3D virtual staining technology enables non-invasive observation of cancer tissue


Moving beyond traditional methods of observing thinly sliced and stained cancer tissues, a collaborative international research team led by KAIST has successfully developed a new technology. This innovation uses advanced optical techniques combined with an artificial intelligence-based deep learning algorithm to create realistic, virtually stained 3D images of cancer tissue without the need for excisional biopsy. This breakthrough is anticipated to pave the way for next-generation noninvasive pathological diagnosis.
A research team led by Professor YongKeun Park of the Department of Physics, in collaboration with Professor Su-Jin Shin’s team at Yonsei University Gangnam Severance Hospital, Professor Tae Hyun Hwang’s team at Mayo Clinic, and Tomocube’s AI research team, has developed an innovative technology capable of vividly displaying the 3D structure of cancer tissues without separate staining.
The research is published in the journal Nature Communications.
For over 200 years, conventional pathology has relied on observing cancer tissues under a microscope, a method that only shows specific cross-sections of the 3D cancer tissue. This has limited the ability to understand the three-dimensional connections and spatial arrangements between cells.
To overcome this, the research team utilized holotomography (HT), an advanced optical technology, to measure the 3D refractive index information of tissues. They then integrated an AI-based deep learning algorithm to successfully generate virtual Hematoxylin & Eosin images—the most widely used staining method for observing pathological tissues. Hematoxylin stains cell nuclei blue, and eosin stains cytoplasm pink.

The research team quantitatively demonstrated that the images generated by this technology are highly similar to actual stained tissue images. Furthermore, the technology exhibited consistent performance across various organs and tissues, proving its versatility and reliability as a next-generation pathological analysis tool.
Moreover, by validating the feasibility of this technology through joint research with hospitals and research institutions in Korea and the United States, utilizing Tomocube’s holotomography equipment, the team demonstrated its potential for full-scale adoption in real-world pathological research settings.
Professor Park stated, “This research is a very significant achievement that expands the unit of pathological analysis from 2D to 3D. It is expected to be widely utilized in various biomedical research and clinical diagnoses, such as analyzing the boundaries of cancer tumors and the spatial distribution of cells in the surrounding areas within the microtumor environment.”
More information:
Juyeon Park et al, Revealing 3D microanatomical structures of unlabeled thick cancer tissues using holotomography and virtual H&E staining, Nature Communications (2025). DOI: 10.1038/s41467-025-59820-0
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3D virtual staining technology enables non-invasive observation of cancer tissue (2025, May 26)
retrieved 26 May 2025
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