S8E17: Beyond lesions: what advanced MRI may reveal about MS.

Bhavana Solanky (00:00)

Total sodium concentration was increased in people with MS, but it was higher depending on what sort of MS you have. So if you had relapsing remitting or secondary progressive or primary progressive, the amount of sodium increase you got was sort of in line with how progressed the disease was and also the sodium concentrations related to disability as well. And this isn’t sodium just in the lesions that you can see in the standard MRI. It’s sodium that’s changing in what looks like normal healthy tissue.

 

Overcoming MS (00:26)

Welcome to the latest edition of the Living Well With MS podcast. Joining me on this edition is Bhavana Solanky. So welcome Bhavana.

 

Bhavana Solanky (01:11)

Hi.

 

Overcoming MS (01:20)

Bhavana is an MRI physicist with over 15 years of experience at the Queen’s Square Centre for Multiple Sclerosis in London England, where her work focuses on developing novel MRI markers to better understand multiple sclerosis. Her research aims to uncover how MS affects the brain at a chemical and cellular level and to translate these insights into tools that can help measure the effectiveness of new treatments and distinguish between different MS subtypes. So welcome, Bhavana, yeah, welcome to the podcast. So to start off with, could you give us a bit of an introduction of yourself and your work?

 

Bhavana Solanky (01:50)

Thank you.

 

Yeah, thank you for the kind introduction you’ve already given. It’s really nice to be on here. So I work as a researcher at the Queen’s Square MS Centre, University College London. And my job as an MRI physicist is to develop MRI scans and to develop biomarkers to help understand MS better at a cellular level, to measure different chemicals in the brain and things like that.

And the way I do that is a bit like using the MRI machine, like a giant SLR camera, where if you want to get a different type of image, you have a different shutter speed or a different lens or a different flash, and you get a different looking image. So what we want is different looking images from our brain or spinal cord to tell us different things about what’s going on.

 

Overcoming MS (02:46)

So it’s a bit because I think most of us probably think of it as a bit like an x-ray but kind of in 3d but you’re saying does a lot more than that.

 

Bhavana Solanky (02:53)

So. It does a lot. So with the x-ray, number one, I guess it’s similar in the same, you get an image of the part of the body with x-rays, mostly bones. With MRI, get a soft tissue contrast. So you’re seeing muscles, fat, fluid in the body that you might not see in an x-ray. And it’s completely non-invasive as well. So it doesn’t matter how many you have. It’s not going to harm you. I, as an MRI researcher, go in the MRI scanner a lot for many many different studies to test sequences that we’ve developed. So yeah, it’s completely non-invasive and it can tell you a lot more.

 

Overcoming MS (03:33)

And so you’ve come from a background as a physicist, but what led to your research interest in multiple sclerosis?

 

Bhavana Solanky (03:40)

So it’s quite weird actually. I started with astrophysics. I really enjoyed it. I wanted to learn how stars are made and things like that. But by the end of my degree, I wanted to do something that more directly helped people. And there’s actually a lot of overlap between the physics involved with looking at distant galaxies and looking inside your brain or spinal cord, because they both use radio waves and they use these little satellites. We call them RF coils and MRI. They use these little satellites to collect the signal and then you use a fancy computer to make that into an image. So a lot of that I’d already sort of covered a bit and I felt, I can help people more directly. So I went off, I did some research into diabetes, liver toxins and stroke models. And then I saw this job at UCL and it was really interesting as an MRI physicist, they were the first center to do something called sodium MRI in the UK. And I thought, well, that’s really exciting. It’ll be, you know, a first.

 

And it worked with this leading MS research group, which was really exciting. But what really sparked my curiosity is the entire MRI scanner had been funded by the MS Society, a charity. So it really sparked my curiosity why they would, you know, invest so heavily in MRI. And I’ve since learned how integral MRI is in MS and understanding it, diagnosing it, monitoring it and I’ve been there 15 years now and there’s just so much more to learn and so much more to do in this field and so many more ways that MRI can help us understand and hopefully stop MS.

 

Overcoming MS (05:17)

Back to the technical side of it, what is an MRI scan and how do they work and what can you see? I think you mentioned a bit about what you can see with it.

 

Bhavana Solanky (05:25)

So it’s a bit like, so when you go for say an MS MRI scan to diagnose or monitor, what we’re getting images of is the water inside your body and the hydrogen atoms. So these hydrogen atoms, if you think of the compass, for example, it acts like a compass needle. So when you’re outside of the MRI machine, you have lots of compass needles all pointing in random directions. When you go inside an MRI machine,

 

It’s a bit like the compass aligning with the north. It will align with the magnetic field. And so all these hydrogen atoms are in alignment. And then what you do is you use a radio wave. what that does is it knocks it out of alignment. All these spins, all these hydrogen atoms out of alignment. That’s a bit like shaking your compass vigorously, right? It’s not going to be pointing north. But when you stop shaking, it goes back to pointing north.

 

So these hydrogen atoms, when they go back to alignment, they give off a tiny signal. And that’s the signal that we use to build an image of our brain or spinal cord in MS, for example, any other part of the body really, to enable an image. And I know you mentioned earlier that, you go in an MRI scanner and you hear all these different noises and it goes like, do, do, do, do, do, do, do, do. That’s really important because if we just got one signal, we wouldn’t know where it came from. So if you did have a lesion, you wouldn’t know where it is. So what that noise is, is something called gradient coils, and they basically label each bit in your body. So the computer knows exactly where that signal came from, and so you can build up an image. And when these hydrogen atoms go back to being in alignment and give off the signal, the rate at which they do that and how they do that really depends on their environment.

 

And that’s really key in MRI because it gives us a contrast between white matter and gray matter, between lesions, between even tumors and your normal appearing matter in the brain. And so there, that’s kind of the nuts and bolts, I guess, of how you would get an image. And what you want to see in MS, for example, is where your lesions are, if there’s a new lesion. And so you want that contrast between the different tissues and the fluids in your body to be able to tell you that.

 

Overcoming MS (07:48)

Can you tell if a lesion is active or not?

 

Bhavana Solanky (07:52)

Yes, so you can tell a lesion is active. Usually you would use something like a contrast which you inject. So I’m an MRI physicist, so clinicians can probably interpret this better than me. But basically what the contrast do, it contains tiny little bits of metal. Gadolinium, for example, is one of them. And that helps any lesions that are active appear really bright.

 

And so you know that you have a new lesion in the MRI.

 

Overcoming MS (08:25)

And why are MRI scans so important? They seem to be like the gold standard now where they didn’t exist 20, 30 years ago. Why are they so important in MS diagnosis and monitoring?

 

Bhavana Solanky (08:40)

So the thing with MS, when a patient with MS presents in a clinic, they can have a number of symptoms which overlap with lots of other conditions. So it’s really difficult to diagnose. But with an MRI, what the clinicians are looking for, and as part of the criteria to diagnose MS is lesions and new lesions. So lesions that are in different places. So there might be a spinal cord, might be in different places in the brain. So spatial dissemination as well as dissemination in time. So if you have a new lesion as well. So having a new lesion shows up there’s something actively happening. There’s more inflammation in your brain leading to the MS lesion. it’s integral to the diagnosis of MS.

 

Overcoming MS (09:25)

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Overcoming MS (09:38)

And so I’ve had some different types of MRIs, but I’m not really sure why they were different. So what are the different types of MRIs that you can have and what different data do you get out of them?

 

Bhavana Solanky (09:50)

So it’s, I mean, there’s so many different types of MRI. There’s ones that measure function in your brain. There’s ones that measure the amount of cellular volume in your brain and things like that. But the really basic ones that you’d get if you went for an MRI scan and you were suspected of having MS or it’s a monitoring scan for MS, you’d probably have four main ones. So the first one is called a T2 weighted scan. Basically what that shows you,

 

is the lesions in your brain show up really bright and so that tells the clinician how much of your brain has been affected by lesions, so your lesion load. But also in this T2-rated scan, your ventricles appear really, really bright and so that can almost get in the way of seeing lesions that are around the ventricles, so that’s the liquid right in the middle of your brain.

 

I don’t know if you’ve ever seen them MRI images, like a sort of butterfly in the middle of your brain. That’s your ventricles. And it appears really bright in this image. So another scan that they usually do is called a flare image. And in that, you’ll see that those ventricles actually appear really dark. So we’ve suppressed any signal from the ventricles. Helps you see those lesions around the periventricular area, so around the ventricles. And that’s really important because what the clinicians are looking for is how many lesions are there? How much space does it take up? Are there any new ones? And so you want to really get that scan in to make sure you’re not missing any. One of the other ones that we do is T1 weighted scans. So that helps see if you’ve got these active lesions with the contrast like we talked about earlier. But another thing T1 weighted scans can do is they’re really good at differentiating between gray and white matter. And that makes them really good for measuring brain volume and brain volume and reductions in brain volume, so brain atrophy, has been shown to predict disability in MS. So it can actually tell a clinician that this person’s symptoms make it worse. And so that’s really important to know as well. A more recent one that’s been added is something called susceptibility weighted imaging. They produce this really weird looking images actually. Sometimes they don’t even look like a brain.

 

But what we’re trying to look for in that is something that they’ve termed PELS, which stands for paramagnetic rim lesions. And basically what they’re telling you if this lesion is active. There’s lots of chronic inflammation. There’s lots of macrophages around it because there’s lots of iron deposited around it, which affects the susceptibility in your MRI image. And so that also tells you about the severity of the disease. So they would be the main sort of core ones that you would be going through if you went for an MS scan.

 

Overcoming MS (12:35)

So are they different machines or is that one machine?

 

Bhavana Solanky (12:39)

That’s all in that one session. So when you’re invited and you have your MRI appointment, they’re running all four of them. Sometimes there might be added extra ones. There might have diffusion to measure the cellular volume and things like that as well. But when you’re in this MRI scanner, you sometimes hear a pause and the noise of the scanner changes. So it might go from, do, do, do, do, do, do, do, do, do, it’s changing, or how it’s collecting things to give you those different contrasts, to give you those different bits of information. So it doesn’t just get one image. You usually have more than one image and each one of those is really helpful in diagnosing and monitoring.

 

Overcoming MS (13:18)

Okay and then what about newer more advanced scans so we’ve heard about: sodium scans and one hour scans and things like this. Yeah what are these ones are these completely different things?

 

Bhavana Solanky (13:28)

So spectroscopy scans and things like that as well. So, yeah, so MR spectroscopy is one of the things I work on. It’s quite an advanced technique. It wouldn’t normally be run in a clinic. And that’s still looking at these hydrogen atoms, but not the hydrogen atoms related to water. We’re looking at different molecules in the brain.

 

So it’s a bit like, you know, if you took a blood test and you can measure lots of different things in it, and depending on what you test for, you can measure that thing. Well, you’re not really going to do that in the brain. So we can use spectroscopy to get a quick snapshot of things like how healthy are the cells there? How healthy are your neurons? Really important for transmitting signal in your brain. You know, how are the cells dying? Or is there cell membrane turnover, what’s the energy metabolism like in the brain? And these sorts of things we can measure with spectroscopy because they all have hydrogen atoms. All of these molecules that are attached to those different processes have hydrogens attached to them. And we can measure that, we can differentiate them so we can tell one from the other. And we know that, for example, in MS, your structural scan that you’ll get when you go for your normal diagnostic scanning. A lot of the tissue in there, for example, the white matter and grey matter, which doesn’t have lesions, it looks completely normal, right? It looks like a normal, healthy person’s brain. However, we know that when we do spectroscopy and say the white matter, the metabolism is actually very different to what our normal, healthy control will be.

 

For example, the markers that we see for neurons with spectroscopy are lot lower in patients with MS. So you can see that even though something will appear structurally normal, metabolically it’s really quite different. You also mentioned sodium MRI. like you said, that’s one of the things I focused on in MS. that’s a bit like, we’re not looking at hydrogen atoms anymore, we’re looking at sodium.

 

And that’s a bit like, say if you wanted to listen to a different radio station and listen to a different song or whatever, you tune your radio to a different frequency, right? That’s exactly what we do with our MRI. We say, listen to this frequency and it listens for signals in sodium, which will behave similar to those hydrogen atoms, but they’ll give you information on sodium instead. So in MS, when we developed these sequences and tested them in MS, we found that not only were they increased, in people, total sodium concentration was increased in people with MS, but it was higher depending on what sort of MS you have. So if you had relapsing remitting or secondary progressive or primary progressive, the amount of sodium increase you got was sort of in line with how progressed the disease was and also the sodium concentrations related to disability as well. And this isn’t sodium just in the lesions that you can see in the standard MRI.

 

It’s sodium that’s changing in what looks like normal healthy tissue.

So we’re looking at things in a more like metabolic way or cellular way to get more information before we see those structural changes.

 

Overcoming MS (16:51)

And so there’s obviously a lot of this is going to feed into research and a lot of it. I know there’s research about MRIs as well. So how can a normal person with MS or their care partners help with those research projects?

 

Bhavana Solanky (17:07)

So in so, so many ways, the research process is quite a long process. You need to get some funding to answer research questions. So even helping to build the research question, what’s important to you? Helping understand that what’s not known, why is it worth a charity or a funding body investing in that? funding bodies are always looking for lay people and their opinions on research as well, because that’s really important. Looking at ethics forms that we hand out for consenting volunteers, are they understandable? Is what we’re wanting to do something that somebody would want to do? Or would you be scared away from it? And if so, how can we adapt it? But for me as an MRI physicist, as somebody who develops MRI biomarkers, there’s nothing I do that doesn’t involve volunteers.

 

I need healthy volunteers, so carers, partners. I need people with pathologies, so people with MS from different groups, from different backgrounds, different ages, genders, ethnicity, to really build up sample sizes which accurately reflect the population. And so my results aren’t biased. My results can, you if I have a large enough group of volunteers to show it, I can show it’s robust, I can show it’s accurate.

 

And so it really underpins. It’s basically not translatable to the clinic. It’s not useful to anybody without the help of the volunteers.

 

Overcoming MS (18:35)

What did your latest research project show then?

 

Bhavana Solanky (18:43)

So the latest research project I did actually carried on from that earlier work where we saw these total sodium concentration changes in normal appearing white matter. Because the next question that came along was, well, what’s increasing it? What you’re measuring there is both things inside a cell, sodium inside a cell, and sodium outside of a cell. So how do we know which one’s increasing? Because the way you would treat that would be really different. If you want to prevent cellular increase in sodium, then you would try and use sodium blockers, for example. So we need to know what is happening there to be able to understand it better. So we know we’ve got these increases. the latest project I did was actually funded by the MS Society. And we used data we already had. We used data on the sodium that we already had. And we used another MRI technique called diffusion weighted imaging. And what that helped us do is quantify how much of the voxel, so how much of each pixel actually contains intracellular volumes. And from that I could calculate the intracellular sodium, so how much sodium there is inside the cells. I mean, did this in healthy volunteers, volunteers with CIS, volunteers with relapsing remitting MS, and secondary progressive MS. And that’s the data we had available to us. And we found that in the secondary progressive MS patients did have intracellular increase in sodium compared to healthy controls and relapsing remitting and CIS. This is all preliminary reasons as well, so we do want to publish this. And we also found that there was this intracellular sodium also correlated with disability. So how far somebody can walk 25 meters or how fast they can walk correlated to how much sodium people have inside the cells in their brain. So that was a really interesting finding and we’re hoping to publish that soon.

 

Overcoming MS (20:39)

But you’re not saying you’re not a sort clinical level. So you’re not saying don’t eat salt. That’s completely different.

 

Bhavana Solanky (20:44)

Oh no, so this isn’t to do with the salt in your diet, this is to do with how your cells are regulating the sodium. So there’s a very delicate balance in the brain between the sodium inside the cells and outside the cells because basically when a neuron fires that changes very, very dramatically to help that neuron fire sodium and transmit signal across the brain. so that you can do other things like tap your fingers and get your heart to beat and things like that. you know, important things. So sodium is very important in helping your brain function. And how it’s regulated in the brain is very, very tightly. And so it’s not to do with the diet. The diet will be taken care of and regulated with, you know, there’s a very tight regulation in the body from what I understand as a physicist that is very tightly regulated. So it’s not to do with how much sodium or salt you’re taking in. It’s to do with how the cells in the brain might have been changed and how they deal with sodium rather than you having too much sodium to begin with, is how they deal with it. Please do not let that be the takeaway message.

 

Overcoming MS (21:55)

Yeah, I just wanted to check because I didn’t want people listening to the podcast and cutting out all salt.

 

And so that’s the latest research. But what projects are you planning going forward as a final question?

 

Bhavana Solanky (22:10)

So yeah, we have quite a few interesting ones. So we want to expand on the one we just did. And we need more volunteers for that so we can have bigger groups, more representative as well, just to ensure that the findings we got were correct and they’re robust, accurate, and how sensitive our model is as well to measure sodium. So it’s following that on. And we’re also bringing together sodium MRI where you’re measuring the amount of sodium in the brain and the spectroscopy I talked about, so measuring different metabolites in the brain. Because those metabolites, some of the ones you can measure are neurotransmitters and like I mentioned, sodium is really important in neurotransmission. So being able to measure the other neurotransmitters may help us pinpoint where things are going wrong and therefore what treatments would be helpful and if that’s different at different stages in MS.

 

So we have a project at the moment where we’re developing the MRI biomarkers, the MR spectroscopy to be able to measure those transmitters and then correlate the two. Another one we’re hoping to work on is, again, we’re just embracing what technology can give us now and embracing new MRI physics. So we want to use really fast MRI for diagnostic scans. So take your diagnostic scans from 20 minutes, 30 minutes to 10 minutes. So hopefully that’s a nicer patient experience. Hopefully it saves NHS money, cuts waiting lists. But obviously, again, we need volunteers, we need people to give their time so that we can check that they’re just as sensitive as the scans people are having now because we wouldn’t want is for them to be not as accurate or inferior in some way. So we want to test that they’re non-inferior to the standard scans that people have. So it’s quite an important project because it would have a lot of impacts because getting the monitoring scans is really important to check for these new lesions. If you have a new lesion, it would suggest that you may need, you’re not responding to the treatment that you’re on anymore and that maybe there’s changes needed in the treatment. And so being able to measure them and being sensitive to them is still really important. So yeah, go for your monitoring scans.

 

Overcoming MS (24:33)

So with that, I’d like to thank you very much for joining us. is certainly for me, it’s fascinating. I literally had no idea how it works. I just went for my regular monitoring and a picture came out of the end of it. But yeah, that’s absolutely fascinating and interesting that there is research and it is going forward and we might, all of these things might progress towards improved treatment, hopefully. So thank you very much for joining us. Bye for now.

 

Bhavana Solanky (25:03)

Thank you.