Super Vision: How New Imaging Technologies Are Transforming Biomedical Research

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This movie from the Kat Hadjantonakis lab shows an 11-day-old mouse embryo with its internal organs labeled in different fluorescence. The video was prepared by postdoc Evan Bardot.
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If you’ve ever explored Google Earth, you know that satellites can spot your house from space. Type in your address and within seconds you zoom from Blue Marble to rooftop. Now imagine being able to do that on a microscopic scale, zipping down from an organ to a specific cellular address. That’s what advanced imaging technologies are all about.

Scientific advances often depend on improved ways of seeing. From the telescope through which Galileo peered to understand the solar system to the microscope that the 18th-century biologist Leeuwenhoek used to see microbes for the first time, tools to enhance our limited human vision have played a crucial role in the expansion of scientific knowledge.

That’s why researchers at the Sloan Kettering Institute are betting that the next big breakthroughs in cancer biology will come from cutting-edge imaging technologies that can bring the molecular details of cancer cells into plain view. Over the next few years, they’ll be acquiring several new microscopes with previously unheard-of imaging capabilities.

“It’s like something out of a James Bond movie,” says immunologist Morgan Huse about a new microscope called the Bruker Luxendo MuVi SPIM light-sheet system. “It’s almost like reading a secret document from space.”

It's like something out of a James Bond movie… like reading a secret document from space.
Morgan Huse immunologist

The MuVi SPIM (pronounced “movie-spim”) works by taking thousands of horizontal scans of a specimen at different depths and then digitally compiling them into a 3-D image. In contrast to a conventional microscope, which scans one specific point at a time, the MuVi SPIM uses a “sheet” of light, making it much faster.

With the 3-D image assembled, the researchers can then visually travel through it, almost like the scientists in Isaac Asimov’s Fantastic Voyage, who journeyed through the bloodstream in a microscopic vessel.

Developmental biologists, for example, can cruise between the cells of a developing embryo to learn what cell-to-cell contacts are important in generating organs and limbs. Cancer biologists can fly over a large territory of tissue, looking for metastatic cancer cells. The microscope brings a whole new level of resolution to the study of hard-to-find cells.

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This video from the Kat Hadjantonakis lab shows developing nerve fibers in a 14.5-day-old mouse embryo. The movie was acquired on the MuVi SPIM light-sheet with a 10x objective and was prepared by postdoc Evan Bardot and advanced microscopist James Muller.
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Drilling Down

In addition to scanning large tissue areas, scientists also want to see what’s happening at the level of individual cells. For that, the Zeiss Elyra super-resolution microscope is the instrument of choice.

Dr. Huse is using a recently acquired Elyra to study what happens when an immune cell called a T cell faces off against a foe such as a cancer cell.

“We used to think of the interface between a T cell and its target as two spheres touching,” Dr. Huse says. “But with this new technology, we can see that the T cell actually extends spike-like protrusions into the target cell. This physical interaction may be an important element of how the T cells kill a target, almost like punching holes in it.”

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This video from the Morgan Huse lab shows a T cell (green) attacking a spherical hydrogel ball that simulates a tumor cell. The T cell extends spike-like extensions into the particle as it attempts to "kill" it. The video was prepared by graduate student Miguel M. de Jesus using a VisiTech Instant SIM microscope.
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Investing in Innovation

Over the next decade, SKI plans to invest heavily in four key technology areas. In addition to imaging, the institute will be acquiring or developing new single-cell imaging tools, precision cancer models, and integrative computing. These innovative technologies will extend the boundaries of what is possible for scientists to see and measure. The scientists’ ultimate goal is to use these tools to solve the problem of cancer relapse and drug resistance.

“Invention is the mother of necessity,” Joan Massagué, Director of SKI says, inverting the common aphorism. “We believe that the next big advances in cancer research are going to come from innovative technological tools, and SKI plans to lead the way.”

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