title: Dynamic contrast-enhanced optical imaging of in vivo organ function.
abstract: Conventional approaches to optical small animal molecular imaging suffer from poor resolution, limited sensitivity, and unreliable quantitation, often reducing their utility in practice. We previously demonstrated that the in vivo dynamics of an injected contrast agent could be exploited to provide high-contrast anatomical registration, owing to the temporal differences in each organ's response to the circulating fluorophore. This study extends this approach to explore whether dynamic contrast-enhanced optical imaging (DyCE) can allow noninvasive, in vivo assessment of organ function by quantifying the differing cellular uptake or wash-out dynamics of an agent in healthy and damaged organs. Specifically, we used DyCE to visualize and measure the organ-specific uptake dynamics of indocyanine green before and after induction of transient liver damage. DyCE imaging was performed longitudinally over nine days, and blood samples collected at each imaging session were analyzed for alanine aminotransferase (ALT), a liver enzyme assessed clinically as a measure of liver damage. We show that changes in DyCE-derived dynamics of liver and kidney dye uptake caused by liver damage correlate linearly with ALT concentrations, with an r2 value of 0.91. Our results demonstrate that DyCE can provide quantitative, in vivo, longitudinal measures of organ function with inexpensive and simple data acquisition.
authors.affiliation: Columbia University, Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, New York 10027, USA. cba2115@columbia.edu
authors.forename: Cyrus B
authors.initials: CB
authors.lastname: Amoozegar
authors.forename: Tracy
authors.initials: T
authors.lastname: Wang
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Bouchard
authors.forename: Addason F H
authors.initials: AF
authors.lastname: McCaslin
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Richard M
authors.initials: RM
authors.lastname: Levenson
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Hillman
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D008111:Liver Function Tests / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D002251:Carbon Tetrachloride; D007208:Indocyanine Green