119 - Daniel Gomez & Ewa Beldzik - MRI imaging study

Episode 119 of the Long Covid Podcast is a fascinating discussion with Ewa Beldzik and Daniel Gomez about the Long Covid study they are doing involving MRI and mapping the brain during tasks.

We dive a load into the study and it's absolutely amazing!

A link to enroll in the study 

And their email for any questions: MGHLCOVID@MGB.ORG

For more information about Long Covid Breathing courses & workshops, please check out LongCovidBreathing.com

(music credit - Brock Hewitt, Rule of Life)

Transcript

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Jackie Baxter  
Hello, and welcome to this episode of the long COVID Podcast. I am absolutely delighted to be joined this evening by Daniel Gomez and Eva Beldzik. And we are diving down the rabbit hole of long COVID research again today. So a very warm welcome to the podcast. And I'm really excited to dive into all of this.

Ewa Beldzik  
Hello, nice to meet you.

Jackie Baxter  
Thank you so much for joining me. So to start with, would you mind just saying a little bit about yourselves and what you do? Before we dive into the actual research part of it.

Daniel Gomez  
I am a postdoctoral fellow at the Massachusetts General Hospital in Boston. And both formation during my studies and my PhD. I'm an engineer, and I work with MRI Imaging. What this means is magnetic resonance where we generate images of the brain using strong magnets. So I'm not a medical doctor, right? 

The path that brought me to long COVID research is to the intricate and curious by involvement in the hospital in a clinical setting. But the research that I'll be talking about, or that we'll be talking about, is mostly how to use the techniques that we'll develop and apply those to imaging long COVID. Or put those techniques in the context of a clinical population. 

Ewa Beldzik  
And hi, I'm a postdoc at Laura Lewis's lab at Massachusetts Institute of Technology, MIT, Boston. I'm a cognitive neuroscientist. But here in Laura's Lab, I'm exploring the sleep neuroscience. 

But I was always interested in brain mechanism that are behind various cognitive processes. And I do explore those with either of brain imaging techniques like functional magnetic resonance imaging or electroencephalography, EEG. And, yes, here I am helping Daniel in his fascinating project about long COVID.

Jackie Baxter  
Amazing, this is so exciting to hear because it's bringing together things, isn't it? You know, it's like the technology and the sort of tech - almost sounds kind of space age to someone who's like, not in that world at all, like me. And then the sort of neuroscience. And you know, sleep is very related to long COVID, as well, in a lot of ways because people with long COVID generally don't get good sleep. So, yeah, this is super exciting. 

So maybe what would be cool to talk about is like, what brought you specifically into this kind of study, like what gave you the idea to do this?

Daniel Gomez  
I think, for me, when I started my postdoc position at the hospital, I had a mindset, eventually, it'll be interesting to try and image clinical populations as well, because all the work that I have been done, up until then had been what we call Healthy control population. Right. 

And in the labs that we work at, so the lab of Laura Lewis that Ewa mentioned, and another lab at Massachusetts General Hospital that I'm involved in, there's a lot of knowledge about how to do advanced acquisition methods to make the contrast of the image sensitive to different things, such as blood oxygenation and blood flow. And with Laura, a lot of knowledge of sleep and arousal and these ideas of what could be underlying the mechanisms of fatigue. 

And because of this started to come up quite a lot in the media during the beginning of COVID. And within the hospital context, we will get emails, you know, whoever can help in whichever way they can help and there were extra funds to help this research, we thought it would be a great idea to to try to help with what we know best, which is to how to do this imaging and how to analyze this data and try to collaborate with medical doctors and get their inputs of how to design a research that will be meaningful for both us and for potentially to the patients as well.

Ewa Beldzik  
I have already had some experience with exploring the neural substrate for a cognitive task, like which brain regions are involved in when we are performing and doing optimal performance of any cognitive task. And just this phenomenon of Long COVID patients suffering from that, from problems with continuing on good performance. 

So finally some knowledge, of basic knowledge, that cognitive neuroscience have can actually be put into use, have some application and perhaps be helpful in diagnosis or, and developing new treatments. So in that sense, it's a very rewarding when expertise can be useful. And so that's why I was drawn to this particular study.

Jackie Baxter  
Yeah. And that's so fascinating about, I find the brain incredibly fascinating. And I think it's partly because to me, it seems a bit mysterious. I don't know if it's less mysterious to someone like yourself, who actually understands it. But it's, you know, all of these different bits of it, that do different things, and how they all interact, and how they then interact with the rest of the body. 

And then what happens when it's not working in the way that it should be. And how that can then impact everything. Because like, the brain kind of is the like, control center, isn't it basically, of everything else. And it's just just incredibly cool. And disastrous when it goes wrong, I suppose.

Ewa Beldzik  
Indeed, for us brain is a mystery too, but that's why we love our jobs.

Daniel Gomez  
Maybe the more you study it, the less we know. So I would say we're not less amazed by how complex the system it is. Especially what you mentioned, this interactions with the body right, which are being more and more attention to more so than that just a brain floating in vacuum, but its interactions with all other physiology that makes it exist.

Ewa Beldzik  
Indeed.

Jackie Baxter  
Yeah, I think sometimes it is, the more you find out, the more you realize that you don't know. And it's a bit overwhelming, but also exciting, I think in some ways. I mean, let's talk a bit more about the study itself. And yeah, what are we doing here?

Daniel Gomez  
That's a very, very good question. Indeed. Very broad question, I'll try for those who haven't heard the study, try to break it down, or unpack it as as well as possible. So this study has multiple parts in it. We cannot, when we talk about long COVID, and imagine anyone that has listening here and you know, Jackie is a very heterogeneous syndrome or manifestation, right, where the patients have all sorts of different symptoms that appear, and some subpopulations have different effects. 

And so the research that we're doing is not trying to approach the entire long COVID spectrum right. So we try to focus on what we think we could contribute it to, which is mostly the parcel of patients that display fatigue, symptoms of fatigue. And we also try to control for other things that could influence our study, for example, if someone has lung issues, right, that that fatigue would maybe not be a fatigue that's mental, let's say, but more of a physical fatigue. So we try to make the distinction first. 

And what we're trying to see here is to separate with our imaging, that's something that we will do in the context of just cognitive neuroscience, right, when we analyze images. With the functional studies where we look as people rest in the scanner over time, we try to identify traces of neuronal responses and traces of physiological responses. So what are, is there anything in the signal that we measure in them are. 

And the listener can imagine that what we're doing is not only images, but we're making videos of the brain as time goes by. And imaging the blood as the blood flows through the brain. And we're trying to see as time goes by, whether the signal that we're measuring is influenced by neuronal activity? And if so, how is it influenced for neuronal activity? And at the same time, how it is influenced by physiology and by physiology, I mean, by heartbeats, by respiration, being the main drivers of this right. 

So what makes it tricky, just in general, to look at this data is that when we look at this signal, there is a mixed contribution of both of these, or all of these effects at the same time, and it's hard to judge really what is contributing to what, when and where. And in every part of the brain, there is a delay between the time in which things happen. So the signals, they come up in different ways. And that's the main idea of what we do just in general without even the context of the long COVID research right. 

And when I talked about looking at neuronal signatures in this signal, we can also try to manipulate experimentally what It will look like by having participants do a task, for example. So if i would flashlight into someone's eyes, then we'll expect to see a trace of some activity in the visual system of the brain that's responding to that task that's been presented. Right. 

Or if someone has a more complex cognitive task, which Ewa will talk about later on, then we'd expect other regions to be involved. And these regions are not always working alone, right? They have to, there is a lot of planning, decision making. So there's a lot of interaction and communication that has to happen. 

Some of these these tasks, we know very well what to expect from previous literature. So if we don't really see what we expect, and you know, it can make us think, Okay, here's something to be investigated. Why is this response not looking like what it's supposed to? 

And so for this COVID study, what we're doing is we're using some of these tests that are very well known, and that we know exactly what to expect. And we're trying to bring this into a setting where we look at them with the highest quality of image possible. So using the best technology that is available to us today, and the techniques that we use in our group, to look at these tasks very closely, both in a healthy control population, and in the subset of long COVID patients that report fatigue, right. 

So we screen them to see that they score certain value in a fatigue assessment and sleep assessment, and we enroll them and then we have them go through these batteries of tests. And because there's there's neuronal responses and physiological responses, a big chunk of our study is also trying to control for the physiology alone. So we have our participants to breath holds and breathing exercises, while we're making these videos of their brain to see how that will trigger responses. Because if there's something that is just physiological, we want to be able to separate that from what's neuronal. 

A lot of what we'll derive from the study, or expect to derive from the study, is not necessarily something that's directly translatable for a diagnosis, or even for treatment. It's, I would say more of a basic science and an understanding of how these techniques could be even used one day in the clinic for this sort of investigation. 

And potentially use a little bit of what we know in our lab from fatigue to try to understand where is it that we should be looking at and how do we look at it? And if so, how can we then in a follow up study, then diving even deeper and say, Okay, this is the region where really, there's potentially something going on that could be interesting within the context of the project on COVID research.

Ewa Beldzik  
Just to summarize, would like have like three tasks that the subjects are conducting in the in the scanner. Which is the breath holding, which targeting mostly this physiological response Daniel mentioned, the simple visual task to evoke as strong as possible sensory visual system response and compare that to the healthy controls to COVID patients. 

Ewa Beldzik  
And let's call it color matching task, that requires a lot of cognitive control processes. And with that task, we can control for several brain regions involved in the cognitive processes. And, again, compare where and how and when alteration may occur, and explore then the questions that Daniel mentioned. So these three are like a basic of the study.

Jackie Baxter  
Yeah, I'm just trying to get my head around this almost. So you're able to kind of see what lights up in the brain while someone is trying to do a certain task, or responding to a stimulus. And you're literally able to map that in real time as they're doing it. That's very cool.

Daniel Gomez  
Some things are easier to map than others, right? So the visual task we like a lot, because the response is just so incredibly strong, that anyone can look at the images with the naked eye. And as long as they know where the visual system is, they will see responses in the intensity of the images with the naked eye. You don't even need to do any analysis for that. 

But for tests that involve more complex control, like the cognitive task that Ewa mentioned, where we asked the participants to read a word, for example, in blue that is written in red color. And then to ask whether the ink is blue or red. So that conflict or that processing is much more difficult to map, is much more distributed. And this responses are not something that you can just look at these images and then extract anything from them.

Ewa Beldzik  
Yeah, but focusing on the fatigue aspect that we hope to see some fatigue, mental fatigue, in subjects that participated in a study. First, perhaps, hopefully behaviorally. So, since patients report that they're more tired when they do a task, we can measure that with simple behavior. They're going to respond slower, or make more errors. That's why this color matching task is a, like a good proxy for, hopefully for fatigue effect. 

And with that, so we have a behavioral outcome, that patients differ from controls. And we have now the brain response while doing this task. And we would like to track down why - why there's this degeneration in performance. Is it one brain region, or is it the global effect of all system in general. And that would be the goal of this cognitive task. 

And Daniel can tell more about the breath holding task, because this is particularly important in terms of whether this alterations might be global or local, physiological, or neural,

Daniel Gomez  
I can talk a little bit about that too. So I mentioned, right, as we're watching this video of the brain and we're looking at things are changing, we can't really see the neuronal activity directly. All we see is a complex change that happens in the blood to many processes that involve the oxygenation of the blood, the speed with which blood is flowing, the amount of blood that is available, right. So we can imagine that very small vessel has less blood, than a big vein. So the signal would have been stronger, where there's blood. That's not necessarily where the activation is happening.

Because we're really looking at blood and trying to infer something about neuronal activity, we try to control for how blood flows just by itself without any interference, if I recall, from your own activity. And that's where the breath comes in. 

Maybe taking a step back for the listeners as well, maybe some people know this, some don't. But the way that our blood is flowing in our brains is very well regulated, right. I think anyone would know this, if they try to run, they'll see that their heartbeat goes fast, because oxygen has to be delivered to the muscles right? 

In the brain, we also have something similar to that even though it's at a much finer scale, extremely fine scale. Every time there's neuronal activity in the region, the oxygen has to be delivered to the region, there is an alteration in the speed with which blood is flowing. And the oxygenation level is extremely localized to the area where that activity is happening, right. 

But there's also this entire supply of blood that's happening all the time, even without any neuronal activity. And because this blood system is so well regulated, we can trigger it without the neural activity by changing the concentration of gases, oxygen and co2, that are in the system. 

That's why the breath hold is interesting, as someone holds their breath, there is no way for us to expel all the carbonic acid, that waste out of our system, and so it stays in our blood, and it causes a response that then leads to a change in the signal that we measure. 

And that will tell us something about the vasculature, that will tell us something about the way that the blood has been transported. And that will give us a physiological signal that we can then try to understand, so that when we're looking at the neuronal signal alone, we can then separate what we believe would be the contribution for physiology alone. 

So that's the breath hold, is a simple task that anyone can do. That's why we chose it. We do a 15 second breath hold, which has some even in our clinical population, and is able to tolerate very well. And that already gives us a sufficiently strong signal to see this global changes in the entire brain. 

And without the breath holds, it's really hard to compare from person to person what's going on from this neuronal signal, because if someone just happens to have more blood or higher hematocrit count or anything else that will change that signal, that will be a huge confound for the inferences that eventually we would like to make. That's why we add that as a physiological control, if I may call it that way.

Jackie Baxter  
Yeah that is very interesting. This fascinates me as well, as a breathing instructor, the idea of breath holds, and you know what it does in your body while it's happening. And then how that would actually show up in your brain. That's the bit that is slightly blowing my mind right now, a little bit. 

But I think, I mean, bringing this all back to fatigue, which was kind of where we started. I don't know if this is something you can even answer, I'm kind of just spitballing here. But we know that, you know, there's all the different kind of types of fatigue. And you know, you've got your physical fatigue, which is more obvious, because, you know, to stop that you'd stop moving. 

But the cognitive fatigue, and the sort of mental exertion was stuff that, for me, was much harder to understand. And I think it's much harder to quantify, in a lot of ways. And much harder to stop as well, because how do you turn your brain off? 

And I feel like, you know, the tasks that that Ewa was describing, with the matching the words and the colors and things, like to somebody without long COVID, that would seem like an incredibly simple task. But for somebody who's got terrible fatigue, maybe some degree of sort of cognitive impairment, being able to do that actually, could be quite an exhausting task, could be very difficult for them. 

And I feel like maybe if you are mapping this in the brain with the imaging, this could be a way of actually being able to measure that in some sort of actual quantifiable way that doesn't really exist anywhere else? Am I making sense of this in the right way? Or did I just make something up?

Ewa Beldzik  
This is exactly the goal, since for our knowledge, long COVID patients have no alteration in anatomy of their brain, but they are still struggle with maintaining their attention on a task, and they do report fatigue. There's something, there should be something underlying those problems. So indeed, we hope that  the functional images will be useful and helpful here. 

So, exactly, we hope that the task that we picked, it's actually we didn't want it to be too difficult. Just because then it would be hard to compare to controls, if somebody makes so much error. So so we stick to the rather simple task, it seems that we train every participants before entering the scanner, so that they do approximately good in a task. And we expect that they might just slightly degrade while the task is going on. It's like about 12 minutes of task, and we hypothesize that they will slightly degrade over time. 

And this is where the fatigue may may show up on. And with that we may see if any of the brain regions that is involved in a task - Is there any particular one, for instance, the cognitive control processes are mostly conducted using our frontal cortex. So not the sensory system like Visual motor of brain regions. 

So this might be one of the questions like, Is this, like lack of attention? Or is there like not the mechanism of the nutritions and oxygen, that Daniel mentioned, that supply those brain regions are perhaps insufficient, and they cause lack of focus and a subjectiveness of fatigue? 

Because it's really hard to study the subjective experiences like I'm feel tired, but we need to measure that somehow. So behavioral responses to a task is the only way. So the cognitive task, we expect to see some changes. But where - this is very open question, since there was no previous study that explored it. So it's the subject general, very, very interesting and very unknown questions that might be addressed with this task.

Daniel Gomez  
And just to add to this idea of the difficulty of studying the subjective feeling right, sometimes what patients will report is not really reflected in was they measure too, or even a healthy control. So sometimes we have patients that do better than healthy controls, right? And then some of the cells were perfectly healthy, then not really responding or showing what could maybe be considered signs of fatigue. 

So it also makes it it hard to pinpoint exactly what's going on. Because of all these other confines, that's what really, I think the goal of this study is to try and figure out how do we separate all these signals? And how do we understand and relate them? What is the best metric of behavior responses? How do we decide? Or how do we judge? When is it that we really see an effect of performance degradation over time? Or is it just a random fluctuation in performance that happened to happen at the end of the 12 minute window that we have? So this is things that we don't have an answer for right now. But we're trying to understand as we go.

Ewa Beldzik  
You could also, Daniel mentioned the underlying of, of our hypothesis, how, what actually we might expect that the virus is doing in the brain. Because Daniel has formed this hypothesis based on a lot of knowledge and expertise.

Daniel Gomez  
The reason why we thought functional studies would be more interesting than just atomicaI I think is from two things. First, that there isn't, as Ewa said, any studies up to a certain very massive large population studies that show minor alterations in the olfactory bulb, to the extent that I'm aware of. But there are no studies that have shown a particular degeneration or any anatomical change. 

And I think there is a study that I saw two years ago already, they're saying that if someone has had long covid and goes to get a clinical MRI scan, only 2% of the patient population would actually show any findings that could be considered to be related to the disease. Right. So what's up with the other 98%, when the scans come up clean, and traditional blood tests come up clean? 

Obviously, this speaks to the inability of an anatomical image to tell us the difference. But functional images are much more sensitive in a way to any change that's happening. And this is a double edged sword. There's a professor actually at Oxford, in the UK that said this at a conference, and mentioned that it is sensitive to everything, which is great, but it is also sensitive to everything, which is bad, because it makes it hard then to distinguish things. 

But the idea back then, was that in patients that had been to the ICU, and sometimes have not survived an acute case of COVID, in post mortem studies of the brain, there have been many lesions associated with lack of oxygenation. And so this is chemic damage that people would call them. And as had seen many, many times in clinic as well as patients that have been in very severe acute state of COVID. 

And this group is, of course, not the group that we're studying. But we thought what if this lack of oxygenation is just not pushed to the way where it creates a total injury, but is disrupted to a certain extent where you wouldn't see in the anatomy, but there is a change in the functional responses, right. And there's oxygenation is in the blood to an extent. I mean, we're interested in the tissue, but the oxygen is carried by the blood. And since the techniques we have image the blood, then maybe there's something to be looked at, in there. 

And then at the same time, there's a lot of evidence coming from groups looking at the blood of patients with COVID. As I imagine, you probably interviewed some people that talked about this, too, about the blood clots, right? This stable blood clots are seen. And these blood clots while they're in the blood, right, the virus attacks the endothia or the vasculature in a certain way, and then causes this. 

We don't know if it's an immune response, inflammatory response, this is beyond my expertise, at least. But there's something potentially in the blood that could alter these responses, right? If blood is not flowing the way it is, or if there's communication within the walls of the vasculature. If this communication as the cells transmit information, or when to dilate, when to change blood flow, if that is impaired, then we should be able to at least see that with the images that are sensitive to that. 

So the hypothesis is if this is clearly a disease that has some contribution within the blood, or the cells that line up the vessels where the blood is carried, then maybe techniques that are looking into blood, like the ones who work with will be more prone to finding some correlates of the disease, whereas the standard anatomical image will not be able to. 

And this is where we start then to think, Okay, if this is really true, then how do we make it as sensitive as possible? And how do we control for everything else that is also sensitive to but it's not relevant for the questions that we're trying to answer. That's where we start to put all this together. 

And then, as Ewa mentioned, okay, but then how do we control for differences in behavior now, and these responses also change across age groups, right? Across sexes, so we also have to balance our study to make sure we enroll patients from all different ages. And as you know, the distribution of long COVID population is not completely homogeneous right. It's harder to find some subpopulations to enroll. And so a big part of our study, and other people that really help in this study that are not hearing this podcast, are helping a lot with the recruitment. So our research team was really, really trying to push to make that work, too. So just like to acknowledge them here as well. 

Jackie Baxter  
Yeah. And because I think one of the chief frustrations with people, when they're unwell, they go to the doctor, and they say, I have these symptoms, or this happened, that happened. And the doctor says, Okay, well, we'll send you for this blood test, we'll send you for this test, some people get ECGs, some people get, you know, different scans on certain areas. And, you know, like, 99% of these people are coming back and their tests are saying, everything's fine. 

And, you know, these people are saying, well, what is wrong with me, then? You know, in some ways, that's great that all my tests are fine. But I can tell you that there's something wrong with me, because I'm not supposed to be feeling like this. 

And I feel like, the way that you're doing this, because you're going to be doing it over time, over the 12 minutes, I think you said, you're able to see not only the changes over time, but also the changes over time while they're doing a thing. And that, as you say, is much more likely to actually pick up something because it's how the body, or the brain is reacting, you know, while it's doing something, rather than while you're laying down while someone takes blood out of your arm, for example. At that point, you're not really doing anything. 

Daniel Gomez  
I find it hard when people talk about blood tests, and the test should be only used to exclude conditions that we're aware of, not to identify, right? Someone of course has a complaint, then let's first check that it's not everything we know about. And doesn't mean that the person doesn't have it or is lying. It means okay for the things that we're familiar with. That's not what this person has. 

That's where the conversation should even start, right? And so trying to identify ways where to look, if it's not blood tests? If it's not that, then where do we look? Which areas we look? Once we know where to look, then we can start asking more interesting questions, right. But first, we need to know how and where to look

Ewa Beldzik  
exactly like chronic fatigue, a lack of symptoms, very difficult to diagnose with something concrete, from a medical point of view. And the variance probably between anyone who experience such symptoms, it's also gigantic. So I guess there's a room to improvement, room to better understand the underlying of such such symptoms. 

This is exactly the goal of this study. Let's try to see while people are conducting some particular task, how the brain responds to it, and what might be underlying it - is it neural, is it local, is it general, physiological vascular response that is failing here, and may cause this fatigue effect. Like to our knowledge, there's so little is known. And the disease is genuinely new. That also adds to its bigger significance of studying such a project. 

Jackie Baxter  
Yeah, and you mentioned chronic fatigue just then, and this interests me as well because, as you say, long COVID is relatively new. You know, it's from this new virus that has actually been around for probably four years now. But you know, I think in terms of science and medicine, four years is quite new. But, like chronic fatigue, ME, they've been around for a very long time. And is there nothing in this sort of area that has been done for either of those conditions either?

Ewa Beldzik  
Well, for medical diagnosis, and treatment, definitely not expertise enough to say. But I would say that it's that still studies need to be conducted, because it's not that well understood.

Jackie Baxter  
Yeah

Daniel Gomez  
I think some of the some of this tasks, even the colour matching task, I think was used in a study of chronic fatigue as well. I don't think though, that trying to put all these ideas together in the way that we're doing has been done before. And maybe, I don't know if we're doing the right thing or not. But we're trying to capitalize on the expertise we already have in the labs that we're working at. Right. 

So some of these ideas are, have already been used in healthy populations and developed for that, to this very high resolution, high quality imaging with the equipments is one of the labs that are working as a lab in physics and instrumentation, so it's really trying to get the images to the best possible, make the best use of the machine and the technologies today. 

And so it's really combining these ideas from our mentors and trying to build a comprehensive protocol that we would have used for interesting research questions in a healthy population anyway. But extend this to try understand fatigue, arousal and, and within the context of, you know, also sleep, right, because fatigue being related to arousal. And so that's why Yeah, our mentor, Laura is also interested and extremely supportive of this study for these reasons.

Jackie Baxter  
Yeah. And like you said earlier, you know, this is a study, it's kind of the first in a long line, I suppose, isn't it? You know, you do one study, and then that leads you to another and another. So you kind of have to start somewhere, don't you? And some of the answers you get may not be the ones that you want or expect. But that's still useful, I think, isn't it? Because you don't know the answer if you don't ask the question, I suppose.

Daniel Gomez  
And also, as we go, we try to collaborate and talk to other researchers in the long COVID space. Our study is not the only one being conducted at MGH, at the Massachusetts General Hospital. So we try to learn from other groups as well, even from how they're recruiting and, you know, scheduling and managing the entire research setting. But also what ideas they have about what could influence those images, and what are they trying to look at? And are there things that we should keep in mind. So we learn a lot from those other studies to, our interactions.

Ewa Beldzik  
Boston is amazing, extremely collaborative environment. There's so many universities here and amazing scientists that can contribute to understanding. And this is the goal, like we're not competing here, who will be the first to discover anything. We really just want to understand it better. 

Jackie Baxter  
So are you still recruiting for the study? And how do people sign up? Is there a sort of criteria that people have to fit? What's the process here?

Daniel Gomez  
We do have a link for those who are interested. Because it's an MRI study, the first criteria for enrollment is being MRI compatible, as we call it, so we cannot enroll anyone that has any metals in their body. But in terms of COVID itself, we ask a couple of questions related to fatigue, to sleep, medication. And as long as they fit this criteria, we're not enrolling anyone who also has substantial lung issues, for example, or anything that could affect respiration, just because there'll be really hard for us to compare. 

But if if anyone that has severe fatigue and notices that this fatigue is in a way mental, if I can call it like that, then we're very interested in having them, you know, participate in our study. And with that link here, anyone within the, you know, broader Boston area, we offer transportation for them to come and go, so we can pick them up at whatever time is convenient for them, and work around their schedule as well. We are actively enrolling, so if anyone is interested in participating, more than welcome to reach out.

Jackie Baxter  
Yeah, and I will make sure that that link goes into the show notes. So if anyone is in the right sort of area and interested then go and check that out because this sounds really interesting. And you know the results from this, I suppose for anyone who doesn't live close enough to actually participate. Because I'm thinking, yeah, that would be a little bit of a trek for me, then you know that that's what we were saying earlier, wasn't it? You know, this is this is the springboard for more. The findings that you get from this will be part of the wider Jigsaw of long COVID that the world is trying to solve, I suppose, isn't it? 

And speaking of results, what is your timeframe for this? You know, you said you're enrolling at the moment. And, you know, obviously, need to do the study itself, how long are you sort of foreseeing that taking before either the study is done, and you're going to get results?

Daniel Gomez  
Started collecting data, after piloting everything, around May of last year, and we've scanned about 12-13, healthy controls, and 10 or 11 patients. And I want to increase that number to at least 30 of each. And the scans, the pace that we can manage this scan is about once or twice a week. 

So we're looking, hopefully finishing the data collection by July, August. And of course, some of the results come early as we look at the data. But I would imagine that the timeframe for conclusion of the study to be closing mid 2025, to maybe end of 2025. 

Ewa Beldzik  
Realistically speaking that unfortunately, that's sometimes how long it takes. 

Jackie Baxter  
Yeah, I think, again, I don't have a researcher or a science background. And it was quite interesting for me starting to speak to researchers like yourself, and to understand the process a bit more. And, you know, I was actually still trying to get my head around the fact that it's 2024. I, every single time I've written the date, so far, it's it's the 10th of January, I don't know when this episode will air, but it's being recorded on the 10th of January. So for the last 10 days, I have written 2023 Every single time. 

But a year and a half to two years from now, like it sounds like an awfully long time. But in the context of how long research takes, that's not that long, really is it? It just, you know, to do things correctly, and to get data that is useful. It does take that long, I think, doesn't it. You would do it quicker if you could, right?!

Daniel Gomez  
We try to operate as accurately as we can. And we can't scan continuously, because there are other groups that also make use of the equipment. So that's one limitation. The recruitment itself. And then the data analysis, we could even do it quickly. But then interpretation and putting all these pieces together. And of course, our time is also divided, there's some attention that has to be given to other projects, right. We're in the lab where we have graduate students as well. 

So there's a lot of other things that take our time, if we had an industry team with 20 people working full time on this, maybe we would get answers within a month or two, but within the limits of our, let's say human resources that we have to dedicate to it. Even if we commit full time to it, it just takes that long to be able to look at all the data. 

Every session require not only the behavioral data, but there's all those images that are generated. So in these videos, we're generating about 6 to 7000 images per session that we do consider all of those. And then we have to deal with minor issues of motion and then putting the images in place and controlling that things are done accurately. We also monitor the respiration by respiratory belt, we have a pulse oximeter in the patient's fingers, they have a mask with which we monitor expired co2, and then all the data is recorded and other computers. So that also has to be analyzed. 

So for every session we collect, just to give a rough estimate, maybe 40 to 50 gigabytes of data. And so think about this we're dealing with terabytes of data that have to be analyzed and transported and cleaned and looked at one by one to make sure that, you know, if the scanner breaks down, and there's something in the images, you know, we cannot analyze that we have to stop and look and then call the team to come and figure out what's going on in the scanner. And then the scanner is down for a week. And so there's a lot of other little things just you know, barriers in the way from us to making those judgment calls. 

Of course, as we go we discover things too. So some of the datasets that we've collected for the healthy population, very preliminary work, we've already written up and submitted to a conference. This is then unrelated to long COVID, Is just showing how we are using these methods, and how we are doing the assessment of neuronal and physiological changes. So some of this comes along as we go. But I think the complete picture including the patient data, I could foresee it taking a little bit longer than we would have liked to say today.

Jackie Baxter  
Well you guys are certainly going to be busy over the next couple of years, that's for sure. 

Ewa Beldzik  
And of course, we would love to share with you once we will reach any results that will be shown, and we'd love to share.

Jackie Baxter  
Yeah, no, I would absolutely love to have you guys back on when you have things to share about results and things, that would be awesome. 

Well, thank you so so much for joining me this evening, or this afternoon, I think for you. It's been absolutely fascinating. And I am so excited to see what your results are when you get them. So I will make sure that all of the links that you've mentioned, go into the show notes. So there's a sign up form and an email address, I think that if anyone wants to get in touch, and yeah, good luck with it all. Thank you.

Ewa Beldzik  
Thank you so much. 

Daniel Gomez  
And we'd like to thank of course, not only our team, but also the patients that you know, volunteer their time to come participate in this study. 

Jackie Baxter  
Yeah, definitely. Yeah.

Transcribed by https://otter.ai