The Role of Micro-CT in Peripheral Artery Disease (PAD)

[Dr. Sabeen Dhand]
That's great. Sometimes some cases need to be done in the hospital, like some of these complex cases. That's great that you have both options there. So, yes. Okay. Micro-CT. I mean, when I heard this topic, I heard micro-CT, I was thinking, is this some microscopic CT scanner? What is it?

[Dr. John Rundback]
You know, that's what I thought too originally. You're not alone in that. This really started, the genesis of this is that we do these interventions all the time, Sabeen, right? We're kind of told mechanisms of action, and we think we understand it, but we don't really understand these things on a fundamental level, what's really happening at that interface between our devices and the tissue, and what the result of that interaction is. So working in this particular case with AngioDynamics, we wanted to get a better understanding of the mechanism of action of their atherectomy device, the Auryon atherectomy.

We talked about how to do that, and came across some of the material which had been published by Shockwave, looking at disruption of calcium that was using micro-CT. Really, a lot of the credit here now goes out to Aloke Finn, who we reached out to at Cardiovascular Path, down in Gaithersburg, Maryland. We reached out to them.

Micro-CT is not a miniaturized CT scanner. As a matter of fact, it's sort of the opposite in the sense that obviously in a CT scanner, the subject is stationary and the image or the fluorosource or the X-ray source rotates in the gantry, and obviously, various technologies around that. In micro-CT, the X-ray source is stationary, but the object is rotating. So that's how you get the three-dimensional perspective. The difference is that, unlike a CAT scanner, which you get maybe 3 millimeter, if you really want to get thin cuts, 1 millimeter resolution, the resolution from micro-CT, which is a non-destructive imaging method, is in the range of 3 to 5 microns, with the Nikon device we use, and in some cases, as low as 1 micron. It's really a microscopic evaluation of the tissues.

[Dr. Sabeen Dhand]
All right. We all see these pretty pictures. If we look, and we'll include it on our podcast notes of what a micro-CT image looks like so people can see it. After you performed different procedures, including the Auryon laser, what did you find? Were there breaks in calcium? Did it restore the compliance like you're mentioning? Did you do anything bringing it back to as you described a white stop sign when the whole vessel was just calcium? Did you look at that too? Tell us your results.

[Dr. John Rundback]
Well, first of all, I learned that there's more than one type of medial calcium. As we get into this, medial calcium has many different patterns. There's a speckled pattern, which as you can imagine, just little islands. There is a shingle pattern, which looks like shingles on a roof, kind of overlapping. There's sort of a sheet pattern where there's non-congruous, incomplete curvilinear sheets, and then there's a plate pattern.

The plate pattern is really what we worry about. That's the worst form of Mönckeberg's medial calcification, because the plate generally is circumferential, uninterrupted, continuous calcium. That's the one that's preventing any pulsatility or expansion of the vessel. That's the one that's physically limiting us. When you go in there and you do your balloon, the balloon won't open. That's plate calcium.

[Dr. Sabeen Dhand]
Fluoroscopically, is that when we see medial calcinosis? Is that the tram tracking, or is there any way to see that plate-like calcification on a non-micro-CT image?

[Dr. John Rundback]
When you have very dense circumferential calcium, that's often plate, but not always plate calcium. The truth is both the sheet calcium and the shingle calcium can look fairly dense, but since it's not contiguous and you can't tell that in any one plane, there is still pulsatility. It is still not contiguous, so the vessel is still able to expand and be compliant. In those cases, generally the balloon will expand. It's when you have this solid kind of plate of calcium circumferentially. I'm not sure you can tell that entirely just by fluoro.

[Dr. Sabeen Dhand]
About these different patterns of medial calcification, what did you find with your results then after that?

[Dr. John Rundback]
When we do atherectomy, and again, we're talking about the Auryon here, but in general, if you think about it, we're giving a lot of energy into the artery, and obviously with laser in particular, there are various modes of tissue interaction. As we all know, you can have a photochemical effect, you can have a photothermal effect, and then you have a photomechanical effect. Each of these work differently, but even the fact that you have a photothermal effect, obviously you're imparting a lot of energy. When you're doing something like orbital atherectomy, this thing is rotating around.

Extirpated atherectomy is a little bit different because it's cutting, it's not delivering energy, but any of these things that are delivering modes of energy, that energy is not necessarily longitudinally transmitted. Previously, the idea is that there's probably radial transmission of that energy into the vessel wall, and that's been called pulsatile waves.

[Dr. Sabeen Dhand]
Okay. Outward.

[Dr. John Rundback]
Right, outward. CSI picked up on this as a mechanism of action whereby they're not just going ahead and sanding intimal calcium, but now they're having an impact on deeper calcium, which is why you can expand balloons at a lower inflation force than you would if you did not do orbital atherectomy. They already had this idea of pulsatile waves, and the belief was that laser is probably doing the same thing. It's a different outward radial force, it's not an orbiting solid crown, but there is tremendous energy being delivered. In the Auryon laser in particular, it's got an extremely short bandwidth, so it's a 10 nanosecond bandwidth.

Think about a jackhammer. You could take something that's sort of moving slowly and try to make your way through the pavement, and you'll make a dent, but with a jackhammer, this short pulse width, it's a very high focal delivery of energy briefly, and as a result, not only is that forward-directed energy to open up any forward-facing plaque, that's outwardly radiating, and that's the idea to get these pulsatile waves, which are disrupting the vessel wall. When we ran the Auryon laser, we found that there are a couple of dependent interactions.

First of all, the 50 millijoules was not as effective as the 60 millijoules, which supports this idea that you need more energy to disrupt the calcium. Secondly, we really only saw the effect on circumferential plate calcium, because otherwise, you have compliant tissue, which would just dissipate that outward radial force.

[Dr. Sabeen Dhand]
It'll absorb it.

[Dr. John Rundback]
Absorb it, right, or it would have give. In the circumferential plate calcium, when you use 60 millijoules, in every single analyzed segment, we saw in our disruption of calcium. What's really amazing is if you look at those micro-CT images, the longitudinal images or the inside-out images like you're looking down the vessel, it looks exactly the same as shockwave.