title: Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography.
abstract: Field carcinogenesis is the initial stage of cancer progression. Understanding field carcinogenesis is valuable for both cancer biology and clinical medicine. Here, we used inverse spectroscopic optical coherence tomography to study colorectal cancer (CRC) and pancreatic cancer (PC) field carcinogenesis. Depth-resolved optical and ultrastructural properties of the mucosa were quantified from histologically normal rectal biopsies from patients with and without colon adenomas (n=85) as well as from histologically normal peri-ampullary duodenal biopsies from patients with and without PC (n=22). Changes in the epithelium and stroma in CRC field carcinogenesis were separately quantified. In both compartments, optical and ultra-structural alterations were consistent. Optical alterations included lower backscattering (μb) and reduced scattering (μs') coefficients and higher anisotropy factor g. Ultrastructurally pronounced alterations were observed at length scales up to ∼450  nm, with the shape of the mass density correlation function having a higher shape factor D, thus implying a shift to larger length scales. Similar alterations were found in the PC field carcinogenesis despite the difference in genetic pathways and etiologies. We further verified that the chromatin clumping in epithelial cells and collagen cross-linking caused D to increase in vitro and could be among the mechanisms responsible for the observed changes in epithelium and stroma, respectively.
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Ji
authors.initials: J
authors.lastname: Yi
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Radosevich
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Stypula-Cyrus
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Nikhil N
authors.initials: NN
authors.lastname: Mutyal
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Samira Michelle
authors.initials: SM
authors.lastname: Azarin
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Horcher
authors.affiliation: NorthShore University Health Systems, Department of Internal Medicine, Evanston, Illinois 60201.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldberg
authors.affiliation: NorthShore University Health Systems, Department of Internal Medicine, Evanston, Illinois 60201.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Bianchi
authors.affiliation: NorthShore University Health Systems, Department of Internal Medicine, Evanston, Illinois 60201.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Bajaj
authors.affiliation: Boston Medical Center, Department of Medicine, Boston, Massachusetts 02118.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Evanston, Illinois 60208.
authors.forename: Vadim
authors.initials: V
authors.lastname: Backman
mesh_terms: D015179:Colorectal Neoplasms / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000648:ultrastructure; D041623:Tomography, Optical Coherence / Q000379:methods*