Abstract

Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.

© 2011 OSA

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2011 (3)

J. P. R. Day, K. F. Domke, G. Rago, H. Kano, H. O. Hamaguchi, E. M. Vartiainen, and M. Bonn, “Quantitative Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 115(24), 7713–7725 (2011).
[CrossRef] [PubMed]

Y. Wang, C.-Y. Lin, A. Nikolaenko, V. Raghunathan, and E. O. Potma, “Four-wave mixing microscopy of nanostructures,” Adv. Opt. Photonics 3(1), 1–52 (2011).
[CrossRef]

G. Rago, B. Bauer, F. Svedberg, L. Gunnarsson, M. B. Ericson, M. Bonn, and A. Enejder, “Uptake of gold nanoparticles in healthy and tumor cells visualized by nonlinear optical microscopy,” J. Phys. Chem. B 115(17), 5008–5016 (2011).
[CrossRef] [PubMed]

2010 (8)

A. M. Schrand, J. J. Schlager, L. M. Dai, and S. M. Hussain, “Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy,” Nat. Protoc. 5(4), 744–757 (2010).
[CrossRef] [PubMed]

J. P. R. Day, G. Rago, K. F. Domke, K. P. Velikov, and M. Bonn, “Label-free imaging of lipophilic bioactive molecules during lipid digestion by multiplex coherent anti-Stokes Raman scattering microspectroscopy,” J. Am. Chem. Soc. 132(24), 8433–8439 (2010).
[CrossRef] [PubMed]

M. Okuno, H. Kano, P. Leproux, V. Couderc, J. P. R. Day, M. Bonn, and H. O. Hamaguchi, “Quantitative CARS molecular fingerprinting of single living cells with the use of the maximum entropy method,” Angew. Chem. Int. Ed. Engl. 49(38), 6773–6777 (2010).
[CrossRef] [PubMed]

A. Enejder, C. Brackmann, and F. Svedberg, “Coherent Anti-Stokes Raman Scattering Microscopy of Cellular Lipid Storage,” IEEE J. Sel. Top. Quantum Electron. 16(3), 506–515 (2010).
[CrossRef]

J. Lodhia, G. Mandarano, Nj. Ferris, P. Eu, and S. F. Cowell, “Development and use of iron oxide nanoparticles (Part 1): Synthesis of iron oxide nanoparticles for MRI,” Biomed Imaging Intervent. J. 6(2), e12 (2010).
[CrossRef] [PubMed]

K. Krause, C. Schneider, K. H. Kuck, and K. Jaquet, “Review: Stem cell therapy in cardiovascular disorders,” Cardiovasc. Ther. 28(5), e101–e110 (2010).
[CrossRef] [PubMed]

T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
[CrossRef] [PubMed]

A. Dhawan, J. Puppi, R. D. Hughes, and R. R. Mitry, “Human hepatocyte transplantation: current experience and future challenges,” Natl. Rev. 7(5), 288–298 (2010).
[CrossRef] [PubMed]

2009 (8)

J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
[CrossRef] [PubMed]

E. Fitzpatrick, R. R. Mitry, and A. Dhawan, “Human hepatocyte transplantation: state of the art,” J. Intern. Med. 266(4), 339–357 (2009).
[CrossRef] [PubMed]

J. W. M. Bulte, “In vivo MRI cell tracking: clinical studies,” AJR Am. J. Roentgenol. 193(2), 314–325 (2009).
[CrossRef] [PubMed]

J. Puppi and M. Modo, “Use of magnetic resonance imaging contrast agents to detect transplanted liver cells,” Top. Magn. Reson. Imaging 20(2), 113–120 (2009).
[CrossRef] [PubMed]

S. Koenig, P. Krause, A. S. A. Hosseini, C. Dullin, M. Rave-Fraenk, S. Kimmina, A. L. Entwistle, R. M. Hermann, C. F. Hess, H. Becker, and H. Christiansen, “Noninvasive imaging of liver repopulation following hepatocyte transplantation,” Cell Transplant. 18(1), 69–78 (2009).
[CrossRef] [PubMed]

W. Liu and J. A. Frank, “Detection and quantification of magnetically labeled cells by cellular MRI,” Eur. J. Radiol. 70(2), 258–264 (2009).
[CrossRef] [PubMed]

S. Schwarz, F. Fernandes, L. Sanroman, M. Hodenius, C. Lang, U. Himmelreich, T. Schmitz-Rode, D. Schueler, M. Hoehn, M. Zenke, and T. Hieronymus, “Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells,” J. Magn. Magn. Mater. 321(10), 1533–1538 (2009).
[CrossRef]

Z. Medarova, P. Vallabhajosyula, A. Tena, N. Evgenov, P. Pantazopoulos, V. Tchipashvili, G. Weir, D. Sachs, and A. Moore, “In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates,” Transplantation 87(11), 1659–1666 (2009).
[CrossRef] [PubMed]

2008 (7)

N. Raschzok, M. H. Morgul, J. Pinkernelle, F. W. R. Vondran, N. Billecke, N. N. Kammer, G. Pless, M. K. Adonopoulou, C. Leist, L. Stelter, U. Teichgraber, R. Schwartlander, and I. M. Sauer, “Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography,” J. Cell. Mol. Med. 12(4), 1384–1394 (2008).
[CrossRef] [PubMed]

M. H. Morgul, N. Raschzok, R. Schwartlander, F. W. Vondran, R. Michel, L. Stelter, J. Pinkernelle, A. Jordan, U. Teichgraber, and I. M. Sauer, “Tracking of primary human hepatocytes with clinical MRI: initial results with Tat-peptide modified superparamagnetic iron oxide particles,” Int. J. Artif. Organs 31(3), 252–257 (2008).
[PubMed]

W. M. Leevy, S. T. Gammon, J. R. Johnson, A. J. Lampkins, H. Jiang, M. Marquez, D. Piwnica-Worms, M. A. Suckow, and B. D. Smith, “Noninvasive optical imaging of staphylococcus aureus bacterial infection in living mice using a Bis-dipicolylamine-Zinc(II) affinity group conjugated to a near-infrared fluorophore,” Bioconjug. Chem. 19(3), 686–692 (2008).
[CrossRef] [PubMed]

A. Quaglia, S. C. Lehec, R. D. Hughes, R. R. Mitry, A. S. Knisely, S. Devereaux, J. Richards, M. Rela, N. D. Heaton, B. C. Portmann, and A. Dhawan, “Liver after hepatocyte transplantation for liver-based metabolic disorders in children,” Cell Transplant. 17(12), 1403–1414 (2008).
[CrossRef] [PubMed]

A. S. Arbab and J. A. Frank, “Cellular MRI and its role in stem cell therapy,” Regen. Med. 3(2), 199–215 (2008).
[CrossRef] [PubMed]

M. Modo, “Noninvasive imaging of transplanted cells,” Curr. Opin. Organ Transplant. 13(6), 654–658 (2008).
[CrossRef] [PubMed]

J. Moger, B. D. Johnston, and C. R. Tyler, “Imaging metal oxide nanoparticles in biological structures with CARS microscopy,” Opt. Express 16(5), 3408–3419 (2008).
[CrossRef] [PubMed]

2007 (5)

D. Gachet, F. Billard, N. Sandeau, and H. Rigneault, “Coherent anti-Stokes Raman scattering (CARS) microscopy imaging at interfaces: evidence of interference effects,” Opt. Express 15(16), 10408–10420 (2007).
[CrossRef] [PubMed]

T. Hellerer, C. Axäng, C. Brackmann, P. Hillertz, M. Pilon, and A. Enejder, “Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(37), 14658–14663 (2007).
[CrossRef] [PubMed]

J. Grimm, M. F. Kircher, and R. Weissleder, “Cell tracking,” Radiologe 47(1), 25–33 (2007).
[CrossRef] [PubMed]

T. D. Henning, O. Saborowski, D. Golovko, S. Boddington, J. S. Bauer, Y. J. Fu, R. Meier, H. Pietsch, B. Sennino, D. M. McDonald, and H. E. Daldrup-Link, “Cell labeling with the positive MR contrast agent Gadofluorine M,” Eur. Radiol. 17(5), 1226–1234 (2007).
[CrossRef] [PubMed]

M. Srinivas, P. A. Morel, L. A. Ernst, D. H. Laidlaw, and E. T. Ahrens, “Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model,” Magn. Reson. Med. 58(4), 725–734 (2007).
[CrossRef] [PubMed]

2006 (3)

A. Dhawan, R. R. Mitry, and R. D. Hughes, “Hepatocyte transplantation for liver-based metabolic disorders,” J. Inherit. Metab. Dis. 29(2-3), 431–435 (2006).
[CrossRef] [PubMed]

R. A. Fisher and S. C. Strom, “Human hepatocyte transplantation: worldwide results,” Transplantation 82(4), 441–449 (2006).
[CrossRef] [PubMed]

E. M. Shapiro, K. Sharer, S. Skrtic, and A. P. Koretsky, “In vivo detection of single cells by MRI,” Magn. Reson. Med. 55(2), 242–249 (2006).
[CrossRef] [PubMed]

2005 (4)

Y. Kawashita, C. Guha, K. Yamanouchi, Y. Ito, Y. Kamohara, and T. Kanematsu, “Liver repopulation: a new concept of hepatocyte transplantation,” Surg. Today 35(9), 705–710 (2005).
[CrossRef] [PubMed]

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

J. Pinkernelle, U. Teichgräber, F. Neumann, L. Lehmkuhl, J. Ricke, R. Scholz, A. Jordan, and H. Bruhn, “Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0 T,” Magn. Reson. Med. 53(5), 1187–1192 (2005).
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E. M. Shapiro, S. Skrtic, and A. P. Koretsky, “Sizing it up: cellular MRI using micron-sized iron oxide particles,” Magn. Reson. Med. 53(2), 329–338 (2005).
[CrossRef] [PubMed]

2004 (6)

N. Himes, J. Y. Min, R. Lee, C. Brown, J. Shea, X. L. Huang, Y. F. Xiao, J. P. Morgan, D. Burstein, and P. Oettgen, “In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction,” Magn. Reson. Med. 52(5), 1214–1219 (2004).
[CrossRef] [PubMed]

S. G. Crich, L. Biancone, V. Cantaluppi, D. Duò, G. Esposito, S. Russo, G. Camussi, and S. Aime, “Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent,” Magn. Reson. Med. 51(5), 938–944 (2004).
[CrossRef] [PubMed]

H. E. Daldrup-Link, M. Rudelius, S. Metz, G. Piontek, B. Pichler, M. Settles, U. Heinzmann, J. Schlegel, R. A. J. Oostendorp, and E. J. Rummeny, “Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy,” Eur. J. Nucl. Med. Mol. Imaging 31(9), 1312–1321 (2004).
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E. M. Shapiro, S. Skrtic, K. Sharer, J. M. Hill, C. E. Dunbar, and A. P. Koretsky, “MRI detection of single particles for cellular imaging,” Proc. Natl. Acad. Sci. U.S.A. 101(30), 10901–10906 (2004).
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J. X. Cheng and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: Instrumentation, theory, and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[CrossRef]

Y. Zheng, G. Holtom, and S. D. Colson, “Multichannel multiphoton imaging of metal oxides nanoparticles in biological system,” Proc. SPIE 5323, 390–399 (2004).
[CrossRef]

2003 (2)

X. L. Nan, J. X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003).
[CrossRef] [PubMed]

K. A. Hinds, J. M. Hill, E. M. Shapiro, M. O. Laukkanen, A. C. Silva, C. A. Combs, T. R. Varney, R. S. Balaban, A. P. Koretsky, and C. E. Dunbar, “Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells,” Blood 102(3), 867–872 (2003).
[CrossRef] [PubMed]

2002 (2)

2000 (1)

N. I. Bohnen, M. Charron, J. Reyes, W. Rubinstein, S. C. Strom, D. Swanson, and R. Towbin, “Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion,” Clin. Nucl. Med. 25(6), 447–450 (2000).
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1999 (1)

S. J. Dodd, M. Williams, J. P. Suhan, D. S. Williams, A. P. Koretsky, and C. Ho, “Detection of single mammalian cells by high-resolution magnetic resonance imaging,” Biophys. J. 76(1), 103–109 (1999).
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1996 (1)

T. Hashimoto, T. Yamada, and T. Yoko, “Third-order nonlinear optical properties of sol-gel derived alpha-Fe2O3, gamma-Fe2O3, and Fe3O4 thin films,” J. Appl. Phys. 80(6), 3184–3190 (1996).
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P. F. Renshaw, C. S. Owen, A. E. Evans, and J. S. Leigh., “Immunospecific NMR contrast agents,” Magn. Reson. Imaging 4(4), 351–357 (1986).
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1985 (2)

Adema, G. J.

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
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Adonopoulou, M. K.

N. Raschzok, M. H. Morgul, J. Pinkernelle, F. W. R. Vondran, N. Billecke, N. N. Kammer, G. Pless, M. K. Adonopoulou, C. Leist, L. Stelter, U. Teichgraber, R. Schwartlander, and I. M. Sauer, “Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography,” J. Cell. Mol. Med. 12(4), 1384–1394 (2008).
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Ahrens, E. T.

M. Srinivas, P. A. Morel, L. A. Ernst, D. H. Laidlaw, and E. T. Ahrens, “Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model,” Magn. Reson. Med. 58(4), 725–734 (2007).
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Aime, S.

S. G. Crich, L. Biancone, V. Cantaluppi, D. Duò, G. Esposito, S. Russo, G. Camussi, and S. Aime, “Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent,” Magn. Reson. Med. 51(5), 938–944 (2004).
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Annett, G.

T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
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Arbab, A. S.

A. S. Arbab and J. A. Frank, “Cellular MRI and its role in stem cell therapy,” Regen. Med. 3(2), 199–215 (2008).
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Axäng, C.

T. Hellerer, C. Axäng, C. Brackmann, P. Hillertz, M. Pilon, and A. Enejder, “Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(37), 14658–14663 (2007).
[CrossRef] [PubMed]

Balaban, R. S.

K. A. Hinds, J. M. Hill, E. M. Shapiro, M. O. Laukkanen, A. C. Silva, C. A. Combs, T. R. Varney, R. S. Balaban, A. P. Koretsky, and C. E. Dunbar, “Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells,” Blood 102(3), 867–872 (2003).
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Barentsz, J. O.

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
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Bauer, B.

G. Rago, B. Bauer, F. Svedberg, L. Gunnarsson, M. B. Ericson, M. Bonn, and A. Enejder, “Uptake of gold nanoparticles in healthy and tumor cells visualized by nonlinear optical microscopy,” J. Phys. Chem. B 115(17), 5008–5016 (2011).
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Bauer, G.

T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
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Bauer, J. S.

T. D. Henning, O. Saborowski, D. Golovko, S. Boddington, J. S. Bauer, Y. J. Fu, R. Meier, H. Pietsch, B. Sennino, D. M. McDonald, and H. E. Daldrup-Link, “Cell labeling with the positive MR contrast agent Gadofluorine M,” Eur. Radiol. 17(5), 1226–1234 (2007).
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Becker, H.

S. Koenig, P. Krause, A. S. A. Hosseini, C. Dullin, M. Rave-Fraenk, S. Kimmina, A. L. Entwistle, R. M. Hermann, C. F. Hess, H. Becker, and H. Christiansen, “Noninvasive imaging of liver repopulation following hepatocyte transplantation,” Cell Transplant. 18(1), 69–78 (2009).
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Bertram, H.

J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
[CrossRef] [PubMed]

Biancone, L.

S. G. Crich, L. Biancone, V. Cantaluppi, D. Duò, G. Esposito, S. Russo, G. Camussi, and S. Aime, “Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent,” Magn. Reson. Med. 51(5), 938–944 (2004).
[CrossRef] [PubMed]

Billard, F.

Billecke, N.

N. Raschzok, M. H. Morgul, J. Pinkernelle, F. W. R. Vondran, N. Billecke, N. N. Kammer, G. Pless, M. K. Adonopoulou, C. Leist, L. Stelter, U. Teichgraber, R. Schwartlander, and I. M. Sauer, “Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography,” J. Cell. Mol. Med. 12(4), 1384–1394 (2008).
[CrossRef] [PubMed]

Boddington, S.

T. D. Henning, O. Saborowski, D. Golovko, S. Boddington, J. S. Bauer, Y. J. Fu, R. Meier, H. Pietsch, B. Sennino, D. M. McDonald, and H. E. Daldrup-Link, “Cell labeling with the positive MR contrast agent Gadofluorine M,” Eur. Radiol. 17(5), 1226–1234 (2007).
[CrossRef] [PubMed]

Boerman, O. C.

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

Boezeman, J. B.

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

Bohnen, N. I.

N. I. Bohnen, M. Charron, J. Reyes, W. Rubinstein, S. C. Strom, D. Swanson, and R. Towbin, “Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion,” Clin. Nucl. Med. 25(6), 447–450 (2000).
[CrossRef] [PubMed]

Bonenkamp, J. J.

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

Bonn, M.

J. P. R. Day, K. F. Domke, G. Rago, H. Kano, H. O. Hamaguchi, E. M. Vartiainen, and M. Bonn, “Quantitative Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 115(24), 7713–7725 (2011).
[CrossRef] [PubMed]

G. Rago, B. Bauer, F. Svedberg, L. Gunnarsson, M. B. Ericson, M. Bonn, and A. Enejder, “Uptake of gold nanoparticles in healthy and tumor cells visualized by nonlinear optical microscopy,” J. Phys. Chem. B 115(17), 5008–5016 (2011).
[CrossRef] [PubMed]

M. Okuno, H. Kano, P. Leproux, V. Couderc, J. P. R. Day, M. Bonn, and H. O. Hamaguchi, “Quantitative CARS molecular fingerprinting of single living cells with the use of the maximum entropy method,” Angew. Chem. Int. Ed. Engl. 49(38), 6773–6777 (2010).
[CrossRef] [PubMed]

J. P. R. Day, G. Rago, K. F. Domke, K. P. Velikov, and M. Bonn, “Label-free imaging of lipophilic bioactive molecules during lipid digestion by multiplex coherent anti-Stokes Raman scattering microspectroscopy,” J. Am. Chem. Soc. 132(24), 8433–8439 (2010).
[CrossRef] [PubMed]

Brackmann, C.

A. Enejder, C. Brackmann, and F. Svedberg, “Coherent Anti-Stokes Raman Scattering Microscopy of Cellular Lipid Storage,” IEEE J. Sel. Top. Quantum Electron. 16(3), 506–515 (2010).
[CrossRef]

T. Hellerer, C. Axäng, C. Brackmann, P. Hillertz, M. Pilon, and A. Enejder, “Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(37), 14658–14663 (2007).
[CrossRef] [PubMed]

Brown, C.

N. Himes, J. Y. Min, R. Lee, C. Brown, J. Shea, X. L. Huang, Y. F. Xiao, J. P. Morgan, D. Burstein, and P. Oettgen, “In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction,” Magn. Reson. Med. 52(5), 1214–1219 (2004).
[CrossRef] [PubMed]

Bruhn, H.

J. Pinkernelle, U. Teichgräber, F. Neumann, L. Lehmkuhl, J. Ricke, R. Scholz, A. Jordan, and H. Bruhn, “Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0 T,” Magn. Reson. Med. 53(5), 1187–1192 (2005).
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Bulte, J. W. M.

J. W. M. Bulte, “In vivo MRI cell tracking: clinical studies,” AJR Am. J. Roentgenol. 193(2), 314–325 (2009).
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I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

Burlina, A.

J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
[CrossRef] [PubMed]

Burris, J.

Burstein, D.

N. Himes, J. Y. Min, R. Lee, C. Brown, J. Shea, X. L. Huang, Y. F. Xiao, J. P. Morgan, D. Burstein, and P. Oettgen, “In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction,” Magn. Reson. Med. 52(5), 1214–1219 (2004).
[CrossRef] [PubMed]

Camussi, G.

S. G. Crich, L. Biancone, V. Cantaluppi, D. Duò, G. Esposito, S. Russo, G. Camussi, and S. Aime, “Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent,” Magn. Reson. Med. 51(5), 938–944 (2004).
[CrossRef] [PubMed]

Cantaluppi, V.

S. G. Crich, L. Biancone, V. Cantaluppi, D. Duò, G. Esposito, S. Russo, G. Camussi, and S. Aime, “Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent,” Magn. Reson. Med. 51(5), 938–944 (2004).
[CrossRef] [PubMed]

Charron, M.

N. I. Bohnen, M. Charron, J. Reyes, W. Rubinstein, S. C. Strom, D. Swanson, and R. Towbin, “Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion,” Clin. Nucl. Med. 25(6), 447–450 (2000).
[CrossRef] [PubMed]

Cheng, J. X.

J. X. Cheng and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: Instrumentation, theory, and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[CrossRef]

X. L. Nan, J. X. Cheng, and X. S. Xie, “Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy,” J. Lipid Res. 44(11), 2202–2208 (2003).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, and X. S. Xie, “Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy,” J. Opt. Soc. Am. B 19(6), 1363–1375 (2002).
[CrossRef]

Christiansen, H.

S. Koenig, P. Krause, A. S. A. Hosseini, C. Dullin, M. Rave-Fraenk, S. Kimmina, A. L. Entwistle, R. M. Hermann, C. F. Hess, H. Becker, and H. Christiansen, “Noninvasive imaging of liver repopulation following hepatocyte transplantation,” Cell Transplant. 18(1), 69–78 (2009).
[CrossRef] [PubMed]

Colson, S. D.

Y. Zheng, G. Holtom, and S. D. Colson, “Multichannel multiphoton imaging of metal oxides nanoparticles in biological system,” Proc. SPIE 5323, 390–399 (2004).
[CrossRef]

Combs, C. A.

K. A. Hinds, J. M. Hill, E. M. Shapiro, M. O. Laukkanen, A. C. Silva, C. A. Combs, T. R. Varney, R. S. Balaban, A. P. Koretsky, and C. E. Dunbar, “Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells,” Blood 102(3), 867–872 (2003).
[CrossRef] [PubMed]

Couderc, V.

M. Okuno, H. Kano, P. Leproux, V. Couderc, J. P. R. Day, M. Bonn, and H. O. Hamaguchi, “Quantitative CARS molecular fingerprinting of single living cells with the use of the maximum entropy method,” Angew. Chem. Int. Ed. Engl. 49(38), 6773–6777 (2010).
[CrossRef] [PubMed]

Cowell, S. F.

J. Lodhia, G. Mandarano, Nj. Ferris, P. Eu, and S. F. Cowell, “Development and use of iron oxide nanoparticles (Part 1): Synthesis of iron oxide nanoparticles for MRI,” Biomed Imaging Intervent. J. 6(2), e12 (2010).
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Crich, S. G.

S. G. Crich, L. Biancone, V. Cantaluppi, D. Duò, G. Esposito, S. Russo, G. Camussi, and S. Aime, “Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent,” Magn. Reson. Med. 51(5), 938–944 (2004).
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Dai, L. M.

A. M. Schrand, J. J. Schlager, L. M. Dai, and S. M. Hussain, “Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy,” Nat. Protoc. 5(4), 744–757 (2010).
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Daldrup-Link, H. E.

T. D. Henning, O. Saborowski, D. Golovko, S. Boddington, J. S. Bauer, Y. J. Fu, R. Meier, H. Pietsch, B. Sennino, D. M. McDonald, and H. E. Daldrup-Link, “Cell labeling with the positive MR contrast agent Gadofluorine M,” Eur. Radiol. 17(5), 1226–1234 (2007).
[CrossRef] [PubMed]

H. E. Daldrup-Link, M. Rudelius, S. Metz, G. Piontek, B. Pichler, M. Settles, U. Heinzmann, J. Schlegel, R. A. J. Oostendorp, and E. J. Rummeny, “Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy,” Eur. J. Nucl. Med. Mol. Imaging 31(9), 1312–1321 (2004).
[CrossRef] [PubMed]

Das, A. M.

J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
[CrossRef] [PubMed]

Day, J. P. R.

J. P. R. Day, K. F. Domke, G. Rago, H. Kano, H. O. Hamaguchi, E. M. Vartiainen, and M. Bonn, “Quantitative Coherent Anti-Stokes Raman Scattering (CARS) Microscopy,” J. Phys. Chem. B 115(24), 7713–7725 (2011).
[CrossRef] [PubMed]

M. Okuno, H. Kano, P. Leproux, V. Couderc, J. P. R. Day, M. Bonn, and H. O. Hamaguchi, “Quantitative CARS molecular fingerprinting of single living cells with the use of the maximum entropy method,” Angew. Chem. Int. Ed. Engl. 49(38), 6773–6777 (2010).
[CrossRef] [PubMed]

J. P. R. Day, G. Rago, K. F. Domke, K. P. Velikov, and M. Bonn, “Label-free imaging of lipophilic bioactive molecules during lipid digestion by multiplex coherent anti-Stokes Raman scattering microspectroscopy,” J. Am. Chem. Soc. 132(24), 8433–8439 (2010).
[CrossRef] [PubMed]

de Vries, I. J. M.

I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

Devereaux, S.

A. Quaglia, S. C. Lehec, R. D. Hughes, R. R. Mitry, A. S. Knisely, S. Devereaux, J. Richards, M. Rela, N. D. Heaton, B. C. Portmann, and A. Dhawan, “Liver after hepatocyte transplantation for liver-based metabolic disorders in children,” Cell Transplant. 17(12), 1403–1414 (2008).
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Dhawan, A.

A. Dhawan, J. Puppi, R. D. Hughes, and R. R. Mitry, “Human hepatocyte transplantation: current experience and future challenges,” Natl. Rev. 7(5), 288–298 (2010).
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E. Fitzpatrick, R. R. Mitry, and A. Dhawan, “Human hepatocyte transplantation: state of the art,” J. Intern. Med. 266(4), 339–357 (2009).
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A. Quaglia, S. C. Lehec, R. D. Hughes, R. R. Mitry, A. S. Knisely, S. Devereaux, J. Richards, M. Rela, N. D. Heaton, B. C. Portmann, and A. Dhawan, “Liver after hepatocyte transplantation for liver-based metabolic disorders in children,” Cell Transplant. 17(12), 1403–1414 (2008).
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A. Dhawan, R. R. Mitry, and R. D. Hughes, “Hepatocyte transplantation for liver-based metabolic disorders,” J. Inherit. Metab. Dis. 29(2-3), 431–435 (2006).
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Dodd, S. J.

S. J. Dodd, M. Williams, J. P. Suhan, D. S. Williams, A. P. Koretsky, and C. Ho, “Detection of single mammalian cells by high-resolution magnetic resonance imaging,” Biophys. J. 76(1), 103–109 (1999).
[CrossRef] [PubMed]

Domke, K. F.

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M. Srinivas, P. A. Morel, L. A. Ernst, D. H. Laidlaw, and E. T. Ahrens, “Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model,” Magn. Reson. Med. 58(4), 725–734 (2007).
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J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
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T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
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[PubMed]

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M. Srinivas, P. A. Morel, L. A. Ernst, D. H. Laidlaw, and E. T. Ahrens, “Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model,” Magn. Reson. Med. 58(4), 725–734 (2007).
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N. Himes, J. Y. Min, R. Lee, C. Brown, J. Shea, X. L. Huang, Y. F. Xiao, J. P. Morgan, D. Burstein, and P. Oettgen, “In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction,” Magn. Reson. Med. 52(5), 1214–1219 (2004).
[CrossRef] [PubMed]

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M. H. Morgul, N. Raschzok, R. Schwartlander, F. W. Vondran, R. Michel, L. Stelter, J. Pinkernelle, A. Jordan, U. Teichgraber, and I. M. Sauer, “Tracking of primary human hepatocytes with clinical MRI: initial results with Tat-peptide modified superparamagnetic iron oxide particles,” Int. J. Artif. Organs 31(3), 252–257 (2008).
[PubMed]

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J. Pinkernelle, U. Teichgräber, F. Neumann, L. Lehmkuhl, J. Ricke, R. Scholz, A. Jordan, and H. Bruhn, “Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0 T,” Magn. Reson. Med. 53(5), 1187–1192 (2005).
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Y. Wang, C.-Y. Lin, A. Nikolaenko, V. Raghunathan, and E. O. Potma, “Four-wave mixing microscopy of nanostructures,” Adv. Opt. Photonics 3(1), 1–52 (2011).
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T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
[CrossRef] [PubMed]

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N. Himes, J. Y. Min, R. Lee, C. Brown, J. Shea, X. L. Huang, Y. F. Xiao, J. P. Morgan, D. Burstein, and P. Oettgen, “In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction,” Magn. Reson. Med. 52(5), 1214–1219 (2004).
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M. Okuno, H. Kano, P. Leproux, V. Couderc, J. P. R. Day, M. Bonn, and H. O. Hamaguchi, “Quantitative CARS molecular fingerprinting of single living cells with the use of the maximum entropy method,” Angew. Chem. Int. Ed. Engl. 49(38), 6773–6777 (2010).
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T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
[CrossRef] [PubMed]

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H. E. Daldrup-Link, M. Rudelius, S. Metz, G. Piontek, B. Pichler, M. Settles, U. Heinzmann, J. Schlegel, R. A. J. Oostendorp, and E. J. Rummeny, “Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy,” Eur. J. Nucl. Med. Mol. Imaging 31(9), 1312–1321 (2004).
[CrossRef] [PubMed]

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J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
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P. F. Renshaw, C. S. Owen, A. E. Evans, and J. S. Leigh., “Immunospecific NMR contrast agents,” Magn. Reson. Imaging 4(4), 351–357 (1986).
[CrossRef] [PubMed]

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I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz, P. Verdijk, J. H. van Krieken, O. C. Boerman, W. J. G. Oyen, J. J. Bonenkamp, J. B. Boezeman, G. J. Adema, J. W. M. Bulte, T. W. J. Scheenen, C. J. A. Punt, A. Heerschap, and C. G. Figdor, “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nat. Biotechnol. 23(11), 1407–1413 (2005).
[CrossRef] [PubMed]

Pantazopoulos, P.

Z. Medarova, P. Vallabhajosyula, A. Tena, N. Evgenov, P. Pantazopoulos, V. Tchipashvili, G. Weir, D. Sachs, and A. Moore, “In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates,” Transplantation 87(11), 1659–1666 (2009).
[CrossRef] [PubMed]

Pettenazzo, A.

J. Meyburg, A. M. Das, F. Hoerster, M. Lindner, H. Kriegbaum, G. Engelmann, J. Schmidt, M. Ott, A. Pettenazzo, T. Luecke, H. Bertram, G. F. Hoffmann, and A. Burlina, “One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects,” Transplantation 87(5), 636–641 (2009).
[CrossRef] [PubMed]

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H. E. Daldrup-Link, M. Rudelius, S. Metz, G. Piontek, B. Pichler, M. Settles, U. Heinzmann, J. Schlegel, R. A. J. Oostendorp, and E. J. Rummeny, “Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy,” Eur. J. Nucl. Med. Mol. Imaging 31(9), 1312–1321 (2004).
[CrossRef] [PubMed]

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T. D. Henning, O. Saborowski, D. Golovko, S. Boddington, J. S. Bauer, Y. J. Fu, R. Meier, H. Pietsch, B. Sennino, D. M. McDonald, and H. E. Daldrup-Link, “Cell labeling with the positive MR contrast agent Gadofluorine M,” Eur. Radiol. 17(5), 1226–1234 (2007).
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T. Hellerer, C. Axäng, C. Brackmann, P. Hillertz, M. Pilon, and A. Enejder, “Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad. Sci. U.S.A. 104(37), 14658–14663 (2007).
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N. Raschzok, M. H. Morgul, J. Pinkernelle, F. W. R. Vondran, N. Billecke, N. N. Kammer, G. Pless, M. K. Adonopoulou, C. Leist, L. Stelter, U. Teichgraber, R. Schwartlander, and I. M. Sauer, “Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography,” J. Cell. Mol. Med. 12(4), 1384–1394 (2008).
[CrossRef] [PubMed]

M. H. Morgul, N. Raschzok, R. Schwartlander, F. W. Vondran, R. Michel, L. Stelter, J. Pinkernelle, A. Jordan, U. Teichgraber, and I. M. Sauer, “Tracking of primary human hepatocytes with clinical MRI: initial results with Tat-peptide modified superparamagnetic iron oxide particles,” Int. J. Artif. Organs 31(3), 252–257 (2008).
[PubMed]

J. Pinkernelle, U. Teichgräber, F. Neumann, L. Lehmkuhl, J. Ricke, R. Scholz, A. Jordan, and H. Bruhn, “Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0 T,” Magn. Reson. Med. 53(5), 1187–1192 (2005).
[CrossRef] [PubMed]

Piontek, G.

H. E. Daldrup-Link, M. Rudelius, S. Metz, G. Piontek, B. Pichler, M. Settles, U. Heinzmann, J. Schlegel, R. A. J. Oostendorp, and E. J. Rummeny, “Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy,” Eur. J. Nucl. Med. Mol. Imaging 31(9), 1312–1321 (2004).
[CrossRef] [PubMed]

Piwnica-Worms, D.

W. M. Leevy, S. T. Gammon, J. R. Johnson, A. J. Lampkins, H. Jiang, M. Marquez, D. Piwnica-Worms, M. A. Suckow, and B. D. Smith, “Noninvasive optical imaging of staphylococcus aureus bacterial infection in living mice using a Bis-dipicolylamine-Zinc(II) affinity group conjugated to a near-infrared fluorophore,” Bioconjug. Chem. 19(3), 686–692 (2008).
[CrossRef] [PubMed]

Pless, G.

N. Raschzok, M. H. Morgul, J. Pinkernelle, F. W. R. Vondran, N. Billecke, N. N. Kammer, G. Pless, M. K. Adonopoulou, C. Leist, L. Stelter, U. Teichgraber, R. Schwartlander, and I. M. Sauer, “Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography,” J. Cell. Mol. Med. 12(4), 1384–1394 (2008).
[CrossRef] [PubMed]

Pontow, S.

T. Meyerrose, S. Olson, S. Pontow, S. Kalomoiris, Y. Jung, G. Annett, G. Bauer, and J. A. Nolta, “Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors,” Adv. Drug Deliv. Rev. 62(12), 1167–1174 (2010).
[CrossRef] [PubMed]

Portmann, B. C.

A. Quaglia, S. C. Lehec, R. D. Hughes, R. R. Mitry, A. S. Knisely, S. Devereaux, J. Richards, M. Rela, N. D. Heaton, B. C. Portmann, and A. Dhawan, “Liver after hepatocyte transplantation for liver-based metabolic disorders in children,” Cell Transplant. 17(12), 1403–1414 (2008).
[CrossRef] [PubMed]

Potma, E. O.

Y. Wang, C.-Y. Lin, A. Nikolaenko, V. Raghunathan, and E. O. Potma, “Four-wave mixing microscopy of nanostructures,” Adv. Opt. Photonics 3(1), 1–52 (2011).
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E. M. Shapiro, S. Skrtic, and A. P. Koretsky, “Sizing it up: cellular MRI using micron-sized iron oxide particles,” Magn. Reson. Med. 53(2), 329–338 (2005).
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Opt. Express (2)

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Proc. Natl. Acad. Sci. U.S.A. (2)

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Proc. SPIE (1)

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Y. Kawashita, C. Guha, K. Yamanouchi, Y. Ito, Y. Kamohara, and T. Kanematsu, “Liver repopulation: a new concept of hepatocyte transplantation,” Surg. Today 35(9), 705–710 (2005).
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J. Puppi and M. Modo, “Use of magnetic resonance imaging contrast agents to detect transplanted liver cells,” Top. Magn. Reson. Imaging 20(2), 113–120 (2009).
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Z. Medarova, P. Vallabhajosyula, A. Tena, N. Evgenov, P. Pantazopoulos, V. Tchipashvili, G. Weir, D. Sachs, and A. Moore, “In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates,” Transplantation 87(11), 1659–1666 (2009).
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Figures (5)

Fig. 1
Fig. 1

Energy schemes of the nonresonant (a and b) and resonant CARS (c) process. (d) Normalized CARS spectrum of tripalmitin; the arrows at 2845 cm−1 and 3000 cm−1 indicate the typical response of biological matter at the frequencies used for on- and off-resonance CARS measurements.

Fig. 2
Fig. 2

Brightfield microscopy (a), on-resonance (b) and off-resonance (c) CARS images of a 10 × 30 μm2 –sized region of dried solution of MPIOs. Scale bar 5 μm. The normalized intensity of the signal measured from MPIOs on- and off resonance is identical within the variations that result from frequency tuning.

Fig. 3
Fig. 3

(a) Brightfield microscopy, (b) on-resonance CARS and(c) off-resonance CARS images of a HuH7 cell in absence of MPIOs labels. Grayscale values vary from 3 to 60 in (b) and from 6 to 20 in (c)

Fig. 4
Fig. 4

(a) On-resonance and (b) off-resonance CARS images of a HuH7 cell incubated with MPIO solution. (c) is the overlay of the on- and off-resonance images where the former appears in red, and the background corrected off-resonance response appears in green. Grayscale values vary from 3 to 40 in (a) and from 3 to 25 in (b). The overlay image obtained from on and off-resonance measurements allows identification of a single iron oxide particle in the lower part of the cell (green spot).

Fig. 5
Fig. 5

(a) Brightfield microscopy image of a HuH7 cell incubated with MPIOs. (b-f) Overlay of on-resonance (red) and off-resonance (green) CARS images of the same cell with descending axial position (separated by 1 μm). Two internalized iron oxide particles (green) can be identified from the overlay images.

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

I C A R S ( ω A S ) | P ( 3 ) ( ω A S ) | 2 = | E 1 | 4 | E 2 | 2 | χ ( 3 ) ( ω A S ) | 2
χ ( 3 ) ( ω A S ) = χ R ( 3 ) ( ω A S ) + χ N R ( 3 )
χ R ( 3 ) ( ω A S ) = j A j Ω j ( ω 1 ω 2 ) i Γ j

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