Faculty Q&A With Elizabeth Hillman
Growing up just outside of London, England, Elizabeth Hillman found it difficult to choose between her favorite subjects, medicine, physics and mathematics. As an undergraduate at University College London, she found the ideal amalgam: medical physics. "I wanted to build the machines that doctors use," she says. "To me, that was the perfect combination of being involved in medicine...Having the pleasure of building things and using the math and computing that I was good at."
Hillman, 32, now an assistant professor of biomedical engineering at The Fu Foundation School of Engineering and Applied Science, is building just such systems here. Her optical imaging tools—devices that use light—will make it possible for her to investigate the relationship between blood flow and nerve cell activity on a living brain. Hillman, who earned her PhD in medical physics and bioengineering also from University College London, wants to learn about the relationship between blood flow and neuronal activity and to do so in real time.
Understanding how these so-called pathways work may provide reams of information about treatment therapies for preventing age-related neurodegeneration, and aid in understanding the brain and how it works. A growing body of literature suggests that whatever couples the blood flow response to the neuronal response, Hillman says, may get broken in diseases like Alzheimer's and other age-related neurodegeration.
"If we can really identify the cells, the pathways, the chemicals in the brain that control these [responses]," adds Hillman, "and really understand how it should look when it's normal, then this gives us an important link to understand how the abnormalities could relate to brain diseases."
In May, Hillman was awarded a $1.66 million grant by the National Institute of Neurological Disorders and Stroke to fund this research for the next five years. Hillman and her team of graduate students will build on their current system of optical imaging technologies—which includes camerabased imaging systems and laser-scanning tools—to make them faster and provide higher-resolution images when investigating the brain, and possibly other organs.
Hillman is also the inaugural recipient of The Rodriguez Family Junior Faculty Development Award, created by SEAS alumni Ana Rodriguez (SEAS'86, '88) and her brother, Marcos (SEAS'83), to support recruitment, retention and recognition of under-represented junior faculty. Hillman will use the fund toward her lab.
Q. What is it about your research that has not been done before?
We're investigating the brain as a machine, and then we're building machines to allow us to do that investigation. It's unique, because we have both the neuroscience expertise and the engineering skills to design and develop specialized imaging systems for this application. Most researchers tend to use commercial systems which are very limited in terms of what they can actually do. The technology development goes hand in hand with the science and we use the two to stimulate each other. A lot of people have tried to look at neurovascular coupling in vitro, where they look at small pieces of the system, but we're talking about [investigating] a working brain with all the neuronal connections and blood vessel system that needs to have blood flowing through it...To understand that system in its entirety, you really need to image it in an intact brain, but imaging an intact brain is very difficult because you have to actually get to the brain...So it's a massive technical challenge to build imaging devices that can see all of this in enough detail to really be able to understand how it's working in real time.
Q. What are the engineering-design challenges you face?
We're trying to rapidly incorporate new technologies such as faster cameras, faster scanning techniques for laser imaging, better lasers, more sensitive detectors—all these things need to be rapidly adopted and incorporated into the systems to make them able to image faster and image deeper with more sensitivity and contrast. We're also layering on the complexity, for example a lot of conventional microscopes only have two channels so they can see two colors, e.g. red and green, whereas our system has red, green and blue channels and it has room to incorporate even more. So where most people can look at two types of cell at once, we can look at four or five different components of the system all at once evolving in the same field of view very, very fast. We also mix together different technologies and translate techniques between different applications. For example, one of the methods that we have developed for 3D brain imaging, we are now also applying to image skin cancer. We have to overcome a lot of engineering challenges to extract information from living tissues.
Q. Are we still in the early stages of optical imaging?
It's difficult to define because optical imaging is so broad. It's not like MRI (magnetic resonance imaging) where everyone knows what an MRI machine looks like. Optical encompasses all kinds of different things, from a standard microscope to spectroscopy systems that measure samples. If you look, there's optical everywhere: Endoscopy is an optical technique, laparoscopy, eye exams, lots of things that image skin cancer are optical. The biggest challenge is to be able to see deeper into tissues with optical methods.
Q. When did you start focusing on the brain?
I went from doing brain studies as an undergraduate to my Ph.D. work where we were looking at developing a system to image the premature infant brain, looking for ways to prevent cerebral palsy. It was primarily during my post-doc when I was at Massachusetts General working in the Martinos Center for Biomedical Imaging that I started to really focus on it. Researchers there were some of the pioneers of functional MRI, and I was immersed in it there for several years and that's what drew me to this question...I realized that by using these high-resolution imaging technologies we can actually see the interactions, we could actually see the single cells. I came to this idea that if we can do enough engineering, we could capture it in action. I'm a bit fixated on this now.
Q. What other projects are you working on?
In addition to applying our brain imaging tools to skin and cardiac tissues, my lab is also developing optical imaging tools for molecular imaging. Our paper in Nature Photonics last year demonstrated a new technique for imaging small animals that exploits the spatiotemporal evolution of fluorescent signals after a bolus injection of dye. This method has been licensed by a company and is now commercially available for researchers and companies doing drug development and disease research. Overall, the theme of my lab is to use engineering to extract as much information as possible from living tissues.
—Interview by Melanie A. Farmer
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