Phasor analysis of NADH FLIM identifies pharmacological disruptions to mitochondrial metabolic processes in the rodent cerebral cortex

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dc.contributor.authorGómez, Carlos A.cs
dc.contributor.authorSutin, Jasoncs
dc.contributor.authorWu, Weichengcs
dc.contributor.authorFu, Buyincs
dc.contributor.authorUhlířová, Hanacs
dc.contributor.authorDevor, Annacs
dc.contributor.authorBoas, David A.cs
dc.contributor.authorSakadžic, Savacs
dc.contributor.authorYaseen, Mohammad Abbascs
dc.coverage.issue3cs
dc.coverage.volume13cs
dc.date.accessioned2020-08-04T11:58:02Z
dc.date.available2020-08-04T11:58:02Z
dc.date.issued2018-03-21cs
dc.description.abstractInvestigating cerebral metabolism in vivo at a microscopic level is essential for understanding brain function and its pathological alterations. The intricate signaling and metabolic dynamics between neurons, glia, and microvasculature requires much more detailed understanding to better comprehend the mechanisms governing brain function and its disease related changes. We recently demonstrated that pharmacologically-induced alterations to different steps of cerebral metabolism can be distinguished utilizing 2-photon fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotide (NADH) fluorescence in vivo. Here, we evaluate the ability of the phasor analysis method to identify these pharmacological metabolic alterations and compare the method's performance with more conventional nonlinear curve-fitting analysis. Visualization of phasor data, both at the fundamental laser repetition frequency and its second harmonic, enables resolution of pharmacologically-induced alterations to mitochondrial metabolic processes from baseline cerebral metabolism. Compared to our previous classification models based on nonlinear curve-fitting, phasor based models required fewer parameters and yielded comparable or improved classification accuracy. Fluorescence lifetime imaging of NADH and phasor analysis shows utility for detecting metabolic alterations and will lead to a deeper understanding of cerebral energetics and its pathological changes.en
dc.formattextcs
dc.format.extente0194578-e0194578cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationPLOS ONE. 2018, vol. 13, issue 3, p. e0194578-e0194578.en
dc.identifier.doi10.1371/journal.pone.0194578cs
dc.identifier.issn1932-6203cs
dc.identifier.other148701cs
dc.identifier.urihttp://hdl.handle.net/11012/193262
dc.language.isoencs
dc.publisherPLOScs
dc.relation.ispartofPLOS ONEcs
dc.relation.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194578cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1932-6203/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectFLUORESCENCE LIFETIME MICROSCOPYen
dc.subjectIN-VIVOen
dc.subjectCELLULAR-METABOLISMen
dc.subjectINTRACELLULAR NADHen
dc.subjectENERGY-METABOLISMen
dc.subjectBRAINen
dc.subjectCELLSen
dc.subjectAUTOFLUORESCENCEen
dc.subjectREPRESENTATIONen
dc.subjectLOCALIZATIONen
dc.titlePhasor analysis of NADH FLIM identifies pharmacological disruptions to mitochondrial metabolic processes in the rodent cerebral cortexen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-148701en
sync.item.dbtypeVAVen
sync.item.insts2021.03.13 00:56:01en
sync.item.modts2021.03.13 00:14:51en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Experimentální biofotonikacs
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