Today, we present an exclusive interview with Jonas Bergquist, MD, PhD, from the OMF Collaborative Center at Uppsala, who shares insights on neuroinflammatory involvement in ME/CFS.
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The Heart of the Matter
- Neuroinflammation and microglia activation are often implicated in ME/CFS, making it important to understand what happens in the central nervous system (CNS).
- Traditional methods of measuring activity in the CNS are invasive, often requiring a lumbar puncture to collect cerebrospinal fluid.
- Dr. Bergquist at the OMF Collaborative Center at Uppsala is conducting a study using novel MRI and PET imaging techniques to help understand what is happening in the CNS through non-invasive methods.
- This study has received IRB approval, which means it has transitioned from the “Study Design, IRB/Ethics Review” stage to the “Recruitment, Data Collection” stage of the research process.
Microglia are cells that surround neurons in the brain. In the event of an infection or trauma to the brain, microglia activate to act as the local immune system, releasing neurotransmitters and cytokines, like interleukin, and initiating neuroinflammation.
Traditional ways to measure neuroinflammation and other activity in the central nervous system (CNS) are invasive, requiring blood draws and collecting cerebrospinal fluid via a lumbar puncture. Dr. Jonas Bergquist, the Director of the Open Medicine Foundation Collaborative Center at Uppsala, has designed a study that will use non-invasive imaging to help understand what’s going on in the CNS.
In this research, the team will use dynamic contrast enhanced magnetic resonance imaging (MRI) and diffusion-based scans to study the migration and activation of microglia cells. In addition, they will use positron emission tomography (PET) scans to identify neuroinflammation. Through these methods, they will study CNS activity in four participant groups: ME/CFS, Long COVID, multiple sclerosis, and healthy controls.
One unique aspect of this study is the MRI technique, which hasn’t been used before in these patient cohorts. Despite the novelty, though, if the technique is successful, it can be easily translated to any clinic that has access to an MRI machine. By comparing this imaging to biosample analysis and survey results, ultimately the team hopes to develop a non-invasive mechanism for supporting ME/CFS diagnosis.
Dr. Bergquist’s neuroinflammation study recently received IRB approval, so it has now entered the next stage in the research process: “Recruitment, Data Collection”.
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Video Transcript
Dr. Meadows: Okay, so welcome back everyone, to another OMF director interview. This week, we are jumping over to the OMF Collaborative Center at Uppsala. So I’m thrilled to be joined by Dr. Jonas Bergquist. Briefly, Dr. Bergquist’s center focuses on targeted molecular diagnosis of ME/CFS, with the eventual goal of providing evidence-based strategies for effective interventions. So welcome, Dr. Bergquist.
Dr. Bergquist: Hi there!
Dr. Meadows: Thanks so much for joining me today. I really wanted to talk to you about one of your newer projects evaluating the magnetic resonance techniques for detecting neuroinflammation. Just to start us off, do you think you could give us just a short overview of some of the background and rationale that’s really kind of led to this study?
Dr. Bergquist: Yes, I’m happy to join you, Danielle, today. What we are doing in Uppsala, I’ve been working for, as long as I’ve been working with ME patients, I’ve been working on neuroinflammation as one of the tracks that we are interested in. Now, it’s over 15 years, actually, we’ve been working on this.
As you know, neuroinflammation in the central nervous system, in the brain is very hard to track with substances that you find in blood. Sometimes you can get some signals from blood, but what we have been working with mostly is the cerebrospinal fluid, the liquid that surrounds the brain. And you have to then collect that by doing lumbar punctures on your patients and your healthy controls also, which is a bit invasive, but we think it’s still a very good tool.
But in parallel to that, what we really would like to do now in this upcoming study is to follow a bit in the tracks of their colleagues, like Jarred Younger, Mike Van Elzakker, and Michelle James, to use imaging. So, noninvasive tools for imaging of the central nervous system. And they have shown in recent studies and also back a few years ago, that imaging can help us to understand better what’s going on in the central nervous system.
We are doing it with a slightly different touch. So, we are focusing specifically on microglia activation. Microglia cells are supporting cells that surround our neurons in the brain. When we get an infection or a trauma to the central nervous system, we typically see an activation of these glial cells, microglia cells. Then they change their form and structure and they also start migrating around in the central nervous system.
So a fantastic change of these cells and the role of the cells is to actually act as our local immune system. So they will survey the cell damage that may occur, and they would also look for antigens that have penetrated into the central nervous system, they will also be able to release these neurotransmitters and also the cytokines, the signaling molecules that the immune cell is using. So typical interleukins, for instance.
This is a very, very dramatic effect that these cells can have on the central nervous system. In our study, what we will do is to use magnetic resonance imaging (MRI), but we will use a special version of it called Dynamic Contrast-Enhanced MRI (DCE-MRI), and also in parallel, we’ll do diffusion-based scans to look at the migration of these cells and activation of microglia cells, specifically. And in parallel, what we also have the opportunity to do here in Uppsala is we will use PET (positron emission tomography) measures on all our individuals to have a positive control for neuroinflammation.
We will use a classic radioactive ligand TSPO, eleven carbon labeled PK 11 195, a classic ligand that we have available here in Uppsala.
In the study, we will include in total 100 individuals, we will have 25 patients with ME, following the Canadian criteria, we’ll have 25 Long COVID patients, We will have 25 multiple sclerosis (MS) patients as a positive control of inflammation, and then we will have 25 healthy controls, and they will all be gender and age-matched controls.
This is the cohort we will study.
Dr. Meadows: Very nice. Thank you for providing that overview. It’s really great to be able to pursue this noninvasive method like you said. So, given kind of the study design you just kind of walked through, can you elaborate a little bit more on what’s really unique about that study design?
Dr. Bergquist: Yeah. First of all, I think the way we have composed our controls and contrast groups, I think that is important for us to understand what is, what kind of inflammation can we measure with the techniques we are applying and how do they differ between different patient cohorts. And, of course, compared with healthy controls. But I think that’s very important and slightly unique, at least.
And also the way we are applying magnetic resonance imaging, the MRI methodology that we will apply, has not been done and used so much earlier in these cohorts. So we are following some Spanish colleagues who have been working on a method for microglia activation, then we have modified that method, and now we are applying it in our setup here at Uppsala.
Dr. Meadows: That’s great! So, really just I want to summarize and see if I’m getting all this correctly. So, you’re using both MRI and PET scans to look at neuroinflammation in the brain and specifically microglia activity. Does that sound correct?
Dr. Bergquist: Yes. And of course, we will, by using this, also be able to see other kinds of reactions that happen in the brain, maybe some anatomical shifts and so on, but our main focus is the microglia activation.
Dr. Meadows: That’s fantastic. Do you have any other kind of outcome measures that you want to make sure that you’re including other than just the imaging?
Dr. Bergquist: Yes. In parallel, what we will do, we will draw samples from all the individual’s body fluids and we will also do quite a battery of surveys that they have to fill out, all the classic severity scales, and so on. Plus we have now also included FUNCAP, which is the functional capacity questionnaire that we are really fond of. So I hope that will pan out well in our cohorts and show us the differences.
Dr. Meadows: Fantastic. So at this point, what kind of stage is the study in now? Are there any updates you can share with us on that front?
Dr. Bergquist: Yeah, the IRB has been approved, so we are now recruiting and including patients and controls. And so far it seems very positive. A lot of interest from our patient cohorts, of course, to be part of the study, but also a very altruistic reaction from healthy individuals and controls to be… Well, first, I think they are not only altruistic to help out with science, they are also very curious to see how their brain looks like in a nice image. So, I think that’s a very nice opportunity we have to include people in this study.
Dr. Meadows: That’s awesome. Congratulations on getting IRB approval. That’s a big step. So, I guess just to wrap up our short interview today, I want to finish by just talking about how might results from this study translate to the clinic in the future. How is this going to help our patients with ME/CFS?
Dr. Bergquist: Yeah. Specifically, using imaging like this and using MRI, which is actually available in most hospitals around the world, and with the settings we are adopting, it will be transferable to many other places around the world. I think this will be, if successful, this will be a very good tool for research, but also for the clinical diagnosis to have extra support when you suspect neuroinflammation.
I have already been approached by other colleagues within other fields not working with post-infectious diseases and inflammation in the brain specifically, but they are also very interested in looking at inflammatory reactions in the periphery, not only related to the central nervous system, microglia activation, but they think that this methodology that we now are looking at will help understanding inflammatory processes in joints or muscle or other organs in the body also.
And I think that could also contribute to better diagnostics in many other fields also not only in ME and post COVID or Long COVID groups. So, I hope that will be the outcome of this.
Dr. Meadows: Yeah, that’s really exciting to have a potential new method that can cross a lot of different disease states. So that’s really exciting. And with that, I am going to wrap things up and say thank you so much for joining me today, Dr. Bergquist. It was great to hear about your study. Thank you for your time.
Dr. Bergquist: Thank you, Danielle. Take care.
Dr. Meadows: You too!
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