Theranostics 2021; 11(7):3074-3088. doi:10.7150/thno.53755

Research Paper

Highly specific and label-free histological identification of microcrystals in fresh human gout tissues with stimulated Raman scattering

Bohan Zhang2#, Hanlin Xu1#, Jun Chen1, Xiaoxia Zhu3, Yu Xue3, Yifan Yang2, Jianpeng Ao2, Yinghui Hua1✉, Minbiao Ji2✉

1. Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
2. State Key Laboratory of Surface Physics and Department of Physics, Human Phenome Institute, Multiscale Research Institute of Complex Systems, Academy for Engineering and Technology, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China.
3. Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
# These authors contributed equally.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Zhang B, Xu H, Chen J, Zhu X, Xue Y, Yang Y, Ao J, Hua Y, Ji M. Highly specific and label-free histological identification of microcrystals in fresh human gout tissues with stimulated Raman scattering. Theranostics 2021; 11(7):3074-3088. doi:10.7150/thno.53755. Available from

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Gout is a common metabolic disease with growing burden, caused by monosodium urate (MSU) microcrystal deposition. In situ and chemical-specific histological identification of MSU is crucial in the diagnosis and management of gout, yet it remains inaccessible for current histological methods.

Methods: Stimulated Raman scattering (SRS) microscopy was utilized to image MSU based on its fingerprint Raman spectra. We first tested SRS for the diagnosis capability of gout and the differentiation power from pseudogout with rat models of acute gout arthritis, calcium pyrophosphate deposition disease (CPDD) and comorbidity. Then, human synovial fluid and surgical specimens (n=120) were were imaged with SRS to obtain the histopathology of MSU and collagen fibers. Finally, quantitative SRS analysis was performed in gout tissue of different physiological phases (n=120) to correlate with traditional histopathology including H&E and immunohistochemistry staining.

Results: We demonstrated that SRS is capable of early diagnosis of gout, rapid detection of MSU in synovial fluid and fresh unprocessed surgical tissues, and accurate differentiation of gout from pseudogout in various pathophysiological conditions. Furthermore, quantitative SRS analysis revealed the optical characteristics of MSU deposition at different pathophysiological stages, which were found to matched well with corresponding immunofluorescence histochemistry features.

Conclusion: Our work demonstrated the potential of SRS microscopy for rapid intraoperative diagnosis of gout and may facilitate future fundamental researches of MSU-based diseases.

Keywords: gout, stimulated Raman scattering, monosodium urate, label-free histology