How sensitive is the reduced scattering coefficient to changes in specific micro-scale biophysical properties of tissue scatterers?

Measuring backscattered light spectra from biological tissue has strong potential to identify early signs of disease and injury. However, most devices that employ this method do not quantify changes in specific microscopic biophysical properties, such as the sizes and refractive indices of organelles. We employ analytical models using Mie Theory to quantify relationships between microscopic changes in turbid media and resulting changes to mesoscopic scattering parameters (scattering coefficient <i>μ</i>_s(λ), anisotropy g(λ), reduced scattering coefficient <i>μ</i>_s^<i>'</i>(λ)) from 400 to 1800 nm. The spectral lineshapes of <i>μ</i>_s(λ) and <i>μ</i>_s^<i>'</i>(λ) differ notably, due to the wavelength dependence of g(λ). However, these discrepancies may not substantially impact the sensitivity of <i>μ</i>_s^<i>'</i>(λ) to specific micro-scale changes. For a pancreatic cell nuclei model, cancer-relevant increases in nuclear size (~28%) and refractive index (~1.7%) raised <i>μ</i>_s(λ) amplitude at 1000 nm by >17-fold and decreased <i>μ</i>_s(λ) slope from 1000 to 1800 nm by ~15%, while increasing <i>μ</i>_s^<i>'</i>(λ) amplitude at 500 nm and slope from 500 to 1800 nm by ~15-fold and 12%, respectively. Characterizing relationships between microscopic and mesoscopic scattering parameters is a key step toward using backscattered light to quantify changes in specific micro-scale tissue components.