Signal degradation by multiple scattering in optical coherence tomography of dense tissue: a Monte Carlo study towards optical clearing of biotissues.

Multiple scattering is a major source that limits light penetration into biotissues, thereby preventing visualization of the deep microstructures for high-resolution optical imaging techniques. The optical clearing approach is a new adventure in biomedical optics for manipulating the optical properties of tissue; for example, the scattering coefficient and the degree of forward scattering of photons, by the use of the chemical administration method in order to improve the optical imaging depth, particularly for the recently developed optical coherence tomography (OCT). This paper investigates systematically how the multiple scattering affects signal attenuation and localization in general, and how the alterations of optical properties of tissue enhance the optical imaging depth and signal localization in particular, by the use of Monte Carlo simulations through the separate considerations of the least scattered photons (LSP) and multiple scattered photons (MSP). The LSP are those photons that contribute to the precise OCT signal, i.e. localization, and the MSP are those that degrade the OCT signal. It is shown that with either the reduction of the scattering coefficient or the increase of the degree of forward scattering, signal localization and imaging depth for OCT is enhanced. Whilst the increase of the anisotropic factor of the medium is more efficient in improving signal localization, it introduces more scattering events for the photons travelling within the tissue for both the LSP and MSP. It is also found that the OCT imaging resolution is almost reduced exponentially with the increase of the probing depth as opposed to the claimed system resolution. We demonstrate that optical clearing could be a useful tool to improve the imaging resolution when the light progressively penetrates the high scattering medium. Experimental results are also presented to show intuitively how multiple scattering affects OCT signal profiles by the use of intralipid solution and healthy human whole blood, representing moderately and highly scattering media respectively.