In 2023, what will happen with zebrafish microscopy?

Dr. Jason Otterstrom discusses the advantages and drawbacks of zebrafish as a developing model for life science research in this interview with NewsMedical. They talk about the new discoveries being made possible by automated methods for evaluating microscope images of Zebrafish samples. They concentrate particularly on Athena, an automated analysis tool driven by AI. The manual quantification bottleneck is eliminated by this breakthrough, which has the potential to increase the rate of discovery to previously unimaginable levels. Athena is currently accessible for download on a cutting-edge pay-per-use model.

Could you perhaps give us a brief explanation of the advantages of using zebrafish as study models?
A promising and fascinating emerging model system for biomedical research in the living sciences is the zebrafish. They differ from current mouse models in a variety of ways, including very quick reproductive times and more cost-effective rearing. Additionally, because of their quick reproductive cycles, increased experimental throughput is feasible.

Additionally, they share 70% of their genetic sequence with humans, making them genetically relevant and allowing for the introduction of fluorescent proteins as a reporter mechanism.

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Another significant benefit is the zebrafish’s size. Zebrafish are translucent in their early stages because they develop into tiny eggs and larvae, which makes them ideal for microscopy.

The fish is easily visible even with bright-field imaging. It is useful for pharmacokinetics, toxicity studies, and genetic knockouts to be able to observe the intricate internal architecture as well as the biological processes taking place in a living, multi-organ system.

The fluorescence also has the advantage of providing a very binary readout with strong contrast. In the next ten years, I think zebrafish will be used in a wide variety of new industries due to their many advantages.

What difficulties do researchers using zebrafish models encounter?
Zebrafish have a lot of great possibilities for the future of life science research, but using them as model organisms for microscopy comes with a number of difficulties. Although they may be viewed on a variety of microscopes and are transparent, positioning them in the proper orientation is a significant difficulty. This is due to the fact that depending on how they are orientated, you may be better able to see certain of their internal organs, or they may become obscured and impossible to observe, both in bright fields and fluorescence.
The problem of orienting the fish to see the important anatomy with the best degree of fidelity is one that many researchers grapple with.

There are various methods to deal with this; some use specific alignment plates, others agarose gels, but none of them completely match the throughput requirements. Such methods need a lot of human labor, which makes it more challenging to solve this problem.

After the photographs have been taken, it can be difficult to extract useful information from them. Although a computer may not always recognize the fish and its organs, the visuals themselves are simple for a human to understand.

To date, many have relied on ImageJ and other types of programable tools to manually pinpoint areas of interest or merely focus on the fluorescence channel without taking into account the anatomical context to produce basic fluorescence readouts. As a result, important information from ignored anatomy is not taken into account.

Would you be able to describe how IDEA Bio-Medical is able to provide viable answers to these problems?
IDEA Bio-Medical is an expert in developing automated tools for picture acquisition and analysis. Around a hundred scholarly journals have referenced our Hermes platform, which consists of the Hermes microscope and related Athena software and supports high-impact research all over the world. Since we are a tiny business, we depend heavily on our clients, and it was thanks to them that the demand for image analysis in zebrafish was discovered.

We at IDEA Bio-Medical have experience with high-content screening that is fully automated. We have more than ten years of experience helping life science researchers automate the picture acquisition and image processing processes for their microscopy research.

Could you describe your working relationship with your clients and how IDEA Bio-Medical supports any modifications to their research?
As I’ve already said, we take pride in working closely with our clients to meet their specific demands as scientific innovators. Through these, we were able to comprehend the difficulty of picture analysis for zebrafish researchers and the bottleneck it creates in their work processes. To meet the strict demand for label-free image acquisition, we and our clients have created a revolutionary deep learning-based algorithm to recognize the fish and its internal anatomy in bright-field photos.

We can extract the fish outline and all of the interior anatomy from that image analysis. Then, using that data to investigate any potential fluorescent signal, we extract quantitative information about the fish’s shape and internal anatomy. As a result, it is able to study the precise localization of the fluorescence within the zebrafish anatomy. In the end, we successfully enable real high-content imaging in zebrafish.

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Do all academics need access to the Hermes platform or is the Athena software widely available?
Athena’s software was previously only incorporated within the Hermes platform. We’re thrilled to support all zebrafish researchers by making Athena available to a wider audience by selling it as a standalone product. To achieve this, we have modified Athena to receive and analyze images from all different kinds of microscopes in just about any image format, whether it be proprietary JPEG or open-source TIFF.

Consequently, images can be captured using a stereo microscope, an inverted microscope, or an upright microscope. By doing this, we intend to assist a wide spectrum of researchers who need to review a few dozen to several hundred Zebrafish photographs each week. There is no throughput cap, and we provide a variety of solutions to accommodate the throughput needs of any lab. Overall, IDEA enables zebrafish researchers to gain greater insight from their data and set more ambitious research objectives.

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