Microscopy method reveals internal structure of live embryos, and is noninvasive

Called gradient light interference microscopy, the method allows imaging of thick, multicellular samples.

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Advanced knowledge regarding the health of embryos could help physicians select those that are most likely to lead to successful pregnancies via in vitro fertilization (IVF). Recognizing this, researchers at the University of Illinois at Urbana-Champaign (Champaign, IL) have developed a microscopy method that produces 3D images of live embryos in cattle to possibly help determine embryo viability before IVF in humans.

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The method brought together electrical and computer engineering professor Gabriel Popescu and animal sciences professor Matthew Wheeler in a collaborative project through the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. Called gradient light interference microscopy (GLIM), the method allows imaging of thick, multicellular samples.

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Marcello Rubessa, Gabriel Popescu, and Matthew B. Wheeler teamed up to produce 3D images of live cattle embryos that could help determine embryo viability before in vitro fertilization in humans. (Photo: L. Brian Stauffer)

In many forms of biomedical microscopy, light is shined through very thin slices of tissue to produce an image. Other methods use chemical or physical markers that allow the operator to find the specific object they are looking for within a thick sample, but those markers can be toxic to living tissue, Popescu says. Also, when looking at thick samples with other methods, the image becomes washed out because of the light bouncing off of all surfaces in the sample, says graduate student Mikhail Kandel, the co-lead author of the study.

GLIM can probe deep into thick samples by controlling the path length over which light travels through the specimen. The technique allows the researchers to produce images from multiple depths that are then composited into a single 3D image.

To demonstrate the new method, Popescu's group joined forces with Wheeler and his team to examine cow embryos. "Having a noninvasive way to correlate to embryo viability is key; before GLIM, we were taking more of an educated guess," Wheeler explains. Those educated guesses are made by examining factors like the color of fluids inside the embryonic cells and the timing of development, among others, but there is no universal marker for determining embryo health, he says.

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A gradient light interference microscopy image of a rendered cow embryo that was cut through the center to reveal internal structures. (Courtesy of Gabriel Popescu)

"This method lets us see the whole picture, like a three-dimensional model of the entire embryo at one time," says Tan Nguyen, the other co-lead author of the study. The next test for the researchers, though, will be to prove that they have picked a healthy embryo and that it has gone on to develop a live calf, says Marcello Rubessa, a postdoctoral researcher and co-author of the study.

The team hopes to apply GLIM technology to human fertility research and treatment, as well as a range of different types of tissue research. Popescu plans to continue collaborating with other biomedical researchers, and already has had success looking at thick samples of brain tissue in marine life for neuroscience studies.

Full details of the work appear in the journal Nature Communications.

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