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Colour-Modified Mice Tissues Allow for Higher-Resolution Imaging
Researchers have developed a mouse model with colour-changing tissues that help to identify and eliminate background noise in photoacoustic imaging.

Researchers at Duke University and the Albert Einstein College of Medicine have successfully engineered a mouse model with colour-changing tissue to produce higher-resolution images in photoacoustic imaging.

In accordance with its namesake, photoacoustic imaging utilises both light and sound to image bodily tissues, cells, and organs. During the imaging process, a pulse of laser light is sent deep into the chosen tissue, leading to the spontaneous heating up and expansion of cells. Consequently, an ultrasonic wave is created, which after translation, provides information about the composition and structure of the tissue of interest.

Unfortunately, although the ultrasound component of photoacoustic imaging has the added advantage of allowing doctors to observe the tissues more deeply, it also creates background noise that lowers the resolution of the final image.

“If we want to image something like how a tumour is growing or shrinking, we have a hard time seeing anything significant because the background ultrasound signals from flowing blood drowns everything out,” said Junjie Yao, Assistant Professor of Biomedical Engineering at Duke. “It’s like trying to observe the stars in daylight –– the light from the sun overpowers all other sources of light.”

Thus, the team of researchers, led by Yao, and Vladislav Verkhusha, Professor at the Albert Einstein College of Medicine, New York, focused their efforts on finding a way to track and eliminate the background noise, cumulating into a genetically-modified mouse model with colour-changing tissues.

To obtain this result, the researchers inserted BphP1, a bacterial, light-sensitive photoreceptor into the cells of the mouse model. This photoreceptor already has existing uses in research due to its unique property of being able to switch from a silent to an active state upon contact with a specific wavelength of light. BphP1 is especially useful as it binds well to biliverdin, a molecule that is found almost exclusively in tissue cells.

After the insertion of BphP1, the modified mouse models were exposed to a particular wavelength of red light, which activated it, resulting in a “colour change” of the mouse tissues. Then, another wavelength of near-infrared light was shone on the model, switching BphP1 to its silent state.

According to Yao, since the blood does not “change colour” when being subjected to the light treatments, the noise from the blood would become a more obvious constant component that can be easily filtered out using data processing methods, allowing for the modified imaging technique to be orders of magnitude more sensitive.

In an exploration of the applications of their creation, the researchers imaged the intestine, liver, spleen, and stomach of the colour-changing mouse models. The resulting images were of higher resolution than those produced by standard PA procedures, in particular the liver and spleen, due to the prevalence of biliverdin in these tissues. The enhanced detail of the noise-reduced images enabled the team to observe changes in the tissues, study processes like liver generation, and monitor the results of different protein delivery methods.

This imaging method also allowed for enhanced observation of gestation in mice as shown by the research findings, where a total of seven embryos could be clearly distinguished from the surrounding maternal organs and vasculature.

In future experiments, the researchers hope to test the use of BphP1 to track the movement of cancer or immune cells in the body to gain a better understanding of how cancer cells spread and the response of immune cells to treatments respectively.

Besides imaging, Verkhusha and his team will dive deeper into exploring how his model may contribute further to optogenetic research, which explores how light may be used to influence cell activity.

“To me, this project was a good marriage between biochemistry and imaging,” said Yao. “The idea of a colour-changing mouse is really exciting on its own, but I’m optimistic we can use this mouse to do some magic.”

Source: Kasatkina et al. (2022). Optogenetic manipulation and photoacoustic imaging using a near-infrared transgenic mouse model. NatureCommunications, 13(1), 2813.

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