Abstract: Biological tissues scatter light very strongly. This prevents efficient light transmission through tissues and severely limits the abilities of optical-based biomedical sensing and imaging technologies to extract useful information from deep tissue regions. We propose to apply unique aspects of a newly discovered bio-optical phenomenon, termed tissue turbidity suppression by optical phase conjugation (TSOPC), to induce a limited form of tissue transparency by suppressing optical scattering, and to develop new and improved classes of optical microscopy, biosensing and optical therapeutic techniques. Tissue scattering may appear random but they are fundamentally deterministic and time- reversible. Specifically, if we can record and reproduce a time-reversed copy of the diffuse light transmission through a tissue, we can actually force the light field to retrace its paths through the tissue and recover the original input light field. We recently uncovered this phenomenon and found that it is surprisingly robust and useful in suppressing scattering light in living tissues. This new way of tackling tissue scattering is highly unusual as it represents a big departure from the ways current optical techniques address tissue scatterings. This application proposes to apply the unique properties of this phenomenon to increase light transmission through tissues, generate tightly focused light spots deep within tissues - capabilities that are unattainable by existing technologies. These capabilities can significantly expand the application range of optical regime sensing and imaging techniques. We propose to adapt these capabilities to create highly sensitive non-invasive biochemical sensors that may eventually allow blood-and-tissue analysis without blood draw, improve high-resolution 3D microscopes, develop a unique deep tissue biochemical imaging system, and implement a flexible means to deliver light deeply and precisely into tissues for photodynamic therapy applications. Public Health Relevance: The proposed work aims to further the research on a newly uncovered bio-optical phenomenon that can induce a limited form of tissue transparency by suppressing optical scattering. We plan to adapt unique features of this phenomenon 1) to build blood-draw-free highly sensitive blood-and-tissue analysis (such as glucose measurement) systems, 2) improve microscopy, 3) to implement a deep tissue biochemical imaging system, and 4) to efficiently deliver light deep into tissues for minimally invasive cancer tumor removal via photodynamic therapy.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
NIH Director’s New Innovator Awards (DP2)
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Special Emphasis Panel (ZGM1-NDIA-O (01))
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Basavappa, Ravi
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California Institute of Technology
Engineering (All Types)
Schools of Engineering
United States
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Ruan, Haowen; Brake, Joshua; Robinson, J Elliott et al. (2017) Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light. Sci Adv 3:eaao5520
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Horstmeyer, Roarke; Ruan, Haowen; Yang, Changhuei (2015) Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue. Nat Photonics 9:563-571
Jang, Mooseok; Ruan, Haowen; Vellekoop, Ivo M et al. (2015) Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin. Biomed Opt Express 6:72-85
Ruan, Haowen; Jang, Mooseok; Yang, Changhuei (2015) Optical focusing inside scattering media with time-reversed ultrasound microbubble encoded light. Nat Commun 6:8968

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