Optical microscopy for pathological imaging: past, present, and future

Abstract

Histopathology, the microscopic examination of stained tissue sections, remains the gold standard for pathology imaging, but its bright-field imaging is largely morphological. Advanced optical microscopy techniques move beyond this by exploiting diverse light-matter interactions, and are increasingly applied to pathological imaging. By capturing signals such as refractive index, polarisation, harmonic generation, Brillouin shift, and molecular vibrations, these microscopy techniques can provide quantitative or semi-quantitative information on tissue structure, mechanics, and chemical or molecular composition. In this review, we summarise the physical principles, key quantitative parameters, and representative pathological applications of seven modalities--optical diffraction tomography, polarisation microscopy, second-harmonic generation microscopy, third-harmonic generation microscopy, Brillouin microscopy, Raman microscopy, and fluorescence microscopy. We also discuss progress in artificial intelligence that supports reconstruction, analysis, and interpretation across these modalities, together with emerging trends in multimodal integration. Overall, this review shows how different optical contrasts can complement routine histopathology, while outlining the challenges and opportunities that will shape their clinical translation.

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BibTeX RIS

BibTeX

@misc{zhang2026optical,
  title = {{Optical microscopy for pathological imaging: past, present, and future}},
  author = {Runchen Zhang and Xiaoyi Shang and Liangyu Deng and Jingyu Wang and Xiaoyu Zheng and Lanyu Cui and Yao Du and Jiaxin Zhuang and Yifei Ma and Wanying Liu and Limei Guo and Lin Luo and Zhiyi Liu and Stephen M. Morris and Honghui He and Chao He},
  howpublished = {arXiv},
  year = {2026},
  month = nov,
  doi = {10.48550/arxiv.2611.09104},
  eprint = {2611.09104},
  archivePrefix = {arXiv},
  url = {https://arxiv.org/abs/2611.09104},
}

RIS

TY  - UNPB
TI  - Optical microscopy for pathological imaging: past, present, and future
AU  - Runchen Zhang
AU  - Xiaoyi Shang
AU  - Liangyu Deng
AU  - Jingyu Wang
AU  - Xiaoyu Zheng
AU  - Lanyu Cui
AU  - Yao Du
AU  - Jiaxin Zhuang
AU  - Yifei Ma
AU  - Wanying Liu
AU  - Limei Guo
AU  - Lin Luo
AU  - Zhiyi Liu
AU  - Stephen M. Morris
AU  - Honghui He
AU  - Chao He
PY  - 2026
DA  - 2026/11/06
PB  - arXiv
DO  - 10.48550/arxiv.2611.09104
UR  - https://arxiv.org/abs/2611.09104
AB  - Histopathology, the microscopic examination of stained tissue sections, remains the gold standard for pathology imaging, but its bright-field imaging is largely morphological. Advanced optical microscopy techniques move beyond this by exploiting diverse light-matter interactions, and are increasingly applied to pathological imaging. By capturing signals such as refractive index, polarisation, harmonic generation, Brillouin shift, and molecular vibrations, these microscopy techniques can provide quantitative or semi-quantitative information on tissue structure, mechanics, and chemical or molecular composition. In this review, we summarise the physical principles, key quantitative parameters, and representative pathological applications of seven modalities--optical diffraction tomography, polarisation microscopy, second-harmonic generation microscopy, third-harmonic generation microscopy, Brillouin microscopy, Raman microscopy, and fluorescence microscopy. We also discuss progress in artificial intelligence that supports reconstruction, analysis, and interpretation across these modalities, together with emerging trends in multimodal integration. Overall, this review shows how different optical contrasts can complement routine histopathology, while outlining the challenges and opportunities that will shape their clinical translation.
ER  -

Abstract

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