Scientists develop 'wildDISCO' method to detect tiny cancerous tumors

Better than previous scanning methods?

Although there exist CUBIC, PACT, PEGASOS, and uDISCO enable whole-body imaging, wildDISCO has helped overcome existing technical limitations posed by previous methods.

Scientists often use mice to study the progression of disease in the human body. In their study, the scientists used mice to produce whole-body cellular and structural maps very much like the Allen Brain Atlas, which lets researchers view the areas in the brain enabling the viewing of neural connections.

Their method was able to detect cancerous tumors in the first stages of formation.

"MRI and PET scans would show you only big tumors. Ours show tumors at the single cell, which they absolutely can't,” Ertürk told BBC. 

A mice map

Similar to how the Allen Brain Atlas is available for anyone to view, the scientists established a website that allows researchers to explore their reference datasets and to make these data available to the scientific community in online atlases. The website contains high-resolution images of whole mouse systems like the nervous system, lymphatic system, and vascular system.

Ertürk explained the vision behind the project in a press release, “Knowing where each protein is expressed in the body is essential for developing a comprehensive understanding of how the body works and what goes wrong in complex diseases”.

Through this website, an online tool has been envisaged which will prove invaluable for biomedical research, allowing scientists to examine these systems in whole mice without the need to replicate the same experiments in the future, said the scientists in their study.

Linking their study with AI

First authors Dr. Hongcheng Mai and Dr. Jie Luo say, "Our online atlases have already generated data for published papers. Other scientists have obtained critical data from our atlases, saving time, and resources, and reducing animal use."

Scientists plan on integrating this method with artificial intelligence (AI) to understand diseases better. “Now imagine what we can do with these maps when you combine them with the power of deep learning,” said Ertürk. 

The team wants to harness the power of machine learning to simulate complex biological systems, in order to develop new treatments.

The study was published in the journal Nature Biotechnology.

Study abstract:

Whole-body imaging techniques play a vital role in exploring the interplay of physiological systems in maintaining health and driving disease. We introduce wildDISCO, a new approach for whole-body immunolabeling, optical clearing and imaging in mice, circumventing the need for transgenic reporter animals or nanobody labeling and so overcoming existing technical limitations. We identified heptakis(2,6-di-O-methyl)-β-cyclodextrin as a potent enhancer of cholesterol extraction and membrane permeabilization, enabling deep, homogeneous penetration of standard antibodies without aggregation. WildDISCO facilitates imaging of peripheral nervous systems, lymphatic vessels and immune cells in whole mice at cellular resolution by labeling diverse endogenous proteins. Additionally, we examined rare proliferating cells and the effects of biological perturbations, as demonstrated in germ-free mice. We applied wildDISCO to map tertiary lymphoid structures in the context of breast cancer, considering both primary tumor and metastases throughout the mouse body. An atlas of high-resolution images showcasing mouse nervous, lymphatic and vascular systems is accessible at http://discotechnologies.org/wildDISCO/atlas/index.php.