The hosts walk through Zhen Xu's 2004 paper on controlled ultrasound tissue erosion, her first major publication as a graduate student at the University of Michigan. The work targeted hypoplastic left heart syndrome, a congenital defect where the left ventricle and atrium are underdeveloped and the valve between them may not even be connected, by testing whether focused ultrasound could open a hole in the atrial septum without a cutting instrument. Using canine models, the team varied pulse duration and repetition rate and found that short, intense pulses eroded tissue precisely through cavitation, creating bubbles that expand and contract to mechanically break tissue apart, in contrast to conventional focused ultrasound that simply heats and cooks tissue. Doppler ultrasound imaging confirmed blood flow through the newly created openings, showing the mechanical erosion approach worked in the model organism.
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The paper appeared in an IEEE conference proceedings and was explicitly experimental, not a clinical treatment.
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The heart's left and right ventricles each pump blood through one circuit (lungs versus body), so a nonfunctional left side leaves only one working pump for the whole system.
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Doppler ultrasound works by detecting red and blue shifts from moving fluid, the same red-blue shift principle used in astrophysics to detect motion.
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5:58So for this segment I wanted to go through five papers that Chu co-authored along her journey from um the 2004 all the way till now. She is obviously the um a professor now at the University of Michigan, but she's actually also an alumni. She did her masters and her PhD there. And the story starts when she was a graduate student at the University of Michigan. Obviously, the University of Michigan hired her cuz they're like, "Yeah, >> she's going to win the Golden Goose Award one day." Um, so it's an early experiment where you have to control cavitation and then try to figure out how it's going to actually work. Right? So the first paper
6:40we're going to look at is in 2004. This is the um original paper that kind of puts her on the map. The original medical problem was hypoplastic left heart syndrome. you alluded to this with um the idea that some newborns the left side of the heart is severely underdeveloped and if the partition you can see over there on the left is a normal heart >> and on the right hand side is a heart with hypoplastic left heart syndrome. The left ventricle and the and the left atrium are much smaller than the right hand side. Right? And the way the heart works is you need both of these ventricles to pump blood in and
7:21out of the lungs, oxygenate it, and then put it back, right? There's one pump for the entire body, and that's the heart. And if the pump has like two motors you can think about, and one of them is missing, it's not very good. Y >> on top of that um the connection valve between the atrium and the ventricle often times it there's no hole >> like they're not even connected. So so >> it's it's very very difficult to even have a normally functioning heart right and that's why hypoplastic left heart syndrome it's a defect of where the the structures on the left hand side are hypoplastic meaning very small or not even formed at all. Okay. So what what
8:04we'd like to do is create a little hole in that valve so that it becomes a valve and it can open and close. Okay. So Ju's group asked whether focused ultrasound might make an opening without putting a cutting in instrument through the tissue which makes sense. It's basically can can we change the structure such that the functionality we're looking for is is a possibility. Yeah. without too much second and third order consequences or damage to the other surrounding areas. >> Yeah, that's right. And in 2004, they have this paper that comes out controlled ultrasound tissue erosion. It's in the ITE E um conference papers.
8:45And the paper does not establish a clinical treatment. Okay, it's just doing experiments on a model organism in this case canines. Um before the bubbles, let's just think about sound waves. Okay, so ultrasound is a soundwave. It's a sound wave is an oscillation in pressure and at at a point in tissue you can focus all the pressure and the pressure alternates between like some ambient value and then above and below that ambient value. Um you've you might have heard about um ultrasound therapy for cancer for example. So in this case what ends up happening is you focus the ultrasound using a transducer into a tumor and those pressure
9:28amplitudes are there away from the region they're not there. This is called acoustic focusing because you're taking sound and you're focusing kind of like a lens. Um and in this conventional focused ultrasound treatment the usual picture is heat in the middle. You just want to heat up that tumor and like burn it off literally, right? Um the tissue absorbs that acoustic energy, the temperature rises, and then the sufficiently hot cells die off. So perhaps you can kill the tumor that way, right? >> Mhm. >> Zu's group was after another outcome. They wanted the tissue to disappear from a very sharply defined region, like an actual opening. You don't want to merely patch the tissue that's like destined to
10:10die later. You want to literally open it up. M >> you want to destroy the mechanically rather than cooking it in some sense. >> Right. And you want it to be precise uh in in 3D space because you're trying to create this opening. Exactly. It's not just some generalized region. >> Exactly. And so their experience they made did a bunch of experiments where they um varied pulse duration, how often the pulses are repeated. um very short intense pulses they found delivered at suitable repetition rates eroded the tissue very effectively and you could see this effect happening. You could see in in the model organisms you can see they're creating holes in the atrial
10:50septum and then on the right hand side they use Doppler ultrasound to observe flow through it. Um, for anyone who has um been lucky enough to um you know have a have a child, you recognize the Doppler ultrasound. That's like when they you look at like the you literally use the Doppler effect. This is something that I saw when I was in the hospital like looking at the um you know the fetus that ultimately became my child. Um, but you can you can look at you can visualize blood flow by look using the Doppler effect to see like stuff that's moving out and stuff that's moving in. Like there's literally you can observe red and blue shifts and and the color coding is red and blue for
11:32like stuff moving away from you and stuff moving closer to you. And I was looking at that going that's pretty cool. That's pretty cool. Right. Usually I I you learn about that stuff in astrophysics when it's like red shift, blue shift, stuff moving away like but here they use the same colors >> to to to show um like movement of fluid >> and and so just briefly as we uh particularly for some of our audio listeners, we're looking at two sets of images. The one on the left is showing basically a before and after >> of this approach of the actual physical tissue. >> Yeah. Yeah. I think these are both after actually. the both after where it's now >> creating >> you're creating these cavities like literal holes in the tissue and on the right hand side you're using the Doppler
12:13effect to show that fluid is moving through that tissue >> which is ultimately the functionality that you're trying to restore >> exactly um and and the way they do this is with cavitation. So cavitation is the idea of um using sound waves to create a bubble and then precisely maneuvering that bubble, the size of it and so on and so forth. And it's a intuitive distinction between cooking versus mechanical disintegration which we talked about earlier, right? Cooking is what we do with the traditional ultrasound therapies when we want to just like heat stuff up. Here we're using a bubble to like expand and contract rapidly and that's going to mess with all of the tissue around it.
12:54And it's incredible that we can do this with sound waves, right? >> Um the the material is still there but the proteins and the structure have changed. And like with with this hystotripsy the you can use that pressure to start this cavitation. The bubbles expand and contract over these short pulses and they create mechanical strain. It's it's very very cool. >> It's it's such an interesting you know it even conceptually as an idea um to to think to do so >> as a sort of clinical approach. >> Exactly. So you you've been able to create a bubble, right? The question now becomes um
13:36how do you control it really really well? >> Right. So we said we we were able to
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