Between 17 and 30 days after conception, an embryo’s neural tube forms and closes, giving rise to the central nervous system. When that tube doesn’t close properly, neural tube defects occur, which affect more than 300,000 babies around the world every year. A simple intervention—adding folic acid to the diets of people who may become pregnant—could prevent up to 70% of neural tube defects.
The underlying mechanisms—how exactly folic acid influences neural tube closure—still elude scientists, and a researcher at Stevens Institute of Technology wants to help change that. In August, assistant professor of biomedical engineering Shang Wang received a $1,910,915 award from the National Institutes of Health (NIH) as part of their Maximizing Investigators’ Research Award (MIRA) program, which seeks to bolster researchers by providing stable funding that’s more flexible than traditional grants. Wang is using the award to develop a multi-contrast, high-resolution imaging platform that’s poised to take developmental biology research to new levels.
From a single cell
“Developmental biology is related to every one of us because we all come from this single cell that is able to develop into a multi-billion cell system that has diverse structures, morphologies and functions,” Wang explained. “In the lab, we're developing new optical imaging techniques to enable the study of fundamental developmental biology questions that are difficult or impossible to study with existing approaches.”
In the process of going from that single cell to a galaxy of complex cells and tissues, cells with identical genes self-organize into very different types of tissues and organs. Understanding the factors that trigger or regulate those cell-level decisions could advance the field of developmental biology and offer clues for how to intervene when things go wrong.
This could help scientists understand how congenital disorders like neural tube defects occur. It could also shed light on the mechanisms that drive aging, developmental diseases and cancer — and even give rise to novel regenerative treatments.
Bringing embryo cultures into focus
The Shang Wang lab has been working at the nexus of optical imaging and developmental biology. The imaging platform they are developing employs the basic principle that is similar to ultrasound imaging, but with one important difference.
Ultrasound works by sending sound waves through tissues and collecting the echoes of the sound. Wang’s development of the platform is based on optical coherence tomography (OCT), which instead sends light waves through tissues and collects the reflections of that light as it bounces back. The major benefit of working with light waves is that the imaging can achieve much higher resolutions, so researchers can see finer details. This is measured in microns, which are 1/1000th of a millimeter. While ultrasound technology can resolve at the scale of hundreds of microns, OCT can resolve at the level of 1-10 microns.
Those gains in resolution require a trade-off in terms of imaging depth. OCT is ideal for applications where researchers only need to look 1 or 2 millimeters deep (versus the centimeter scale for ultrasound)—which is exactly right for studying embryo cultures. Bringing OCT for developmental biology addresses critical imaging needs and opens the door to new studies, especially for understanding the dynamic process of development.
“I think this is one of the powers of multidisciplinary research: you’re not only working in one discipline but you’re bridging with another discipline,” explained Wang. “For us, we are serving the biology side with imaging.”
The power of contrast
Based on OCT, Wang’s lab is developing methods for multi-contrast imaging, which means researchers can achieve different views and collect different types of data from the same sample. This is similar to how medical imaging techniques can use color contrast to enhance the visibility of specific structures. Instead of color, the platform will enable structural contrast to reveal tissue architecture, functional contrast to show things like blood supply, molecular contrast to visualize specific molecules like proteins, and biomechanical contrast to highlight tissue differences like elasticity.
“Over the years, studies have found that there are various physical, chemical or mechanical factors that all can contribute or regulate the developmental process,” Wang said. “So, all these factors could play a role in a process, and if you can't image their dynamics during that process, it's hard to study what exact role they're really playing.”
Ultimately, Wang hopes his imaging platform will be an accessible research tool that supports research in a wide range of labs. “The goal is for this type of multi-contrast imaging system to be used by as many developmental biologists as possible so the whole field can benefit from it,” he noted. “I’m definitely very, very excited. It’s a great opportunity to work on this idea.”
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