Journal
THERANOSTICS
Volume 11, Issue 7, Pages 3074-3088Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.53755
Keywords
gout; stimulated Raman scattering; monosodium urate; label-free histology
Categories
Funding
- National Natural Science Foundation of China [81671725, 81974272, 61975033]
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01, 2018SHZDZX01]
- Shanghai Municipal Science and Technology Project [17441900900]
- Specialized Research Project of the Shanghai Health and Family Planning Commission on Smart Medicine [2018ZHYL0204]
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This study demonstrates the potential of Stimulated Raman Scattering (SRS) microscopy for rapid diagnosis of gout, quick detection of MSU in synovial fluid and surgical tissues, and accurate differentiation of gout from pseudogout under various pathophysiological conditions. Quantitative SRS analysis reveals the optical characteristics of MSU deposition at different stages, correlating well with traditional histopathology features.
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.
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