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.