just to get one set of images. It would take about ten to fifteen minutes. That's extremely long time to do this so we have to validate some of the techniques trying to.

[00:20:50]
Trying to make this faster and this is one of the techniques we use is called modest lifestyle boy are in this case that we can shorten the time four to eight times this are the comparisons of the top image shows what is the traditional way of doing one slice at a time the bottom image here shows that if you were to cut the time by using modern slice and this is saving time you cut the time down four times and this is what you see you get pretty comparable images but noticing that you do suffer certain signal loss in this case by because of the time is shorter time is shorter.

[00:21:31]
This type of modest slice imaging can be. Can be pretty if effective of looking at the distribution of lesions like shown in the cement. This is another one that is basically shows where the carotid says if you were to use rather rather than acquiring images this way you acquire images this way along the artery.

[00:21:54]
This is what you can get this was very nicely worded lesion NS and the distribution of the lesion and also that this type of images for. Us when we do this in our protocol that we use this little point here. This little flow divider as our landmark to really align patients.

[00:22:12]
If we want to do them repeatedly such that each time we do imaging we pretty much bring them to the same location and this type of images of looking at where the bifurcation is to listen to Steve usually is for us we used as primarily as a land to achieve to obtain the landmark this is a different view of looking at it from the same dataset.

[00:22:36]
The second thing we did is that we design a protocol that we believe can actually provide the most useful information about the tissue composition of a plaque we believe that in this protocol that it needs to have at least two types of images one is flow enhanced images.

[00:22:55]
This is what I'm going to talk a little bit about. This is the internal carotids in this case that the system external noticing that extra noise almost disease free in this case internal This is where the luminous and this is a time of light image you see the woman very well where the flow is you also see something of the wall actually in this image that actually turns out to be a fairly useful image.

[00:23:20]
This is the same location on a T. one weighted images in this case blood flow is suppressed. So what you see here is you see dark lumens in internal carotid also dark moments in the external carotid also you see the different. There are different signal features in the indicating different issue.

[00:23:41]
Groups You see in the. In the war this are similarly taken with the prominence they waited and waited and also that flow is suppressed in either one of theirs but you also notice that different tissues appear very differently. Such that if you look to look at a luminous Iranian woman.

[00:23:59]
There's a bright band on T two and it's now. Really looking it is not apparent on any other images. So what this tells you is that in order to get a fairly complete information about the teacher composition that you truly have to look at a different context weightings this was documented very nicely by this publication from from Mount Sinai in New York and also by our group in ninety seven.

[00:24:28]
The thirty area is that. Once you get images like this as a sequence or stack of images of the carotids start from the common carotid going up into the bifurcation and into the internal and external that you clearly can measure areas and this is we have developed a snake based agri isms and designed to track the lumen boundaries and to a boundaries and once you can track those ponderous you can pretty much calculate what is the size of the war and also you can actually use this type of data to generate a whole series of so-called morphological distribution of lesions such as whether the lesion distribution is concentric or is centric by the way that if you think about this in an intuitive way a concentric lesion where deletion is sort of a uniformly distributed around the artery versus if you have a lesion that is very is centric where there are a lot of leaves impute on one side of the lesion.

[00:25:28]
Of the artery versus the other that is centric lesion usually pose much more danger than the concentrate lesion that's just in tooth. In field curative like saying but this type of technique clearly can tell you that by not only looking at this can give you all this quantitative information to describe those.

[00:25:50]
And we have to. In the scan variability study by framing the same patient through the scanner twice within two weeks time and assumption is there are no significant change over this time. And this are what you can get from time one versus time two at different locations from the same subject.

[00:26:08]
What is actually interesting as if you were to look at this location here. If you were to measure the movement of this diseased left carotids in this case where my point is pointing to and then you measure the internal carotid on the right side which is almost completely normal the lumen size is almost identical in this two cases but look at this here that the plaque buildup is fairly extensive already.

[00:26:35]
That this really is a very nice example of the so-called expensive remodeling there the lesion grow outwards first in an artery rather than grow in words. So keep that in mind if you keep anything if you remember anything from the seminar. Is that Snow says doesn't tell you that information at all.

[00:26:55]
So an accurate measurement of Snow says can only give you a very limited information about where the lesion is and what lesion poses a real threat to patients. And this is an overall variability that based on a study of ten patients that was published in. M.R. am in two thousand.

[00:27:17]
Overall that if you were to look at the one point and then the two where it images the volume variations anywhere from three point eight to four point six percent. This has been repeated by many other groups of looking at different arteries and it seems to be the range of variation of while the measurement is of this area.

[00:27:36]
This actually is. A comparing with the existing techniques of looking at. Vessel wall that a real a real technique of looking at vessel war is an intro into a basket of ultrasound that we can you can you can bring a catheter into the. Corner Office to look at this but that is a highly invasive technique and the variability of volume measurement is actually higher.

[00:28:02]
Than this numbers significantly higher. Another thing that we look at also it's based on. Area of volume measurement is we look at whether that limit stenosis as with fun. We we measure clinically versus what we're measuring now we use one parameter in this is called maximal war area.

[00:28:26]
This is very very simply right from a stack of images looking at which location has the maximum area pluck area in this case and this usually is labeled as a plaque burden and we look at thirty seven patients and it's all obtained from weighted images and a question we ask is this the information of the gnosis as reflected as the minimum woman area and the maximum war area.

[00:28:52]
Do they correlate with each other at all what this shows is this is the distribution. There is a pretty weak association between those two with the R. value of only point two seven What this tells us is is a placard really is an independent measure of lesion severeness versus what the Gnosis is providing as I have been emphasizing that this is.

[00:29:18]
We are looking at a completely different set of parameters. They are directly measuring the lesion rather than that. So Gnosis is in direct measurement of lesions. And then the other thing as I mentioned is we try to use this so-called contrast M.R. images to see whether we can actually determine different lesion types based on age definition of lesions and this is what we can.

[00:29:49]
This is some of the sample images of normal or early lesions. I think within the space resolution we can get of M.R.I. images we really cannot tell the differences of an absolute normal artery versus a. And that is a very early sign of those usually those are labeled as a fairly straight in the deposit in the arteries and we cannot tell the differences of those two.

[00:30:11]
So we combine those into one group. And their appearances are shown here. Basically it's a wide open dark lumen and you see relatively uniform bright ring that surrounding that that's a sign of a relatively normal artery. And then you can also look at almost the other side of this is the more advanced lesions.

[00:30:34]
This is a type six lesion in the Ha definition. This is where the histology shows of what this looks like the major part of lesion into plaque hemorrhage. And then there's a cap actually formed here that actually is. It's not very uniform but it's definitely exist. This is what you see on time of images.

[00:30:57]
Interestingly that this region where the hemorrhage is looks about as bright as what the movement would look like. So if you don't have black blood images like this to tell you that what this is this image the people may actually interpret this image by saying that there are two lumens in this the flow is thrown there and also there but this region really is hammering edge and it's actually that showing very differently on the other contrast weightings.

[00:31:28]
So based on images of this this type and also based on a. Ha. That line guidelines of lesion types. This is what we come up with what M.R. can do. This is the lesion type start from relatively early or normal to up to the type eight type A is a highly strung Arctic.

[00:31:51]
Fiberoptic lesion. And if you were to look at the sensitivity and specificity of each group start from Type three to type seven. We have very reasonable. Sensitivity and very high specificity of detection. The only two groups we have relatively no numbers. I want us to type one and Type two and the other one is type six.

[00:32:13]
The reason we believe of this relatively low number on sensor sensitivity on those is because we don't have enough samples this are taking from patients who have had surgery. So we are truly looking at a very biased group of lesions and if we started looking at a group of our subjects like like you guys sitting in this room.

[00:32:36]
We should see a lot more in this group relatively normal cases. This is a technique that we have been using to look at Fabrice's cap this primarily is a time of flight based technique and if you look at the images on your left. This is the lesion and this is where the luminous and this is where the warp Andriy is in between Newman this relatively bright signal.

[00:33:04]
You see this region that actually has giant bright signal in this region it's. Indicating this actually is hemorrhage again but separating this area to that area there is a dark area that is separating the two this we pretty much figured from the his stall A-G. that. That this is a layer of Fabrice cap.

[00:33:25]
Or the fibrous tissue that separates. Toolman on your right here is another lesion that this is where the Lumineers and this is where the origin of war is. This gray area is the lesion Pollock. And if you were to compare this image versus that's an image you realize that the start band sort of this is not visualized we usually label cases like this where the movement boundary is still relatively small.

[00:33:53]
But we cannot see the start band as having a thin fabric kept in other words that the cap's thickness is within it's below the resolution of the spatial rest rules. One of those M.R.I. images we can get. This is a comparison of what we see in M.R.I. images where we see in his stall a gene in this that this is the woman and this is the plaque and you see there's a little area there dark band becomes discontinued right here.

[00:34:22]
This is where his knowledge shows. That's exactly where the site where a rupture actually has happened. So it's a very nicely correlated study in this case. What is more interesting is that we based on this kind of M.R. quite here years of simply labeling lesions into three categories as ruptured kept think kept and also think Cap we look at whether that this information we get from M.R.I. images actually correlates with the patient's symptoms when they're having surgery.

[00:34:52]
This is the study that we looked at fifty three patients. Among those twenty five are asymptomatic and twenty eight are symptomatic they had a difference of this is really that patients at our institution that whenever you have a stenosis over certain level for example if it is seventy percent stenosis regardless whether you have symptoms or not symptoms all those patients will be operated on.

[00:35:18]
That's why we have a fair amount of a cinematic patients in this group and we categorized the Febreze cap based on what I mentioned as a Take care thin or raptured cap. This is the overall profile of this to two group of patients. They age the gender smokers and also the.

[00:35:39]
If you look at whether they are diabetes hypertension and whether there's. Other product this is the most interesting one in this group really is the house the Gnostic others lesions based on a doppler ultrasound reading. None of this showed any significant difference at all between these two groups.

[00:36:03]
And this is what you see based on capped readings that we see in M.R.I. was if a patients carotids lesion that we after the exam the entire lesion we conclude that. The fabric kept exist and also it's thick. It's a thick cap only nine percent of these patients have had symptoms but on the other side.

[00:36:28]
If we identify a patient had a ruptured cap simony percent of those patients have had symptoms. If you were to look at this in a different way of looking at the odds ratio of a patient who have a thick cap to have symptoms if the odds ratio is one that is twenty three times more likely to have symptoms if the cap is ruptured.

[00:36:52]
So this clearly shows that with this type of M.R. imaging work airing. And we're getting some very useful information about plug stability by ship simply looking at what the cap status is. The other area that is seems to be very interesting is to use contest agent in studies.

[00:37:17]
There's actually in this case there's a three different patients. And we use identical contrast agent is clinically available as a magnet. What is the name of this man. Meghna versed. But if you were to look at this three lesions. It shows three different effects in this case the lumen is right here that it's very teeny and then you have a giant plaque next to it.

[00:37:48]
The layer next to lumen is significantly enhanced in this and then you also see the Evan tissue layer enhanced in this case. This case is even more interesting that. This almost is a stereotypical so. Unstable pluck. The shoulder region of the cap actually has ruptured in this region there are pretty extensive Michael vassals beauty into this region has a significant enhanced mint and this region is almost completely now being Hansing and this is the limited rich region.

[00:38:19]
So by comparing this image and this image you can actually get a fairly extensive a picture of what the lesion the tissue is the third one is it's a relatively early lesion and you see that there's a pocket of enhanced been shown in this area region there also this little band that is completely nodding and seeing.

[00:38:39]
So this contest enhanced mint in this case clearly that helps one is to look at to see improved tissue contrast to is that this terrible image may actually tell you something about the activity levels within the lesion that astri flatted by the distribution of Michael vassals. This is a timeline of how we do the study that we do a pretty contrast M.R.I. as a Tier one weighted and then we do a dynamic M.R.I. I would show some data to serve very briefly.

[00:39:14]
And then we do post contrasts M.R.I. but usually it's a three minutes after the time of injection. And this is the parameters that we used in a study. This is what you would see in a dynamic phase of injection. This is pretty contrast and you see the contrast get in at this time.

[00:39:31]
That's usually correlate it's a corresponding to the second time when we do the dynamic study and you see this actually these signals from lumen washes out fairly quickly and gradually goes away but if you were to play this as a movie. You actually were see that there are different faces of enhanced when in the wall they become visualize.

[00:39:53]
There is shown here that. But before we can actually used to stand I make data in a five effective fashion. We have to. Deal with problems like this. This is how much motion. You will see during. Injection. By the way this is supposed to supposedly the patients supposed to hold still.

[00:40:14]
And this is a three minute study and this is what you see as a motion certainly this is a this. This is a this is not a terribly terribly good patient as far as keeping him motion still keeping motionless. But we have to deal with this if you want to truly analyze the data so current Bill Cohen that he is he's currently Actually it's a faculty in the lab now that developed a technique that can actually future this type of motion out from the data such that a pixel based analysis can be used for that.

[00:40:50]
And this is what we find from. From a study that just published in circulation recently is we look at the fractional. Vascular area as determined by histology in this case we simply just measure. Michael Vassell as we see in the his knowledge a map and add all those areas up as a fractional map area map.

[00:41:14]
This is where we can get so-called A Connecticut modeling use M.R. data dynamic data as a fraction of blood volume seen within the plaque and we showed based on this many cases I think this is twenty something cases. There's a pretty strong correlation between the two. What this tells us is that the dynamic.

[00:41:34]
M.R. study can probably provide information about not only where the medical vessels are also the how extensive are the Michael vessels whether that you have a lot of them of whether you have very little of them in other words we should be able to you based on this kind of accreditation to gave not only where the Michael Wessells exist and also the extensiveness of those medical vessels.

[00:41:59]
And then we also look at the concept of. Suppose we look at so-called delayed ing handsome and if we follow patients over a twenty minutes of time whether the enhanced when we see in the Namak face versus indeed delayed phase we're going to see differences this again is a lesion that is showing here.

[00:42:19]
On the left is the NOMIC data. This is what you see of the enhancement start from the woman to the war. You also see the evolution of the enhanced Mint within the wall and then on this image here. This is delayed enhanced min of data taking from three to twenty minutes minutes by the way that in this case we use a technique we call this a quote Dr inversion recovery that idea is you can have effective flow suppression.

[00:42:50]
Regardless of what the key. One is of the blood. It's turns out to be fairly effective of for this type of occasions. So looking at this two sets of data that you can tell pretty clearly. The information we're getting from so-called dynamic phase versus the delayed phase actually are quite different and we at this moment are analyzing this type of data and we don't really have.

[00:43:17]
Conclusive answers. Carotid all those are carotid arteries. The last thing I'd like to talk to spray flee is that we have a span almost. I would say that within the lab half of the people are considering this type of work is trying to quantify the information that we get from those images those smaller contrast images.

[00:43:44]
This is the ultimately what we want to see is we can get images like this from different contrast weightings we hope that we can integrate all this information into a map like this this not only will tell you where the different tissues are this will. Also tell you the size of them and their distribution and this is ultimately where we want and we have been developing a system called.

[00:44:11]
Quantitative vascular analysis system that that was this as the major goal. At this moment we have capabilities of looking at areas volumes is interested is and listen to is to be. And also that we have a pretty effective what thickness measurement algorithm the idea is that. If you can get aluminum boundary traced and if you can get out of a boundary traced this algorithm can give you automatically what the water thickness is where the maximum thickness is and the minimum thickness is and also the to mean across the entire artery and also that the nice thing of this algorithm is that this is not dependent of the size of the.

[00:45:01]
Of the lumen and also of the other were boundary they could be of arbitrary shape. If you were to think about this from a theoretical point of view is thickness definition is primarily coming out from circular subjects that whenever you say thickness of a war. There's some fairness they have to be circular or at least the worst case is some kind of oval shape.

[00:45:22]
That's where you can pretty much stop once this becomes arbitrary shape the thickness measurement becomes pretty much on definable because of the especially if the movement is actually of some kind of funny shape. It's not a circular oval shape at all but this algorithm can actually handle all those cases to give you a company hand to give you an answer that actually is in agreement with what a human would like to agree upon.

[00:45:51]
So I think it's a pretty nice thing to have. I would like to to finish my talk was two recent images that we have showing one case is showing progress. Ssion of lesion this is a patient that we have followed over a period of eighteen months and this is the lesion you see at baseline and this is the lesion that we see at eighteen months between this time patient has developed symptoms and this is so the patient was had a surgery and this is what you see in the solid gene that correlates very well of this lesion and we are actually doing a study that it's a natural history study to follow patients this way to see that over this time.

[00:46:32]
How does the lesion actually progresses from a type whatever to or a second a more advanced lesion and how that what what physically has happened over that time those information have not been available. Up to this point. The second one is actually a regression study that this again is a patient actually is taking statens is cholesterol lowering treatment.

[00:46:59]
This is what you see at time one and this is what you see a time to in between this time. This is only about half a month half a year time and you see that there are pretty significant changes already happened especially at this location here that illumine is why wouldn't you almost feel like that part of the plant has washed.

[00:47:19]
Washed out that is basically is depleted from the artery. What is also interesting as you actually see is there is some evolution that has happened within this region this at a time one or two pieces of calcium. That is separated by some other materials in the middle that time to this two pieces of calcium actually has pretty much merged into one piece and whatever the material in the middle has basically disappeared in this and this basically becomes a heavily calcified lesion with this treatment and also the calcium seems to be have evolved from a piecewise into a solid chunk in the US This again is a study.

[00:48:02]
The at this moment it's an ongoing so we simply say that we can see this type of changes in by looking at M.R.I. images and the implication of this at this moment. Certainly is is is going to be something that very interesting to look at yes. We used by for cation as a landmark to realign patients.

[00:48:27]
Each time. That's why the when we do a. Do a study showed a carotid artery that is actually launch student know where you see the bifurcation we always go back to that bifurcation each time when we do our political by saying suppose if you want to do fifteen images we ask that the savants image always is where the bifurcation is by doing this.

[00:48:52]
It has been fairly consistent where you can get each time in the. In a progression or regression studies. So in summary high resolution M.R.I. with the application of face to record lows and also the combination of using black and bright blood techniques that we are able to look at a list of different tissues and different aspects and I think that.

[00:49:25]
Most of the so-called information up to this point about what a vulnerable plaque means is coming from histology. What this is giving us is that now we have a noninvasive tool we can actually follow patients over time to see that what has truly changes in real patients and we're hoping that with this type of techniques and with quantitative information about this different type of tissues we should be able to come to a point of that it's an imaging based vulnerable plaque definition that can be used clinically for better.

[00:50:02]
Or for people selection of patients for proper treatment. And then this is I would I would like to acknowledge the group of people that work with us that. This clearly is a moderate disciplinary project involve people from radiology for solid G. electrical engineering and also statistics consulting and then.

[00:50:25]
This is the group of people that we work with. And it's funding is coming from and I and also from pharmaceutical companies. Thank you very much. Thank you thank you. We don't date on Tier one. We. I think that. If you if you look at the younger generation of patients that are getting it is more important for this type of patient most of the patients we do are in their sixty's and seventy's that arteries are hardened enough that.

[00:51:08]
They don't move much at all during the doing the our heart contraction. With the resolution is the pixel size of most of those images you see our point two five point two five millimeters. And I think. Two millimeters thick section of image and that's the pixel size but that is after the interpellation was a so-called zero padded for your transformer.

[00:51:41]
So the real resolution is point five millimeter in those images. Yes. Yes. I think carotids is whatever we get is pretty much optimized it doesn't really buy by giving more we have actually seen as with design those coils those coils were first published in ninety six we have actually looked at different designs whether we can improve the scene.

[00:52:35]
No we have not been able to actually for whatever reason the first round of design actually turns out to be the optimal design but three T. for sure will help. We have actually just gotten some reason images was a duplicate design of the coil that works on free T. we got beautiful images at the first run.

[00:52:57]
So I believe that treaty will definitely help. I don't know what would happen with seventy in this case or higher field for carotids I think that these subjects are relatively superficial So maybe beneficial but you also have to do is this is an area that you have a lot of interface.

[00:53:16]
Of between bones airs fat and so on so that the the assists have the ability would become a real problem in that area. I think my my motto of course is I believe that in twenty years time but you can't quote me as that every patient will wear a clothes that is choreo build and then when they are getting into the scanners you just flip around different course at different body parts and you get this.

[00:53:43]
So in that sense I think this. Coil Monaco design will probably pay peepin official for certain aspects of this. They they probably should. Yeah. I think that's actually it's a very interesting question. I I believe that calcium cannot be interpreted in one sentence. It can be I believe that if you will.

[00:54:34]
I don't know whether you follow the lead to assure that. Reign over money public I think it's almost viewed as the for solace now doing rascal of Allergy and looking up and. Her data showed in corner arteries that they're pretty significant proportion of patients actually the cause of death is because of calcium happens to be on the surface of the arteries those.

[00:55:02]
And. But there are also data showing that calcium seems to be is the is the healing process even remodelling and it's you know if you see calcium is is already at a later stage of lesion development and we believe that. This should actually be looked at in in many different and goes.

[00:55:23]
I believe that certain type of calcium smear be good. Certain may actually be bad. I can imagine that the plaque was. Was solid chunk of calcium at one place and neighboring with a soft plaque on the other can be stable because you have this pretty mechanical stress right in the face there.

[00:55:43]
I was hoping you wouldn't get there but. But that's then nobody knows that could clearly that. Calcium is changing. When you have started treatment and was the fact of that at this moment I think it's remained to be seen. Yeah. So. Here. I think it has a lot to do with that.

[00:56:44]
I think that that. That seems to be it's a very strong area of. Charge attack in Emory here. That should really be studied and it's I strongly believe that has to be the impact of this cannot be just into. The if you believe that lesion the so called The early development has everything to do with the flow dynamics and the share stress of the area and then your say this has nothing to do one solution develops as just not possible.

[00:57:21]
I think it's it's definitely going to be interactive. People should find out. We'll find out that it's an interactive relationship. Thanks.