Spatially offset spectroscopy offers an alternative non-invasive method for enabling deep probing of structures and chemical molecules, which is clinically significant for the characterization of chemical and physical alterations in human skin. However, a more precise depth-resolved quantification using the spatially offset measurements still remains a challenge due to the mixed inhomogeneous scattering. Herein, we report a Monte-Carlo-based quantification modeling platform combined with a novel, to the best of our knowledge, scattering spectrum decomposition method to explore the depth-dependent optical scattering contributions in human skin. In the simplified modeling, human skin was empirically set to be composed of multiple layers, and each layer possessed different photon weights for the spatially offset scattering intensity measurements. The modeling results of photon transportation in-and-out of the layered skin substantially discovered that the layer-dependent scattering contribution was compositely encoded into the spatially offset measurements and varied with the illumination incidence angle. For calibrating the layer-dependent scattering contribution, a modified nonlinear independent component processing algorithm was applied to the spatially offset measurements by decomposing the photon weights of each layer. The calibration results figured out the major scattering contribution of each layer along the offset axis under different incidence angles, which were consistent with previous experimental observations. The proposed theoretical framework establishes a feasible approach for spatially offset optical spectroscopies enabling non-invasive quantitative A-line characterization of the concentrations of skin components.
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