← MS Living Well: Key Info from Multiple Sclerosis Experts
MS Living Well: Key Info from Multiple Sclerosis Experts
Beyond White Spots: Rethinking MRI in MS
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Foreign.
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Welcome to the Ms. Living well podcast. I'm your host, Dr. Barry Singer, director of the Ms. Center for Innovations and Care at Missouri Baptist Medical center here in St. Louis. Today's episode is Beyond White Rethinking MRI in Ms. This episode is sponsored by TG Therapeutics. Imaging plays a vital role in diagnosing and managing ms, helping clinicians detect lesions in the brain, spinal cord, and optic nerves. While distinguishing Ms. From other conditions that can look similar, MRI also helps us track disease activity over time and guide treatment decisions. For people living with ms, imaging can offer a clear understanding of what may or may not be happening beneath the surface. Later in the show, Professor Frederick Barkov will talk with us about the future of Ms. Imaging. We'll discuss new and exciting innovations in the space, including myelin repair and artificial intelligence. But first, I'd like to introduce Dr. Anthony Trabulci, professor of Neurology at the University of British Columbia and director of the UBC Ms. MRI Research Group in Vancouver. Internationally recognized for his work in MRI and Ms. Clinical trials, he has helped shape how MRI is used to diagnose, monitor, and better understand multiple sclerosis. Dr. Shalbusi, welcome to the Ms. Living well podcast.
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A
Hey, Barry.
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B
So if someone's diagnosed with ms, Tony, why is MRI so important?
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A
MRI is just such a great tool to have just to get more information of what might be going on, because many of the symptoms of Ms. Aren't necessarily specific to Ms. So the brain MRI especially, is particularly important as one of the first steps in establishing, establishing a diagnosis of Ms. Or ruling out an alternate cause.
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B
So imaging the spinal cord, does that help?
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A
I love the spinal cord imaging. It really gives more specific information. For example, with brain imaging, it's not unusual to see a few white spots in the general population, which can cause stress and confusion. But if there is a white spot in the spinal cord, it has pathologic meaning. It's really important in trying to figure out what's going on. So, love the spinal cord imaging. It's more difficult to do than the brain, but worth it.
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B
Yeah. Because a lot of times, like you said, you can have spots in the brain and they could be from other causes, and we'll get into that a little bit later. But it's pretty unusual to have lesions in the spinal cord due to other causes.
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A
Absolutely.
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B
Yeah. So what does contrast add to an mri?
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A
The contrast can be really helpful, especially in that first diagnostic mri. It really has at least two major roles. One role is it can help sort out things that can mimic Multiple sclerosis. There's a list of different diseases that sound like ms, but when you give the contrast, they look so completely different on the mri. It really cleans the playing field for us. And the second rule, and I still think it's important, if we see some white spots and one or two of those white spots light up with the contrast, it gives us that sense that this is a dynamic biological process. In other words, there's lesions that are old and lesions that are new. New lesions are illustrated by the contrast. Incredibly helpful to have that information. And I'd say about 30% of people being investigated for early Ms. Are going to show a positive sign with the contrast. So it's a high yield test and very, very safe to use as well.
- [03:34]
B
So the contrast leaks out of the blood vessels that are actively inflamed, and that only lasts about one to two months. Right. So an active lesion only stays active for a short period of time. And if it's still bright with contrast a few months later, you're probably looking at something else.
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A
Exactly.
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B
McDonald criteria were originally designed to help diagnose Ms. Earlier so that we could initiate treatment sooner. The 2024 update added the optic nerve is the fifth area that we look for evidence of Ms. On MRI. Can you walk us through where Ms. Typically shows up on MRI and what those locations mean for patients?
- [04:12]
A
I was really interested by this addition of the optic nerve because about 30% of patients start with optic neuritis or inflammation of the optic nerve as a presenting symptom. So it was there as a criteria, but that was more of a clinical criteria. I think what we're looking at now is adding the optic nerve for when someone has not had optic neuritis. So you can use that as a second space location and either detecting that with an MRI or with visual potentials or another technique called oct, both really easy techniques to do. The whole idea of multiple sclerosis is that it's multiple scars in different locations throughout the central nervous system to distinguish it from diseases that just might affect the spinal cord or might just affect the optic nerve. And so having at least two locations affect it, such as the optic nerve and spinal cord or optic nerve and brain, really increases the confidence. You're dealing with multiple sclerosis and not one of the mimics that's out there.
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B
And so the other areas, where do we look for lesions? Like when we're looking at the brain,
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A
some of the other common areas in the brain that actually fit into what's called the dissemination in space. Or the multiple locations in the nervous system is the lower part of the brain, called the brain stem. Another location is adjacent to the water spaces in the brain called ventricles. So those lesions need to touch that space, and then the final location is at the very edge of the brain, close to the cortex, where all of our gray matter is. Being in those specific locations really increases the confidence. You're dealing with multiple sclerosis, where sometimes there's been misdiagnosis based on MRI has been the misclassification of those lesions. For example, a lesion just in the brain, but not quite touc the cortex or not quite touching the ventricle. Being mislabeled has been a common cause of misdiagnosis of early Ms. Yeah, so
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B
that's really critical, knowing what you're looking at, right?
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A
Absolutely.
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B
So Ms. Used to be always diagnosed by dissemination and time. So it was a critical component where you want to see some changes at one point, and then six months or a year later, there was a new attack, for example, or new MRI lesions. Why is this not always required anymore?
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A
I don't think it's completely been eliminated, but it's not a definite requirement anymore. And where that came from, really, was a lot of what are called natural history studies, where people at the earliest stages of Ms. Have been followed for over 10 years. And then looking back at their original MRI features saying, oh, if you have A plus B plus C in terms of these MRI features, you've got Ms. We don't need to wait five years for you to have new symptoms or new MRI lesions to firm that up. And so this new criteria can essentially eliminate that need to wait for time to show a dynamic disease. They're so predictive, it really allows an earlier diagnosis, which allows an earlier conversation about what it means to use an individual.
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B
Let's talk about some new technology that's helping us be more definitive about a diagnosis of Ms. One of those is the central vein sign. Can you describe what that is to our audience?
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A
This is a really cool new way to look at Ms. Lesions. It's a technique that could be done on most scanners. And the whole idea is Ms. Lesions grow around veins in the brain or blood vessels. And blood vessels show up because of iron inside the blood. It can show up on this new technique called iron imaging or susceptibility weighted imaging. And so you can create this beautiful map of all the blood vessels in the brain, and you can marry that map to a map of lesions. And so you can see if there are these veins inside the lesions, and no other disease really does that. And so if we see all these veins inside all the different lesions, it increases the confidence that those lesions are there because of Ms. And not because of high blood pressure, diabetes, or getting older and getting these non specific white spots, it's not easy to do. So I suspect looking for the central vein sign isn't going to be done on every scan every time, but it's going to be a really important tool for the more challenging cases. The older patient over age 50 that we think might have MS, there's still a big learning curve on how to use that technology, so stay tuned on that one.
- [08:27]
B
Yeah, I've been using it for a few years in the clinic and particularly I do it on patients where I'm not sure do they really have Ms. Or not. Sometimes it's very clear. There's some people that have been followed for years, negative spinal taps. And it's very clear almost all the white matter spots have central veins. But sometimes it's not so clear. I've seen people who have less than 50% have these veins and they have definitive MS, positive spinal fluid, positive lesions in the spinal cord. So, yeah, I think it's to be determined the new McDonald criteria is six or more central veins as opposed to initially it was considered like most of the lesions should have central veins.
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A
I do like the 6 rule because if you're looking at 30 or 40 lesions, you only have to find 6 that have the central vein sign.
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B
Yeah, I've definitely seen some people that have a. A lot of veins in the brain, though. It makes it a little more challenging. Have you seen that as well?
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A
Yeah, absolutely. Yeah.
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B
So let's talk about. You mentioned these nonspecific white matter change. People read this all the time in the reports. What does this actually mean? And you mentioned hypertension could be one of the causes. What are the other causes of non specific white matter change?
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A
Yeah, they're pretty common. And up here we call them unidentified bright objects or UBOs. They just increase with age and sometimes the cause is never known. Hypertension would be one of the common causes. The normal aging brain, cardiovascular disease, diabetes, smoking, and even migraine headaches. So the important thing is not to worry about it. When one sees that report. The MRI needs to be reviewed in the context. What symptoms do they have? Why was the MRI done? To interpret these white spots, if they're of any concern or not.
- [10:06]
B
Now a lot really depends on the age of the patient. Right, Tony? So almost everyone over the age of 50 starts to get these white matter spots in the brain. So if a patient is 35 years old and we find 10 lesions on the brain, it's a lot more concerning than let's say a patient was 65.
- [10:23]
A
And that's where you might do the MRI of the spinal cord or look for the central vein sign.
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B
There you go. What are the most common reasons why someone might get misdiagnosed with ms? Based on their mri?
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A
I can think of at least two major classifications for that. One is misclassifying the lesions or the white spots seen on MRIs. They're being called periventricular juxtacortil, but they're not truly those classifications. And the other group would be misinterpretation of symptoms. People with migraine can have an aura with their headache where they get blurring of vision, and that could be misdiagnosed as optic neuritis. Or a herniated disc in the back causing a numb leg could be misdiagnosis, inflammation of the spinal cord. So it's on both ends, the clinical interpretation of the symptoms, but also the clinical interpretation of the MRI lesions being misclassified.
- [11:10]
B
Here's a common question that comes up. Can someone have Ms. Even if their MRI looks normal?
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A
That makes me really uncomfortable. So I guess in medicine anything's possible. But that would be what we call a huge red flag and that we should be looking for other causes. Let's say someone presented with loss of vision, optic neuritis and a normal brain remarrier. We're going to be thinking about alternates such as neuromyelitis optica, for example. I think it's always possible, but I would keep that person on my radar with close monitoring over time just in case something different creeps up.
- [11:43]
B
Yeah, some people have optic neuritis and maybe a couple small spinal cord lesions and nothing in the brain. So that could be one way. But if you have nothing in your brain's spinal cord, Ms. Is pretty unlikely. I've seen a few people right at the beginning of their disease, someone with a numb face and a numb leg, and sure enough, spinal fluid was positive, but they had no lesions. So there's a rare person out there. But over time the these patients have developed lesions. So I've seen a few of those over my entire career. So once someone is diagnosed and starts disease modifying therapy, when do you repeat the mri?
- [12:19]
A
It depends on the different scenarios. So someone relatively newly diagnosed with Ms. Starting treatment. We recommend doing MRIs about once a year just to make sure the treatment's working for them that they're not developing any new lesions. And when they go into a nice steady state of not having any new lesions or symptoms, you could do it every couple of years. And we're certainly seeing that. With patients on high, highly effective treatments, MRIs become so wonderfully boring, nothing new happens. I love it. But then there are some patients on certain medications that might have some safety risk, such as pml, which is a type of brain infection. In those patients we would image more frequently in the later stages of ms, especially in progressive ms, we don't tend to see new lesions on MRI despite ongoing progression. And in that case there seems to be less value in doing regular monitoring of mri. And there's some other special scenarios such as after having a baby, re establishing the baseline MRI or switching treatments, you want to reestablish the baseline MRI with a bit of a gap of time to let the new medication kick in fully.
- [13:19]
B
Great insight. What about contrast? Some routine follow up scans. There's autopsy studies have shown traces of contrast still in people's brains. We haven't seen a specific disease. What do you do with the contrast?
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A
In the past people would be doing contrast on every follow up scan, but especially with the new treatments nowadays it's so rare to see new contrast enhancing lesions. So generally speaking we're not recommending contrast on routine follow up scans. There are some very specific scenarios where it might be quite helpful if you're rethinking the diagnosis, which can happen at any point. It's always good for some patients who aren't following a course you think they should follow to rethink the diagnosis. Repeat the imaging from head to toe and use contrast changing to. Some medications require a contrast scan. Or if you don't have any background imaging on this individual, it's been ages since they've had an MRI scan. Getting contrast just to get a new line in the sand where they're at in terms of fresh inflammation can be really helpful.
- [14:14]
B
So one of the other questions that comes up is about spinal cord MRI imaging. Do you routinely monitor the spinal cord and are there guidelines on this?
- [14:24]
A
Yeah, our guidelines we're suggesting to not routinely monitor the spinal cord. Now there are scenarios again where it could be very helpful, such as if a patient's having a relapse, you might want to confirm radiologically that there's a new lesion there. And that's where spinal cord imaging can be very helpful if it's new symptoms referable to the spinal cord. There are some patients where it really feels like it's spinal cord dominant ms, where all their attacks seem to affect their spinal cord. And those patients might want to incorporate more routine spinal cord imaging. But generally speaking, if there's new inflammation going on in the spinal cord, often the patient's going to have symptoms. Whereas if there's new inflammation going on in the brain, that's the silent part of the nervous system. So less likely to have symptoms. And that's where we get the biggest bang for our buck with imaging is picking up things someone might not feel.
- [15:14]
B
It's interesting. Over the years I've been doing a lot of cervical spinal cord imaging. If they don't have any spinal cord disease and I'm not doing that routinely, I mostly do cervical spine but people on modest efficacy treatment. I'm starting to dip down lower into the thoracic spine and I have seen people with brain cervical look pretty good. But the thoracic spine is taking some hits over the time and we may want to upper game in terms of treatment. On three Tesla MRIs, you can start to see some pretty small lesions in the spinal cord that may be asymptomatic, which means you're not having any symptoms.
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A
It's probably worth re baselining every once in a while because we're following these folks for 20, 30 years.
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B
Exactly. Doesn't matter where you obtain your MRI scan.
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A
It does. You want to go to a center that is following the Ms. Protocol because quality matters, especially if we're looking at a condition that goes on for many years. You want to compare apples to apples and ideally going to the same center year after year would be perfect because even multiple centers following the same protocol, there still can be some technical differences between scan sets.
- [16:21]
B
I think one of the biggest challenges in the US because health insurance, sometimes people have high deductibles so they prefer to do it at an open MRI or place with less strong magnet because it's going to be a lot cheaper than at the hospital. And then sometimes you are comparing apples to oranges. Especially the spinal cord is the caliber of a pinky. So it's hard to see tiny lesions if your magnets aren't strong enough. So you're imaging on three Tesla magnets. So the Tesla is not your car, it's how strong your magnet is.
- [16:49]
A
We have A mix of 1.5s and 3 Teslas and 1.5 has been the main workhorse internationally. And as people get news scanners, they're usually replacing them with the 3 Tesla which does improve the image quality. That said, size doesn't always matter. It's again, how the site does their protocol. I've seen some really crappy 3 Tesla images and fantastic 1.5 Tesla images. So it really comes down to the care that the MRI center puts into their protocols to get the best quality images out.
- [17:21]
B
So any advice for the people who feel claustrophobic, which is not a small group of patients?
- [17:27]
A
Yeah, it's tough. Depending on your region, how many scanners are available? There might be some that have a more open bore or that's the opening that you go in. And they have some neat tricks in there like headphones and television screens that play a movie or nice background. So that can be very helpful. Of course, don't drink coffee before going in or too much caffeinated products. But it can be really tough. Even despite all those things, we're playing with a really cool new technology, which is a portable MRI, which is kind of hairsy.
- [17:55]
B
Yeah, the portable MRIs, I'm not. I've been. I'm not too impressed with the pictures. Usually our go to is diazepam, so 5 milligrams an hour before, and if you're freaking out, another 5 milligrams right before that. Seems to work. And just no driving home. You got to get a ride.
- [18:11]
A
Exactly.
- [18:12]
B
So final question. What do you wish every person living with Ms. Understood about their MRI scans?
- [18:18]
A
It's just a tool. It's a test. It's a piece of information to help us put the whole puzzle together. I think is one of the important things, especially early on with making the diagnosis and then later on in monitoring the disease. It's so sensitive for picking up new lesions, which could be an indication of the need for medication or need for switching medication. But where it becomes limited is later on in Ms. You've probably had the same conversation with people who start developing progression, say, well, what does my MRI show? Well, it looks exactly the same as it did before. Lesions are just the tip of the iceberg. And what could be going on. And that's where we need more tools. We're working on more tools to better understand what's happening in the brain, to predict who could have progression, how we can stop that.
- [19:01]
B
Yeah, that's actually a perfect segue to Dr. Barkoff, who is our next guest. He's going to talk about the future of imaging and monitoring and how we're going to look at progression and potentially remyelination. Well, Tony, it was a pleasure having you on the Ms. Living well podcast. Thank you for all your contributions to the world of Ms. And looking forward to collaborating in the future.
- [19:21]
A
Thanks, Barry. It's been a pleasure as well.
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B
I'm really pleased to introduce my next guest, Professor Frederick Barkoff, professor of Neuroradiology at Amsterdam UMC and University College London, and one of the world's leading experts in MRI imaging and multiple sclerosis. His groundbreaking work that helped establish MRI criteria has allowed clinicians to diagnose Ms. Earlier and with greater accuracy around the world. Professor Barkoff, welcome to the show.
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C
Thank you, Barry. Pleasure to be here.
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B
Wonderful. So let's talk about imaging, specifically about brain shrinkage or atrophy. What do those terms mean and why do they matter so much for people living with multiple sclerosis?
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C
When we make MRI scans of the brain in people with Ms. Or suspected to have ms, we typically look for small focal abnormalities in the brain tissue. White matter lesions. And based on the number and location, we try to make the diagnosis. But beyond these focal lesions, one can also look at the overall volume of the brain and the shape of it. And this can change over time. And. And as we get older, the brain tends to shrink a little bit, a term we refer to as atrophy. But in various diseases, including ms, you can see that there's a little bit more brain shrinkage than you would expect for age, which probably means that some tissue loss occurred due to the damage caused by the lesions, but perhaps also to other processes.
- [21:01]
B
Yeah. And is this a useful thing to track for individual patients over time?
- [21:06]
C
You would think so, because intuitively you would think if you lose brain volume, it's not a good thing, and you'd like to track that and see if you can prevent it. For example, if somebody's doubting between low and high efficacy drugs and you see there's brain volume, you might want to step up on the treatment. The reality is that it's a slow process, fortunately. So we're talking about, with normal aging, brain volume loss at the rate of, let's say, half a percent per year, which is not something you can see with the naked eye, so you need computer software to calculate it. And then perhaps in MS, it could be 1% per year. But even that is within the measurement error. So, for example, if you would be scanned on a different machine next time, it will be difficult to compare. So it's not that easy to implement it in clinical practice. So we don't have good guidelines. What is normal? What is abnormal? When should you act on it? And can you act on it?
- [22:06]
B
Yeah. And if you have a lot of water, you know, you're well hydrated before you're scan, your brain will look a little plumper.
- [22:13]
C
That's another thing. Drinking a serious amount of alcohol will lead to brain shrinkage. That's why we get a headache when we're hungover. Then obviously if you rehydrate, it comes back to normal. And likewise, if you do lots of physical exercise, you may have a bit of brain volume changes. Or if you take corticosteroids, which is not uncommon when we treat Ms. Relapses, that also tends to squeeze out the water from your brain. So that's yet another reason why it's not easy to use brain volume Ms. Management at the moment.
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B
So we're hearing a lot about smoldering Ms. Over the past few years. So let's dive into that. Specifically, what are slowly expanding lesions and paramagnetic rim lesions, which are pearls?
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C
If new lesions occur in ms, they tend to have an acute inflammatory phase. So in terms of analogies to the smoldering, that's like a big open fire. And when that big open fire subsides, then we think that the lesion becomes inactive. But we now know that some of these lesions maintain a residual amount of inflammation, mostly at the border of the lesion, which is called smoldering activity, which is very difficult to visualize on routine Ms. Scans. But we know from pathology studies and also from PET studies that you can show active inflammation going on in the border of these lesions. And if you then follow them over the course of multiple years, you can see that they very slowly increase in size. And, and that's what people refer to as slowly expanding lesions. Again, not something you can easily appreciate with the naked eye. You need dedicated software and multiple scans to determine whether lesions are slowly expanding. Another Mr. Technique has been developed alongside, which is called susceptibility weighted imaging, which is a technique that is very sensitive to iron because it perturbs the magnetic fields that we use for Mr. Scans. And if you have a little bit of iron in the rim of the lesions, you will see a paramagnetic rim or dark line on the specific sequences. And because Mr. Is very sensitive to iron, you need only a small amount of iron in these chronic active cells that reside in the rims of the lesions to visualize them. So these paramagnetic rim lesions, or pearls, are an Mr. Signature of lesions that remain chronically active.
- [24:45]
B
And that iron comes from the myelin, right?
- [24:48]
C
Yes and no. So iron occurs normally in myelin. So you would argue that if you then lose myelin, that the iron goes down, but here it goes up and the myelin is eaten up by inflammatory cells, so they accumulate the iron. But these inflammatory cells by themselves also contain iron. So that's the reason why there's more iron, especially in the rim of those lesions.
- [25:12]
B
And these lesions are a sign we see these more in progressive patients, correct?
- [25:16]
C
Well, you would think so, but it's actually not true. Even patients with a first symptom of MS, so the clinically isolated symptom, approximately 50% of the patients will have such a lesion. And even patients who are discovered incidentally, so called radiological isolated syndrome, or RIS, 50% of them have pearls, whereas people with progressive MS, about 50% of them have pearls. So it's more a patient bound phenomenon than a disease stage phenomenon. Some people are more likely to develop these chronic active lesions and others don't.
- [25:53]
B
And we don't know why, right?
- [25:55]
C
No, we don't know why. If one lesion is chronic active, the next one is likely to be chronic active, whereas other people don't have it. So it must be something that is genetically determined.
- [26:06]
B
Well, that's fascinating. So maybe based on the presence of these pearls, we might end up treating people differently.
- [26:13]
C
That's my personal feeling that this is a patient bound signature that should inform treatment decisions. For example, you may want to look for drugs that better reach the brain parenchyma. A lot of drugs that we use now stays within the bloodstream. Only a very small percentage is able to penetrate into the brain. And probably for these smoldering lesions you need drugs that will better penetrate into the brain tissue.
- [26:41]
B
You mentioned PET scans, so can you explain to the audience what PET scan is and how they might help us in this regard?
- [26:48]
C
PET scans is a complex and expensive scan. Most people will know it. For cancer treatment, for example, where you do an FDG PET scan. FDG is a little molecule that looks like glucose or like sugar. And if you inject it into the bloodstream, it will go to the brain. If you then radio label it with a specific agent, it will emit a positron. And that's why it's called positron emission tomography, which you can detect. So contrary to Mr. Where you don't have to inject anything for pet, you have to inject a radioactive chemical which is not easy to produce and can only be injected on very special circumstances. The nice thing is in addition to labeling glucose, you can also label a whole series of other molecules where they radiolabel, for example, molecules that bind to inflammatory cells or molecules that bind to myelin. So you can produce very specific traces and highlight very specific processes, but only one at a time, and as I said, with lots of constraints. So this is not something for direct patient care. It's more a research tool, unless we were to develop a drug that would target a very specific type of cells. But at the moment, there's not a clinical indication to use PET scans.
- [28:13]
B
So, Frederic, how much Ms. Activity is happening quietly even when there are no new lesions on mri?
- [28:20]
C
That's a good question, Barry. I think the answer is we don't know. So what we do know, if people don't experience any symptoms, there can be new lesions. It's estimated that probably 90% of new lesions are silent. That's the reason why we do yearly MRI monitoring, even if patients are doing well. Now, obviously, MRI scans also have a limited resolution, so we can pick up big lesions easily, smaller lesions if you have some experience. But obviously there are even smaller lesions which go beyond the resolution of the scans. So if we look in the white matter in between lesions which were very sensitive. Mr. Techniques. We can see that there are abnormalities, and these abnormalities increase over time. And whether this is due to really small lesions that we can't picture or more diffuse processes that occur in the brain, we don't know. Or perhaps it's a combination thereof. But there's definitely something happening outside the focal bigger lesions that we see as bright spots on the scans. And perhaps this is one of the reasons why this brain volume changes that we discussed earlier.
- [29:29]
B
Yeah, and a lot of patients say, okay, their symptoms seem to be worsening, but their MRI comes back unchanged. So could this have something to do with changes in the normal appearing white matter?
- [29:40]
C
It could definitely. Either in the white matter or in the gray matter. And coming back to the phenomenon of aging, obviously, as we age, we all lose a little bit of capacity. But if you have some damage due to whatever neurological disease, including Ms. Or perhaps due to a small stroke, when you age, you run out of capacity earlier. So that's another reason why people can progress without having too much new focal inflammatory activity. But as you said, it could also be the smoldering lesions or changes in the normal pain white matter that continue to accumulate damage.
- [30:18]
B
Let's turn to the gray matter. You mentioned that. So we know progressive patients have a lot of gray matter disease, but when we do routine MRIs, like, for example, a flare scan, we don't really see lesions well in the gray matter. So are we making any progress on visualizing the gray matter?
- [30:37]
C
Some, but it's slow. I think important thing is the awareness. And there are certain Mr. Techniques that will bring them out better, like flare or double inversion recovery or other sequences that people play around with. It helps also if you go to higher field strengths, a free Tesla or even 7 Tesla, you will see more. But even at 7 Tesla, we miss the vast majority of them. And that is not surprising because we're trying to look for myelin loss, and the cortex has very little myelin.
- [31:07]
B
That's true, but it's important, so hopefully some progress will happen.
- [31:10]
C
Yeah, it's unfortunate because it's probably very relevant for lots of aspects of Ms. For example, cognitive deficit are probably mostly determined by cortical pathology, and it's really a pity that we can't depict it better.
- [31:26]
B
So what about functional mri? Functional MRI looks how the brain is working and not just structure. What does that taught us about changes in people with ms?
- [31:35]
C
So functional MRI is a nice tool. It allows us to examine the brain without injecting anything. You just ask people to perform a task or, or even when they don't perform a task. Usually functional networks in the brain, and on a group level, you can see that people with Ms. Have alterations in their brain connectivity. So certain brain regions are a little bit more active, others are less active. The connections between brain regions gets altered. And in part, that is probably showing some adaptation of the brain, because the brain has millions of connections and multiple ways you can carry out a task. So if, if some connections are damaged because there's a lesion, the brain is smart enough to circumvent that and use an alternative pathway. But at some stage, this compensatory mechanism gets exhausted, and then the, the network really is stressed and collapses. So that is the moment that people start to experience, for example, cognitive problems or problems with ambulation even. Just because these compensatory mechanisms fail.
- [32:51]
B
Yeah. And sometimes you have to activate more areas of the brain to do the same task. Correct.
- [32:56]
C
Just need to work harder.
- [32:58]
B
Yeah. A lot of our patients describe fatigue, cog fog. But there may be so many physiologic findings on functional MRI that supports that.
- [33:06]
C
That could be the reason. Just you have to work hard to get the same result, and that must be, of course, causing fatigue.
- [33:12]
B
What about myelin repair? We're hopeful that one day we're going to have an agent that can turn on those oligo precursor cells, those immature oligo cells, make mature myelin and repair. I know. I've been working on this with clinical trials over the years. Are we getting closer to being able to make measure that on imaging.
- [33:32]
C
We try. We have measures that can determine the amount of myelin. These are not the routine imaging techniques, but also not too difficult quantitative MRI techniques. They correlate reasonably well with myelin density. If the myelin goes down, the signal goes down, and if remyelination occurs, it goes up again.
- [33:53]
B
So Frederik, what are those specific tools that you use or sequences that you use to look at this?
- [33:59]
C
There's a series of them and one of them is called magnetization transfer imaging, which is a special property of myelin to influence the water protein interactions may allow you to visualize myelin. One of them is a pet. We talked about PET previously. There are some PET tracers that bind selectively to myelin. They might be the most specific signal that we have. And there's a series of additional quantitative Mr. Techniques that one can use.
- [34:26]
B
Okay, great. Well, hopefully we'll have more agents and we're going to need you to help us design the trials so that we can see if there's some imaging response. All right, so there's a lot of excitement around AI. It's everywhere in our lives these days. How might it change how MRIs are read and used in Ms. Care?
- [34:45]
C
There's definitely a lot of noise around AI. And about 10 years ago, one of the the founders of DeepMind predicted that in five years time, radiologists will be extinct. And around that time also people predict we will be driving in AI driven cars. But the reality is radiologists still exist and they have to drive their own cars. So it's a lot of promises, good
- [35:08]
B
for good job security right there.
- [35:10]
C
Jokes aside, AI is at the moment best at sort of simple tasks. For example, if you have a brain scan and you need to find and count the number of lesions, the AI tools can segment the scan and tell you, okay, I found 10 lesions and this is their volume and help you perhaps track it over time. So that if people have routine monitoring scans, you can more easily and more reliably detect whether there are new lesions or not. Especially if people are scanned on the same scanner. What AI is less good in is making more high level medical decisions like does this patient have Ms. Or could it be another diagnosis? They clearly can play a supportive role. AI can also help in the acquisition of the images. So if you lie in the scanner, you have to lie there for let's say 15, 20 minutes because you need to send a lot of RF pulses and collect back the information. And with AI, you can actually scan a lot shorter and then still reconstruct the full image. And that is a big game because a lot of patients find it difficult to lie still in the scanner for sufficient amounts of time. It's also good for shortening examination times and perhaps making the scans cheaper. If you can scan three or four or five times quicker, obviously you could scan more patients. But you could also argue if you just scan the same time, you get much better signal to noise, so you get much better images with better resolution, perhaps pick up these small leashes that now disappear in a normal white matter. Or you can perform routinely quantitative techniques like MTR to provide complementary information. So this provides a lot of opportunities, I think.
- [36:57]
B
Yeah. So it's exciting that we'll have much more information, hopefully making our decisions well, Frederic, thanks so much for being a leader in the field of neuroimaging for a long time in the world of Ms. So thank you so much for your insights and for being here.
- [37:12]
C
Pleasure to be with you, Barry.
- [37:21]
B
Today's conversation with Dr. Trabulci and Professor Barkoff highlighted how imaging has become one of the most powerful tools we have for understanding multiple sclerosis, for making earlier, more accurate diagnosis, to uncovering the hidden biology driving progression. As MRI technology continues to evolve, it may also help us measure, repair, monitor smoldering disease, and personalize treatment decisions for people living with Ms. Thanks again to TG Therapeutics for sponsoring this episode. Keep in mind the topics we discuss on the show are strictly informational and not medical advice. Any change in your treatment should be discussed directly with your healthcare providers first. Our show is hosted by me, Dr. Barry Singer and Dr. Jamie Holloman and produced by Carriette Harmon. Our theme music is Buy Broke for Free. If you like the episode, please share it with others living with multiple sclerosis and we would love it if you could post a positive review on Apple Podcasts. It really makes a difference to us and allows more people to learn about the show. You can follow me on X at Dr. Barry Singer and Dr. Jamie Holloman at BrainBoyNeuro. One more information about our guests and their websites can be found in the show notes for this episode in the blog section on mslivingwell.org thanks so much for listening. This has been an Ms. Living well podcast.