Virtual Staining Technology Paves Way for Non-Invasive Pathological Diagnosis

For more than 200 years, traditional pathology has depended on the technique of examining cancer tissues under a microscope, a method that provides only limited, specific cross-sections of the 3D structure of cancer cells. This restriction has hindered the ability to fully comprehend the three-dimensional relationships and spatial organization of cells within the tumor. Researchers have now introduced an innovative virtual staining technology that offers a detailed, 3D view of cancer tissues without the need for separate staining, surpassing the conventional methods that involve observing thinly sliced and stained tissue sections.

This cutting-edge technology, developed by an international team led by the Korea Advanced Institute of Science and Technology (KAIST, Daejeon, Republic of Korea), combines advanced optical techniques with an artificial intelligence (AI)-driven deep learning algorithm to produce realistic, virtually stained 3D images of cancer tissue. The team employed holotomography (HT), an advanced optical technology, to measure the 3D refractive index of tissue samples. The AI-based deep learning algorithm was then integrated to generate virtually stained H&E images. This breakthrough is expected to revolutionize pathological diagnostics by enabling non-invasive, next-generation cancer analysis.

Image: Results of AI-based 3D virtual H&E staining and quantitative analysis of pathological tissue (Photo courtesy of Nature Communications, DOI:10.1038/s41467-025-59820-0)

In their study, published in Nature Communications, the researchers quantitatively demonstrated that the images produced by this technology closely resemble actual stained tissue samples. Additionally, the technology showed reliable performance across different organs and tissue types, confirming its versatility and potential as an advanced tool for pathological analysis. Through collaborative research with hospitals and institutions in Korea and the United States, utilizing Tomocube's holotomography equipment, the team validated the feasibility of the technology and showcased its potential for widespread implementation in real-world pathological research environments.

"This research marks a major advancement by transitioning pathological analysis from conventional 2D methods to comprehensive 3D imaging,” said KAIST Professor YongKeun Park who led the research team. “It will greatly enhance biomedical research and clinical diagnostics, particularly in understanding cancer tumor boundaries and the intricate spatial arrangements of cells within tumor microenvironments."