Optimization of a flexible fiber-optic probe for epi-mode quantitative phase imaging

Area of Science:

• Biomedical Optics
• Microscopy
• Optical Imaging

Background:

• Quantitative oblique back-illumination microscopy (qOBM) is an emerging label-free optical imaging technology.
• It enables 3D, tomographic quantitative phase imaging (QPI) with epi-illumination in thick scattering samples.

Purpose of the Study:

• To present a robust optimization of a flexible, fiber-optic-based qOBM system.
• To enable in silico optimization of the phase signal-to-noise-ratio, avoiding tedious experimental tuning.
• To assess sensitivity limits and validate the optimized probe experimentally.

Main Methods:

• In silico optimization of the phase signal-to-noise-ratio over a wide parameter space.
• Development of a flexible, fiber-optic-based qOBM probe.
• Experimental validation and sensitivity assessment of the optimized probe.
• Imaging of rat brain tumor models and human neurosurgery brain tissues.

Main Results:

• The optimized probe is lightweight (∼40g), compact (8mm diameter), and achieves 2µm lateral resolution, 6µm axial resolution, and a 300µm field of view.
• Near video-rate operation (10Hz) with phase sensitivity <20nm (single acquisition) and ∼3 nm (multi-frame averaging).
• Acquired qOBM images of brain tissues showed excellent agreement with free-space qOBM and gold-standard histopathology.

Conclusions:

• The optimized flexible fiber-optic qOBM probe offers a robust, high-performance solution for label-free 3D imaging of thick scattering biological samples.
• This technology demonstrates significant utility in visualizing complex biological structures like brain tissues.
• The in silico optimization approach streamlines system development and enhances imaging performance.