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Download fileMolecular Imaging of Ischemia and Reperfusion in Vivo with Mitochondrial Autofluorescence
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posted on 2014-05-20, 00:00 authored by Hsueh-Han Lu, Yao-Ming Wu, Wei-Tien Chang, Teng Luo, Yi-Cyun Yang, Hung-Der Cho, Ian LiauIschemia and reperfusion (IR) injury
constitutes a pivotal mechanism
of tissue damage in pathological conditions such as stroke, myocardial
infarction, vascular surgery, and organ transplant. Imaging or monitoring
of the change of an organ at a molecular level in real time during
IR is essential to improve our understanding of the underlying pathophysiology
and to guide therapeutic strategies. Herein, we report molecular imaging
of a rat model of hepatic IR with the autofluorescence of mitochondrial
flavins. We demonstrate a revelation of the histological characteristics
of a liver in vivo with no exogenous stain and show that intravital
autofluorescent images exhibited a distinctive spatiotemporal variation
during IR. The autofluorescence decayed rapidly from the baseline
immediately after 20-min ischemia (approximately 30% decrease in 5
min) but recovered gradually during reperfusion (to approximately
99% of the baseline 9 min after the onset of reperfusion). The autofluorescent
images acquired during reperfusion correlated strongly with the reperfused
blood flow. We show further that the autofluorescence was produced
predominantly from mitochondria, and the distinctive autofluorescent
variation during IR was mechanically linked to the altered balance
between the flavins in the oxidized and reduced forms residing in
the mitochondrial electron-transport chain. Our approach opens an
unprecedented route to interrogate the deoxygenation and reoxygenation
of mitochondria, the machinery central to the pathophysiology of IR
injury, with great molecular specificity and spatiotemporal resolution
and can be prospectively translated into a medical device capable
of molecular imaging. We envisage that the realization thereof should
shed new light on clinical diagnostics and therapeutic interventions
targeting IR injuries of not only the liver but also other vital organs
including the brain and heart.
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rat modelhistological characteristicsMitochondrial AutofluorescenceIschemiaspatiotemporal variationreperfusionIR injuryhepatic IRimagingIR injuriesexogenous stainbaseline 9 minspatiotemporal resolutionautofluorescent variationmitochondrial flavins5 minautofluorescent imagestissue damageorgan transplantMolecular Imagingintravital autofluorescent imagesreperfused blood flowautofluorescence