title: In vivo measurement of epidermal thickness changes associated with tumor promotion in murine models.
abstract: The characterization of tissue morphology in murine models of pathogenesis has traditionally been carried out by excision of affected tissues with subsequent immunohistological examination. Excision-based histology provides a limited two-dimensional presentation of tissue morphology at the cost of halting disease progression at a single time point and sacrifice of the animal. We investigate the use of noninvasive reflectance mode confocal scanning laser microscopy (rCSLM) as an alternative tool to biopsy in documenting epidermal hyperplasia in murine models exposed to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). An automated technique utilizing average axial rCSLM reflectance profiles is used to extract epidermal thickness values from rCSLM data cubes. In comparisons to epidermal thicknesses determined from hematoxylin and eosin (H&E) stained tissue sections, we find no significant correlation to rCSLM-derived thickness values. This results from method-specific artifacts: physical alterations of tissue during H&E preparation in standard histology and specimen-induced abberations in rCSLM imaging. Despite their disagreement, both histology and rCSLM methods reliably measure statistically significant thickness changes in response to TPA exposure. Our results demonstrate that in vivo rCSLM imaging provides epithelial biologists an accurate noninvasive means to monitor cutaneous pathogenesis.
authors.affiliation: Oregon Health and Science University, Department of Dermatology, Portland, Oregon 97201, USA. phillkev@ohsu.edu
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Phillips
authors.forename: Ravikant
authors.initials: R
authors.lastname: Samatham
authors.forename: Niloy
authors.initials: N
authors.lastname: Choudhury
authors.forename: James C
authors.initials: JC
authors.lastname: Gladish
authors.forename: Philippe
authors.initials: P
authors.lastname: Thuillier
authors.forename: Steven L
authors.initials: SL
authors.lastname: Jacques
mesh_terms: D000465:Algorithms; D000818:Animals; D004817:Epidermis / Q000473:pathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate
chemical_list: D013755:Tetradecanoylphorbol Acetate
references.citation: Opt Lett. 1995 Nov 1;20(21):2258
references.pmid: 19862316
references.citation: Phys Med Biol. 2007 Mar 7;52(5):N75-85
references.pmid: 17301448
references.citation: J Biomed Opt. 2004 Mar-Apr;9(2):274-81
references.pmid: 15065891
references.citation: CRC Crit Rev Toxicol. 1974 Jan;2(4):419-43
references.pmid: 4822436
references.citation: J Eur Acad Dermatol Venereol. 2006 Aug;20(7):791-5
references.pmid: 16898899
references.citation: J Invest Dermatol. 1999 Sep;113(3):293-303
references.pmid: 10469324