Inverse-scattering in biological samples via beam-propagation

Area of Science:

• Biophysics
• Optical Imaging
• Computational Microscopy

Background:

• Multiple scattering in biological samples degrades optical imaging quality by obscuring sample-specific details.
• Physics-based inverse-scattering methods computationally reconstruct samples but face challenges due to non-convex optimization, leading to inaccuracies in highly scattering media.

Purpose of the Study:

• To investigate how different implementation strategies for inverse-scattering methods impact reconstruction quality.
• To develop a robust inverse-scattering approach for high-resolution, label-free 3D imaging in thick biological samples.

Main Methods:

• Utilized multi-slice beam propagation (MSBP), a non-convex inverse-scattering technique, to reconstruct the 3D refractive index (RI) of scattering samples.
• Systematically evaluated MSBP performance on phantoms and biological samples.
• Employed an amplitude-only cost function within the inverse-solver and incorporated angular and defocus diversity in scattering measurements.

Main Results:

• Demonstrated that specific implementation strategies significantly influence inverse-scattering reconstruction quality.
• Achieved high-quality, fully-volumetric RI imaging with subcellular resolution and label-free 3D contrast.
• Successfully imaged diverse, multiple-scattering samples, including thick biological tissues.

Conclusions:

• Optimized inverse-scattering strategies, particularly using amplitude-only cost functions and diverse measurements, enable robust 3D RI imaging.
• This work establishes a foundation for applying inverse-scattering techniques to deep-tissue imaging in multicellular samples.
• Introduces a novel paradigm for deep-tissue computational imaging with biologically interpretable results.