Waqas Majeed (GA Tech) & Alex Poplawsky (Emory), Intercollegiate Gatekeepers
Originally published September 2007.
Dr. Shella Keilholz obtained her Ph.D. in Medical Physics. She completed her post-doc at the NIH and is currently an assistant professor in the Biomedical Engineering Department at GA Tech / Emory University. Her research interests include imaging of brain function and connectivity, utilizing MRI as her primary tool. She has very recently become a Neuroscience faculty member at Emory University.
Waqas: From your background, I can see that you arrived at the NIH with no prior experience with neuroscience, but left as an emerging expert. How did your graduate research prepare you to enter the neurosciences?
Shella: Well, I was trained as a physicist, and in grad school my primary interest was in finding better ways to image perfusion of mobile organs like the lungs or the kidneys. One of my friends was constantly trying to convince me to do some work on the brain, but I thought the brain was just incredibly boring. It didn’t move! At the time, I had a pretty naïve view of functional brain imaging. I thought that you just took images while the subject did a task or received a stimulus, and then looked to see what parts of the brain were active. It sounded more like a field for psychologists than for a physicist.
W: What brought you to the NIH?
S: The NIH had an 11.7 T MRI system, one of only two in the world at that time. For comparison, a typical clinical scanner is 1.5-3.0 T. I thought it would be fascinating to work on a state-of-the-art system. My postdoctoral advisor focused on functional brain imaging in small rodents, and I started off by helping to develop an improved sequence for fast, high-resolution imaging. From there, we developed an imaging protocol to map the activation over the whole rat brain during somatosensory stimulation.
W: Is that project what prompted you to begin your neuroscience research?
S: Absolutely. While I worked on that project, I finally began to realize how little we understood about the signals we were mapping and the way the brain works. I was fascinated by the idea that the brain was made up of multi-scale complex networks and astonished that we had no good way to get the data we needed to decipher them. It seemed like MRI might become a good tool for exploring the brain’s network structure, and I’ve been working on that ever since.
W: Once you were sick of the nation’s capitol and wanted to get a real job, what brought you to Atlanta?
S: I was invited to the joint Emory/GA Tech BME department for an interview, and the visit convinced me immediately that it was the place I’d like to be. The department had great vibes. Everyone seemed excited about the program and there was so much terrific research happening. The ties between Tech and Emory provide a lot of momentum for combining medicine, biology, and engineering. The other important issue for me in the job hunt was that I wanted to go somewhere that my fiancé (now my husband) would be able to find a job. For our first two years here, he was a postdoc in plasma physics at Auburn University, and he recently started a new job at the Georgia Tech Research Institute. We’re both really excited to be working in the same city for a change.
W: Should we expect little Ramblin’ Wrecks anytime soon?
S: Maybe someday. Training students is enough responsibility for now!
W: I agree. You are in an interesting position, straddled between Emory and GA Tech. As a faculty member, how has the relationship between these universities contributed to your research?
S: It’s interesting that you use the word straddled, because that usually makes me think of an uncomfortable position—and sometimes it’s uncomfortable to be caught between the two institutions, to be sure! On the whole, though, it’s a great opportunity to act as a bridge between the engineers at Tech and the biologists and clinicians at Emory. One of the things my lab is interested in is how functional networks in the brain change because of learning, and we’ve found terrific collaborators at Emory. Dr. Mike Davis and Dr. Kerry Ressler are experts in fear conditioning and have been enormously helpful to us, both in interpreting our results and helping us evaluate the usefulness of MRI techniques for observing these changes. We’ve been testing a technique called manganese-enhanced MRI, which uses manganese to provide activitydependent contrast in neural tracts in standard MR images.
W: You definitely sold manganese contrast to two very prominent neuroscientists here at Emory! How is this tool attractive to neuroscience research?
S: It’s a great tool because it provides a potentially noninvasive method for detecting altered brain activity. Manganese is a calcium analogue and is taken up preferentially by activated neurons through voltage-gated calcium channels. It’s transported via microtubules to the synapse, released with the neurotransmitters, and can then be taken up by the next neuron. So it can trace active neural tracts. We are still analyzing the final data from the fear conditioning study, but a preliminary study showed that when mice were given manganese and exposed to a strong odor, there was less uptake and transport of the manganese throughout the bulb and olfactory tract than in mice that were simply returned to their home cage. These results are promising for future studies that will focus on subtle changes in activity caused by learning.
W: Do you think this technique will ever have a potential for human studies?
S: I wouldn’t rule it out, but it won’t happen any time soon. Manganese is a known neurotoxin and too much exposure can cause symptoms similar to Parkinson’s disease. However, the amounts needed for tract-tracing are small and many animal studies have reported no obvious ill effects after manganese administration. Anyway, even if we can never reduce the exposure to levels where we’re comfortable administering manganese to humans, there will still be much to learn from animal models.
W: Besides manganese contrast, what other projects are you working on that you would like to mention?
S: Another technique that we’re using to study networks within the brain is called connectivity MRI. Basically, MRI can be sensitive to hemodynamic parameters such as blood oxygenation that change whenever the brain is active. The idea behind MRI functional connectivity studies is that if you look at the ‘noise’ in the MRI data acquired while the subject is just relaxed, doing nothing, you can find correlations in areas that are known to be strongly connected, like bilateral motor cortex. It’s widely assumed that this correlation is caused by some kind of coordinated neural activity, but the actual relationship between the neural activity and the correlated MRI signals hasn’t been explored, probably because most of the work on functional connectivity was done in humans. We are developing a rat model of functional connectivity so that we can combine electrophysiology and MRI to explore the relationship between the two.
W: Do you foresee functional connectivity being a useful tool for the neurosciences?
S: There are already some indications that functional connectivity changes in patients with neurological disorders like Alzheimer’s disease or multiple sclerosis. I think the question is really whether these changes tell us anything about the actual neural activity. One of the problems with MRI measures of functional connectivity is that they can easily be contaminated by other physiological processes like respiration or the cardiac cycle. Again, these are some of the questions we hope to answer with an animal model.
W: For your final words, if you could name one thing that you would change in your graduate experience and one thing you wouldn’t change, what would they be?
S: Probably the best thing I did in graduate school was to arrive early and start research the summer before classes began. Coming early let me get started in a lab before the stress of classes set in, and since I got to work in the lab full time for the summer, I had a good grasp of the basics and was able to make much more progress during the first year than I would have otherwise. As for things I would change, I’d take an electronics class to improve my circuit-building. And maybe I’d learn something about the brain!