Breaking the Scattering Barrier: Multimodal Non-invasive Deep Tissue Imaging Using Reflection Matrix Based Wavefront Shaping

PROJECT SUMMARY
This proposal aims to develop a high-speed, multimodal deep tissue imaging system that
integrates reflection matrix optical coherence tomography (RM-OCT) with wavefront shaping to overcome
the fundamental limitations of light scattering in biological tissues. By leveraging high-speed lock-in
cameras, high-speed spatial light modulators (SLMs), and Tikhonov-regularized matrix inversion, the
system will achieve real-time, non-invasive imaging with cellular resolution at unprecedented depths, enabling
in vivo applications. This technology will synergize RM-OCT with multiphoton microscopy
(MPM) and photoacoustic microscopy (PAM), providing a unified platform for comprehensive structural,
metabolic, and hemodynamic imaging. The specific aims are: (1) Develop reflection matrix-based wavefront
shaping and demonstrate the enhanced imaging depth ex vivo; (2) Optimize system performance for
deep tissue imaging and integrate RM-OCT with MPM and PAM; (3) Achieve, validate, and characterize in
vivo multimodal deep tissue imaging in animal models.
This project proposes a transformative solution with three key advantages: (1) It uses a model energy matrix to
visualize light distribution inside scattering samples, effectively acting as an internal "camera" to assess focusing
quality; (2) It achieves guide-star-free focusing deep within scattering media; and (3) It designs optimal
wavefronts to focus light across entire target planes, rather than single spots. By overcoming the speed-depth
trade-off, this technology will enable researchers to study dynamic biological processes in vivo with
unprecedented spatiotemporal precision. The proposed system has broad applications in neuroscience, cancer
research, and cardiovascular diseases, enabling researchers to study dynamic biological processes in vivo with
unprecedented precision. By breaking the scattering barrier, this technology will transform biomedical research
and accelerate the development of new therapies.

Grant Number: 1UG3DA065120-01
NIH Institute/Center: NIH
Principal Investigator: ZHONGPING CHEN