Quantitative Kinetic Models from Intravital Microscopy: A Case Study Using Hepatic Transport

dc.contributor.authorTsekouras, Konstantinos
dc.contributor.authorDay, Richard
dc.contributor.authorDunn, Kenneth W.
dc.contributor.authorPressé, Steve
dc.contributor.departmentPhysics, School of Scienceen_US
dc.date.accessioned2020-01-03T20:15:55Z
dc.date.available2020-01-03T20:15:55Z
dc.date.issued2019-08-29
dc.description.abstractThe liver performs critical physiological functions, including metabolizing and removing substances, such as toxins and drugs, from the bloodstream. Hepatotoxicity itself is intimately linked to abnormal hepatic transport, and hepatotoxicity remains the primary reason drugs in development fail and approved drugs are withdrawn from the market. For this reason, we propose to analyze, across liver compartments, the transport kinetics of fluorescein-a fluorescent marker used as a proxy for drug molecules-using intravital microscopy data. To resolve the transport kinetics quantitatively from fluorescence data, we account for the effect that different liver compartments (with different chemical properties) have on fluorescein's emission rate. To do so, we develop ordinary differential equation transport models from the data where the kinetics is related to the observable fluorescence levels by "measurement parameters" that vary across different liver compartments. On account of the steep non-linearities in the kinetics and stochasticity inherent to the model, we infer kinetic and measurement parameters by generalizing the method of parameter cascades. For this application, the method of parameter cascades ensures fast and precise parameter estimates from noisy time traces.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationTavakoli, M., Tsekouras, K., Day, R., Dunn, K. W., & Pressé, S. (2019). Quantitative Kinetic Models from Intravital Microscopy: A Case Study Using Hepatic Transport. The journal of physical chemistry. B, 123(34), 7302–7312. doi:10.1021/acs.jpcb.9b04729en_US
dc.identifier.urihttps://hdl.handle.net/1805/21727
dc.language.isoen_USen_US
dc.publisherACSen_US
dc.relation.isversionof10.1021/acs.jpcb.9b04729en_US
dc.relation.journalThe Journal of Physical Chemistry Ben_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectLiveren_US
dc.subjectHepatotoxicityen_US
dc.subjectFluorescein-a fluorescent markersen_US
dc.subjectTransport kineticsen_US
dc.subjectFluorescence dataen_US
dc.titleQuantitative Kinetic Models from Intravital Microscopy: A Case Study Using Hepatic Transporten_US
dc.typeArticleen_US
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