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

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

Light sheet microscopy used to image optically cleared lung tissue.

Bronchopulmonary dysplasia (BPD) is the most severe and life-threating disease of preterm babies. BPD affects the smallest and most premature newborns and is quite common. 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.

Dr. Kent Willis is a neonatologist physician-scientist at the University of Alabama at Birmingham (USA). 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). Light sheet microscopy is a new technology he has incorporated to his research to enhance his studies of the lung.

Dr. Kent Willis, University of Alabama at Birmingham, USA

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.

Dr. Kent Willis

with staff researcher, Ahmed Abdelgawad, MS, University of Alabama at Birmingham, USA

Neural-Immune Interactions in the Developing Lung

Imaged using Light Sheet Microscopy

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

Visualizing the Lung with Light Sheet Microscopy

One of Dr. Willis's main research goals is to explore how the microbiome helps shape immune development in newborns and how this potentially goes awry in preterms. They are expanding their use of light sheet microscopy to several of our projects under this main goal but the particular project for 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). Imaged using light sheet microscopy.

Advantages of Light Sheet Microscopy

Previously, Dr. Willis had used confocal microscopy, but using iDISCO+-based tissue clearing and light sheet microscopy allows him to greatly expand the scale of the imaging. This is very important for thin, complex 3D structures like pulmonary nerves. Using more traditional microscopy, the lung tissue must be cut into hundreds of slides that at most would only contain a very short segment (or cross section) of an individual nerve, which must  be reconstructed using imaging software. While sample preparation may take longer for cleared tissues, the entire lung is imaged in 3D in a matter of minutes. 

The light sheet microscope shows us extremely complex neural networks without spending hours trying to piece the images back together.

Dr. Kent Willis

University of Alabama at Birgminham, USA


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