Charles Matouk, MD, chief of neurovascular surgery and associate professor at Yale University talks about how magnetic resonance vessel wall imaging can help identify aneurysms.
What are some of the traditional ways that you treat stroke patients?
Dr. Matouk: For many years, the only treatment that we had for patients that were coming in with acute strokes was a clot busting medication administered intravenously through the veins. That was called TPA. It is still used today and remains the standard of care. There are several problems with intravenous TPA, but the main problem is the time window. The amount of time between when you have a stroke and when you must administer the medication for it to be safe and effective is ridiculously small. In the U.S. we say about four and a half hours from stroke onset or symptom onset. So, the type of symptoms that somebody might have are weakness or paralysis on one side of their body, an asymmetric smile, have trouble finding the words or understanding people, and maybe have vision loss in one eye, those types of problems that would indicate that a stroke was happening makes the timer start, and you have to get a patient to a hospital, get a CAT scan, have a neurologist, and somebody that’s capable of administering an intravenous TPA available at that hospital 24/7 for the medication to be effective. So you can imagine that the number of people that were eligible for this therapy was very small, especially in rural communities or in dense cities like New York where it’s very difficult to get from A to B during the day. So, that is one disadvantage of the intravenous TPA. The second disadvantage was that it was much more effective at breaking up the medicine, and small blood clots that were stuck in smaller blood vessels and it was less effective at breaking up bigger blood clots stuck in bigger blood vessels. So it was better for small strokes and not as effective for big strokes, the type that would leave someone disabled and have them go to a nursing home, take them out of the work force, and take them away from their family. So that has been available for over 20 years and it remains available to many, and it is highly effective. But again, the number of folks that were eligible for this type of treatment was relatively small. In 2015, there was a series of five papers that were published about randomized controlled trials on different continents and different countries that showed you can mechanically remove the clot from the person’s blood vessel, especially for big blood clots that are stuck in the blood vessels. That is what the papers in 2015 demonstrated. It really changed the standard of care in the U.S. and around the world for how we manage acute stroke patients, because now we have another therapy that is potentially a tremendous benefit to patients. The other advantage of this therapy is in select patients you have a much longer window of opportunity to act. So, in carefully selected patients, you can have up to twenty-four hours after stroke onset as opposed to only four and a half hours for the intravenous medication. That really increases the number of folks that are eligible for this type of treatment. It is a watershed moment in acute stroke care. Those papers were published in 2018 and now in 2020, we are all having to react to this new reality and the public has to be aware that like a heart attack, when you’re having crushing chest pain, everyone knows to go to the hospital because you are having a heart attack. Now, folks know that if you are having stroke symptoms, there is something that can be done about it but the treatments are time sensitive and you need to get to a hospital that can treat the stroke.
With that as background, can you talk to me a little bit about the procedure?
Dr. Matouk: First, let me describe how a typical procedure is done. 90 percent of the time, we navigate to the blood clot in your head from the groin. That is our standard access, and it has been like that for years. It is a large blood vessel, and it is a forgiving vessel so if there is a problem it can be corrected, and you do not have some major problems associated with it. You can get big devices in through that blood vessel. We navigate using a using an X-ray machine to guide our catheters and wires from the leg into the blood vessels in the neck, and all the way up into the blood vessels in the brain then we can use either an aspiration catheter, which literally sucks the clot out like a vacuum type system or we can deploy a stent. The stent sort of grabs on to the blood clot and when we pull the stent out, hopefully the blood clot comes with it. So that is the standard approach many folks are using around the world and it is that approach that was validated in the clinical trials in 2015 and 2018. A lot of folks that have strokes are older, they are in their 80s, even in their 90s and this type of treatment can be effective at making potentially big strokes into much smaller strokes that folks can recover from. The problem is, as we get older our blood vessels become twisted, and they become more difficult to navigate. In some folks, it is impossible to get from the leg through all the blood vessels in your abdomen and chest and to the blood vessels in your neck to remove the blood clot. It is a shame when you must give up on the procedure or the procedure takes hours because now you have now lost time and it is also a time sensitive procedure. So, a few years ago, we decided to bring back an old technique called catheter angiography. Catheter angiography was typically done by neurosurgeons and it was done by a direct puncture in the neck. We moved away from that because if you damage the blood vessel in the neck that supplies the brain, that could lead to a stroke. But with all the advances in catheter technology and access technology we thought bypassing all the trouble and going directly through the neck would be beneficial to folks. That is essentially what our paper showed. When we converted quickly to direct puncture of the carotid artery and then put our stroke tools directly through the artery, folks did much better than if we gave up and did not even try. We stopped the procedure and said, we cannot do it. That is the major finding of the paper that we just published in the Journal of Neurosurgery.
How many patients did you look at?
Dr. Matouk: We looked at roughly 20 patients with the direct carotid puncture method. We compared them to folks that came in with strokes that we tried to go up from the leg, but then we aborted because we just could not do it. So, when we compared those two groups, there was a clear benefit to trying, even though it is a riskier procedure, because it is a more delicate blood vessel than the one on your leg.
Which patients benefit the most from this procedure?
Dr. Matouk: It is important to note that we are not advocating this should be the way the procedure is performed. This procedure is very well suited for folks that are older and have a diseased vascular anatomy. For example, some folks have no blood vessels. The big blood vessels in their legs have collapsed or they are occluded because of disease. Those folks would not be eligible for the standard access route. Other folks have extraordinarily complex aneurysms or even an occluded aorta which is the big blood vessel in your abdomen and chest. For those folks, this traditional way would not be available. So, for those patients, this would be one of the only alternatives.
What percentage of patients would this be appropriate for?
Dr. Matouk: It is about 10 percent, which is a significant number.
What are the risks for the patient?
Dr. Matouk: The major risk happens to be in how and when we take the catheter out. We had one patient die after a successful procedure because she had bleeding from that side. We have since learned that the best way to plug the hole is by holding pressure. If you hold pressure for 20 minutes, that seems to do the trick. We do this with the patient asleep and a breathing tube in their mouth. The advantage of that is they can stay overnight and give their blood vessel a chance to heal. So that is the protocol that we have adopted and published in this recent publication.
Are there medical and research centers that are using this procedure?
Dr. Matouk: I think in extreme situations many of the large academic centers. The University of Buffalo which is a large neurosurgical center, has published about this technique or a version of the technique. What we are proposing is particularly novel. We have some modifications of the technique itself, but it is integrated into our standard workflow. So, it is not only for patients where the leg vessels are completely occluded but it is also for patients where it will be difficult to get from the leg into the head. This is exponentially safer and faster than struggling for an hour or two trying to get there from the groin.
Have there been aborted procedures?
Dr. Matouk: We had one patient where we aborted the procedure early. There is a bit of a learning curve in understanding how to get the catheters in safely. So, for those patients, it is just too bad. They are now trying from the arm and that has its own issues. But it is nice to have options so if one way does not work, there are other options we can use.
How does Yale do it differently than the other centers?
Dr. Matouk: One of the ways that we are different is that we only spend 10 to 15 minutes from the groin before deciding that we are not going to pursue this technique anymore. Then we do a Trans Carotid technique. So that is one of the main differences. The second difference is the integration into our standard workflow. This is not something where we are scrambling to get the right equipment or saying what goes with what. We have a protocol for when to decide to do it, about what equipment to use and the actual technique. So, we puncture in the same place every time and it is something that we have given a lot of thought and consideration to. For example, the carotid artery bifurcates is devised into two in the middle of your neck. One artery goes up in your face and the other one goes up into your brain. We puncture much lower down where it is a larger vessel, a common trunk in a space that is formed by the triangle. It has the borders of two muscles that attach to your breastbone and your proximal collarbone and that creates a very convenient space where we are going to miss all the nerves and veins that case through your neck and gives us easy access to the carotid artery. So that is one thing we have introduced as a standard technique.
How quickly can you get from puncturing to accessing the clot?
Dr. Matouk: From puncturing to accessing the clot, it can be anywhere from 5 to 15 minutes in a procedure that would have potentially taken more than an hour.
Is there anything else I did not ask you about this procedure that you would want our viewers to know?
Dr. Matouk: The big thing is we have a procedure that can remove clots from the brain very efficiently. The technology has advanced to a point now where 80 to 90 percent of the time we are going to be able to remove the blood clot from your brain and potentially make a big stroke into a little stroke. What we are proposing is another option so that patients that would not be able to benefit are now eligible for the procedure. It increases the number of folks that are eligible to get better after their stroke.
What is vessel wall imaging? What does the procedure entail?
Dr. Matouk: It is a technique to look at that blood vessels in the brain. The traditional ways we look at blood vessels would be a C.T. angiogram, MRI (magnetic resonance angiogram) or a diagnostic catheter angiogram, which is an invasive procedure. These techniques essentially look at the inside of the blood vessel, so the lumen of the blood vessel or the inside of the pipe. It is ironic because we are really interested in looking at what becomes diseased in the wall of the blood vessel. Until about 10 years ago, we were not able to see images of the wall of the blood vessel in a dedicated way and that’s in part because the blood vessel wall is so very thin and also because the blood vessels in the brain have a lot of twists and turns. That is difficult for imaging to deal with, especially when you are focusing on the vessel wall, which is such a small structure. About 10 years ago two groups came up with protocols on how to image the vessel and one of those groups was Johns Hopkins University. The other group was from the University of Toronto in Canada, which is where I trained and there is a diagnostic radiologist there David Mickolus who helped develop the technique. They started to look at several different disease processes using Bezalel imaging. What they were most interested in was after atherosclerotic disease, the thing that affects your heart or affects the blood vessels in your legs, can also affect the blood vessels in your brain. I trained there as a neurosurgeon and as an interventional neuro radiologist and I was exposed to some of the research going on. When I started at Yale in November 2011, we adapted that technique and looked at my neurosurgical interest, which was brain aneurysms. No one had looked at brain aneurysms using vessel wall imaging and when we did, we were shocked by some of the results. We saw that things that looked the same through traditional imaging techniques that look at the vessel lumen can look quite different. The reason that is of interest in the aneurysm community is that aneurysms are quite common. About one in a hundred folks walking around have a small brain aneurysm. The risk of a small brain aneurysm bleeding which could be catastrophic and even potentially fatal is exceedingly small. So, small aneurysms have a small risk of bleeding and bigger aneurysms have a higher risk of bleeding. But the paradox is that when folks come in with ruptured aneurysms, the overwhelming majority are small. So, small and ruptured aneurysms have a low risk of bleeding, but most ruptured aneurysms are small. So, there is a disconnect and the question is, can we identify which small aneurysms are most at risk of bleeding? The research that we and others have conducted over the last 10 years have started to build a story that vessel wall enhancement can be taken up by the aneurysm wall in unstable aneurysms and stable aneurysms tend not to show that vessel wall enhancement. That concept is coming into maturity, as many groups around the country are studying it again. Good examples would be the University of California, San Francisco, Johns Hopkins, and University of Toronto. There is also a group in Paris and a group at the University of Iowa. I think they have really pushed the story line.
So how would it work?
Dr. Matouk: You would come into the hospital and we would use your clinical grade, just the usual (MRI) magnetic resonance imaging that you would get done on your brain. There are two MRI’s that are in clinical use. One is called a one point five Tesla magnet which is a low strength magnet. The other three Tesla magnets must be done on a three T magnet because you need a stronger magnet to help resolve that very thin wall. But it is the same magnet that is available at most hospitals across the U.S. The nice thing about this technique is that it can be made universally available to any hospital that has a three T magnet, which is most of the U.S.
Would patients have something injected?
Dr. Matouk: Before the scan is conducted, you would get imaged without anything being injected and then we inject the dye into your hand. That dye can be seen on the MRI scan and then you are your rescanned. This all happens when you are in the magnet itself. But it is a standard technique that is done for all different kinds of brain pathology. But the physics trex that the MRI sequence employs is really geared to looking at the vessel wall and then you can detect the enhancement. So that dye that we are injecting will get picked up in the wall of this very tiny two to three-millimeter aneurysm in your brain.
When you are looking at the image, is it clear evidence?
Dr. Matouk: It looks like a light bulb. When you look at an MRI scan it is black and some shades of grey. This will look like a little very bright white glowing rim, almost like a halo around the aneurysm. It is very conspicuous and very evident to the naked eye.
The ones that light up tell you what?
Dr. Matouk: We are learning what it means but what it means from a clinical standpoint is why does the vessel wall enhance? We think it has something to do with inflammation, but we do not know for sure. That story is still being written. What we do know is if you have evidence of bleeding in the brain, have multiple aneurysms and do not know which aneurysm bled this technique is extremely useful in figuring that out because the aneurysm that bled almost always enhances. It glows like a light bulb. So that is extremely helpful in the clinical context because you are going to target the right aneurysm. In the case of enraptured aneurysms, it is very unusual for a small and ruptured aneurysm in the brain to bleed, but also to enhance. An exceedingly small fraction enhances. We have looked at thousands of aneurysms all over the world and that phenotype is unusual. There are studies that are ongoing and published that have shown that you are more likely to have an enhancing aneurysm if you come into the emergency department with a severe headache, and no evidence of blood, which is very interesting to me, because that probably means the aneurysm is acting up. When we look over time at enhancing versus un-enhancing aneurysms, enhancing aneurysms are more likely to grow. When we look at the shape of aneurysms that are enhancing, they are likely to be bumpy as opposed to smooth, which has always been a high-risk feature of aneurysms that have a high risk of rupture.
What is the implication for having a tool like this?
Dr. Matouk: The treatments for aneurysms, unfortunately, are not benign. So, whenever you are in someone’s brain, whether it is through the blood vessels or by opening the skull bad things can happen. So, you do not want to put people in harm’s way of a procedure when the risk of the aneurysm causing a problem is extremely low. The implication is if we do not see enhancement and the aneurysm is small, then maybe those are aneurysms that can be safely watched. Whereas if you have a small aneurysm, but it enhances, that at least informs that this is one of the rare small aneurysms that has a high risk of acting up. We already know from some papers that they have a higher risk of growing over time and there are a few papers that show they might even have a high risk of rupture. So, this is information that can help the conversation with your surgeon about whether the risk of a procedure is warranted.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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