Nonlinear Interferometric Vibrational Imaging

Abstract

Coherent Anti-Stokes Raman Scattering (CARS) processes are "coherent," but the phase of the anti-Stokes radiation is usually lost by most incoherent spectroscopic CARS measurements. We propose a novel Raman microscopy imaging method called Nonlinear Interferometric Vibrational Imaging, which measures Raman spectra by obtaining the temporal anti-Stokes signal through nonlinear interferometry. With a more complete knowledge of the anti-Stokes signal, we show through simulations that a high-resolution Raman spectrum can be obtained of a molecule in a single pulse using broadband radiation. This could be useful for identifying the three-dimensional spatial distribution of molecular species in tissue.

Nanotechnology Approaches to Contrast Enhancement in Optical Imaging and Disease‐Targeted Therapy

“…Polarization-sensitive OCT is used to measure phase retardation in birefringent tissue which has application in retinal imaging [110], burn-depth determination [111], atherosclerosis imaging [112], muscular dystrophy [113], and detection of basal cell carcinomas [114]. Pump-probe OCT [115,116] and nonlinear interferometric vibrational imaging [117] are also promising methods to sense endogenous biomolecules based on their nonlinear optical susceptibilities. Although these endogenous methods are attractive as they do not require the addition of exogenous agents for contrast, they may be limited in scope because many diagnostic markers do not exhibit a detectible optical signal.…”

Pulse shaping strategies for nonlinear interferometric vibrational imaging optimized for biomolecular imaging

“…To separate the signals due to different Raman resonances, we proposed [16] using interferometry to measure both the amplitude and phase of the anti-Stokes radiation. When a weak interaction is assumed, the anti-Stokes electric field E o (ω) is a linear function of the Raman spectrum χ (3) (Ω):…”

“…2. Proposed pulse shaping mechanism for NIVI One advantage of this scheme over that previously discussed [16] is that a perfectly linear chirp need not be applied to the pulses. With ultrabroadband pulses, it is much more difficult to achieve a linear chirp.…”

Contrast enhancement methods for optical coherence tomography

“…Our group has recently developed a molecular imaging technique called Nonlinear Interferometric Vibrational Imaging (NIVI) [7,8] that utilizes Coherent Anti-Stokes Raman Scattering (CARS) spectroscopy principles for molecular sensitivity and contrast enhancement. The coherent nature of the CARS signal is exploited in a nonlinear interferometric set-up similar to OCT.…”

“…In recent years, groups have begun to investigate the use of hyperosmotic agents [l], exogenous contrast agents such as air-filled microbubbles [2] and engineered microspheres [3], molecular-sensitive pump-probe techniques [4], and adaptations of near-infrared fluorescent dyes utilizing their absorption rather than their fluorescent properties [5]. Endogenous molecular-specific contrast enhancement has been possible using spectroscopic OCT methods [6] as well as nonlinear optical methods to identify molecular bonds [7] and ultrastructural order in biological structures [SI. We expect that contrast enhancing methods utilizing exogenous agents and endogenous molecules will enhance the diagnostic capabilities and clinical utility of OCT.…”