Mapping O2 concentration in ex-vivo tissue samples on a fast PLIM macro-imager

Sen, Rajannya; Zhdanov, Alexander V.; Bastiaanssen, Thomaz F.  S.; Hirvonen, Liisa M.; Svihra, Peter; Fitzgerald, Patrick; Cryan, John F.; Andersson-Engels, Stefan; Nomerotski, Andrei; Papkovsky, Dmitri B.

doi:10.1038/s41598-020-75928-3

Mapping O₂ concentration in ex-vivo tissue samples on a fast PLIM macro-imager

Journal Article · Wed Nov 04 04:00:00 EST 2020 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-020-75928-3· OSTI ID:1815680

Sen, Rajannya ^[1]; Zhdanov, Alexander V. ^[2]; Bastiaanssen, Thomaz F. S. ^[3]; Hirvonen, Liisa M. ^[4]; Svihra, Peter ^[5]; Fitzgerald, Patrick ^[6]; Cryan, John F. ^[3]; Andersson-Engels, Stefan ^[7]; Nomerotski, Andrei ^[8]; Papkovsky, Dmitri B. ^[2]

Univ. College Cork (Ireland). School of Bichemistry and Cell Biology; OSTI
Univ. College Cork (Ireland). School of Bichemistry and Cell Biology
Univ. College Cork (Ireland). APC Microbiome Ireland; Univ. College Cork (Ireland). Dept. of Anatomy and Neuroscience
The Univ. of Western Australia, Crawley, WA (Australia). Centre for Microscopy, Characterisation and Analysis (CMCA)
Czech Technical Univ., Prague (Czech Republic). Faculty of Nuclear Sciences and Physical Engineering. Dept. of Physics; Univ. of Manchester (United Kingdom). School of Natural Sciences. Dept. of Physics and Astronomy
Univ. College Cork (Ireland). APC Microbiome Ireland
Tyndall National Inst., Cork (Ireland). Irish Photonics Integration Centre
Brookhaven National Lab. (BNL), Upton, NY (United States). Physics Dept.

O₂ PLIM microscopy was employed in various studies, however current platforms have limitations in sensitivity, image acquisition speed, accuracy and general usability. We describe a new PLIM imager based on the Timepix3 camera (Tpx3cam) and its application for imaging of O₂ concentration in various tissue samples stained with a nanoparticle based probe, NanO₂-IR. Upon passive staining of mouse brain, lung or intestinal tissue surface with minute quantities of NanO₂-IR or by microinjecting the probe into the lumen of small or large intestine fragments, robust phosphorescence intensity and lifetime signals were produced, which allow mapping of O₂ in the tissue within 20 s. Inhibition of tissue respiration or limitation of O₂ diffusion to tissue produced the anticipated increases or decreases in O₂ levels, respectively. The difference in O₂ concentration between the colonic lumen and air-exposed serosal surface was around 140 µM. Furthermore, subcutaneous injection of 5 µg of the probe in intact organs (a paw or tail of sacrificed mice) enabled efficient O₂ imaging at tissue depths of up to 0.5 mm. Overall, the PLIM imager holds promise for metabolic imaging studies with various ex vivo models of animal tissue, and also for use in live animals.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0012704

OSTI ID:: 1815680

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 10; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (52)

A Phosphorescent Nanoparticle-Based Probe for Sensing and Imaging of (Intra)Cellular Oxygen in Multiple Detection Modalities Kondrashina, Alina V.; Dmitriev, Ruslan I.; Borisov, Sergey M. Advanced Functional Materials, Vol. 22, Issue 23 https://doi.org/10.1002/adfm.201201387	journal	July 2012
Quantitative analysis of mucosal oxygenation using ex vivo imaging of healthy and inflamed mammalian colon tissue Zhdanov, Alexander V.; Okkelman, Irina A.; Golubeva, Anna V. Cellular and Molecular Life Sciences, Vol. 74, Issue 1 https://doi.org/10.1007/s00018-016-2323-x	journal	August 2016
Imaging of oxygen and hypoxia in cell and tissue samples Papkovsky, Dmitri B.; Dmitriev, Ruslan I. Cellular and Molecular Life Sciences, Vol. 75, Issue 16 https://doi.org/10.1007/s00018-018-2840-x	journal	May 2018
Imaging of neurosphere oxygenation with phosphorescent probes Dmitriev, Ruslan I.; Zhdanov, Alexander V.; Nolan, Yvonne M. Biomaterials, Vol. 34, Issue 37 https://doi.org/10.1016/j.biomaterials.2013.08.065	journal	December 2013
High-resolution in vivo optical imaging of stroke injury and repair Sakadžić, Sava; Lee, Jonghwan; Boas, David A. Brain Research, Vol. 1623 https://doi.org/10.1016/j.brainres.2015.04.044	journal	October 2015
Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection Pircalabioru, Gratiela; Aviello, Gabriella; Kubica, Malgorzata Cell Host & Microbe, Vol. 19, Issue 5 https://doi.org/10.1016/j.chom.2016.04.007	journal	May 2016
Oxyphor 2P: A High-Performance Probe for Deep-Tissue Longitudinal Oxygen Imaging Esipova, Tatiana V.; Barrett, Matthew J. P.; Erlebach, Eva Cell Metabolism, Vol. 29, Issue 3 https://doi.org/10.1016/j.cmet.2018.12.022	journal	March 2019
In vivo imaging of brain metabolism activity using a phosphorescent oxygen-sensitive probe Tsytsarev, Vassiliy; Arakawa, Hiroyuki; Borisov, Sergei Journal of Neuroscience Methods, Vol. 216, Issue 2 https://doi.org/10.1016/j.jneumeth.2013.04.005	journal	June 2013
Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena Journal of Neuroscience Methods, Vol. 281 https://doi.org/10.1016/j.jneumeth.2017.02.005	journal	April 2017
Fluorescence lifetime imaging (FLIM): Basic concepts and some recent developments Suhling, Klaus; Hirvonen, Liisa M.; Levitt, James A. Medical Photonics, Vol. 27 https://doi.org/10.1016/j.medpho.2014.12.001	journal	May 2015
Imaging and time stamping of photons with nanosecond resolution in Timepix based optical cameras Nomerotski, Andrei Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 937 https://doi.org/10.1016/j.nima.2019.05.034	journal	September 2019
A deeper understanding of intestinal organoid metabolism revealed by combining fluorescence lifetime imaging microscopy (FLIM) and extracellular flux analyses Okkelman, Irina A.; Neto, Nuno; Papkovsky, Dmitri B. Redox Biology, Vol. 30 https://doi.org/10.1016/j.redox.2019.101420	journal	February 2020
Characterization of planar phosphorescence based oxygen sensors on a TCSPC-PLIM macro-imager Sen, Rajannya; Zhdanov, Alexander V.; Hirvonen, Liisa M. Sensors and Actuators B: Chemical, Vol. 321 https://doi.org/10.1016/j.snb.2020.128459	journal	October 2020
High-Frequency Ultrasound for In Vivo Measurement of Colon Wall Thickness in Mice Abdelrahman, Mostafa A.; Marston, Gemma; Hull, Mark A. Ultrasound in Medicine & Biology, Vol. 38, Issue 3 https://doi.org/10.1016/j.ultrasmedbio.2011.12.011	journal	March 2012
Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems Lebedev, Artem Y.; Cheprakov, Andrei V.; Sakadžić, Sava ACS Applied Materials & Interfaces, Vol. 1, Issue 6 https://doi.org/10.1021/am9001698	journal	May 2009
Intracellular O ₂ Sensing Probe Based on Cell-Penetrating Phosphorescent Nanoparticles Fercher, Andreas; Borisov, Sergey M.; Zhdanov, Alexander V. ACS Nano, Vol. 5, Issue 7 https://doi.org/10.1021/nn200807g	journal	June 2011
Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice Press, Eric; Alaga, Katanya C.; Barr, Kevin Cell Death & Disease, Vol. 8, Issue 6 https://doi.org/10.1038/cddis.2017.234	journal	June 2017
Frontiers in Optical Imaging of Cerebral Blood Flow and Metabolism Devor, Anna; Sakadžić, Sava; Srinivasan, Vivek J. Journal of Cerebral Blood Flow & Metabolism, Vol. 32, Issue 7 https://doi.org/10.1038/jcbfm.2011.195	journal	January 2012
Direct measurement of local oxygen concentration in the bone marrow of live animals Spencer, Joel A.; Ferraro, Francesca; Roussakis, Emmanuel Nature, Vol. 508, Issue 7495 https://doi.org/10.1038/nature13034	journal	March 2014
Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen Liakath-Ali, Kifayathullah; Vancollie, Valerie E.; Heath, Emma Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4540	journal	April 2014
Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels Lecoq, Jérôme; Parpaleix, Alexandre; Roussakis, Emmanuel Nature Medicine, Vol. 17, Issue 7 https://doi.org/10.1038/nm.2394	journal	June 2011
NIH Image to ImageJ: 25 years of image analysis Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W. Nature Methods, Vol. 9, Issue 7 https://doi.org/10.1038/nmeth.2089	journal	June 2012
Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX Mik, Egbert G.; Stap, Jan; Sinaasappel, Michiel Nature Methods, Vol. 3, Issue 11 https://doi.org/10.1038/nmeth940	journal	October 2006
Frequency-multiplexed in vivo multiphoton phosphorescence lifetime microscopy Howard, Scott S.; Straub, Adam; Horton, Nicholas G. Nature Photonics, Vol. 7, Issue 1 https://doi.org/10.1038/nphoton.2012.307	journal	December 2012
Fast camera spatial characterization of photonic polarization entanglement Ianzano, Christopher; Svihra, Peter; Flament, Mael Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-62020-z	journal	April 2020
DNA double-strand breaks alter the spatial arrangement of homologous loci in plant cells Hirakawa, Takeshi; Katagiri, Yohei; Ando, Tadashi Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep11058	journal	June 2015
Small molecule phosphorescent probes for O ₂ imaging in 3D tissue models Dmitriev, Ruslan I.; Kondrashina, Alina V.; Koren, Klaus Biomater. Sci., Vol. 2, Issue 6 https://doi.org/10.1039/C3BM60272A	journal	January 2014
Optical methods for sensing and imaging oxygen: materials, spectroscopies and applications Wang, Xu-dong; Wolfbeis, Otto S. Chem. Soc. Rev., Vol. 43, Issue 10 https://doi.org/10.1039/C4CS00039K	journal	January 2014
Water-soluble cyclometalated platinum( ii ) and iridium( iii ) complexes: synthesis, tuning of the photophysical properties, and in vitro and in vivo phosphorescence lifetime imaging Solomatina, Anastasia I.; Su, Shih-Hao; Lukina, Maria M. RSC Advances, Vol. 8, Issue 31 https://doi.org/10.1039/C8RA02742K	journal	January 2018
Bafilomycin A1 activates HIF-dependent signalling in human colon cancer cells via mitochondrial uncoupling Zhdanov, Alexander V.; Dmitriev, Ruslan I.; Papkovsky, Dmitri B. Bioscience Reports, Vol. 32, Issue 6 https://doi.org/10.1042/BSR20120085	journal	October 2012
Combined fluorescence and phosphorescence lifetime imaging Shcheslavskiy, V. I.; Neubauer, A.; Bukowiecki, R. Applied Physics Letters, Vol. 108, Issue 9 https://doi.org/10.1063/1.4943265	journal	February 2016
Photon counting phosphorescence lifetime imaging with TimepixCam Hirvonen, Liisa M.; Fisher-Levine, Merlin; Suhling, Klaus Review of Scientific Instruments, Vol. 88, Issue 1 https://doi.org/10.1063/1.4973717	journal	January 2017
In Vivo Phosphorescence Imaging of p O ₂ Using Planar Oxygen Sensors Babilas, Philipp; Liebsch, Gregor; Schacht, Vivien Microcirculation, Vol. 12, Issue 6 https://doi.org/10.1080/10739680591003314	journal	January 2005
SPIDR: a read-out system for Medipix3 & Timepix3 Visser, J.; Beuzekom, M. van; Boterenbrood, Henk Journal of Instrumentation, Vol. 10, Issue 12 https://doi.org/10.1088/1748-0221/10/12/C12028	journal	December 2015
TimepixCam: a fast optical imager with time-stamping Fisher-Levine, M.; Nomerotski, A. Journal of Instrumentation, Vol. 11, Issue 03 https://doi.org/10.1088/1748-0221/11/03/C03016	journal	March 2016
Timepix3: a 65K channel hybrid pixel readout chip with simultaneous ToA/ToT and sparse readout Poikela, T.; Plosila, J.; Westerlund, T. Journal of Instrumentation, Vol. 9, Issue 05 https://doi.org/10.1088/1748-0221/9/05/C05013	journal	May 2014
Multiphoton time-domain fluorescence lifetime imaging microscopy: practical application to protein–protein interactions using global analysis Barber, P. R.; Ameer-Beg, S. M.; Gilbey, J. Journal of The Royal Society Interface, Vol. 6, Issue suppl_1 https://doi.org/10.1098/rsif.2008.0451.focus	journal	August 2008
Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia Carreau, Aude; Hafny-Rahbi, Bouchra El; Matejuk, Agata Journal of Cellular and Molecular Medicine, Vol. 15, Issue 6 https://doi.org/10.1111/j.1582-4934.2011.01258.x	journal	May 2011
Transcutaneous pO ₂ imaging during tourniquet-induced forearm ischemia using planar optical oxygen sensors Babilas, Philipp; Lamby, Philipp; Prantl, Lukas Skin Research and Technology, Vol. 14, Issue 3 https://doi.org/10.1111/j.1600-0846.2008.00295.x	journal	August 2008
A new macro-imager based on Tpx3Cam optical camera for PLIM applications Sen, Rajannya; Zhdanov, Alexander; Hirvonen, Liisa M. Biomedical Spectroscopy, Microscopy, and Imaging https://doi.org/10.1117/12.2555387	conference	April 2020
Fast rasterscanning enables FLIM in macroscopic samples up to several centimeters Koberling, F.; Buschmann, V.; Hille, C. BiOS, SPIE Proceedings https://doi.org/10.1117/12.843453	conference	February 2010
Imaging of Phosphorescence: A Novel Method for Measuring Oxygen Distribution in Perfused Tissue Rumsey, William L.; Vanderkooi, Jane M.; Wilson, David F. Science, Vol. 241, Issue 4873 https://doi.org/10.1126/science.3420417	journal	September 1988
Imaging of oxygen gradients in giant umbrella cells: an ex vivo PLIM study Zhdanov, A. V.; Golubeva, A. V.; Okkelman, I. A. American Journal of Physiology-Cell Physiology, Vol. 309, Issue 7 https://doi.org/10.1152/ajpcell.00121.2015	journal	October 2015
P o ₂ measurements in the microcirculation using phosphorescence quenching microscopy at high magnification Golub, Aleksander S.; Pittman, Roland N. American Journal of Physiology-Heart and Circulatory Physiology, Vol. 294, Issue 6 https://doi.org/10.1152/ajpheart.01347.2007	journal	June 2008
Phosphorescence quenching method for measurement of intracellular P O 2 in isolated skeletal muscle fibers Hogan, Michael C. Journal of Applied Physiology, Vol. 86, Issue 2 https://doi.org/10.1152/jappl.1999.86.2.720	journal	February 1999
Brain tissue oxygen tension in clinical brain death: a case series Smith, Michael Louis; Counelis, George J.; Maloney-Wilensky, Eileen Neurological Research, Vol. 29, Issue 7 https://doi.org/10.1179/016164107X208121	journal	October 2007
Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method Shonat, Ross D.; Wilson, David F.; Riva, Charles E. Applied Optics, Vol. 31, Issue 19 https://doi.org/10.1364/AO.31.003711	journal	January 1992
Tomographic imaging of oxygen by phosphorescence lifetime Apreleva, Sovia V.; Wilson, David F.; Vinogradov, Sergei A. Applied Optics, Vol. 45, Issue 33 https://doi.org/10.1364/AO.45.008547	journal	January 2006
New luminescence lifetime macro-imager based on a Tpx3Cam optical camera Sen, Rajannya; Hirvonen, Liisa M.; Zhdanov, Alexander Biomedical Optics Express, Vol. 11, Issue 1 https://doi.org/10.1364/BOE.11.000077	journal	December 2019
Fluorescence time-resolved macroimaging Shcheslavskiy, Vladislav I.; Shirmanova, Marina V.; Dudenkova, Varvara V. Optics Letters, Vol. 43, Issue 13 https://doi.org/10.1364/OL.43.003152	journal	January 2018
"Overshoot" of O2 Is Required to Maintain Baseline Tissue Oxygenation at Locations Distal to Blood Vessels Devor, A.; Sakadzic, S.; Saisan, P. A. Journal of Neuroscience, Vol. 31, Issue 38 https://doi.org/10.1523/JNEUROSCI.1968-11.2011	journal	September 2011
In vivo imaging with a water immersion objective affects brain temperature, blood flow and oxygenation Roche, Morgane; Chaigneau, Emmanuelle; Rungta, Ravi L. eLife, Vol. 8 https://doi.org/10.7554/eLife.47324	journal	August 2019

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