Estimation of subcellular particle size histograms with electron microscopy for prediction of optical scattering in breast tissue.

Diffuse near-infrared tomography of tissue reveals scattering changes that originate from the submicroscopic features of the tissue; yet the existing tools to use this information to predict which features contribute to the scattering spectrum are limited by the lack of direct data quantifying the particle sizes. Breast tissue was examined with electron microscopy, and analysis showed that the distributions of particle sizes appear in double exponential functions for most cellular tissues. The average particle size histograms of high-grade cancer, low-grade cancer, fibroglandular tissue, and adipose tissue were examined. The particle histograms were progressively decreasing in magnitude for these tissue types, and the average size of the particles increased, for these four tissues, respectively. Typical particle sizes in the range of 10 to 500 nm for these tissue types, with biexponential fitting, gave two particle distributions: one near 20 to 25 nm for the smaller size and one at 110 to 230 nm for the larger distributions. Mie scatter theory was used to take these particle distributions and calculate scattering spectra. The ability to image reduced scattering coefficient spectra of bulk breast tissues exists, and so this data provides insight into how bulk imaging may be mapped over to predict factors related to the tissue ultrastructure.