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"In Vivo" Optical Imaging Laboratory
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Illustration by Barbara Martin |
| Schematic of “in vivo” optical imaging system |
It was only a few decades ago that neuroscientists could only dream of the day that they would be able to look directly at brain activity. At the time they were limited to measuring the activity of neurons one by one using microelectrodes inserted into the cortex. Today, this dream has been realized. Researchers now have several methods for directly viewing activity in the brain, each of which has different advantages and disadvantages.
One of these techniques uses visible light and is called “in vivo” optical imaging. Because visible light cannot penetrate bone, part of the skull must be removed to reveal the brain’s surface. Unlike the other major brain mapping technique, functional magnetic resonance imaging (fMRI), optical imaging is confined to the surface of the cortex. It takes about the same time as fMRI to make an image  but it can resolve details about one-fifth the size of fMRI.
Since its development as a research tool, optical imaging has found a number of clinical applications. For example, it is used as a part of surgical procedures to treat epilepsy and it has been applied to imaging the retina, where it has led to major advances in ophthalmic diagnostics.
For nearly 50 years, scientists knew that the optical properties of brain tissue changes by a tiny amount (about one part in 10,000) when it becomes active. Active neurons consume oxygen, which causes an increase in the concentration of hemoglobin molecules stripped of oxygen atoms in their vicinity. When viewed in red light, these “deoxyhemoglobin” molecules reflect slightly less light than oxyhemoglobin molecules. When they were discovered, however, these changes were far too small to use for imaging. In fact, it was not until the mid-1980’s that optical imaging technology and techniques advanced enough so directly measure these intrinsic changes.
In the 1970’s, Amiram Grinvald of the Weizmann Institute of Science in Israel pioneered the development of an optical system that used voltage-sensitive dyes to detect brain activity. He formed a company that produced this system commercially. Although it produced exciting new information, the system’s output initially took the form of a series of graphs that required a lot of experience to interpret. Then a Harvard University neuroscientist, Gary Blasdel, developed a new method for analyzing the results from Grinvald’s system that produced visual maps of brain activity. Not only were these much easier to understand, but it turned out that Blasdel’s procedure was sensitive enough to record the intrinsic optical changes of brain tissue without using special dyes. Blasdel’s improvement was incorporated into the commercial system. Today, there are 33 of these systems in U.S. laboratories and another 50 installed in other countries.
In 1986, Vivien Casagrande attended the seminar where Blasdel presented his new maps. “I loved the beauty of it. I’ve always loved anatomy and his maps showed the functional anatomy of the brain more clearly than anything else that I had seen until then,” she recalls. “We’d always known that neurons don’t work one at a time and this showed how groups of neurons worked together just beautifully.”
As a result, Casagrande returned from the meeting with the desire to start up an optical imaging laboratory at Vanderbilt. However, it was nearly 10 years before she could take the next step. In 1995, she arranged a series of short visits to the laboratory of David Fitzpatrick at Duke University who had successfully set up one of these systems. The experience strengthened her determination to bring the optical imaging techniques to the campus. So she began the difficult process of gathering support for the idea among her fellow researchers and finding the funding required.
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Photo by Daniel Dubois |
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| Xiangmin Xu, left, and Vivien Casagrande in optical imaging laboratory. |
She was successful in 1999 when she and five other Vanderbilt investigators were awarded a National Center for Research Resources Shared Instrumentation Grant for this purpose. The co-investigators included Prof. A.B. Bonds III in Electrical Engineering and Computer Sciences and Profs. Ford Ebner and Jeffrey Schall in Psychology. Building on the original grant, both the Kennedy Center and the Vanderbilt Vision Research Center (VVRC) applied for and received additional money to support imaging cores. These cores have, in turn, provided both monetary and technical support to the Optical Imaging Laboratory.
The additional support proved to be unexpectedly helpful when setting up the laboratory proved to be quite a bit more difficult than Casagrande had anticipated. “Part of the problem was that I hadn’t learned everything I needed during my time in Fitzpatrick’s lab,” she acknowledges. But defective equipment and other problems turned the set-up process into something of a nightmare.
Fortunately, neuroimaging engineer Jim Stefansic and programmer Dan Shima from VVRC came to the rescue and helped Casagrande solve her start-up problems. As a result, the optical imaging lab was finally up and running in 2001. Since then the lab has been extremely busy and a number of experiments have been carried out. A new associate professor in psychology, Anna Roe, has purchased a second optical imaging system. She and Casagrande have joined with several other vision researchers to purchase a new camera system that will allow them to record brain activity in real time.
Casagrande and her students have used the laboratory to complete several experiments and to start several more. These include a study to determine the impact that visual lifestyle (diurnal versus nocturnal) has on the organization of the visual cortex in primates; mapping the areas in the primate visual cortex that respond preferentially to specific forms; and an examination of the way in which the visual field maps onto the primary visual cortex of bush babies and owl monkeys that demonstrated optical imaging can be used as a high resolution mapping tool.
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Photo by Daniel Dubois |
| Vivien Casagrande, left, and Xiangmin Xu examining data from optical imaging study. |
In collaboration with the laboratory of Jon Kaas, Casagrande’s group has investigated the organization of the third visual area (V-3) in owl monkeys. In particular, they are mapping the dorsal visual pathway in V-3 that carries information about what the animal is seeing. Their results support he idea that V-3 is a single visual area that surrounds the second visual area and is not composed of two different areas as some have proposed.
Meanwhile, students in A. B. Bonds’ laboratory have successfully used optical imaging to study the feedback that occurs between different visual centers. Descriptions of the visual system invariably describe the flow of sensory information from the eyes to the primary visual cortex and from the primary visual center to the other visual centers in the brain. However, many more connections run in the opposite direction and Bonds’ students are studying the influence that secondary visual centers exert on the primary center.
Most recently, Casagrande has established a collaboration with psychology professor Joseph Lappin to use optical imaging to answer some questions that arose as the result of a series of psychophysical experiments that Lappin’s group conducted on motion detection. [See related story “Researchers gain new insights into how we perceive motion”] This involves a clever system, called center-surround organization, that nature has developed for filtering out spurious signals caused by shifting patterns of light that fall on the retina that don’t have anything to do with the movement of objects in the external world.
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