Theoretical comparison of the sensitivity of molecular contrast optical coherence tomography techniques

Molecular contrast optical coherence tomography (MCOCT) is an extension of OCT in which contrast resulting from the interaction of light with a contrast agent, leads to the enhanced visualization of a specific morphology or biochemical process in a target specimen. In order to improve the sensitivity and specificity of MCOCT, several spectroscopic techniques have recently been introduced which depend upon coherent detection of scattered light which has been modified by interaction with the molecules of interest in a sample. These techniques include harmonic generation, coherent anti-Stokes Raman scattering, linear absorption, and several different forms of pump-probe spectroscopy. We have developed a theoretical framework to facilitate the comparison of the sensitivity of different MCOCT techniques. This framework is based upon the observation that since the noise floor is defined by the reference field power in a shot-noise limited OCT system, the relevant comparison among the techniques is isolated to the available molecular contrast signal power and the algorithm used to extract the signal. We have derived theoretical expressions for the signal power and signal-to-noise ratio for the MCOCT techniques described in the literature based on molecular spectroscopy, as well as several new techniques introduced here.