Imaging the Developing Lung to Explore a Critical Disease in Preterm Babies

Dr. Kent Willis is a neonatologist physician-scientist at the University of Alabama at Birmingham (USA). He splits his time between critical care for preterm newborns and running a lab focused on exploring how the early life microbiome influences disease in newborn babies.

His lab uses a number of gnotobiotic mouse models, ex vivo lung culture and in vitro lung organoid and tissue models primarily focused on understanding the gut-lung axis in bronchopulmonary dysplasia (BPD).

An image that Dr. Willis posted on Twitter of a whole, adult mouse lung captured using light sheet fluorescence microscopy caught our eye. We reached out to learn more about his research.

How did you become interested in bronchopulmonary dysplasia (BPD)?

Dr. Kent Willis (right) and Ahmed Abdelgawad, MS of the University of Alabama at Birmingham (USA)

Dr. Kent Willis MD (right) and staff researcher, Ahmed Abdelgawad, MS, who performed the tissue clearing and sample preparation for the imaging featured in this article.

BPD is the most severe and life-threating disease of preterm babies. BPD affects the smallest and most premature newborns and is quite common (more than half of extremely preterm newborns). Sadly, it also has a very high mortality. More newborns die of BPD per year than children of any age die of all forms of childhood cancer.

As a neonatologist, BPD is one of the most dangerous diseases that may affect my patients, and since it only happens in preterm babies less is understood about it than many adult lung diseases.

What big research goals are you currently focusing on?

Our main research goals are to explore how the microbiome helps shape immune development in newborns and how this potentially goes awry in preterms. We are expanding our use of light sheet microscopy to several of our projects under this main goal but the particular project these images are from is focused on exploring neural-immune interactions in the developing lung.

Adult mouse lung with sympathetic nerves stained with tyrosine hydroxylase (TH) (magenta) and tissue autofluorescence in green. Imaged using light sheet microscopy.

How is light sheet microscopy enabling your research?

Previously we have used confocal microscopy, but we are using iDISCO+-based tissue clearing and light sheet microscopy because it allows us to greatly expand the scale of the imaging we can perform. This is very important for thin, complex 3D structures like pulmonary nerves. Using more traditional microscopy you would need to cut the lung tissue into hundreds of slides that at most would only contain a very short segment (or cross section) of an individual nerve, then try to reconstruct the 3D shape afterwards using imaging software. While sample preparation may take awhile for cleared tissues, we can scan the entire lung in 3D in a matter of minutes and the light sheet microscope shows us extremely complex neural networks without spending hours trying to piece the images back together.

Adult mouse lung with sympathetic nerves stained with tyrosine hydroxylase (TH). Imaged using light sheet microscopy.

Learn More

Visit Dr. Willis’s lab webpage or read a recent publication from Dr. Willis and his colleagues: The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet. Link

Learn about ZEISS solutions for light sheet microscopy.

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