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 approach do not quantify changes in specific microscopic biophysical properties, such as sizes and refractive indices of organelles. We use computational models to quantify relationships between microscopic changes within turbid media and resulting changes to mesoscopic scattering parameters (scattering coefficient 𝜇s(λ), anisotropy g(λ), reduced scattering coefficient 𝜇s’(λ)) from 400-1800 nm. The spectral lineshapes of 𝜇s(λ) and 𝜇s’(λ) differ notably, due to the wavelength dependence of g(λ). However, these discrepancies may not substantially impact the sensitivity of 𝜇s’(λ) to specific micro-scale changes. For a pancreatic cell nuclei model, cancer-relevant changes to nuclear size and refractive index increased the 𝜇s(λ) amplitude at 1000 nm by >17-fold and decreased the 𝜇s(λ) slope from 1000-1800 nm by ~15%, while the 𝜇s’(λ) amplitude at 500 nm and slope from 500-1800 nm increased by ~15-fold and 12%, respectively. Characterizing relationships between microscopic and mesoscopic scattering parameters is a crucial initial step toward using backscattered light to quantify changes in specific micro-scale tissue components.