Methods for the optimization of a/LCI for clinical use are presented. First, the use of the T-matrix light scattering model to simulate scattering from spheroidal particles is presented as a more appropriate simulation of cell nuclei scattering than the previously used Mie theory. In addition, the use of a broadband light source with a bandwidth greater than 50nm similar to those utilized in OCT applications is demonstrated. Accurate sizing of scatterers in tissue phantoms containing stretched and unstretched polystyrene microspheres along with measurements of unstretched polystyrene microspheres in solution are presented, demonstrating advances in system performance and design. In addition, preliminary human in vivo esophageal tissue data are presented. © 2009 SPIE.