Biopsy-Free in Vivo Virtual Histology of Skin Using Deep Learning
Open accessAbstract
An invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin tumors. The process is cumbersome and time-consuming, often leading to unnecessary biopsies and scars. Emerging noninvasive optical technologies such as reflectance confocal microscopy (RCM) can provide label-free, cellular-level resolution, in vivo images of skin without performing a biopsy. Although RCM is a useful diagnostic tool, it requires specialized training because the acquired images are grayscale, lack nuclear features, and are difficult to correlate with tissue pathology. Here, we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution, enabling visualization of the epidermis, dermal-epidermal junction, and superficial dermis layers. The network was trained under an adversarial learning scheme, which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground truth. We show that this trained neural network can be used to rapidly perform virtual histology of in vivo, label-free RCM images of normal skin structure, basal cell carcinoma, and melanocytic nevi with pigmented melanocytes, demonstrating similar histological features to traditional histology from the same excised tissue. This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.
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3D image processing is adopted to perform AI-based virtual staining for non-invasive approaches.
“or to perform AI-based virtual staining for non-invasive approaches [61].”
From Artificial Intelligence in the Histopathological Assessment of Non-Neoplastic Skin Disorders: A Narrative Review with Future Perspectives (2025) · cites this paper as [61]
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Sorted by citations
Della Mura, M., Sorino, J., Colagrande, A., Daruish, M., Ingravallo, G., Massaro, A., Cazzato, G., Lupo, C., Casatta, N., Ribatti, D., et al. (2025) · Medical Sciences · doi:10.3390/medsci13020070 · Cited by 6 · see citing works
- Authors
- Li, J., Garfinkel, J., Zhang, X., Wu, D., Zhang, Y., de Haan, K., Wang, H., Liu, T., Bai, B., Rivenson, Y., Rubinstein, G., Scumpia, P. O., & Ozcan, A.
- Affiliations
- California NanoSystems Institute (US)
- University of California, Los Angeles (US)
- Corresponding author
- Rubinstein, Gennady
- Scumpia, Philip O.
- ORCID
- Venue
- Light: Science & Applications
- Published
- 2021-11-18
- Volume
- 10
- Issue
- 1
- Pages
- 233-233
- ISSN
- 2047-7538 (ISSN-L)
- PMC
- PMC8602311
- OpenAlex
- W3214082102
- Cited by
- 109
- References
- 7
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 30 · 2023: 19 · 2022: 18 · 2021: 1
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Light Science & Applications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Keywords
- virtual histology, reflectance confocal microscopy, skin tumors, basal cell carcinoma, melanocytic nevi, virtual staining, hematoxylin and eosin, convolutional neural networks, adversarial learning, epidermis, basement membrane zone, non-invasive skin imaging
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