18F-FDG uptake in digital tissues of healthy horses

Drs. Andrea Oliver and Andrew van Eps authors of "Effect of ambulation following 18F-fluorodeoxyglucose injection on standing positron emission tomography of the healthy equine digit in: American Journal of Veterinary Research Volume 84 Issue 9 (2023) (avma.org)" discuss 18F-FDG uptake values for healthy horses undergoing standing PET imaging. Hosted by Associate Editor Dr. Sarah Wright and Editor-in-Chief Dr. Lisa Fortier.

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Transcript

Sarah Wright: 0:00

You're listening to Veterinary Vertex a podcast, the AVMA Journals. In this episode we chat about the effect of ambulation following 18 F fluorodeoxyglucose injection on standing Positron Emission Tomography of the healthy equine digit with our guests, Andrea Oliver and Andrew van Eps.

Lisa Fortier: 0:26

Welcome to Veterinary Vertex, I'm Editor-in-Chief Lisa Fortier. And I'm joined by Associate Editor Sarah Wright. Today we have Andrea and Andrew joining us. And thank you both so much for taking time out of your busy schedules. And Andrea, we heard you have only been at Colorado State your first faculty position for two weeks and you still made the time to be here with us today. So thank you very much.

Andrea Oliver: 0:47

Absolutely.

Sarah Wright: 0:50

All right, let's dive right in. Andrew, your manuscript in AJVR discusses the effect of ambulation on 18 F fluorodeoxyglucose. uptake in healthy horses. Can you explain to our listeners what 18 F fluorodeoxyglucose is? It's quite a mouthful.

Andrew van Eps: 1:06

Yes, so we can call it FDG. So it's a it's a labeled glucose tracer that can be used in PET scanning Positron Emission Tomography. And what it does is it accumulates in tissues, and reflects the metabolic rate and level of perfusion. So it's a pretty nice marker of, of metabolism and function in tissues, that tends to accumulate more in tissues where there is cell division where there's inflammation. So it's commonly used as a trace of cancer in other species, but it's potentially useful. Actually, it is useful in soft tissues and musculoskeletal disease. So, tendons, ligaments, and lamellae of the feet, as well for looking at active inflammation or other damage processes.

Sarah Wright: 2:10

That's fascinating. And I mentioned this before we got started. But your manuscript did gain a lot of attention on social media, so much so that we're also featuring a little blurb from it in print JAVMA as well. So we're really excited that you guys chose to submit this manuscript to AJVR. So for our listeners, what were some of the important findings from the study?

Andrew van Eps: 2:30

Well, I guess, our main one, because we think this could be quite a useful marker for looking at the function of of the lamella tissue, rather than just structural damage. We really wanted to investigate whether physiologic events would alter its uptake and perhaps interfere even with our interpretation of changes that we see on a PET scan. And one of the things that we found in our own research over the years is that ambulation walking tends to affect the blood perfusion and microvascular perfusion of the lamellae. And it seems to be the major thing that affects the micro perfusion of the lamellae. When they don't walk much, it's under perfused. When they walk a lot, it's perfused more highly. So I guess we were concerned as a first step. In looking at this as a marker of laminitis. Potentially, we were wanting to look at ambulation as a factor as to whether after you inject the horse, and before you scan it, because there's about a 45 minute delay after you jack them before you scan them. If they walk around a lot in that period of time versus not walking around at all, how much will that affect uptake in the feed? And is it to an extent where it will interfere with our diagnosis of of laminitis. And I guess what we found is that there are differences. We took the same set of horses and we walked them actively after injection, on one arm of the study, and on the other arm of the study, we actually crossed tied them loosely in the stall. And what we found was that there was a significant increase in FDG uptake in the lamellae in the horses when they walked around after injection versus not. But for the most part, it wasn't a sufficient increase to interfere with what we would normally consider the type of changes that we see with laminitis. So it was a smaller increase than would be likely to interfere with that diagnosis. I think one of the most interesting things that we found was that the biggest affective walking was in the medial quarter of the front leg. And we find that's the area where horses particularly, when they're developing supporting limb, laminitis, that tends to be where they get the biggest issues that are perhaps associated with low perfusion when they're not walking around enough. So when they have a fracture in the opposite limb, for instance, so you know, this has opened up kind of some new avenues for us. And we're doing some more work looking at using PET to monitor perfusion in horses when their weight bearing conditions change when they have fractures and other problems.

Lisa Fortier: 5:46

Yeah, it's pretty fascinating. Anderw, you know, I'm an orthopedic surgeon. So support limb laminitis is, you know, you think about it even before you start doing any surgery. And that medial wall can certainly certainly be the bane of your existence. And I remember decades ago, Jeff Watkins, presented on a new form of pastern arthrodesis that he had done. And one of his cases was this kind of a crazy horse that weaved savagely like one leg on the ground at a time. And of course, everybody's thinking, oh, that horse is going to break all the hardware, but the horse actually never foundered. So there's been this like idea of, we need to keep them moving. We've known that, you know, compression on the digital cushions is important and that you guys now have the ability to put some really strong science behind that. And I think you're gonna revolutionize how we treat animals with support limb laminitis. So thank you.

Andrea Oliver: 6:41

Yeah, well, part of the part of our aim. And initially, Andrew and I, when we, when we put this study plan together, we had included an arm of these dynamic PET scans that we had planned to do, and we did some of them. But it turned out that it was too much to fit into this initial paper. But there's some exciting stuff in those in terms of that, hopefully, we'll talk to you maybe in a while about when we submit another paper. But it's amazing when horses stand still. And you inject them and they're standing still. The regional deficits in perfusion and metabolism in the foot are incredible. And they vary widely from horse to horse. But it's a real eye opener in terms of how much they do rely on walking, and load cycling to get blood perfusing. The oval lamellae of the feet and the sole papilla as well. Interesting one. Yeah, it's so much for testing hoof warmth that we make all the students do, right. The amazing thing about PET scanning is it's, you know, it's a three dimensional image, you know, it's not a 2d thing. So you're getting a three dimensional functional map of what's metabolically happening in that tissue, which, you know, what's really fascinating to look at.

Lisa Fortier: 8:21

Yeah, thank you. Andrea, we'll turn to you for a few minutes. Sounds like you'll have lots of fun things to do at Colorado State taking away from Penn from this manuscript but what what originally sparked your research interest in PET scanning?

Andrea Oliver: 8:34

Yeah, you know, so unfortunately for me, I think laminitis has been a disease that's been very close to me for one reason or another. I've had some personal horses who have who have dealt with it and then of course, a lot of cases that you know, you worked very, very hard on and end up losing to to laminitis, rather than their primary disease process. And, and I think what's most frustrating about it is that you know, once you once you notice what's going on, it's it's far too late. It's you know, with the radiographs it's like you're looking at the wreckage, you know, what's already happened, and especially now with, you know, with the PET modality, just being able to see, you know, just how late the radiographs really are in representing laminitis. You know, I think it becomes really exciting that perhaps there's a way to, you know, if not catch the disease early it just to understand what's going on in that more critical period, which is, I think, some of you we've never really had before.

Lisa Fortier: 9:25

Yeah, that's really fascinating. And then, so that's when all the personal experience you have it would really inspired you to write this manuscript and selfishly share it with us at a AJVR?

Andrea Oliver: 9:37

Oh, gosh, I mean, I think, you know, obviously, as a resident, it's, you know, important for was important for me to to make sure I was super involved in the literature and getting those manuscripts out there. And I think, especially for for this project, you know, we're seeing so many additional projects down the line, you know, as we were writing this manuscript, it was already obvious, you know, you know, five more projects that come from this. And so, particularly for this manuscript, you know, getting it out there as soon as possible to know what the protocol needs to be, and make sure that that is solidified before we can do any of the other exciting things that branch off from this, you know, is is was important and frankly motivational in a way to be able to get to more of the meat of pet in the law melange.

Lisa Fortier: 10:25

Super inspiring. Maybe not what was the most important finding? But what is for you? What was the most surprising finding from your manuscript?

Andrea Oliver: 10:34

Well, I yeah, you know, I think something that doesn't come across maybe in the manuscript as well is just really how easy this technique is to do. You know, it sounds like it should be hard, you know, a PET scan of a horse's foot, but using the, the long mile PET scanner that we have, which is developed for horses in a standing setting. You know, it's remarkably user friendly, you know, it takes five minutes to scan a foot, if they wiggle around a little bit, it's not a big deal, the images still come up really nicely. And frankly, it takes longer to get them sedated than it does to actually acquire the images. So for me, that was really the most surprising thing was just really how easy it was to do. It was it was very friendly.

Sarah Wright: 11:16

So Andrea, as you mentioned, you just finished up your residency. Congratulations, and are now Colorado, of course.

Andrea Oliver: 11:22

Thank you.

Sarah Wright: 11:23

So how would you say your advanced training helped you to prepare to write this manuscript?

Andrea Oliver: 11:28

Yeah, you know, I guess I've been really lucky to be trained by some really, really busy hospitals. And yet, you know, even in private practice, where I was, it was, there was still a really strong focus on evidence based practice. And so you know, even in those private practice type settings, we would have journal clubs. And, you know, it's a really strong emphasis on not only reading literature for the sake of the conclusion, but also reading literature for the sake of understanding if it's a good manuscript, and you know, is it is it rigorously done? And is it accessible to read, you know, so when you when you are reading it, is it? Is it written? Well, is it something that everyone can pick up and understand what happened? And so I think, you know, across both, you know, internship and residency and everything like that, just being exposed to that sort of literature evaluation, was really helpful for me going into this.

Sarah Wright: 12:22

Yeah, I would agree, it's always important to have that really critical understanding of how to evaluate literature, especially to practice the best evidence based medicine that we can. So really, really good advice. Thank you. This next set of questions are very important for our listeners. So first, we're going to start with the veterinarian. So Andrea, what is one piece of information the veterinarian should know before discussing this topic with a client?

Andrea Oliver: 12:45

Yeah, so probably just that, you know, FDG PET is is honestly fairly repeatable, at least in our population of horses. It was relatively sensitive for detecting abnormalities within the lamella. And the fact that it's not greatly affected by conditions in the pre- and post-scan period. Which is nice, because it means that you don't really have to micromanage the setting prior to the scan. So that's really lovely. We don't have to worry too much about you know, how much is the horse, you know, walking around in the stall, you don't have to worry about sedating it or counting their steps, you know, to the extent of being able to diagnose laminitis, at least, you know, yeah, sure. It'll change it a little bit. But in general, it's an easy enough procedure to get through. So yeah.

Sarah Wright: 13:29

Thank you, Andrew, anything to add for what the veterinarian should know?

Andrew van Eps: 13:37

I think, you know, this is an imaging modality that's developing some traction, particularly in orthopedics and in horses, and particularly as a pre race screening thing. We're in the very early days with it yet, but I think it's going to open our eyes a little in terms of what's what's going on inside feet from a laminitis perspective. And because it's relatively simple, I mean, it's something that can be achieved you know, in with these portable systems, you know, it's possible, you know, a lot of different things that are possible in terms of bringing a scanner to the patient to monitor the metabolic health of a foot, which, you know, we perhaps never envisaged would be possible in the past.

Sarah Wright: 14:27

That's so cool. I'm not even a equine clinician, like that's not my wheelhouse, but even I can appreciate how cool the sounds and how groundbreaking it is. Alright, and then on the other side of the relationship, Andrea was one piece of information the client should know about this topic?

Andrea Oliver: 14:43

Yeah, so I think the biggest thing for clients is is more or less just understanding what PET gets you in terms of imaging rather than just being you know, a very, you know, pretty image with a lot of color. It really truly is showing you function of the tissue rather than just structure itself, which is just so much more insight into what the tissue is doing. And so, you know, it's like I said, it's just so much further ahead of what we see radiographically and frankly, will be much better for assessment of, you know, how is the disease progressing? What is the effect of, of, you know, therapeutics, on that on that progress and things like that. So I think just really being able to nail down the difference between, you know, taking a static picture versus understanding what the function of the tissue is.

Sarah Wright: 15:30

Andrew, anything to add to that?

Andrew van Eps: 15:33

Yeah, along the same lines, like I think we, you know, with tendon injury or ligament injury, we use ultrasound, and we can see when, you know, we can have some idea of structurally a when we have healing and when the animal might be ready to resume exercise. And we can monitor that. You know, with laminitis, we really are guessing most of the time, but something like this that has that, that gives us an idea about what's functionally happening in the tissue, could give us the ability to make decisions or make more informed decisions about when that tissue was quiescent, and perhaps ready to be loaded again. You know I think these are the questions that PET might be able to answer for us and help us with not only, you know, diagnosis that is really a massive challenge, because it's often a clinical diagnosis. Although sometimes it is a challenge, you know, and PET can really help in that regard. But what it's going to help us with, I think, is monitoring where we are in the disease process. And what that tissue is doing underneath because it's so hard to image. Otherwise, it's only, you know, typically three or four millimeters in width. It's a tiny amount of tissue, and it's encased in a hoof capsule that doesn't allow us to use a lot of traditional imaging modalities to to effectively see it. So your functional modality can help us decide where we are in the process, perhaps when we're ready to take next steps in terms of rehabilitation. And, you know, I think that's one of the more exciting features of this. And the other thing that I'll add is that FDG is just one tracer that you can use for PET scanning. Traditionally, what we use for bone is sodium fluoride. And there's a number of other metabolic traces that are have a lot shorter half life, and are faster acting, that can be used. And so the sky's the limit in terms of what if you had a specific process that you wanted to look for in feed, you can develop a tag for that, and know when that's going on, or when it isn't. And I think that's what's really exciting about this type of imaging. This is kind of just the first step. It's pretty fascinating. When you think about you can do something for prevention or early detection, at least. And rehab.

Lisa Fortier: 18:13

You know, I think PET scanning honestly is going to go down with ivermectin and how it's gonna revolutionize health, horse health in general, for medicine, clinicians, surgeons, owners, it's just It's groundbreaking. So thank you again for sharing your information with us.

Andrew van Eps: 18:30

Yeah.

Lisa Fortier: 18:32

Andrea, you're clearly a superstar in the making. Colorado State's lucky to have you sorry, Penn. Sorry, Cornell.

Andrew van Eps: 18:41

I don't know about that.

Lisa Fortier: 18:42

To get through everything that you're doing in your crazy enthusiasm. I can see already where did your resilience, inspiration, determination? Whatever you want to call it? Where did it come from?

Andrea Oliver: 18:54

You know, that's a that's a really great question. And, you know, truthfully, I think when I, when I thought about this, and I think about this, you know, what keeps you going every day, it's probably similar to a lot of people. And that's just, you know, sometimes I just want to see how good can we do for these patients, you know, and what can we do for the future of the horse industry? You know, how much better can we make things and I think that's a, you know, a challenge that never really has an endpoint. And you know, some days, that's just working really hard on the clinic floor, but other days, that means just really digging in and getting to the bottom of some of these questions that we have in a research setting. And, you know, to me, especially in academia, I think both of these aspects are equally vital. But there's something really special in research about being able to create almost a map, if you will, that will help guide you know, veterinarians and clinicians and scientists of the future and I think that's just really special.

Lisa Fortier: 19:43

Yeah, yeah, it is. Being able to answer some questions and then more questions come up and more questions. And then we wind down with a little bit more of a personal question and answer and I love the answers to this one. We'll start with Andrew and then go to Andrea. What is the oldest, the most interesting item in your desk drawer or on your desk?

Andrew van Eps: 20:07

I'm gonna cheat a little bit, it's in my wallet. I carry with me an ammonite fossil that is somewhere between 60 and 400 million years old. It's a fragment of an ammonite fossils that I found in Wales when I was looking for fossils of my sons. But I find it a nice reminder of how insignificant we are and our little period here on on Earth as particularly even just as researchers, when, you know 50 to 400 million years ago, this animal was developing. And also it's a good reminder of how long evolution had to to create these things like lamellae, which we're now marveling over, and the sort of problems that exist, you know, and just how, you know how much time has gone into to creating life as we know it here.

Lisa Fortier: 21:12

You're thinking the horse lamellae and the anatomy of the GI tract would have evolved a little bit better. But that's why we still have jobs and research projects. The problem is they evolved to you know, to outrun the saber toothed tiger and that was that was about it. And then after, after that, we're dealing with the fallout.

Sarah Wright: 21:34

I'd like to add the rabbit to that list.

Lisa Fortier: 21:41

Andrea you get up to go get something What have you got to share?

Andrea Oliver: 21:45

Mine is just so much less profound than that, but I have a stuffed kidney. Little plush kidney here that has a happy side and a sad side. And I turn it over depending on how my patient's kidneys are doing in hospital. And that just keeps me going.

Lisa Fortier: 22:02

And so do people know to like keep going past your office if they see the sad side they just like look down right shoes and keep walking. Awesome.

Sarah Wright: 22:15

Spoken like a true internist.

Andrea Oliver: 22:22

With every residency, you should receive a stuffed kidney. I think that should be a standardgift, right standard issue kidney.

Sarah Wright: 22:32

That's fantastic. Thank you both so much again for joining us today. And thank you for your contribution to AJVR.

Andrea Oliver: 22:42

Thank you very much.

Sarah Wright: 22:44

And to our listeners, you can read Andrea and Andrew's manuscripts on our journals website. I'm Sarah Wright with Lisa Fortier. I want to thank each of you for joining us on this episode of the Veterinary Vertex podcast. We love sharing cutting edge Veterinary Research with you and we want to hear from you. Be sure to leave us a rating and review on Apple podcast or whatever platform you listen to