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Optical Imaging in Human Disease and Biological Research pp 63–82Cite as

Two-Photon Phosphorescence Lifetime Microscopy

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Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 3233)

Abstract

Two-photon Phosphorescence Lifetime Microscopy (2PLM) is an emerging nonlinear optical technique that has great potential to improve our understanding of the basic biology underlying human health and disease. Although analogous to 2-photon Fluorescence Lifetime Imaging Microscopy (2P-FLIM), the contrast in 2PLM is fundamentally different from various intensity-based forms of imaging since it is based on the lifetime of an excited state and can be regarded as a “functional imaging” technique. 2PLM signal originates from the deactivation of the excited triplet state (phosphorescence) [1, 2]. Typically, this triplet state is a much longer-lived excited state than the singlet excited state resulting in phosphorescence emission times of microseconds to milliseconds at room temperature as opposed to nanoseconds for fluorescence emission [3]. The long-lived nature of the triplet state makes it highly sensitive to quenching molecules in the surrounding environment such as biomolecular oxygen (O2). Therefore, 2PLM can provide not only information on the distribution pattern of the probe in the sample (via intensity) but also determine the local oxygen tension (via phosphorescence lifetime quenching) [1]. The ability to create three-dimensional optical sections in the plane of focus within a thick biological specimen while maintaining relatively low phototoxicity due to the use of near-infrared wavelengths for two-photon excitation gives 2PLM powerful advantages over other techniques for longitudinal imaging and monitoring of oxygen within living organisms [4]. In this chapter, we will provide background on the development of 2PLM, discuss the most common oxygen sensing measurement methods and concepts, and explain the general principles and optical configuration of a 2PLM system. We also discuss the key characteristics and strategies for improvement of the technique. Finally, we will present an overview of the current primary scientific literature of how 2PLM has been used for oxygen sensing in biological applications and how this technique is improving our understanding of the basic biology underlying several areas of human health.

Keywords

  • 2PLM
  • PQM
  • Phosphorescence lifetime microscopy
  • Phosphorescence quenching
  • Two-photon excitation
  • Oxygen sensing
  • Tissue oxygenation

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References

  1. Chelushkin PS, Tunik SP (2019) Phosphorescence lifetime imaging (PLIM): state of the art and perspectives. In: Yamanouchi K, Tunik S, Makarov V (eds) Progress in photon science, vol 119. Springer International Publishing, Cham, pp 109–128

    CrossRef  Google Scholar 

  2. Shcheslavskiy I, Neubauer A, Bukowiecki R, Dinter F, Becker W (2016) Combined fluorescence and phosphorescence lifetime imaging. Appl Phys Lett 108(9):091111. https://doi.org/10.1063/1.4943265

    CrossRef  CAS  Google Scholar 

  3. McGown LB, Nithipatikom K (2000) Molecular fluorescence and phosphorescence. Appl Spectrosc Rev 35(4):353–393. https://doi.org/10.1081/ASR-100101229

    CrossRef  CAS  Google Scholar 

  4. Yamanouchi K, Tunik S, Makarov V (eds) (2019) Progress in photon science: recent advances, vol 119. Springer International Publishing, Cham

    Google Scholar 

  5. Clerici WJ, Hensley K, DiMartino DL, Butterfield DA (1996) Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 98(1–2):116–124. https://doi.org/10.1016/0378-5955(96)00075-5.

    CrossRef  PubMed  CAS  Google Scholar 

  6. Kizaka-Kondoh S, Konse-Nagasawa H (2009) Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia. Cancer Sci 100(8):1366–1373. https://doi.org/10.1111/j.1349-7006.2009.01195.x

    CrossRef  PubMed  CAS  Google Scholar 

  7. Papkovsky DB (2004) Methods in optical oxygen sensing: protocols and critical analyses. In: Methods in enzymology, vol 381. Elsevier, Amsterdam, pp 715–735

    Google Scholar 

  8. Swartz HM, Walczak T (1998) Developing in vivo EPR oximetry for clinical use. In: Hudetz AG, Bruley DF (eds) Oxygen transport to tissue XX, vol 454. Springer, Boston, MA, pp 243–252

    CrossRef  Google Scholar 

  9. International Society on Oxygen Transport to Tissue, Takahashi E, Bruley DF (2010) Oxygen transport to tissue XXXI. Springer, New York, NY

    Google Scholar 

  10. Swartz HM et al (2004) Clinical applications of EPR: overview and perspectives. NMR Biomed 17(5):335–351. https://doi.org/10.1002/nbm.911.

    CrossRef  PubMed  CAS  Google Scholar 

  11. Swartz HM et al (2014) Clinical EPR. Acad Radiol 21(2):197–206. https://doi.org/10.1016/j.acra.2013.10.011.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  12. Schafer R, Gmitro AF (2015) Dynamic oxygenation measurements using a phosphorescent coating within a mammary window chamber mouse model. Biomed Opt Express 6(2):639. https://doi.org/10.1364/BOE.6.000639.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  13. Raleigh JA, Chou S-C, Arteel GE, Horsman MR (1999) Comparisons among pimonidazole binding, oxygen electrode measurements, and radiation response in C3H mouse tumors. Radiat Res 151(5):580. https://doi.org/10.2307/3580034.

    CrossRef  PubMed  CAS  Google Scholar 

  14. Chitneni SK, Palmer GM, Zalutsky MR, Dewhirst MW (Feb. 2011) Molecular imaging of hypoxia. J Nucl Med 52(2):165–168. https://doi.org/10.2967/jnumed.110.075663

    CrossRef  PubMed  CAS  Google Scholar 

  15. Clark LC, Wolf R, Granger D, Taylor Z (Sep. 1953) Continuous recording of blood oxygen tensions by polarography. J Appl Physiol 6(3):189–193. https://doi.org/10.1152/jappl.1953.6.3.189

    CrossRef  PubMed  CAS  Google Scholar 

  16. Niazi A (2016) Real time measurement of oxygen by integrating a clark sensor with low cost printed circuit board technology and solid electrolyte membrane. University of Birmingham, Birmingham, p 138

    Google Scholar 

  17. Shell JR, LaRochelle EP, Bruza P, Gunn JR, Jarvis LA, Gladstone DJ (2019) Comparison of phosphorescent agents for noninvasive sensing of tumor oxygenation via Cherenkov-excited luminescence imaging. J Biomed Opt 24(03):1. https://doi.org/10.1117/1.JBO.24.3.036001.

    CrossRef  PubMed  Google Scholar 

  18. Wolfbeis OS (2015) Luminescent sensing and imaging of oxygen: fierce competition to the Clark electrode. BioEssays 37(8):921–928. https://doi.org/10.1002/bies.201500002

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  19. Kautsky H (1939) Quenching of luminescence by oxygen. Trans Faraday Soc 35:216. https://doi.org/10.1039/tf9393500216

    CrossRef  CAS  Google Scholar 

  20. Pollack M, Pringsheim P, Terwoord D (1944) A method for determining small quantities of oxygen. J Chem Phys 12(7):295–299. https://doi.org/10.1063/1.1723942

    CrossRef  CAS  Google Scholar 

  21. Bergman I (1968) Rapid-response Atmospheric oxygen monitor based on fluorescence quenching. Nature 218(5139):396–396. https://doi.org/10.1038/218396a0

    CrossRef  CAS  Google Scholar 

  22. Peterson JI, Fitzgerald RV (1980) New technique of surface flow visualization based on oxygen quenching of fluorescence. Rev Sci Instrum 51(5):670–671. https://doi.org/10.1063/1.1136277

    CrossRef  CAS  Google Scholar 

  23. Vanderkooi JM, Wilson DF (1986) A new method for measuring oxygen concentration in biological systems. In: Longmuir IS (ed) Oxygen transport to tissue VIII, vol 200. Springer, Boston, MA, pp 189–193

    CrossRef  Google Scholar 

  24. Rumsey WL, Vanderkooi JM, Wilson DF (1988) Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue. Sci New Ser 241(4873):1649–1651

    CAS  Google Scholar 

  25. Dewhirst MW et al (1999) Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia. Br J Cancer 79(11–12):1717–1722. https://doi.org/10.1038/sj.bjc.6690273.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  26. Zheng L, Golub AS, Pittman RN (1996) Determination of PO2 and its heterogeneity in single capillaries. Am J Physiol Heart Circ Physiol 271(1):H365–H372. https://doi.org/10.1152/ajpheart.1996.271.1.H365

    CrossRef  CAS  Google Scholar 

  27. Göppert-Mayer M (1931) Über Elementarakte mit zwei Quantensprüngen. Ann Phys 401(3):273–294. https://doi.org/10.1002/andp.19314010303

    CrossRef  Google Scholar 

  28. Denk W, Strickler J, Webb W (1990) Two-photon laser scanning fluorescence microscopy. Science 248(4951):73–76. https://doi.org/10.1126/science.2321027

    CrossRef  PubMed  CAS  Google Scholar 

  29. So PTC, Dong CY, Masters BR, Berland KM (2000) Two-photon excitation fluorescence microscopy. Annu Rev Biomed Eng 2:399

    CrossRef  CAS  PubMed  Google Scholar 

  30. Estrada AD, Ponticorvo A, Ford TN, Dunn AK (2008) Microvascular oxygen quantification using two-photon microscopy. Opt Lett 33(10):1038. https://doi.org/10.1364/OL.33.001038.

    CrossRef  PubMed  CAS  Google Scholar 

  31. Briñas RP, Troxler T, Hochstrasser RM, Vinogradov SA (2005) Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna. J Am Chem Soc 127(33):11851–11862. https://doi.org/10.1021/ja052947c

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  32. Finikova OS et al (2008) Oxygen microscopy by two-photon-excited phosphorescence. ChemPhysChem 9(12):1673–1679. https://doi.org/10.1002/cphc.200800296

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  33. Esipova TV, Barrett MJP, Erlebach E, Masunov AE, Weber B, Vinogradov SA (2019) Oxyphor 2P: a high-performance probe for deep-tissue longitudinal oxygen imaging. Cell Metab 29(3):736–744.e7. https://doi.org/10.1016/j.cmet.2018.12.022

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  34. Lichtman JW, Conchello J-A (2005) Fluorescence microscopy. Nat Methods 2(12):910–919. https://doi.org/10.1038/nmeth817

    CrossRef  PubMed  CAS  Google Scholar 

  35. Terenziani F, Katan C, Badaeva E, Tretiak S, Blanchard-Desce M (2008) Enhanced two-photon absorption of organic chromophores: theoretical and experimental assessments. Adv Mater 20(24):4641–4678. https://doi.org/10.1002/adma.200800402

    CrossRef  CAS  Google Scholar 

  36. Jaffe HH, Miller AL (1966) The fates of electronic excitation energy. J Chem Educ 43(9):469. https://doi.org/10.1021/ed043p469.

    CrossRef  CAS  Google Scholar 

  37. Evale BG, Hanagodimath SM (2010) Static and dynamic quenching of biologically active coumarin derivative by aniline in benzene–acetonitrile mixtures. J Lumin 130(8):1330–1337. https://doi.org/10.1016/j.jlumin.2010.03.011.

    CrossRef  CAS  Google Scholar 

  38. Laws WR, Contino PB (1992) [21] Fluorescence quenching studies: analysis of nonlinear Stern-Volmer data. In: Methods in enzymology, vol 210. Elsevier, Amsterdam, pp 448–463

    Google Scholar 

  39. Fraiji LK, Hayes DM, Werner TC (1992) Static and dynamic fluorescence quenching experiments for the physical chemistry laboratory. J Chem Educ 69(5):424. https://doi.org/10.1021/ed069p424.

    CrossRef  CAS  Google Scholar 

  40. Quaranta M, Borisov SM, Klimant I (2012) Indicators for optical oxygen sensors. Bioanal Rev 4(2–4):115–157. https://doi.org/10.1007/s12566-012-0032-y

    CrossRef  PubMed  PubMed Central  Google Scholar 

  41. Schweitzer C, Schmidt R (2003) Physical mechanisms of generation and deactivation of singlet oxygen. Chem Rev 103(5):1685–1758. https://doi.org/10.1021/cr010371d

    CrossRef  PubMed  CAS  Google Scholar 

  42. Agostinis P et al (2011) Photodynamic therapy of cancer: an update. CA Cancer J Clin 61(4):250–281. https://doi.org/10.3322/caac.20114

    CrossRef  PubMed  PubMed Central  Google Scholar 

  43. Ho AH-P (2017) Handbook of photonics for biomedical engineering, 1st edn. Springer, New York, NY

    CrossRef  Google Scholar 

  44. Spencer JA et al (2014) Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature 508(7495):269–273. https://doi.org/10.1038/nature13034.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  45. Sakadžic S et al (2016) Two-photon microscopy measurement of cerebral metabolic rate of oxygen using periarteriolar oxygen concentration gradients. Neurophotonics 3(4):045005. https://doi.org/10.1117/1.NPh.3.4.045005.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  46. Moeini M et al (2018) Compromised microvascular oxygen delivery increases brain tissue vulnerability with age. Sci Rep 8(1):8219. https://doi.org/10.1038/s41598-018-26543-w.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  47. Li B et al (2019) More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction. elife 8:e42299. https://doi.org/10.7554/eLife.42299

    CrossRef  PubMed  PubMed Central  Google Scholar 

  48. Redondo CS et al (2017) Interplay of fluorescence and phosphorescence in organic biluminescent emitters. J Phys Chem C 121(27):14946

    CrossRef  CAS  Google Scholar 

  49. Baggaley E, Weinstein JA, Williams JAG (2014) Time-resolved emission imaging microscopy using phosphorescent metal complexes: taking FLIM and PLIM to new lengths. In: Lo KK-W (ed) Luminescent and photoactive transition metal complexes as biomolecular probes and cellular reagents, vol 165. Springer, Berlin, pp 205–256

    CrossRef  Google Scholar 

  50. Choi H et al (2012) 3D-resolved fluorescence and phosphorescence lifetime imaging using temporal focusing wide-field two-photon excitation. Opt Express 20(24):26219. https://doi.org/10.1364/OE.20.026219.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  51. Christodoulou C et al (2020) Live-animal imaging of native haematopoietic stem and progenitor cells. Nature 578(7794):278–283. https://doi.org/10.1038/s41586-020-1971-z.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  52. Becker W (2005) Advanced time-correlated single photon counting techniques. Springer, New York, NY

    CrossRef  Google Scholar 

  53. Jiménez-Banzo A, Ragàs X, Kapusta P, Nonell S (2008) Time-resolved methods in biophysics. 7. Photon counting vs. analog time-resolved singlet oxygen phosphorescence detection. Photochem Photobiol Sci 7(9):1003. https://doi.org/10.1039/b804333g

    CrossRef  PubMed  CAS  Google Scholar 

  54. Rytelewski M et al (2019) Merger of dynamic two-photon and phosphorescence lifetime microscopy reveals dependence of lymphocyte motility on oxygen in solid and hematological tumors. J Immunother Cancer 7(1):78. https://doi.org/10.1186/s40425-019-0543-y.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  55. Fricke M, Nielsen T (2005) Two-dimensional imaging without scanning by multifocal multiphoton microscopy. Appl Opt 44(15):2984. https://doi.org/10.1364/AO.44.002984.

    CrossRef  PubMed  Google Scholar 

  56. Howard SS, Straub A, Horton NG, Kobat D, Xu C (2013) Frequency-multiplexed in vivo multiphoton phosphorescence lifetime microscopy. Nat Photonics 7(1):33–37. https://doi.org/10.1038/nphoton.2012.307

    CrossRef  PubMed  CAS  Google Scholar 

  57. Denk W, Piston DW, Webb WW (1995) Two-photon molecular excitation in laser-scanning microscopy. In: Pawley JB (ed) Handbook of biological confocal microscopy. Springer, Boston, MA, pp 445–458

    CrossRef  Google Scholar 

  58. Larson DR (2003) Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300(5624):1434–1436. https://doi.org/10.1126/science.1083780

    CrossRef  PubMed  Google Scholar 

  59. Sakadžić S et al (2010) Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue. Nat Methods 7(9):755–759. https://doi.org/10.1038/nmeth.1490.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  60. Fittinghoff DN, Wiseman PW, Squier JA (2000) Widefield multiphoton and temporally decorrelated multifocal multiphoton microscopy. Opt Express 7(8):273. https://doi.org/10.1364/OE.7.000273.

    CrossRef  PubMed  CAS  Google Scholar 

  61. Spencer JA (2012) Characterization of bone marrow intravascular pO2 by 2-photon phosphorescence quenching method. Doctoral Dissertation. Retrieved from ProQuest Dissertations and Theses (Accession Order No. AAT 3541737)

    Google Scholar 

  62. Lebedev AY, Cheprakov AV, Sakadžić S, Boas DA, Wilson DF, Vinogradov SA (2009) Dendritic phosphorescent probes for oxygen imaging in biological systems. ACS Appl Mater Interfaces 1(6):1292–1304. https://doi.org/10.1021/am9001698

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  63. Esipova TV, Karagodov A, Miller J, Wilson DF, Busch TM, Vinogradov SA (2011) Two new ‘protected’ oxyphors for biological oximetry: properties and application in tumor imaging. Anal Chem 83(22):8756–8765. https://doi.org/10.1021/ac2022234

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  64. Dunphy I, Vinogradov SA, Wilson DF (2002) Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. Anal Biochem 310:191

    CrossRef  CAS  PubMed  Google Scholar 

  65. Wilson DF, Lee WMF, Makonnen S, Finikova O, Apreleva S, Vinogradov SA (2006) Oxygen pressures in the interstitial space and their relationship to those in the blood plasma in resting skeletal muscle. J Appl Physiol 101(6):1648–1656. https://doi.org/10.1152/japplphysiol.00394.2006

    CrossRef  PubMed  CAS  Google Scholar 

  66. Lo L-W, Koch CJ, Wilson DF (1996) Calibration of oxygen-dependent quenching of the phosphorescence of Pd-meso-tetra (4-carboxyphenyl) porphine: a phosphor with general application for measuring oxygen concentration in biological systems. Anal Biochem 236(1):153–160. https://doi.org/10.1006/abio.1996.0144

    CrossRef  PubMed  CAS  Google Scholar 

  67. Roussakis E, Spencer JA, Lin CP, Vinogradov SA (2014) Two-photon antenna-core oxygen probe with enhanced performance. Anal Chem 86(12):5937–5945. https://doi.org/10.1021/ac501028m

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  68. Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 12(12):723–738. https://doi.org/10.1038/nrn3114

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  69. Montagne A, Zhao Z, Zlokovic BV (2017) Alzheimer’s disease: a matter of blood–brain barrier dysfunction? J Exp Med 214(11):3151–3169. https://doi.org/10.1084/jem.20171406

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  70. Al-Bachari S, Vidyasagar R, Emsley HC, Parkes LM (2017) Structural and physiological neurovascular changes in idiopathic Parkinson’s disease and its clinical phenotypes. J Cereb Blood Flow Metab 37(10):3409–3421. https://doi.org/10.1177/0271678X16688919

    CrossRef  PubMed  PubMed Central  Google Scholar 

  71. Lim RG et al (2017) Huntington’s disease iPSC-derived brain microvascular endothelial cells reveal WNT-mediated angiogenic and blood-brain barrier deficits. Cell Rep 19(7):1365–1377. https://doi.org/10.1016/j.celrep.2017.04.021.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  72. Devor A et al (2011) ‘Overshoot’ of O2 is required to maintain baseline tissue oxygenation at locations distal to blood vessels. J Neurosci 31(38):13676–13681. https://doi.org/10.1523/JNEUROSCI.1968-11.2011

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  73. Parpaleix A, Houssen YG, Charpak S (2013) Imaging local neuronal activity by monitoring PO2 transients in capillaries. Nat Med 19(2):241–246. https://doi.org/10.1038/nm.3059

    CrossRef  PubMed  CAS  Google Scholar 

  74. Lecoq J et al (2011) Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels. Nat Med 17(7):893–898. https://doi.org/10.1038/nm.2394.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  75. Sakadžić S et al (2014) Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat Commun 5(1):5734. https://doi.org/10.1038/ncomms6734.

    CrossRef  PubMed  Google Scholar 

  76. Kazmi SMS et al (2013) Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion. Biomed Opt Express 4(7):1061. https://doi.org/10.1364/BOE.4.001061.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  77. Kisler K et al (2017) Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nat Neurosci 20(3):406–416. https://doi.org/10.1038/nn.4489.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  78. Lyons DG, Parpaleix A, Roche M, Charpak S (2016) Mapping oxygen concentration in the awake mouse brain. elife 5:e12024. https://doi.org/10.7554/eLife.12024

    CrossRef  PubMed  PubMed Central  Google Scholar 

  79. Roche M, Chaigneau E, Rungta RL, Boido D, Weber B, Charpak S (2019) In vivo imaging with a water immersion objective affects brain temperature, blood flow and oxygenation. elife 8:e47324. https://doi.org/10.7554/eLife.47324

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  80. Zhang Q et al (2019) Cerebral oxygenation during locomotion is modulated by respiration. Neuroscience. https://doi.org/10.1101/639419

  81. Moeini M, Cloutier-Tremblay C, Lu X et al (2020) Cerebral tissue pO2 response to treadmill exercise in awake mice. Sci Rep 10:13358. https://doi.org/10.1038/s41598-020-70413-3

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  82. Şencan İ, Esipova T, Kılıç K, Li B, Desjardins M, Yaseen MA, Wang H, Porter JE, Kura S, Fu B, Secomb TW, Boas DA, Vinogradov SA, Devor A, Sakadžić S (2020) Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation. J Cereb Blood Flow Metab. https://doi.org/10.1177/0271678X20928011

  83. Rytelewski M, Harutyunyan K, Baran N, Mallampati S, Zal MA, Cavazos A, Butler JM, Konoplev S, El Khatib M, Plunkett S, Marszalek JR, Andreeff M, Zal T, Konopleva M (2020) Inhibition of oxidative phosphorylation reverses bone marrow hypoxia visualized in imageable syngeneic B-ALL mouse model. Front Oncol 10:991. https://doi.org/10.3389/fonc.2020.00991

    CrossRef  PubMed  PubMed Central  Google Scholar 

  84. Şencan I et al (2018) Two-photon phosphorescence lifetime microscopy of retinal capillary plexus oxygenation in mice. J Biomed Opt 23(12):1. https://doi.org/10.1117/1.JBO.23.12.126501

    CrossRef  PubMed  Google Scholar 

  85. Kritchenkov IS, Elistratova AA, Sokolov VV, Chelushkin PS, Shirmanova MV, Lukina MM, Dudenkova VV, Shcheslavskiy VI, Kalinina S, Reeß K, Rück A, Tunik SP (2020) A biocompatible phosphorescent Ir(iii) oxygen sensor functionalized with oligo(ethylene glycol) groups: synthesis, photophysics and application in PLIM experiments. New J Chem 44(25):10459–10471. https://doi.org/10.1039/D0NJ01405B

    CrossRef  CAS  Google Scholar 

  86. Schilling K et al (2019) Electrospun fiber mesh for high-resolution measurements of oxygen tension in cranial bone defect repair. ACS Appl Mater Interfaces 11(37):33548–33558. https://doi.org/10.1021/acsami.9b08341.

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Bioengineering, University of California Merced, Merced, CA, USA

    Nastaran Abbasizadeh & Joel A. Spencer

  2. NSF-CREST Center for Cellular and Biomolecular Machines and the Health Science Research Institute, University of California Merced, Merced, CA, USA

    Nastaran Abbasizadeh & Joel A. Spencer

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  1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Dr. Xunbin Wei

  2. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Dr. Bobo Gu

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Abbasizadeh, N., Spencer, J.A. (2021). Two-Photon Phosphorescence Lifetime Microscopy. In: Wei, X., Gu, B. (eds) Optical Imaging in Human Disease and Biological Research. Advances in Experimental Medicine and Biology, vol 3233. Springer, Singapore. https://doi.org/10.1007/978-981-15-7627-0_4

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