title: Detectability of contrast agents for confocal reflectance imaging of skin and microcirculation.
abstract: Confocal reflectance microscopy of skin and other tissues in vivo is currently limited to imaging at the cellular, nuclear and general architectural levels due to the lack of microstructure-specific contrast. Morphologic and functional imaging at specific organelle and microstructure levels may require the use of exogenous contrast agents in small (nontoxic) concentrations, from which weakly backscattered light must be detected in real time. We report an analysis based on Mie theory to predict detectability, in terms of signal-to-background and signal-to-noise ratios, of reflectance contrast agents within skin and microcirculation. The analysis was experimentally verified by detectability of (a) intravenously injected polystyrene microspheres that enhance the contrast of dermal microcirculation in Sprague-Dawley rats, and (b) acetic acid-induced compaction of chromatin that enhances nuclear morphology in normal and cancerous human skin. Such analyses and experiments provide a quantitative basis for developing the opto-biochemical properties and use of contrast agents and for designing confocal instrumentation to enable real-time detectability in vivo.
authors.affiliation: Northeastern University, Center for Subsurface Sensing and Imaging Systems, 302 Stearns Center, Boston, Massachusetts 02115, USA. rajadmil@ece.neu.edu
authors.forename: Milind
authors.initials: M
authors.lastname: Rajadhyaksha
authors.forename: Salvador
authors.initials: S
authors.lastname: Gonzalez
authors.forename: James M
authors.initials: JM
authors.lastname: Zavislan
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003287:Contrast Media; D004817:Epidermis / Q000648:ultrastructure; D006801:Humans; D007275:Injections, Intravenous; D008833:Microcirculation; D018613:Microscopy, Confocal; D008863:Microspheres; D008962:Models, Theoretical; D011137:Polystyrenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation; D012867:Skin / Q000033:anatomy & histology* / Q000098:blood supply
chemical_list: D003287:Contrast Media; D011137:Polystyrenes; D019342:Acetic Acid