A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics

Area of Science:

• Biomedical Optics
• Microscopy
• Medical Diagnostics

Background:

• Nonlinear optical microscopy enables deep tissue penetration, 3D sectioning, and molecular contrast for disease investigation.
• Current systems are often large, costly, and require specialized training, limiting clinical adoption.

Purpose of the Study:

• To develop a compact, user-friendly multimodal nonlinear optical imaging platform for label-free tissue analysis.
• To integrate a novel fiber laser system into a laser scanning microscope for enhanced imaging capabilities.

Main Methods:

• Implementation of a compact fiber laser system into a tailored laser scanning microscope.
• Simultaneous acquisition of second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and coherent anti-Stokes Raman scattering (CARS) signals.
• Optimized CARS contrast for lipid imaging in label-free tissue investigation.

Main Results:

• A small-footprint, easy-to-use multimodal imaging platform was created.
• The system achieved high near-infrared (NIR) transmission and a fourfold enlarged field of view.
• High imaging speed (1 megapixel/second) and diffraction-limited spatial resolution were demonstrated on HNSCC and atherosclerosis models.

Conclusions:

• The developed microscope offers a flexible, turnkey solution for label-free tissue morphochemistry analysis.
• It provides valuable molecularly specific information for disease progression monitoring at the cellular level.
• Future applications include in vivo imaging and endoscopic integration for disease grading and plaque characterization.