Can Sound Be Used to Diagnose Arteriosclerosis?

Because cardiovascular disease is the world's leading cause of death, researchers have been looking for ways to diagnose it early. Low-frequency sounds have been used to assess the elasticity of blood vessels, but until now,  the elastic waves being studied were too fast to get precise measurements. Sibylle Gregoire (INSERM) discusses how here team has been able to image a different type of elastic wave, opening up the possibility to more precise assessments and diagnosis of cardiovascular disease in the future. 

Associated paper: Sibylle Gregoire, Gabrielle Laloy-Borgna, Johannes Aichele, Fabrice Lemoult, and Stefan Catheline. "Flexural pulse wave velocity in blood vessels." J. Acoust. Soc. Am. 155, 2948–2958 (2024). https://doi.org/10.1121/10.0025855.

Read more from The Journal of the Acoustical Society of America (JASA).
Learn more about Acoustical Society of America Publications.

Music Credit: Min 2019 by minwbu from Pixabay. 

Transcript

Kat Setzer  00:06

Welcome to Across Acoustics, the official podcast of the Acoustical Society of America's publications office. On this podcast, we will highlight research from our four publications. I'm your host, Kat Setzer, editorial associate for the ASA.

Kat Setzer  00:26

Today we're diving into the world of biomedical acoustics-- specifically how acoustics can be used to diagnose arteriosclerosis, a major risk factor for cardiovascular disease. I'll be talking to Sibylle Gregoire, whose article, "Flexural pulse wave velocity in blood vessels," published in the May issue of JASA. Thanks for taking the time to speak with me today, Sibylle, how are you?

Sibylle Gregoire  00:45

Yeah, I'm fine. Thanks for talking with me, of course.

Kat Setzer  00:49

So first, tell us a bit about your research background.

Sibylle Gregoire  00:52

I'm from an engineering background. I'm part of the Laboratory of Therapeutic Ultrasound that is located in Lyon in France. And this laboratory is part of National Research Institute, that is called Inserm. It's the research institute for medicine. And I'm currently doing a PhD in the field that is called elastography. So elastography aims at probing the elasticity of the organs and of the biological tissues. And it's a thing that emerged in the 80s, more or less. And the idea is to use elastic waves to characterize the biologic tissues. And the elastic waves are actually interesting because they are driven by these viscoelasticity properties of the material. So if you are able to image by any imaging technique, the propagation of the elastic waves, you will be able to quantify the viscoelasticity of the material. And today, it is used clinically to facilitate the diagnosis. In clinic, like for instance, for the liver, and specifically for pathology that is called cirrhosis. So it's the liver fibrosis. And people with this pathology tends to have a stiffer liver. So you use ultrasound to create waves in the liver, you image the propagation of ultrasound using also ultrasound. And if you're able to quantify the speed of the propagation of the elastic waves, you're able to know if the liver is soft or stiff. So yeah, that's more or less the field I'm in, and I really like this subject because it's at the interface between physics and medicine. And as a student, you have to understand the acoustics, or complicated physics in complicated materials, such as biological tissue, and at the same time, you always have a pathology in mind. So it's really cool because you are not losing the sight of the global goal of your research.

Kat Setzer  03:03

Yeah, that sounds really fun. And it sounds like it has a lot of applications and usefulness, which we will discuss now. So we're talking about, you know, like you said, like elasticity and biological organs and such. So what does arterial stiffness have to do with cardiac health?

Sibylle Gregoire  03:19

Yeah, so as I said, like elastrogaphy aims at probing the elasticity to facilitate diagnosis in clinic. And the elasticity of artery is actually a major issue, because 30% of all of us is going to die from cardiovascular events. And the stiffening of the arteries is a risk factor for cardiovascular accident. It's what we call atherosclerosis. So stiffening of the arteries is actually a natural process due to aging, but research has identified a bunch of factors that get the phenomenon faster. So if you have hypertension, if you lack of physical activity, if you smoke, you have diabetes, all your arteries are going to be stiffer. So being able to follow this process is of great interest.

Kat Setzer  04:17

Okay, yeah. So how do we currently assess arterial elasticity? And what does that have to do with acoustics?

Sibylle Gregoire  04:24

So one of the ideas to assess after elasticities is to use the pulse wave-- waves that are delivered by the heart. So at each heartbeat, the aorta is deform when blood is ejected from the ventricles. So this local deformation will propagate in all your arterial tree and the speed of these elastic waves is related to the elasticity of the vessel. So if you measure the speed of this pulse wave that is just sent back to your heart, you are doing an estimation of the elasticity of all your arterial tree. So people try to use this pulse wave, so they're trying to measure its velocity, for instance, they measure  the time it takes the pulse wave to go from the heart to the femoral artery or to the heart from the carotid artery. And they are doing a rough distance estimation, and it gives them the velocity of the wave, and so the elasticity of the arterial tree of the patient. And other people have tried to use ultrasound device to do the same thing, but more locally, so they put the ultrasound probe on the neck of the patient. And they can see the carotid artery of the patient. And just looking at the edge of a carotid artery, they see the deformation as the pulse wave travels through the carotid artery. And following this deformation, they can have the speed of the wave. But it's quite difficult because it's a very fast wave, and it's difficult to have a precise information about its velocity.

Kat Setzer  06:11

Okay, so that actually gets into the next question, what are the limitations of this technique?

Sibylle Gregoire  06:15

As I said, the wave is very fast, so it takes only a few frames with an ultrafast ultrasound device to get the wave from one side of the field of view to the other. So we struggle to have a precise quantification that can help really the patient to see, like a change, like if a patient stop smoking, does it change the elasticity of the artery? It's difficult to see this for instance.

Kat Setzer  06:43

Okay, okay. So, what are modes and how do they relate to the waves generated by the heart? 

Sibylle Gregoire  06:49

So, as I said, when the heartbeat via aorta is deformed, due to the blood ejection, this energy is going to travel as mechanical waves into the arteries. And this wave could deform the aorta in an infinity of manner. But as we live on earth, like, as physics tells us, it will take the one that costs the least energy. And at physiological frequencies, the ones that are delivered by the heart, only three types of mode can exist. So the breathing mode, so you can see this as a bulge, an expanding, that spreads along the artery like a snake that swallows something and it goes down its body. 

Kat Setzer  07:37

Oh, yeah. 

Sibylle Gregoire  07:39

More or less. And it's the most studied. It goes back to Thomas Young in the very beginning of the 19th century. So we know this wave for a long time. It's a lot studied. We know exactly how to link velocity of this wave to the elasticity of the vessel through a formula that is called Moens Korteweg formula. And yeah, this mode is very studied. It's symmetric with respect to the center of the artery, so it expands symmetrically. And at physiological frequency, you could also have other types of mode. You can have the flexural mode. So the breathing mode I just mentioned and you can also have the flexural mode. And it can be seen more as a snake that just moves and undulates. And it is the mode that we are looking at today. And then you could also have other types of mode, like the torsional mode, and it's more like a rotation along the tube, but with no expansion of the tube. So yeah, that's more or less what can exists at physiological frequencies. 

Kat Setzer  08:45

Okay. Okay. So then you mentioned the flexural wave. Why were you interested in studying the propagation of flexural waves in arteries?

Sibylle Gregoire  08:54

It's actually people from my team. So before I arrived, they worked with people from optic and digital holographic devices. And with those digital holographic devices, they were able to film the retina at very high resolution, and they can see the microvessel of the retina. And with a quite high frame rate, and they could see, like, some waves in the retina. So they said, like, we see some waves in the retina; we can do an elasticity measurement. And because we know from the Moens Korteweg formula, how it's supposed to be linked to elasticity. But they discovered the wave, but that was way too slow to be the breathing mode. And so they stopped to look around, like, what could it be? And so, they found that actually, when you look at the physical propagation, you could have several modes, so the flexural mode, as as I mentioned earlier, and this mode is very slow at a physiological frequency. So like it fit perfectly the data, actually. 

Sibylle Gregoire  10:03

So they look also at other parts of the body, of the arteries, and they found it also in the carotid artery. So it was the first time people observed the flexural mode, actually. And it's very promising because it's very slow, so we could be able to have more precise measurement. 

Kat Setzer  10:22

Oh, that's very exciting. 

Sibylle Gregoire  10:24

Yeah. But it was very promising, but it's like the one thing, like the clear link from velocity to elasticity for the flexural mode, we didn't have it. Like it's not like the breathing mode, where we know that velocity is into elasticity with the Moens Korteweg formula. For the flexural mode, we we do not have this formula, and it was the aim, like the goal of the paper we are discussing today. It was really to fill this gap of a model, like we need this model of propagation to link velocity of the elastic wave to actual elasticity. 

Kat Setzer  11:02

How did you actually test whether flexural wave velocity is related to arterial stiffness?

Sibylle Gregoire  11:06

So we started with a control medium, so that we know what we are looking at. So we created the control setup, where we use a camera to film the displacement in a fake artery. So I actually made a phantom of arteries, so something that really looks like an artery in terms of elasticity, but is made of a polyvinyl alcohol. So it's like a polymer. And we were looking, like we were filming the displacement in the arteries, and we were generating flexural waves using a shaker at the same frequency we find in vivo. And we use these control setup to test all our hypothesis on the link between the velocity of this mode, like the flexural mode, with the elasticity of the fake arteries that we know truely how stiff they are.

Kat Setzer  11:58

Okay, what is the Euler-Bernoulli beam theory, and how does it relate to the flexural waves and arterial stiffness? Why did you want to use it instead of the equations typically used with the breathing mode? 

Sibylle Gregoire  12:09

Usually, when you do acoustics, you tend to use the linear general theory of elasticity. It links stress and strain with an elasticity tensor, containing numerous parameters, that we call the elasticity coefficient. And it's like a reflex in acoustics, like we we usually use this. So we tried to do this, of course, but even knowing like the boundary condition of our problems, a specific geometry, the symmetry of our wave, it was not possible for us to derive an analytical formula between velocity and elasticity. So we had to go for another theory, which is to go from Euler-Bernoulli beam theory, because so Euler-Bernoulli beam theory, it was developed in the 18th century, it was more for the construction field to know which constraints you can apply to a beam before it breaks. But we use Euler-Bernoulli  beam theory for our very specific problem, because it fits well, our application, because the hurt is delivering frequency content that is very low frequency, it's like under 20 hertz. So we are the range of validity of Euler-Bernoulli beam theory, or at least it was our hypothesis at first. And the main results that this theory gives us, it's like the link between... like so if you apply a flexural moment to beam, you will have a flexural wavee traveling down the beam, where the velocity links to the square root of the elasticity. So it gives us this dependency, and also how it's supposed to depend from the radius and the thickness of the tube. So it gives us a first hint. 

Sibylle Gregoire  13:58

And we also had to take into account the effect of the blood inside the artery. So we also did an extra hypothesis, it was bad blood was only increasing the inertia of the system, and we changed the formula from the beam theory accordingly. And we obtained a formula that links the velocity of the flexural wave with the elasticity. We've also hypothesized on the frequency, like very low frequency, and also that the fluid structure interactions between the blood and the tube were only an increase in inertia. So it was very strong, strong hypothesis.

Kat Setzer  14:42

Very cool. So how did you use simulations to better understand how the beam theory relates to flexural waves?

Sibylle Gregoire  14:49

So we use simulation, so it was finite element simulations, actually, the software is called Comsol, and it was great to test the effect of the parameters on the velocity of a wave, so it's very easy to change parameters using finite element simulation. Once you have it, you can change or reduce the thickness, the volumetric mass as you want, and see what effect it has on the velocity of a wave. So that's why we use it to do something numerically that we cannot do by hand, or with difficulty.

Kat Setzer  15:26

Okay, yeah, that makes total sense. So what did you end up learning from your experiments?

Sibylle Gregoire  15:31

We compared the formula derived from the beam theory to the data acquired with the experiment, so with the fake arteries and the optical setup. And we actually found like good comparison between the data, the experimental data and our formula from the beam theory. So we validated the formula from the beam theory. And also we validated it because the parameter study we did with the simulation, the finite element simulation, was in accordance with the dependence we show with the dependence from the beam theory. So for instance, if you expected velocity to be linked with the square of the radius of the tube, we validated it with the simulations. I don't know if I'm clear.

Kat Setzer  16:20

Yeah, that's exciting. So how does the flexural mode ultimately compared to the breathing mode when assessing the elasticity of arteries?

Sibylle Gregoire  16:29

So we cannot jump to conclusions yet, because we don't have this comparative study between the breathing mode and the flexural mode in vivo, that tells us which is more precise. But we can have some expectations. So at low frequency, as the flexural mode is like, at least ten times slower than a breathing mode, we expected the measure of elasticity to be more precise. And also we know that the flexural mode is dispersive. So it's linked to the frequency, like, if you change the frequency, the velocity changes.  It's not the case for the breathing mode; it always go at the same velocity, no matter the frequency. So the fact that it's dispersive, it allows us to do like estimation of several parameters in the same time. Like, if you do, like, three measurements at three frequency, you can actually hope that you can derive both the elasticity and the radius, something like that, but you cannot do with the breathing mode.

Kat Setzer  17:37

So it's like a bit more versatile, it sounds like? 

Sibylle Gregoire  17:39

Yeah. 

Kat Setzer  17:40

So what are the next steps in this research? Can these findings be used towards new diagnostics for arteriosclerosis?

Sibylle Gregoire  17:46

The next step, so we have several. So first, we want to use the flexural mode to image arterial plaque, because... so arterial plaque is like deposits of lipids in the arterial walls, and this causes like the arterial walls to necrose. And at some point, this arterial plaque can distach, and when they distach, it can lead to heart attack or stroke, because they prevent the blood to pass. So we could do use the flexural mode to characterize the viscoelasticity properties of this plaque, and to know are they going to distach soon or not. We can also use the flexural mode for other type of applications. For instance, it's very slow, so we could use slow imaging technique to image for flexural mode as it's very slow. So, for instance, x-rays are the gold standard to image your blood vessel, for instance, when you want to know if a patient has a nascent plaque in a stenosis, in its coronary arteries, and if you want to have a stent on it, you do x-rays, you do angiography, I'm not familiar with the terms. And so using x-ray, like being able to do elastography with x-ray could be of great interest. Because right now, it's too slow to let us do elastography. 

Kat Setzer  19:17

Okay, 

Sibylle Gregoire  19:17

So using flexural mode, which are very slow waves, it could be maybe possible.

Kat Setzer  19:24

Okay. It's so exciting how sound can be used for non-invasive diagnostics like what you're describing, in this paper as a future. Hopefully your research will help improve how doctors assess their patient's health. Thank you again for taking time to speak with me today and I wish you the best of luck in your future research.

Sibylle Gregoire  19:41

You're welcome. It was a pleasure.

Kat Setzer  19:46

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