Nonlinear interferometric vibrational imaging: Optical ranging and spatial localization of CARS

Diagnostic imaging trends are progressing toward the molecular level with the advent of molecular imaging techniques. Optical molecular imaging techniques that utilize targeted exogenous contrast agents or detect endogenous molecular signatures will significantly extend our ability to detect early pathological changes in biological tissue, and treat diseases early when they are most amenable to be cured. We have developed a technique called Nonlinear Interferometric Vibrational Imaging (NIVI) that takes advantage of the coherent nature of coherent anti-Stokes Raman scattering (CARS) processes and the coherent optical ranging and imaging capabilities of optical coherence tomography (OCT). OCT uses interferometry and heterodyne detection in the time or spectral domain to localize reflections of near-infrared light deep from within highly-scattering tissues. OCT has found wide biological and medical applications, and recently, molecular imaging methods have been developed. By utilizing the molecular-sensitivity of CARS, NIVI performs optical ranging and multi-dimensional molecular imaging with OCT-like optical systems, enabling the retrieval of not only χ⁽³⁾ [chi⁽³⁾] amplitude but also phase information, the rejection of problematic non-resonant background four-wave-mixing signals, enhanced sensitivity from heterodyne detection, and a relaxation of the high-numerical aperture focusing requirements present in CARS microscopy. We present recent progress and advances in NIVI, including depth-ranging capabilities that extend significantly deeper than current CARS microscopy methods and are potentially more suitable for cross-sectional deep-tissue in vivo imaging.