Holographic optical coherence imaging of living tissue.

摘要

Coherence-domain imaging has become a well-established biomedical imaging technique with a wide range of applications. The most mature technique of this class is optical coherence tomography, which uses rapid point-by-point scanning detection for signal demodulation and computed reconstruction. Another approach in coherence-domain imaging is holographic optical coherence imaging (HOCI) that permits a direct wide-field depth-gated imaging by acquiring en face images at a fixed depth inside scattering media without the need to scan. Two approaches have been used in the development of real-time HOCI system: photorefractive holography and digital holography. In previous approaches, image-domain holograms in photorefractive holography and Fresnel off-axis digital holograms in digital holography have been used. In this thesis, Fourier-domain holograms are used to obtain real-time images of structure inside living tissue and turbid media. Much better performance was achieved in Fourier-domain HOCI over image-domain photorefractive holography and Fresnel off-axis digital holography. Furthermore, significant improvement in sensitivity and resolution was achieved in Fourier-domain digital HOCI compared with Fourier-domain photorefractive HOCI. Using the improved performance of Fourier-domain HOCI, functional HOCI is applied to tumor spheroids to quantify the motility of tissue at depth using dynamic speckle. By defining a motility metric based on the coefficient of intensity variance per pixel, we convert cellular motility into a novel imaging contrast agent. We demonstrate that the motility metric enables direct visualization of the effect of cytoskeletal anti-cancer drugs on tissue, allowing time-course measurements of tissue response to drugs, which could be useful for applications of high-throughput assays to monitor tissue response to drug candidates in drug development.