title: Wide-field quantitative imaging of tissue microstructure using sub-diffuse spatial frequency domain imaging.
abstract: Localized measurements of scattering in biological tissue provide sensitivity to microstructural morphology but have limited utility to wide-field applications, such as surgical guidance. This study introduces sub-diffusive spatial frequency domain imaging (sd-SFDI), which uses high spatial frequency illumination to achieve wide-field sampling of localized reflectances. Model-based inversion recovers macroscopic variations in the reduced scattering coefficient [Formula: see text] and the phase function backscatter parameter (γ). Measurements in optical phantoms show quantitative imaging of user-tuned phase-function-based contrast with accurate decoupling of parameters that define both the density and the size-scale distribution of scatterers. Measurements of fresh ex vivo breast tissue samples revealed, for the first time, unique clustering of sub-diffusive scattering properties for different tissue types. The results support that sd-SFDI provides maps of microscopic structural biomarkers that cannot be obtained with diffuse wide-field imaging and characterizes spatial variations not resolved by point-based optical sampling.
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, New Hampshire 03755, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: McClatchy
authors.affiliation: Department of Pathology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Rizzo
authors.affiliation: Department of Pathology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wells
authors.affiliation: Quantum Elecromagnetics Division, National Institute of Standards and Technology, 325 Broadway Street, Boulder, Colorado 80305, USA.
authors.forename: Philip P
authors.initials: PP
authors.lastname: Cheney
authors.affiliation: Quantum Elecromagnetics Division, National Institute of Standards and Technology, 325 Broadway Street, Boulder, Colorado 80305, USA.
authors.forename: Jeeseong C
authors.initials: JC
authors.lastname: Hwang
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, New Hampshire 03755, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, New Hampshire 03755, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, New Hampshire 03755, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Kanick