Magnetic resonance imaging (MRI) is a complex and powerful diagnostic tool in modern medicine. By expanding the capabilities of the technology and developing new magnetic resonance imaging techniques, Dr. Melanie Martin and her research team are hoping to improve the diagnosis and treatment of nervous system disorders like Alzheimer’s disease and Schizophrenia.

On this episode the research question is: “How does magnetic resonance imaging help detect nervous system disorders?”

MELANIE MARTIN: So someone once asked me if I could have any superpower in the world, what would it be?

KENT DAVIES: That’s Dr. Melanie Martin professor of physics at the University of Winnipeg.

MELANIE MARTIN: And honestly it didn’t take me too long to think because I knew that I wanted to see inside the human body small things non-invasively.

KENT DAVIES: Martin is speaking from a TEDx talk she gave in 2019 entitled: “beyond the human eye.”[i]

MELANIE MARTIN: I have been bitten by a spider. A real, actual spider. I work with radiation all the time and still no superpower. [laughs] I eventually realized the only way I was going to get my superpower was to make it myself.

KENT DAVIES: Martin’s research specialty is the development of non-invasive magnetic resonance imaging or MRI methods to diagnose and understand different central nervous system diseases.

On this episode the research question may not be as catchy as if you could have any superpower what would it be? But it does highlight the superpower like feats of MRI technology and how techniques developed by Dr. Melanie Martin are advancing research in medical science.

So, on this episode, the research question is: “How does magnetic resonance imaging help detect nervous system disorders?”

From the University of Winnipeg Oral History Centre, you’re listening to Research Question- amplifying the impact of discovery of researchers of the University of Winnipeg.

 

KENT DAVIES: From an early age, Melanie Martin knew she had the drive to do great things.

MELANIE MARTIN: I grew up right here in Winnipeg. I was one of three children from my single mom. And she really motivated us all to be the best we could be and make sure we could be independent. I grew up in River Heights and I was at Grant Park High School from grade seven to twelve. I took all the advanced placement classes. My most fun at Grant Park was being part of the track team. No matter how much I pushed myself, I can always see myself improving in track. Whereas as I got up into the upper years of school with the different science classes, I was getting a hundred percent in all my classes, so I pushed myself as hard as I could and I was still only getting a hundred percent. So, I quite enjoyed track, that I could see the results of pushing myself and improving.

KENT DAVIES: Throughout grade school Martin had several ideas of what she wanted to do in terms of a career?

MELANIE MARTIN: In grade eight, I wrote that I wanted to be a dentist. In grade ten I wrote that I wanted to be a P.I., a private investigator like Remington Steele. But really what sparked my interest in science is doing science fair projects. And my goal was to terraform Mars, I wanted to change Mars into a planet like Earth where people could live on it. So, in grade six. I got some bacteria and some agar plates and I got access to a minus 70 degree freezer and I put the stuff in the freezer and then I took it out and I tried to grow it and most of it survived. So, it was proof that you can have stuff survive on Mars, even in minus 70. And I worked with one of my classmates in grade eleven to actually build a model city on Mars, which was quite fun.

KENT DAVIES: Also during grade eleven Martin learned about a program called Shad Valley where she could meet other high-achieving students with similar goals.

MELANIE MARTIN: And that really was the domino that changed my life. I— I wasn’t really outgoing. And then there, there were forty-five of us, all of us very motivated, very smart people. So, it was the first time in that environment. And I really came out of my shell. And with that program, it opens other doors.

So, in the summer between grade twelve, and university, I was part of the US Department of Energy Program. And I got to go to Brookhaven National Lab and do some work on the synchrotron.

So, my undergraduate was done at University of Manitoba. I was in honours physics. So, that led to an NSERC USRA, Undergraduate Student Research Award. And I worked for University of Western Ontario at the Canadian Light Source in Wisconsin. Then from there, I got the National Research Council Women in Engineering and Science Award. I worked out at the Institute for Marine Dynamics. And I worked on a project to study the bridge between P.E.I. and the mainland. And I was looking for how ice arches would form in the pillars of the bridge. And it was quite fun but I kind of knew that wasn’t what I wanted to do. So, with NRC, they allowed me to switch institutes. So, I went through all the promotional material. And I stumbled upon a magnetic resonance image of an abdomen. And I just stared at it for hours. I was just amazed how could you see inside someone’s body and not have to cut them open, not have to hurt them? How did this get done? So, I had to do it. So, I eventually decided, okay, I’m going to try this institute. And I looked down and I found out it was in Winnipeg. And I was slightly disappointed because I really liked traveling over the summer, but I asked to be put in that Institute. And there I did a lot more computer simulations, I learned a little bit about how MRI worked, and I decided that that’s what I have to do.

KENT DAVIES: MRI machines are the combination of quantum mechanics, superconducting magnets, computer science and mathematics.[ii] One of medical science’s most powerful tools, the capabilities of MRI’s might as well be regarded as superpower. Prior to MRI’s, medical practitioners used potentially harmful ionizing x-rays or low quality ultrasounds.[iii] The fact that MRI’s are safe, non-invasive and have incredibly detailed resolution is what makes them so valuable.[iv] Ultrasound imaging relies on how sound waves bounce off tissues of different densities. While MRI’s rely on something far less intuitive, the quantum properties of the hydrogen atom.[v]

MELANIE MARTIN: So, what happens is, when we look in the body, we’re not actually looking at the body tissues, we’re not actually looking at the liver, the heart, we’re looking at the water. We use water because there’s lots of it. And because we’re not actually looking at the water molecules, we’re looking at the hydrogen. So, water is two hydrogens and one oxygen. And so, we focus on the hydrogen. And so, the nucleus in a hydrogen atom is just a proton. And so, we’re looking at the proton in the hydrogen attached water. And the body is made up of so much water that we can get a big enough signal to make an image. And so, what happens is the nucleus, that proton in hydrogen acts as a little bar magnet. And if we just have them out in everyday life with you and me just sitting here, the bar magnets are pointing in random directions. So, you can actually tell there’s any magnetic field at all. But if you put them inside the magnetic field of the MRI machine, it’s a really, really strong magnetic field. So, all the little bar magnets either aligned with the field or against the field. Still boring, it doesn’t do anything. But if you put in a little burst of energy, the bar magnets will start processing it’s almost like they’re spinning like a top. And it’s that precession changing magnetic fields cause electric fields and currents. So, if we put coils, wires around the person, we can actually detect the spinning little bar magnets of the hydrogen nuclei.

KENT DAVIES: The strength of an MRI’s magnetic field is approximately 300 times stronger than that of a common fridge magnet.[vi] You do not want any metal near an MRI. What can happen is what you might have seen in superhero movies. It is a field so strong it can literally make metal things fly from across the room.[vii]

Higher magnetic fields require higher electric currents, currents that would normally melt ordinary wires. To achieve higher currents, engineers require superconducting coils.[viii] Superconductors have a whole other super power. Temperature affects all metallic conductors, with resistance gradually lowering with temperature. Super conducting materials however, are special in that their resistance drops to zero at temperatures close to minus 273 degrees Celsius.[ix] That means an electric current could travel in a superconducting loop indefinitely, leaving the MRI magnet permanently on. The main consumption of energy is just to keep the coil cooled down. To achieve the incredible lower temperatures needed for superconductivity, some modern MRI’s submerge their superconducting wires in liquid helium in a super-electric refrigerant cycle that uses a vacuum sealed chamber preventing the helium from evaporating.[x]

Phew, so there’s a lot of moving parts already and we haven’t even got to the imaging yet.

MELANIE MARTIN:  So with most big scientific discoveries, it was an accident. It was Bloch and Purcell who noticed that these— the precession frequencies and how they related to the magnetic field. So Lauterbur and Mansfield, they’re the ones who started putting it into imaging. So, what I described before with those bar magnets, you put in that burst of energy, it’s specific to the magnetic field. So, you put in a burst of energy with that frequency, and they’ll spin. But the problem is, all the hydrogen nuclei in the body will spin together so that in the head that in the foot, the right and the left foot, they’ll all spin together. So, you need something to tell them apart. Whether it’s the head, the right side, the left side, closer to the belly or the back. And so, they put on what are called magnetic field gradients. And say you put it on from head to toe. So, it’ll be a little bit stronger field at the head a little bit weaker field at the toe. And so, the hydrogen nuclei, the bar magnets inside them at the head will spin a little bit faster than the toe. So, if you can find out how fast they’re spinning, you can get an idea where they are from head to toe. And they did other little tricks like that to make them different head to toe, right to left front to back.

KENT DAVIES: By altering the local magnetic field by these small increments, different slices of the body will resonate as different frequencies. The frequency information contained in the signal from each slice is converted into an image which is then displayed in grayscale in an array of pixels. By varying the sequence of pulses applied and collected, different types of images are created.[xi] Of course there are more layers of complexity involved. There are many different combinations of imaging, different methods to achieve a better image. Needless to say, since its inception, MRI technology and techniques have constantly been evolving.

MELANIE MARTIN: There’s lots of different technology changes. Right now we have giant rooms with shielding for radio frequencies, because the burst of energies that we use are all in radio frequencies. So, if there’s a radio in the room, it can affect the signal. So, we have to put everything in a cage called a Faraday cage to keep the radio frequencies out. Now they’re starting to make it so they could just put caps on the end of the magnet. And the radio frequency, you don’t need a special room, it just closes over the bore.

They’re the magnetic fields that we used way back when and mostly still today need superconducting wires. Superconductors, at least back then we’re running very, very cold temperatures. So, at four degrees Kelvin, which is minus 269 degrees Celsius. So even in Winnipeg, you can’t run them outside. So, it took a lot of helium to cool the coils. And then typically you don’t want the liquid helium Dewars sent out to atmospheres, so they put around the liquid helium, liquid nitrogen. Now they’ve got ways that they could just use liquid helium and use refrigeration units that as the helium boils away, they can change it from gas to liquid and pour it back in. And they’re even now able to do some of the magnetic fields with superconductors with higher temperatures, so they could do it with just liquid nitrogen or gaseous helium instead of liquid. So that’s made a huge change.

There’s been a push to go to higher field strengths. Higher field strengths tend to give you better resolution and better pictures. The details now compared to what they were early in 1990 are quite amazing.

KENT DAVIES: MRI technology has undergone significant advancements and improvements over the years with higher magnetic field strength, improved image quality, and a more sustainable infrastructure.[xii] However, these improvements haven’t necessarily led to MRI technology being more cost effective, practical, and useful in the field. One of Martin’s main research goals is to do just that.[xiii]

MELANIE MARTIN: Yeah. So, the NRC IBD (National Research Council Institute for Biodiagnostics) that I ended up working at after my third and fourth year of university, it was very much focused on medical imaging. And one of the scientists there, John Saunders, he ended up working with Garnet Sutherland. He was noticing that he really needed to have an image within the operating room, because you’d close up a patient. And you’d leave a little bit of tumor behind and not realize it. And then it’s back to the beginning. So John Saunders started this company IMRIS. And they made these interoperative magnets, they were really heavy magnets that moved across the ceiling, they could sit in a regular hospital room for most of the time being a regular hospital MRI, and when needed, it could move into the operating room. And one of the studies they told me about was with a dog that had essentially a fatal brain tumor. And so the surgeon removed the brain tumor, they moved the magnet in, they took an image, they found out they left a little piece of the tumor behind. So the surgeon went took out a little piece of tumor. The magnet moved back over the dog again, tumors gone. They close up the dog, the dog actually lived a full life. So that’s the hope with people if we can get the whole tumor out, brain cancer is gone. The problem with these big IMRIS magnets is they cost a fortune. And you need tons of renovations to get them into the operating room for them to move across the ceiling. So the operating room is closed for about a month, which in the US is a lot of money. And in Canada, we already have these huge wait times, we don’t want to increase them. So the company I’m working with now has taken it from moving across the ceiling to moving on the floor, they put the magnet on essentially tank wheels. So normally, when a magnet is delivered, they have to cut a big hole either in a wall or window with ceiling and they lower the magnet in this magnet, they put the tank wheels down on the ground outside, they lower the magnet onto the tank wheels and it drove itself into place. So the hope is that the operating room will only be closed for a day to get it all set up. And then it just drives over the patient takes the image drives back and surgeons can see what’s going on.

I’m also with a group that’s pushing to go to lower field strength. People up in northern Manitoba have to fly to Winnipeg to get an MRI. If they could have one of these more cost effective ones and do an image up there. Even if the image had to be emailed to a radiologist here in Winnipeg, they can have a quick look and say, Yeah, this needs to be followed up come to Winnipeg, or Nope, you’re safe, you can stay, saves a lot of heartache, time, trouble, money. And another application is there are certain Alzheimer’s treatments that need immediate feedback. So if they had one of these cost effective machines, right within the pharmaceutical industry building, they could do a quick check right there if what they have is working.

KENT DAVIES: Since the first days of MRI imaging, researchers and healthcare practitioners have been finding new ways to use the technology to detect and diagnose different disorders and impairments. One of the most significant contributions was made Dr. Michael Moseley.[xiv]

MELANIE MARTIN:  So, Mike Moseley was actually the one who made MRI, clinically useful. So, he discovered, I believe it was in a cat, that you could see the stroke as it happened. So, before him, it took about eight hours to be able to tell that there was a stroke, and eight hours is critical to get the treatment in. So, if you could see immediately you can start the treatment immediately. And since 1990, when Mike Mosley discovered you could see the stroke, stroke outcomes have improved greatly.

KENT DAVIES: Dr. Michael Moseley used a specialized type of imaging called diffusion-weighted imaging for stroke detection that measures the random movement of water molecules within tissues.[xv]

MELANIE MARTIN: So it turns out that molecules don’t just sit there they move, if they have any temperature at all, they’re above that absolute zero minus 273 degrees Celsius, whether they’re in a solid, liquid or gas, they’re going to move around. So the water in your body moves around. And it’s called diffusion. It’s almost looking like a drunk walk. So, it starts moving, it’ll bump into another molecule, and then change direction and bump into another one. So detecting that motion can detect strokes. When MRI was first used, they used to think that that motion was going to cause something like blurring so you wouldn’t be able to get good enough resolutions to see anything. We now know that we can take that motion, that diffusion, make the image have contrast that depends on the diffusion, how much that water is moving. They think what’s happening is the cells are expanding the spaces are getting smaller, so, you get less diffusion, which causes an increase in the signal, because the diffusion would randomize the signal now there’s less of it. So, there’s less of a random signal. And you’d get these bright spots in the images to know there’s a stroke.

KENT DAVIES: Martin, herself has furthered the parameters of diffusion imaging using a specialized technique she created during her time at Yale University, where she received her PHD.

MELANIE MARTIN: When I went to Yale, I studied—  It’s this new technique. It was published in 1969 as something that could work, but no one had done it by then. And so, my advisor said, well, why don’t you make it work. And it’s one of those things that I have in my personality that if someone tells me something’s not going to work, I look at them and I say, “challenge accepted, it’s going to work.”

KENT DAVIES: The oscillating gradient spin echo sequence combines a spin echo technique with an oscillating gradient. This fluctuating gradient helps reveal additional details about the tissue properties, such as its microscopic structure or the diffusion of water molecules within it. By analyzing the responses of the protons to the changing gradient, researchers can extract useful information about the tissue’s characteristics. This can be particularly helpful in studying brain tissue, muscle fibers, and other complex structures.[xvi]

MELANIE MARTIN: It took a lot of struggles. It took a little bit of talking to some people, but I got the method actually working for the first time and twenty years later, I go to a conference and everyone’s using it now and it’s doing some amazing things.

KENT DAVIES: Martin is focused on expanding the potential of MRI’s to help health practitioners diagnose different disorders more effectively.

Which brings us to our research question: “How do MRI’s detect central nervous system disorders?”  

MELANIE MARTIN:  If you go with Alzheimer’s disease, the hippocampus is one of the first things and Alzheimer’s to start being affected, at least that we could see. And the hippocampus is in charge of memory. So that’s why Alzheimer’s has this memory issue. And so you can start seeing the hippocampus shrink. Again, there’s no way we could see that unless we cut your head open, or we find an imaging technique. And so I’ve got a few papers out there trying to measure the hippocampus trying to do it auto automated instead of having someone draw it out and to see how it shrinks. With the Alzheimer’s and hippocampus, something they found is that positron emission tomography, PET imaging, actually can do a really good job diagnosing Alzheimer’s.

You inject a radio tracer into the person, the radiotracer could be fluorodeoxyglucose, so it looks like glucose, but they’ve taken an oxygen out and put in a radioactive fluorine instead. So, the body takes it up and uses it like glucose until a certain process. And then it shows you how glucose is used. And it turns out, a healthy brain will show a different uptake than a brain with dementia than a brain with Alzheimer’s or different kinds of dementia. So, they’re able to look at how glucose is used across the brain with PET. The catch with PET is it’s a functional imaging technique. So, it only shows you where the glucose is, it’s not showing you the anatomy. So, you just see this hotspot, but you don’t know what’s underneath it. What we’re doing is trying to put the PET scanner inside the MRI, and take an MRI and the PET scan at the same time. So, the MRI gives the anatomy and the PET scan gives the function. Sounds simple. It’s not that simple. But that’s what we’re doing. [laughs]

KENT DAVIES: MRI’s plays a significant role in diagnosing and studying neurodegenerative disorders like Alzheimer’s.[xvii] By using multimodal imaging by combining MRI and PET scans, health practitioners are able to detect a shrunk hippocampus and then how well it’s functioning, enhancing diagnostic accuracy.[xviii] However, a clinical diagnosis is typically made by considering multiple factors and ruling out other possible causes of cognitive decline. The hope is that with MRI’s health practitioners may one day find a reversible cause for cognitive decline that, with the proper treatment, can be reversed and cognitive functioning can be restored.

MELANIE MARTIN: I’m always looking at things for challenges and how to do things. But I do have family members who had some dementia. So it’s nice to know that I can do something. But the sad part is I can’t do something for my loved ones right now, what I’m doing now is probably not going to help for a decade or two or more, but maybe they’ll help my children or my grandchildren. We can diagnose stroke eight hours sooner. Eight hours. That’s it. And the outcomes are so much better. Imagine with Alzheimer’s that we’re doing diagnosing it three decades earlier. We have three decades to figure something out.

KENT DAVIES: Martin is also doing research with MRI’s to explore potential brain abnormalities associated with schizophrenia. Using the oscillating gradient technique she developed, Martin, and other researchers are identifying patterns of brain abnormalities associated with the disorder.[xix]

MELANIE MARTIN: So, I have a few other projects on the go. And so one of them uses that diffusion of the water, so the water moves around. And if it’s inside a nerve cell, so there’s neurons, which have a large cell body, and then they have this wire, which is called an axon, it’s almost like an electric cord. The wire, the electric signals go down there, and then there’s myelin around it, which is like the rubber that shields that and then it comes out the other end, it comes to the other end and sends the electric message on to the next neuron.

And so what they found is those axons are usually bundled together in fibers. They’re finding that schizophrenia fibers are less densely packed. But it’s all through autopsy. So there’s no way to find out when it happened. If they’re born like that, if something changes at some point, there’s no way to measure how that changes function. So, I had that oscillating gradient technique which I made at Yale, and there were other people using diffusion in general to measure how big things were. So if you imagine water inside those neurons and you take the axonal wall, kind of like the edge of the wire and fatty substance around the myelin, if we say the water can’t get out then the water can only move at most the diameter of the axon. So if you can measure how much it moves, you can get an idea of the size of the axon. And in fact, there are people out there that are so smart, they found functions. So if you know how big the axon is, and you know that it’s a cylinder, you expect the MR signal to look like a certain function as a function of time. So when it starts moving, the water molecules won’t touch the boundaries if they’re in the middle, and as you wait longer and longer, more and more of them touch the boundary. So you get signal changes. So with that you can figure out how big things are. But what I noticed that the conferences, they were using just regular diffusion methods, and they couldn’t get small enough measurements. So I sat in the audience watching these talks, and I’m like, Well, why are they using the traditional MR methods of diffusion? Why can’t they use my oscillating method, it measures much shorter time, so much shorter distances, and we can get to those much, much smaller axons. And that’s exactly what we did.

KENT DAVIES: By applying the specialized oscillating gradient spin echo sequence, researchers are now able to measure axons in a smaller range. Recent studies indicate possible changes in axon diameter distributions associated with diseases such as Alzheimer’s, autism, dyslexia, and schizophrenia. The more researchers can understand how this happens, the better chance health practitioners have of accurately diagnosing and finding treatments for these disorders.[xx]

MELANIE MARTIN: My biggest eureka moment of recent history, I had Sheryl Herrera, she was the postdoc at the time, she was doing the measurements. So she made all the measurements with MR then did electron microscopy, which is the gold standard. We cut up the brain, we look at the sizes, and they didn’t quite match. So we were slightly bigger. So I looked at the image. And I’m like, you know, these axon cross sections aren’t quite circles, maybe we’re taking a measurement at the angle. So how about instead of just measuring the diameter, you take the largest width of the kind of like oval shape, if you cut a carrot in an angle, you get an oval. So she did that. And then it was too big. And I’m like, This is so close. And Maxina Sheft came to work for me. And as I was describing these measurements to her, I’m like, this is a little strange. Why don’t we do something completely unconventional. And you measure how far across you’re going in these weird shape ovals in one direction. So you just do it horizontally. And so she went away. And she made 6000 measurements of these horizontal lines. And she came back with a number and it pretty much exactly matched what we got with MR. I don’t think I calmed down for several days. [laughs] I was so excited that it actually worked.

The measurement Sheryl took was actually on an autopsy sample. So it took five days. As much as you probably want your diagnosis, I can not see you staying still in the magnet for five solid days. So we have to take it down from five days to five minutes. So I had another student Kaihim Wong, he took the old data, the whole five days worth, and he started sorting through it to see which ones are the most important ones, and how much we can just throw away and just focus on shorter data. And through his method of throwing things out, he got down from five days to about twelve hours worth of data. Getting there, still don’t want you holding still for twelve hours. So, Melissa Anderson came on, and she was able to get some decent measurements in an hour. Madison Chisholm did a bit on a fixed sample for her honours thesis. And again, I think it was overnight. So, like twelve hours. So we know that that much data would work as long as we pick the right parameters. And so she’s going to focus on the right parameters and try to get some measurements.

What could it lead to? We don’t know what happens with schizophrenia. It’s typically diagnosed in the twenties. Imagine if people were just born with their fibers with less axons. And it didn’t have any effect until they were in their twenties. Well, then we could do a quick image somewhere in their young years and see, okay, these people have lower density axons, maybe we need to do something.

KENT DAVIES: Fostering the next generation of researchers is important to Martin who has been heavily involved in programs like Pathways to Graduate Studies (P2GS) and the UWinnipeg chapter of the Canadian Indigenous Science and Engineering Society, where she was named Advisor of the Year in 2022.[xxi]

MELANIE MARTIN: I personally don’t want to hog my superpower all to myself. I’ve been training lots of people to use my superpower. So go find your superpower and go make freedom for all of us. Thank you. [applause]  

MELANIE MARTIN: Any of my big successes are all from the students. The students are doing the work now. The students are making the results, the students are making the presentations. Before the pandemic, my students were always nervous to give talks, but they always gave them and as soon as they gave their first talk, they were like, that’s not a problem. I can do these talks now. And they would sign up. So now that they’re back to giving talks in person, I’m trying to give them as many opportunities as I can to see them give the talks. I want them to publish what they’re doing. I want to see them get into great schools, get great degrees, get great jobs. And I just I’m so proud of all my students and what they can do.

KENT DAVIES: Martin is now focused on a variety of research projects from working towards new magnetic resonance imaging techniques to developing new intraoperative MRI systems. All of which will further our understanding of neurological disorders, improving our healthcare for future generations.

MELANIE MARTIN: I will be mind blown when I see any one of these methods actually working in the clinic. If I can get— If I can see this MRI, the intraoperative MRI work in the hospital, I’ll be happy. If I can see the schizophrenia method get down to five minutes and actually start working in the clinic. That’s when I’m going to be mind blown. And then leave my students with the with the skills and the knowledge. And publish it, so everyone else has the skills and knowledge that if I can’t quite get it down to the five minutes, someone else will be able to.

 

KENT DAVIES: You’ve been listening to Research Question. Research Question is produced by the University of Winnipeg Research Office and Oral History Centre.

The University of Winnipeg is located on Treaty 1 Territory, the heartland of the Metis people.

Written, narrated and produced by Kent Davies.

Our theme music is by Lee Rosevere.

For more on University of Winnipeg research, go to uwinnipeg.ca/research

For more information on the University of Winnipeg oral history centre, and the work that we do, go to oralhistorycentre.ca.

Thanks for listening.

 

[i] Dr. Melanie Martin, “Beyond the Human Eye” filmed March 16, 2019 at TEDxUniversityofWinnipeg, Winnipeg, MB, video, 10:45, https://www.youtube.com/watch?v=4AbgQDDgQF0, Accessed May 2, 2023.

[ii] Vijay PB Grover, Joshua M. Tognarelli, Mary ME Crossey, I. Jane Cox, Simon D. Taylor-Robinson, and Mark JW McPhail. “Magnetic resonance imaging: principles and techniques: lessons for clinicians.” Journal of clinical and experimental hepatology 5, no. 3 (2015): 246-255; Robert C. Smith, and Shirley McCarthy. “Physics of magnetic resonance.” The Journal of Reproductive Medicine 37, no. 1 (1992): 19-26.

[iii] Vijay PB Grover, Joshua M. Tognarelli, Mary ME Crossey, I. Jane Cox, Simon D. Taylor-Robinson, and Mark JW McPhail. “Magnetic resonance imaging: principles and techniques: lessons for clinicians.” Journal of clinical and experimental hepatology 5, no. 3 (2015): 246-255; Robert C. Smith, and Shirley McCarthy. “Physics of magnetic resonance.” The Journal of Reproductive Medicine 37, no. 1 (1992): 19-26.

[iv] Lars G. Hanson “Introduction to magnetic resonance imaging techniques.” Danish Research Centre for Magnetic Resonance (2009); “Magnetic Resonance Explained,” Danish Research Centre for Magnetic Resonance (2009). Accessed May 3, 2023.

[v] Plewes, Donald B., and Walter Kucharczyk. “Physics of MRI: a primer.” Journal of magnetic resonance imaging 35, no. 5 (2012): 1038-1054; Hanson, Lars G. “Introduction to magnetic resonance imaging techniques.” Danish Research Centre for Magnetic Resonance (2009); “Magnetic Resonance Explained,” Danish Research Centre for Magnetic Resonance (2009). Accessed May 3, 2023

[vi] “Magnetic Field,” Society for Cardiovascular Magnetic Resonance. Accessed May 9, 2023. 

[vii] “How strong are the magnets in an MRI machine?” 9 August 2001. Accessed May 9, 2023.
HowStuffWorks.com. https://science.howstuffworks.com/question698.htm.

[viii] Donald B. Plewes and Walter Kucharczyk. “Physics of MRI: a primer.” Journal of magnetic resonance imaging 35, no. 5 (2012): 1038-1054

[ix] Thomas C. Cosmus, and Michael Parizh. “Advances in whole-body MRI magnets.” IEEE Transactions on applied superconductivity 21, no. 3 (2010): 2104-2109.

[x] Thomas C. Cosmus, and Michael Parizh. “Advances in whole-body MRI magnets.” IEEE Transactions on applied superconductivity 21, no. 3 (2010): 2104-2109.

[xi] Donald B. Plewes and Walter Kucharczyk. “Physics of MRI: a primer.” Journal of magnetic resonance imaging 35, no. 5 (2012): 1038-1054; “Introduction to the basics of magnetic resonance imaging.” Molecular Imaging in the Clinical Neurosciences (2012): 75-98; Lars G. Hanson, “Introduction to magnetic resonance imaging techniques.” Danish Research Centre for Magnetic Resonance (2009); “Magnetic Resonance Explained,” Danish Research Centre for Magnetic Resonance (2009). Accessed May 3, 2023.

[xii] Thomas C. Cosmus, and Michael Parizh. “Advances in whole-body MRI magnets.” IEEE Transactions on applied superconductivity 21, no. 3 (2010): 2104-2109.

[xiii] Michael L. Lang, Qiang Zhang, Xiaolei Chen, Niandong Yan, Haoqin Zhu, Melanie Martin, Feng Yu, Chaoshi Niu, Gong Zhang, and Qiang Zeng. “First ground-based, high-field, cryogen-free, mobile intraoperative magnetic resonance imaging system.” Magnetic Resonance Imaging 99 (2023): 34-40.

[xiv] M. E. Moseley, J. Kucharczyk, J. Mintorovitch, Y. Cohen, J. Kurhanewicz, N. Derugin, H. Asgari, and D. Norman. “Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats.” American Journal of Neuroradiology 11, no. 3 (1990): 423-429.

[xv] M. E. Moseley, J. Kucharczyk, J. Mintorovitch, Y. Cohen, J. Kurhanewicz, N. Derugin, H. Asgari, and D. Norman. “Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats.” American Journal of Neuroradiology 11, no. 3 (1990): 423-429.

[xvi] Melanie Martin. “Measuring restriction sizes using diffusion weighted magnetic resonance imaging: a review.” Magnetic Resonance Insights 6 (2013): 35 MRI-S11149; Morgan Mercredi, Trevor J. Vincent, Christopher P. Bidinosti, and Melanie Martin; Sheryl L. Herrera, Maxina Sheft, Morgan E. Mercredi, Richard Buist, Kant M. Matsuda, and Melanie Martin. “Axon diameter inferences in the human corpus callosum using oscillating gradient spin echo sequences.” Magnetic Resonance Imaging 85 (2022): 64-70; Sheryl Lyn Herrera. “Inferring axon diameters using magnetic resonance imaging oscillating gradient spin echo sequences.” PhD Thesis, U of Manitoba, 2018.

[xvii] Kerrie Hayes, R. Buist, T.J. Vincent, J.D. Thiessen, Y. Zhang, J. Wang, A.R. Summers, J. Kong, X.M. Li, and M. Martin, M., 2014. Comparison of manual and semi-automated segmentation methods to evaluate hippocampus volume in APP and PS1 transgenic mice obtained via in vivo magnetic resonance imaging. Journal of neuroscience methods, 221, pp.103-111.

[xviii] Yonglin Chen, Huabin Wang, Gong Zhang, Xiao Liu, Wei Huang, Xianjun Han, Xuejun Li, Melanie Martin, and Liang Tao. “Contrastive Learning for Prediction of Alzheimer’s Disease Using Brain 18F-FDG PET.” IEEE Journal of Biomedical and Health Informatics (2022).

[xix] Sheryl L. Herrera, Maxina Sheft, Morgan E. Mercredi, Richard Buist, Kant M. Matsuda, and Melanie Martin. “Axon diameter inferences in the human corpus callosum using oscillating gradient spin echo sequences.” Magnetic Resonance Imaging 85 (2022): 64-70; Sheryl Lyn Herrera. “Inferring axon diameters using magnetic resonance imaging oscillating gradient spin echo sequences.” PhD Thesis, U of Manitoba, 2018.

[xx]  Sheryl Lyn Herrera. “Inferring axon diameters using magnetic resonance imaging oscillating gradient spin echo sequences.” PhD Thesis, U of Manitoba, 2018.

[xxi] “UWinnipeg’s Chapter of .caISES honoured with award,” UWinnipeg, accessed April 26, 2023.