Abstract

Conventional histology with light microscopy is essential in the diagnosis of most liver diseases. Recently, a concept of real-time histology with optical biopsy has been advocated. In this study, live mice livers (normal, with fibrosis, steatosis, hepatocellular carcinoma and ischemia-reperfusion injury) were imaged by MPM-FLIM for stain-free real-time histology. The acquired MPM-FLIM images were compared with conventional histological images. MPM-FLIM imaged subsurface cellular and subcellular histopathological hallmarks of live liver in mice models at high resolution. Additional information such as distribution of stellate cell associated autofluorescence and fluorescence lifetime changes was also gathered by MPM-FLIM simultaneously, which cannot be obtained from conventional histology. MPM-FLIM could simultaneously image and quantify the cellular morphology and microenvironment of live livers without conventional biopsy or fluorescent dyes. We anticipate that in the near future MPM-FLIM will be evaluated from bench to bedside, leading to real-time histology and dynamic monitoring of human liver diseases.

© 2015 Optical Society of America

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2015 (1)

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

2014 (3)

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

P. Uhl, G. Fricker, U. Haberkorn, and W. Mier, “Current status in the therapy of liver diseases,” Int. J. Mol. Sci. 15(5), 7500–7512 (2014).
[Crossref] [PubMed]

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
[Crossref] [PubMed]

2012 (4)

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37(8), 1349–1351 (2012).
[Crossref] [PubMed]

W. Becker, “Fluorescence lifetime imaging--techniques and applications,” J. Microsc. 247(2), 119–136 (2012).
[Crossref] [PubMed]

I. Vidal and L. Richert, “The nude mouse as model for liver deficiency study and treatment and xenotransplantation,” Int. J. Hepatol. 2012, 140147 (2012).
[Crossref] [PubMed]

2011 (4)

Q. Wang, W. Luan, V. Goz, S. J. Burakoff, and S. P. Hiotis, “Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice,” Liver Int. 31(8), 1200–1208 (2011).
[Crossref] [PubMed]

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
[Crossref] [PubMed]

2010 (1)

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

2009 (3)

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

2008 (4)

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

2007 (1)

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

2006 (2)

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Q. M. Anstee and R. D. Goldin, “Mouse models in non-alcoholic fatty liver disease and steatohepatitis research,” Int. J. Exp. Pathol. 87(1), 1–16 (2006).
[Crossref] [PubMed]

2005 (4)

R. Bataller and D. A. Brenner, “Liver fibrosis,” J. Clin. Invest. 115(2), 209–218 (2005).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

D. A. Sass, P. Chang, and K. B. Chopra, “Nonalcoholic fatty liver disease: a clinical review,” Dig. Dis. Sci. 50(1), 171–180 (2005).
[Crossref] [PubMed]

2004 (1)

H. Senoo, “Structure and function of hepatic stellate cells,” Med. Electron Microsc. 37(1), 3–15 (2004).
[Crossref] [PubMed]

2003 (2)

D. Bird and M. Gu, “Two-photon fluorescence endoscopy with a micro-optic scanning head,” Opt. Lett. 28(17), 1552–1554 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

2001 (1)

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

1998 (1)

B. Vollmar, S. Siegmund, and M. D. Menger, “An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats,” Hepatology 27(6), 1544–1553 (1998).
[Crossref] [PubMed]

1997 (1)

R. G. Cameron, M. G. Neuman, N. Shear, and L. M. Blendis, “Multivesicular stellate cells in primary biliary cirrhosis,” Hepatology 26(4), 819–822 (1997).
[Crossref] [PubMed]

1994 (1)

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

1992 (1)

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

1989 (1)

S. Banerjee and D. K. Bhatt, “Histochemical studies on the distribution of certain dehydrogenases in squamous cell carcinoma of cheek,” Indian J. Cancer 26(1), 21–30 (1989).
[PubMed]

Adamek, H. E.

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

Ahn, Y. C.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Anstee, Q. M.

Q. M. Anstee and R. D. Goldin, “Mouse models in non-alcoholic fatty liver disease and steatohepatitis research,” Int. J. Exp. Pathol. 87(1), 1–16 (2006).
[Crossref] [PubMed]

Arnold, J. C.

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

Asopa, S.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

Baffet, G.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Bain, A. J.

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

Banerjee, S.

S. Banerjee and D. K. Bhatt, “Histochemical studies on the distribution of certain dehydrogenases in squamous cell carcinoma of cheek,” Indian J. Cancer 26(1), 21–30 (1989).
[PubMed]

Bataller, R.

R. Bataller and D. A. Brenner, “Liver fibrosis,” J. Clin. Invest. 115(2), 209–218 (2005).
[Crossref] [PubMed]

Beaurepaire, E.

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Becker, W.

W. Becker, “Fluorescence lifetime imaging--techniques and applications,” J. Microsc. 247(2), 119–136 (2012).
[Crossref] [PubMed]

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Benz, C.

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

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J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
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L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
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Bird, D. K.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
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T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
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R. G. Cameron, M. G. Neuman, N. Shear, and L. M. Blendis, “Multivesicular stellate cells in primary biliary cirrhosis,” Hepatology 26(4), 819–822 (1997).
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T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
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Burakoff, S. J.

Q. Wang, W. Luan, V. Goz, S. J. Burakoff, and S. P. Hiotis, “Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice,” Liver Int. 31(8), 1200–1208 (2011).
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C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
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C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
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R. G. Cameron, M. G. Neuman, N. Shear, and L. M. Blendis, “Multivesicular stellate cells in primary biliary cirrhosis,” Hepatology 26(4), 819–822 (1997).
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D. A. Sass, P. Chang, and K. B. Chopra, “Nonalcoholic fatty liver disease: a clinical review,” Dig. Dis. Sci. 50(1), 171–180 (2005).
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H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
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Chen, G.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
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Chen, J.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
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Chen, T.

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
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Chen, Z.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
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Chopra, K. B.

D. A. Sass, P. Chang, and K. B. Chopra, “Nonalcoholic fatty liver disease: a clinical review,” Dig. Dis. Sci. 50(1), 171–180 (2005).
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Cicalese, L.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
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Cogger, V. C.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Crawford, D.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

Crawford, D. H.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Dancik, Y.

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Delaney, P.

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Désille, Y.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Dewhirst, M. W.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
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Dienes, H. P.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Dingemans, K. P.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Drebber, U.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Duchen, M. R.

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

Eickhoff, J.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

Eliceiri, K. W.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Ezan, F.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Fletcher, L. M.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
[Crossref] [PubMed]

Forbes, S. J.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Frémin, C.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Fricker, G.

P. Uhl, G. Fricker, U. Haberkorn, and W. Mier, “Current status in the therapy of liver diseases,” Int. J. Mol. Sci. 15(5), 7500–7512 (2014).
[Crossref] [PubMed]

Funch-Jensen, P.

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

Gailhouste, L.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Gale, J. E.

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

Galle, P. R.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

Gendron-Fitzpatrick, A.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

Gobe, G. C.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
[Crossref] [PubMed]

Godeau, G.

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Goetz, M.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

Goldin, R. D.

Q. M. Anstee and R. D. Goldin, “Mouse models in non-alcoholic fatty liver disease and steatohepatitis research,” Int. J. Exp. Pathol. 87(1), 1–16 (2006).
[Crossref] [PubMed]

Gordon-Walker, T. T.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Goz, V.

Q. Wang, W. Luan, V. Goz, S. J. Burakoff, and S. P. Hiotis, “Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice,” Liver Int. 31(8), 1200–1208 (2011).
[Crossref] [PubMed]

Grice, J. E.

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Groen, A. K.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Grønbæk, H.

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

Gu, M.

Guilbert, T.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Gukassyan, V.

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

Guo, H. W.

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

Guyader, D.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Haberkorn, U.

P. Uhl, G. Fricker, U. Haberkorn, and W. Mier, “Current status in the therapy of liver diseases,” Int. J. Mol. Sci. 15(5), 7500–7512 (2014).
[Crossref] [PubMed]

Hao, Y.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Hartland, S.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Hiotis, S. P.

Q. Wang, W. Luan, V. Goz, S. J. Burakoff, and S. P. Hiotis, “Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice,” Liver Int. 31(8), 1200–1208 (2011).
[Crossref] [PubMed]

Hoffman, A.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Hume, D. A.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Iredale, J. P.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Jakobs, R.

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

Jemal, A.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Jia, F.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Jiang, J.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Jin, L.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

Johnson, M.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Jørgensen, R. L.

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

Jung, W.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Kannerup, A. S.

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

Kanzler, S.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

Kao, F. J.

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

Keely, P. J.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Kiesslich, R.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

König, K.

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Lakowicz, J. R.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Lau, D.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Le Couteur, D. G.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Le Grand, Y.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Lemon, S. M.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Li, Z.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Liang, X.

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
[Crossref] [PubMed]

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Liang, Y.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Lin, L. L.

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Liu, D.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Liu, X.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
[Crossref] [PubMed]

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Luan, W.

Q. Wang, W. Luan, V. Goz, S. J. Burakoff, and S. P. Hiotis, “Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice,” Liver Int. 31(8), 1200–1208 (2011).
[Crossref] [PubMed]

Mann, Z. F.

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

Mauad, T. H.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

McCormick, D.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Menger, M. D.

B. Vollmar, S. Siegmund, and M. D. Menger, “An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats,” Hepatology 27(6), 1544–1553 (1998).
[Crossref] [PubMed]

Mier, W.

P. Uhl, G. Fricker, U. Haberkorn, and W. Mier, “Current status in the therapy of liver diseases,” Int. J. Mol. Sci. 15(5), 7500–7512 (2014).
[Crossref] [PubMed]

Mortensen, F. V.

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

Murr, E.

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Murray, T.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Neuman, M. G.

R. G. Cameron, M. G. Neuman, N. Shear, and L. M. Blendis, “Multivesicular stellate cells in primary biliary cirrhosis,” Hepatology 26(4), 819–822 (1997).
[Crossref] [PubMed]

Neurath, M. F.

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Notenboom, R. G.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Nowaczyk, K.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Odin, C.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Oude Elferink, R. P.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Ouzounov, D. G.

Pagès, N.

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Peltz, C.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

Pena, A. M.

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Pope, C.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Prow, T. W.

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Ramachandran, P.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Ramanujam, N.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Richert, L.

I. Vidal and L. Richert, “The nude mouse as model for liver deficiency study and treatment and xenotransplantation,” Int. J. Hepatol. 2012, 140147 (2012).
[Crossref] [PubMed]

Riching, K. M.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

Riemann, J. F.

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

Rivera, D. R.

Roberts, M. S.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
[Crossref] [PubMed]

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Robertson, T. A.

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Robson, A. J.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Sanchez, W. Y.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Sass, D. A.

D. A. Sass, P. Chang, and K. B. Chopra, “Nonalcoholic fatty liver disease: a clinical review,” Dig. Dis. Sci. 50(1), 171–180 (2005).
[Crossref] [PubMed]

Sauviat, M. P.

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Schanne-Klein, M. C.

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
[Crossref] [PubMed]

Schinkel, A. H.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Schneider, A. R.

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

Schroeder, T.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

Senoo, H.

H. Senoo, “Structure and function of hepatic stellate cells,” Med. Electron Microsc. 37(1), 3–15 (2004).
[Crossref] [PubMed]

Shear, N.

R. G. Cameron, M. G. Neuman, N. Shear, and L. M. Blendis, “Multivesicular stellate cells in primary biliary cirrhosis,” Hepatology 26(4), 819–822 (1997).
[Crossref] [PubMed]

Shilagard, T.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Siegel, R.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Siegmund, S.

B. Vollmar, S. Siegmund, and M. D. Menger, “An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats,” Hepatology 27(6), 1544–1553 (1998).
[Crossref] [PubMed]

Skala, M. C.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

Smit, J. J.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Snyder, N.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Song, Y.

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
[Crossref] [PubMed]

Su, J.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Szabadkai, G.

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

Szmacinski, H.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

Tang, S.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Theret, N.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Thomas, J. A.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Thorling, C. A.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt. 16(11), 116011 (2011).
[Crossref] [PubMed]

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Thun, M. J.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Tromberg, B. J.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Turlin, B.

L. Gailhouste, Y. Le Grand, C. Odin, D. Guyader, B. Turlin, F. Ezan, Y. Désille, T. Guilbert, A. Bessard, C. Frémin, N. Theret, and G. Baffet, “Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis,” J. Hepatol. 52(3), 398–406 (2010).
[Crossref] [PubMed]

Uhl, P.

P. Uhl, G. Fricker, U. Haberkorn, and W. Mier, “Current status in the therapy of liver diseases,” Int. J. Mol. Sci. 15(5), 7500–7512 (2014).
[Crossref] [PubMed]

Van Deemter, M.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

van den Bergh Weerman, M. A.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

van Nieuwkerk, C. M.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Vargas, G.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Vaughan, E. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Verkruisen, R. P.

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Vidal, I.

I. Vidal and L. Richert, “The nude mouse as model for liver deficiency study and treatment and xenotransplantation,” Int. J. Hepatol. 2012, 140147 (2012).
[Crossref] [PubMed]

Vieth, M.

M. Goetz, M. Vieth, S. Kanzler, P. R. Galle, P. Delaney, M. F. Neurath, and R. Kiesslich, “In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease,” J. Hepatol. 48(1), 91–97 (2008).
[Crossref] [PubMed]

Viglianti, B. L.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

Vollmar, B.

B. Vollmar, S. Siegmund, and M. D. Menger, “An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats,” Hepatology 27(6), 1544–1553 (1998).
[Crossref] [PubMed]

Vrotsos, K. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Vujaskovic, Z.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

Wang, H.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
[Crossref] [PubMed]

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
[Crossref] [PubMed]

Wang, H. W.

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

Wang, J.

H. Wang, H. Wang, T. Chen, X. Liang, Y. Song, and J. Wang, “Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma,” World J. Surg. Oncol. 12(1), 191 (2014).
[Crossref] [PubMed]

Wang, Q.

Q. Wang, W. Luan, V. Goz, S. J. Burakoff, and S. P. Hiotis, “Non-invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice,” Liver Int. 31(8), 1200–1208 (2011).
[Crossref] [PubMed]

Ward, E.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Webb, W. W.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37(8), 1349–1351 (2012).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Wei, Y. H.

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

Weiss, H.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Weiss, M.

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

White, J. G.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Wojtacha, D.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

Wu, X.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Xiao, S. Y.

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Xie, S.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Xie, T.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

Xu, C.

Xu, J.

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Xu, Z. P.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Yan, J.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Yan, L.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Ying, M.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Yu, J. S.

H. W. Wang, V. Gukassyan, C. T. Chen, Y. H. Wei, H. W. Guo, J. S. Yu, and F. J. Kao, “Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells,” J. Biomed. Opt. 13(5), 054011 (2008).
[Crossref] [PubMed]

Yuan, H.

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

Zhou, D.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Zhou, J.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Zhu, Y.

X. Liang, J. E. Grice, Y. Zhu, D. Liu, W. Y. Sanchez, Z. Li, D. H. Crawford, D. G. Le Couteur, V. C. Cogger, X. Liu, Z. P. Xu, and M. S. Roberts, “Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells,” Small (2014), doi:.
[Crossref]

Zhuo, S.

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

Ziegler, M.

T. S. Blacker, Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai, and M. R. Duchen, “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM,” Nat. Commun. 5, 3936 (2014).
[Crossref] [PubMed]

Zipfel, W. R.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Am. J. Pathol. (1)

T. H. Mauad, C. M. van Nieuwkerk, K. P. Dingemans, J. J. Smit, A. H. Schinkel, R. G. Notenboom, M. A. van den Bergh Weerman, R. P. Verkruisen, A. K. Groen, and R. P. Oude Elferink, “Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis,” Am. J. Pathol. 145(5), 1237–1245 (1994).
[PubMed]

Anal. Biochem. (1)

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt, and M. Johnson, “Fluorescence lifetime imaging,” Anal. Biochem. 202(2), 316–330 (1992).
[Crossref] [PubMed]

CA Cancer J. Clin. (1)

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, and M. J. Thun, “Cancer statistics, 2008,” CA Cancer J. Clin. 58(2), 71–96 (2008).
[Crossref] [PubMed]

Cancer Res. (2)

T. Schroeder, H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic, and M. W. Dewhirst, “Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat,” Cancer Res. 65(12), 5163–5171 (2005).
[Crossref] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[Crossref] [PubMed]

Cytometry A (1)

T. Boulesteix, A. M. Pena, N. Pagès, G. Godeau, M. P. Sauviat, E. Beaurepaire, and M. C. Schanne-Klein, “Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure,” Cytometry A 69(1), 20–26 (2006).
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Dig. Dis. Sci. (1)

D. A. Sass, P. Chang, and K. B. Chopra, “Nonalcoholic fatty liver disease: a clinical review,” Dig. Dis. Sci. 50(1), 171–180 (2005).
[Crossref] [PubMed]

Drug Metab. Dispos. (1)

C. A. Thorling, L. Jin, M. Weiss, D. Crawford, X. Liu, F. J. Burczynski, D. Liu, H. Wang, and M. S. Roberts, “Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition,” Drug Metab. Dispos. 43(1), 154–162 (2015).
[Crossref] [PubMed]

Endoscopy (1)

M. Goetz, R. Kiesslich, H. P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. R. Galle, P. Delaney, and M. F. Neurath, “In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time,” Endoscopy 40(7), 554–562 (2008).
[Crossref] [PubMed]

Eur. J. Pharm. Biopharm. (1)

M. S. Roberts, Y. Dancik, T. W. Prow, C. A. Thorling, L. L. Lin, J. E. Grice, T. A. Robertson, K. König, and W. Becker, “Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy,” Eur. J. Pharm. Biopharm. 77(3), 469–488 (2011).
[Crossref] [PubMed]

Gastroenterology (1)

Y. Liang, T. Shilagard, S. Y. Xiao, N. Snyder, D. Lau, L. Cicalese, H. Weiss, G. Vargas, and S. M. Lemon, “Visualizing hepatitis C virus infections in human liver by two-photon microscopy,” Gastroenterology 137(4), 1448–1458 (2009).
[Crossref] [PubMed]

Gastrointest. Endosc. (1)

A. R. Schneider, C. Benz, H. E. Adamek, R. Jakobs, J. F. Riemann, and J. C. Arnold, “Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases,” Gastrointest. Endosc. 53(7), 771–775 (2001).
[Crossref] [PubMed]

Hepatol. Int. (1)

A. S. Kannerup, H. Grønbæk, P. Funch-Jensen, R. L. Jørgensen, and F. V. Mortensen, “The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis,” Hepatol. Int. 3(1), 310–315 (2009).
[Crossref] [PubMed]

Hepatology (3)

R. G. Cameron, M. G. Neuman, N. Shear, and L. M. Blendis, “Multivesicular stellate cells in primary biliary cirrhosis,” Hepatology 26(4), 819–822 (1997).
[Crossref] [PubMed]

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, “Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function,” Hepatology 53(6), 2003–2015 (2011).
[Crossref] [PubMed]

B. Vollmar, S. Siegmund, and M. D. Menger, “An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats,” Hepatology 27(6), 1544–1553 (1998).
[Crossref] [PubMed]

Indian J. Cancer (1)

S. Banerjee and D. K. Bhatt, “Histochemical studies on the distribution of certain dehydrogenases in squamous cell carcinoma of cheek,” Indian J. Cancer 26(1), 21–30 (1989).
[PubMed]

Int. J. Exp. Pathol. (1)

Q. M. Anstee and R. D. Goldin, “Mouse models in non-alcoholic fatty liver disease and steatohepatitis research,” Int. J. Exp. Pathol. 87(1), 1–16 (2006).
[Crossref] [PubMed]

Int. J. Hepatol. (1)

I. Vidal and L. Richert, “The nude mouse as model for liver deficiency study and treatment and xenotransplantation,” Int. J. Hepatol. 2012, 140147 (2012).
[Crossref] [PubMed]

Int. J. Mol. Sci. (1)

P. Uhl, G. Fricker, U. Haberkorn, and W. Mier, “Current status in the therapy of liver diseases,” Int. J. Mol. Sci. 15(5), 7500–7512 (2014).
[Crossref] [PubMed]

J. Biomed. Opt. (4)

J. Yan, S. Zhuo, G. Chen, X. Wu, D. Zhou, S. Xie, J. Jiang, M. Ying, F. Jia, J. Chen, and J. Zhou, “Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions,” J. Biomed. Opt. 17(2), 026004 (2012).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14(3), 034005 (2009).
[Crossref] [PubMed]

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Figures (4)

Fig. 1
Fig. 1 MPM-FLIM and conventional histopathological images of liver in healthy mice, Mdr2−/− mice and mice with CCl4 induced liver fibrosis at low magnification (10 × ) (scale bar: 80 μm). A, F and K: Fluorescence intensity image recorded at λExcEm: 740/350 to 650 nm; B, G and L: Fluorescence intensity image recorded at λExcEm: 800/350 to 650 nm; C, H and M: Pseudocolored fluorescence lifetime image (τm: 0-2500 ps; blue-green-red) recorded at λExcEm: 740/350 to 450 nm; D, I and N: Pseudocolored fluorescence lifetime image (τm: 0-2500 ps; blue-green-red) recorded at λExcEm: 800/350 to 450 nm; E, J and O: Conventional histological images were collected on Van Gieson’s stained section. Opened arrows indicate collagen; asterisks indicate bile duct; curved arrow indicates bridges formed by stellate cells; and filled arrows indicate postsinusoidal venules.
Fig. 2
Fig. 2 MPM-FLIM and conventional histopathological images of liver in healthy mice, Mdr2−/− mice and mice with CCl4 induced liver fibrosis at high magnification (40 × ) (scale bar: 20 μm). A, F and K: Fluorescence intensity image recorded at λExcEm: 740/350 to 650 nm; B, G and L: Fluorescence intensity image recorded at λExcEm: 800/350 to 650 nm; C, H and M: Pseudocolored fluorescence lifetime image (τm: 0-2500 ps; blue-green-red) recorded at λExcEm: 740/350 to 450 nm; D, I and N: Pseudocolored fluorescence lifetime image (τm: 0-2500 ps; blue-green-red) recorded at λExcEm: 800/350 to 450 nm; E, J and O: Conventional histological images were collected on Van Gieson’s stained section. Curved arrow indicates hepatic sinusoids; red square indicates hepatocytes; red circle indicates stellate cells associated autofluorescence; opened arrows indicate collagen; and filled arrows indicate cellular necrosis.
Fig. 3
Fig. 3 Mean and 95% confidence interval of lifetime variables excited at 740 and 800 nm (n = 6 for each group). A: τm recorded at λExcEm: 740/350 to 450 nm; B: τm recorded at λExcEm: 800/350 to 450 nm; C: The lifetimes corresponding to free and protein-bound NADH (τ1 and τ2), and contribution of protein-bound NADH of normal liver, hepatocellular carcinoma and liver with ischemia-reperfusion injury (6 h of reperfusion). Columns represent the mean value of each group while the bars represent standard deviation; * p < 0.05 compared with normal liver.
Fig. 4
Fig. 4 MPM-FLIM and conventional histopathological images of liver in mice with fatty liver disease, hepatocellular carcinoma and ischemia-reperfusion injury (6 h of reperfusion) at high magnification (40 × ) (scale bar: 20 μm). A, F and K: Fluorescence intensity image recorded at λExcEm: 740/350 to 650 nm; B, G and L: Fluorescence intensity image recorded at λExcEm: 800/350 to 650 nm; C, H and M: Pseudocolored fluorescence lifetime image (τm:0-2500 ps; blue-green-red) recorded at λExcEm: 740/350 to 450 nm; D, I and N: Pseudocolored fluorescence lifetime image (τm: 0-2500 ps; blue-green-red) recorded at λExcEm: 800/350 to 450 nm; E, J and O: Conventional histological images were collected on H&E stained section. Opened arrows indicate intracellular fat vacuole; red square indicates hepatocellular carcinoma cells with increased nuclear to cytoplasmic ratio; curved arrows indicate collagen; and narrow arrows indicate cellular necrosis.

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