Imaging zebrafish movements in 3D to better understand ALS disease

An interdisciplinary team of the Institut national de la recherche scientifique (INRS) used an innovative imaging technique for a better understanding of motor deficits in Amyotrophic Lateral Sclerosis (ALS). The researchers were able to follow the escape behaviour of normal and disease zebrafish models, in 3D. Their results have recently been published in Optica, the flagship journal of the Optical Society (OSA).

Professor Jinyang Liang, expert in ultra-fast imaging and biophotonics, joined an effort with Professor Kessen Patten, specialist in genetics and neurodegenerative diseases. The two groups were able to track the position of zebrafish in real time and capture the 3D motion, using a special imaging technique called dispersion-eliminated coded-aperture light field, or DECALF.

“It is a unique feature for the analysis of animal behaviours from a neurodevelopment perspective. Otherwise, we would only be able to see the movement in a plane. Losing one dimension can be misleading when studying the movement. You may think zebrafish move one way, but the reality is quite different,” said the expert.

Their data revealed asymmetrical orientation angles of the left and right fins, indicating drastic changes in direction during the normal zebrafish’ s escape from the stimulus. In contrast, the diseased zebrafish model showed slow responses and limited movement capacity due to motor deficits.

Conventional light field cameras capture the information not only in x and y, but also the angle at which the light rays are coming from. This way, you can trace them back to focus on where you want. According to Professor Liang, the problem with this technology is the tradeoff. The image can have a high spatial resolution or a high angle resolution, but not both. The solution for this is the coded aperture light field (CALF) imaging, which can be achieved using digital micromirror devices (DMD).

An Innovative Design

The DMD acts like a diffraction element and separates the white light into a rainbow. A DMD alone cannot use it with ambient light or sunlight. “You could always use a single-wavelength light, but it leads to other disadvantages, since the colour of the light may interfere with the nerve system and affect the experiments. For example, red light could make people aggressive, and blue light is also known to affect the mood,” Professor Liang explains.

To bypass this limitation, the research team used a second DMD to cancel the rainbow induce by the other one. “We are the first to use this design to manage the colour dispersion within the entire visible spectrum, which allows us to use white light for this experiment,” says Dr. Jingdan Liu, a postdoctoral fellow at INRS and the first author of this paper. “DECALF imaging could open up a new avenue for neuroimaging. For example, we could use this system to see neurons’ activity. We could track the emitted light when a neuron ‘fires’ to know where the neuron is located in the brain and its connectivity,” says Professor Liang.

“Thanks to the work of Professor Liang, we were able to see the macroscopic behaviour of zebrafish with ALS-like symptoms. We could go even further in the study of this disease by looking at the microscopic scale.Using this innovative imaging approach, we could learn about what is happening in the neural system in normal and disease states in a non-invasive manner,” Professor Patten says.

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About the Study

The article “Coded-aperture broadband light field imaging using digital micromirror devices”, by Jingdan Liu, Charlotte Zaouter, Xianglei Liu, Shunmoogum A Patten and Jinyang Liang, was published in the February 2021 issue of the journal of Optica. Researchers received financial support from the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation, Fonds de recherche du Québec – Nature et technologies (FRQNT), and Fonds de Recherche du Québec – Santé (FRQS). Professor Kessen Patten acknowledges the support from the Anna Sforza Djoukhadjian Research Chair in ALS.

About INRS

INRS is a university dedicated exclusively to graduate level research and training. Since its creation in 1969, INRS has played an active role in Quebec’s economic, social, and cultural development and is ranked first for research intensity in Quebec and in Canada. INRS is made up of four interdisciplinary research and training centres in Quebec City, Montreal, Laval, and Varennes, with expertise in strategic sectors: Eau Terre Environnement, Énergie Matériaux Télécommunications, Urbanisation Culture Société, and Armand-Frappier Santé Biotechnologie. The INRS community includes more than 1,400 students, postdoctoral fellows, faculty members, and staff.

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