Oxyphor 2P: A High-Performance Probe for Deep-Tissue Longitudinal Oxygen Imaging

Tatiana V Esipova; Matthew J P Barrett; Eva Erlebach; Artëm E Masunov; Bruno Weber; Sergei A Vinogradov

doi:10.1016/j.cmet.2018.12.022

Oxyphor 2P: A High-Performance Probe for Deep-Tissue Longitudinal Oxygen Imaging

Cell Metab. 2019 Mar 5;29(3):736-744.e7. doi: 10.1016/j.cmet.2018.12.022. Epub 2019 Jan 24.

Authors

Tatiana V Esipova¹, Matthew J P Barrett², Eva Erlebach³, Artëm E Masunov⁴, Bruno Weber⁵, Sergei A Vinogradov⁶

Affiliations

¹ Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Institute of Pharmacology and Toxicology, University of Zurich, Zürich 8057, Switzerland.
³ Institute of Pharmacology and Toxicology, University of Zurich, Zürich 8057, Switzerland; Neuroscience Center, University of Zurich, Zurich 8057, Switzerland.
⁴ NanoScience Technology Center, Department of Chemistry, University of Central Florida, Orlando, FL 32826, USA; School of Modeling, Simulation and Training, University of Central Florida, Orlando, FL 32826, USA; National Research Nuclear University MEPhI, Kashirskoye Shosse 31, Moscow 115409, Russia; South Ural State University, Lenin Pr. 76, Chelyabinsk 454080, Russia.
⁵ Institute of Pharmacology and Toxicology, University of Zurich, Zürich 8057, Switzerland; Neuroscience Center, University of Zurich, Zurich 8057, Switzerland. Electronic address: bweber@pharma.uzh.ch.
⁶ Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: vinograd.upenn@gmail.com.

Abstract

Quantitative imaging of oxygen distributions in tissue can provide invaluable information about metabolism in normal and diseased states. Two-photon phosphorescence lifetime microscopy (2PLM) has been developed to perform measurements of oxygen in vivo with micron-scale resolution in 3D; however, the method's potential has not yet been fully realized due to the limitations of current phosphorescent probe technology. Here, we report a new sensor, Oxyphor 2P, that enables oxygen microscopy twice as deep (up to 600 μm below the tissue surface) and with ∼60 times higher speed than previously possible. Oxyphor 2P allows longitudinal oxygen measurements without having to inject the probe directly into the imaged region. As proof of principle, we monitored oxygen dynamics for days following micro-stroke induced by occlusion of a single capillary in the mouse brain. Oxyphor 2P opens up new possibilities for studies of tissue metabolic states using 2PLM in a wide range of biomedical research areas.

Keywords: dendrimer; extravascular delivery; hypoxia; oxygen imaging; phosphorescence; porphyrin; stroke; two-photon microscopy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / diagnostic imaging*
Capillaries / diagnostic imaging*
Female
Luminescent Measurements / methods*
Mice
Mice, Inbred C57BL
Microscopy, Confocal / methods*
Oxygen / metabolism*
Photons

Substances

Oxygen

Abstract

Publication types

MeSH terms

Substances

Grants and funding