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Updated: Jun 7, 2026

Simultaneous Label-Free Autofluorescence Multi-Harmonic Microscopy
Published on: August 29, 2025
Imaging of normal and pathologic joint synovium using nonlinear optical microscopy as a potential diagnostic tool
Nivedan Tiwari1, Sanjay Chabra, Sheherbano Mehdi
1University of California, Irvine, Beckman Laser Institute, 1002 Health Sciences Road, Irvine, California 92612, USA. ntiwari@uci.edu
Nonlinear optical microscopy (NLOM) visualizes rheumatoid arthritis (RA) synovial tissue structure and cells without staining. This technique offers a new way to study RA progression and potentially manage the disease.
Area of Science:
- Biomedical Optics
- Rheumatology
- Microscopy
Background:
- Rheumatoid arthritis (RA) affects 1.3 million Americans, causing joint damage.
- Early RA diagnosis and intervention are crucial to prevent permanent joint alterations.
Purpose of the Study:
- To determine if nonlinear optical microscopy (NLOM) can image fresh, unfixed synovial tissue.
- To visualize the structural and cellular composition of normal and pathologic synovial tissue using intrinsic fluorescence.
Main Methods:
- NLOM was performed on rabbit knee joint synovial samples.
- Excitation wavelengths of 730- and 800-nm were used with a 40×, 0.8-NA water immersion objective.
- Low excitation power (<30 mW) allowed imaging up to 70 microm depth without tissue damage.
Main Results:
- NLOM successfully visualized cellular structures, including synoviocytes and adipocytes.
- Collagen, vascular structures, and inflammatory infiltrates were identified in synovial tissue.
- Imaging was achieved without the need for tissue processing or staining.
Conclusions:
- NLOM can visualize the cellular and structural composition of fresh synovial tissue.
- The technique holds potential for assessing rheumatoid arthritis (RA) pathology.
- Further research is warranted to explore NLOM's role in RA disease management.
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