Abstract

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue.

© 2015 Optical Society of America

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2015 (1)

2014 (2)

2013 (3)

2012 (10)

L. Scolaro, D. Lorenser, R. A. McLaughlin, B. C. Quirk, R. W. Kirk, and D. D. Sampson, “High-sensitivity anastigmatic imaging needle for optical coherence tomography,” Opt. Lett. 37(24), 5247–5249 (2012).
[Crossref] [PubMed]

K. M. Tan, M. Shishkov, A. Chee, M. B. Applegate, B. E. Bouma, and M. J. Suter, “Flexible transbronchial optical frequency domain imaging smart needle for biopsy guidance,” Biomed. Opt. Express 3(8), 1947–1954 (2012).
[Crossref] [PubMed]

R. A. McLaughlin, B. C. Quirk, A. Curatolo, R. W. Kirk, L. Scolaro, D. Lorenser, P. D. Robbins, B. A. Wood, C. M. Saunders, and D. D. Sampson, “Imaging of breast cancer with optical coherence tomography needle probes: Feasibility and initial results,” IEEE J. Sel. Top. Quantum Electron. 18(3), 1184–1191 (2012).
[Crossref]

R. A. McLaughlin, X. Yang, B. C. Quirk, D. Lorenser, R. W. Kirk, P. B. Noble, and D. D. Sampson, “Static and dynamic imaging of alveoli using optical coherence tomography needle probes,” J. Appl. Physiol. 113(6), 967–974 (2012).
[Crossref] [PubMed]

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
[Crossref] [PubMed]

A. Hellebust and R. Richards-Kortum, “Advances in molecular imaging: Targeted optical contrast agents for cancer diagnostics,” Nanomedicine (Lond) 7(3), 429–445 (2012).
[Crossref] [PubMed]

J. Mavadia, J. Xi, Y. Chen, and X. Li, “An all-fiber-optic endoscopy platform for simultaneous OCT and fluorescence imaging,” Biomed. Opt. Express 3(11), 2851–2859 (2012).
[Crossref] [PubMed]

J. Xi, Y. Chen, Y. Zhang, K. Murari, M. J. Li, and X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
[Crossref] [PubMed]

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
[Crossref] [PubMed]

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

2011 (6)

R. S. Pillai, D. Lorenser, and D. D. Sampson, “Deep-tissue access with confocal fluorescence microendoscopy through hypodermic needles,” Opt. Express 19(8), 7213–7221 (2011).
[Crossref] [PubMed]

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
[Crossref] [PubMed]

H. Kobayashi and P. L. Choyke, “Target-cancer-cell-specific activatable fluorescence imaging probes: Rational design and in vivo applications,” Acc. Chem. Res. 44(2), 83–90 (2011).
[Crossref] [PubMed]

M. Haase and H. Schäfer, “Upconverting nanoparticles,” Angew. Chem. Int. Ed. Engl. 50(26), 5808–5829 (2011).
[Crossref] [PubMed]

D. Lorenser, X. Yang, R. W. Kirk, B. C. Quirk, R. A. McLaughlin, and D. D. Sampson, “Ultrathin side-viewing needle probe for optical coherence tomography,” Opt. Lett. 36(19), 3894–3896 (2011).
[Crossref] [PubMed]

B. C. Quirk, R. A. McLaughlin, A. Curatolo, R. W. Kirk, P. B. Noble, and D. D. Sampson, “In situ imaging of lung alveoli with an optical coherence tomography needle probe,” J. Biomed. Opt. 16(3), 036009 (2011).
[Crossref] [PubMed]

2010 (8)

Y. C. Wu, J. F. Xi, L. Huo, J. Padvorac, E. J. Shin, S. A. Giday, A. M. Lennon, M. I. F. Canto, J. H. Hwang, and X. D. Li, “Robust high-resolution fine OCT needle for side-viewing interstitial tissue imaging,” IEEE J. Sel. Top. Quantum Electron. 16(4), 863–869 (2010).
[Crossref]

E. A. te Velde, T. Veerman, V. Subramaniam, and T. Ruers, “The use of fluorescent dyes and probes in surgical oncology,” Eur. J. Surg. Oncol. 36(1), 6–15 (2010).
[Crossref] [PubMed]

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B-Biol. 98(1), 77–94 (2010).

R. P. Baum, V. Prasad, D. Müller, C. Schuchardt, A. Orlova, A. Wennborg, V. Tolmachev, and J. Feldwisch, “Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules,” J. Nucl. Med. 51(6), 892–897 (2010).
[Crossref] [PubMed]

A. Nordberg, J. O. Rinne, A. Kadir, and B. Långström, “The use of PET in Alzheimer disease,” Nat. Rev. Neurol. 6(2), 78–87 (2010).
[Crossref] [PubMed]

S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
[Crossref] [PubMed]

S. Lemire-Renaud, M. Rivard, M. Strupler, D. Morneau, F. Verpillat, X. Daxhelet, N. Godbout, and C. Boudoux, “Double-clad fiber coupler for endoscopy,” Opt. Express 18(10), 9755–9764 (2010).
[Crossref] [PubMed]

C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, and E. J. Seibel, “Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging,” J. Biophotonics 3(5-6), 385–407 (2010).
[Crossref] [PubMed]

2009 (1)

R. Nandhagopal, L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, C. S. Lee, J. McKenzie, S. McCormick, A. Samii, A. Troiano, T. J. Ruth, V. Sossi, R. de la Fuente-Fernandez, D. B. Calne, and A. J. Stoessl, “Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study,” Brain 132(11), 2970–2979 (2009).
[Crossref] [PubMed]

2008 (4)

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
[Crossref] [PubMed]

C. J. Engelbrecht, R. S. Johnston, E. J. Seibel, and F. Helmchen, “Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo,” Opt. Express 16(8), 5556–5564 (2008).
[Crossref] [PubMed]

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[PubMed]

S. Y. Ryu, H. Y. Choi, J. Na, E. S. Choi, and B. H. Lee, “Combined system of optical coherence tomography and fluorescence spectroscopy based on double-cladding fiber,” Opt. Lett. 33(20), 2347–2349 (2008).
[Crossref] [PubMed]

2007 (3)

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express 15(25), 16413–16423 (2007).
[Crossref] [PubMed]

T. Barrett, Y. Koyama, Y. Hama, G. Ravizzini, I. S. Shin, B. S. Jang, C. H. Paik, Y. Urano, P. L. Choyke, and H. Kobayashi, “In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies,” Clin. Cancer Res. 13(22), 6639–6648 (2007).
[Crossref] [PubMed]

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: Recent advances,” Curr. Opin. Biotechnol. 18(1), 17–25 (2007).
[Crossref] [PubMed]

2006 (1)

W. M. Kuebler, K. Parthasarathi, J. Lindert, and J. Bhattacharya, “Real-time lung microscopy,” J. Appl. Physiol. 102(3), 1255–1264 (2006).
[Crossref] [PubMed]

2005 (1)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

2004 (3)

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

K. Shah, A. Jacobs, X. O. Breakefield, and R. Weissleder, “Molecular imaging of gene therapy for cancer,” Gene Ther. 11(15), 1175–1187 (2004).
[Crossref] [PubMed]

2003 (5)

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: New technological advances that enable in vivo molecular imaging,” Eur. Radiol. 13(1), 195–208 (2003).
[PubMed]

C. J. Daly and J. C. McGrath, “Fluorescent ligands, antibodies, and proteins for the study of receptors,” Pharmacol. Ther. 100(2), 101–118 (2003).
[Crossref] [PubMed]

T. F. Massoud and S. S. Gambhir, “Molecular imaging in living subjects: Seeing fundamental biological processes in a new light,” Genes Dev. 17(5), 545–580 (2003).
[Crossref] [PubMed]

Y. T. Pan, T. Q. Xie, C. W. Du, S. Bastacky, S. Meyers, and M. L. Zeidel, “Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography,” Opt. Lett. 28(24), 2485–2487 (2003).
[Crossref] [PubMed]

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol. 7(5), 626–634 (2003).
[Crossref] [PubMed]

2002 (1)

S. S. Gambhir, “Molecular imaging of cancer with positron emission tomography,” Nat. Rev. Cancer 2(9), 683–693 (2002).
[Crossref] [PubMed]

2000 (1)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Akopian, V.

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
[Crossref] [PubMed]

Aksay, E.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Applegate, M. B.

Auger, M.

Barrett, T.

T. Barrett, Y. Koyama, Y. Hama, G. Ravizzini, I. S. Shin, B. S. Jang, C. H. Paik, Y. Urano, P. L. Choyke, and H. Kobayashi, “In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies,” Clin. Cancer Res. 13(22), 6639–6648 (2007).
[Crossref] [PubMed]

Barretto, R. P. J.

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[PubMed]

Bastacky, S.

Baum, R. P.

R. P. Baum, V. Prasad, D. Müller, C. Schuchardt, A. Orlova, A. Wennborg, V. Tolmachev, and J. Feldwisch, “Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules,” J. Nucl. Med. 51(6), 892–897 (2010).
[Crossref] [PubMed]

Bhattacharya, J.

W. M. Kuebler, K. Parthasarathi, J. Lindert, and J. Bhattacharya, “Real-time lung microscopy,” J. Appl. Physiol. 102(3), 1255–1264 (2006).
[Crossref] [PubMed]

Boudoux, C.

Bouma, B. E.

K. M. Tan, M. Shishkov, A. Chee, M. B. Applegate, B. E. Bouma, and M. J. Suter, “Flexible transbronchial optical frequency domain imaging smart needle for biopsy guidance,” Biomed. Opt. Express 3(8), 1947–1954 (2012).
[Crossref] [PubMed]

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
[Crossref] [PubMed]

Braxton, D. R.

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
[Crossref] [PubMed]

Breakefield, X. O.

K. Shah, A. Jacobs, X. O. Breakefield, and R. Weissleder, “Molecular imaging of gene therapy for cancer,” Gene Ther. 11(15), 1175–1187 (2004).
[Crossref] [PubMed]

Bremer, C.

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: New technological advances that enable in vivo molecular imaging,” Eur. Radiol. 13(1), 195–208 (2003).
[PubMed]

Cable, A.

S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
[Crossref] [PubMed]

Cahill, L.

Calne, D. B.

R. Nandhagopal, L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, C. S. Lee, J. McKenzie, S. McCormick, A. Samii, A. Troiano, T. J. Ruth, V. Sossi, R. de la Fuente-Fernandez, D. B. Calne, and A. J. Stoessl, “Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study,” Brain 132(11), 2970–2979 (2009).
[Crossref] [PubMed]

Canto, M. I. F.

Y. C. Wu, J. F. Xi, L. Huo, J. Padvorac, E. J. Shin, S. A. Giday, A. M. Lennon, M. I. F. Canto, J. H. Hwang, and X. D. Li, “Robust high-resolution fine OCT needle for side-viewing interstitial tissue imaging,” IEEE J. Sel. Top. Quantum Electron. 16(4), 863–869 (2010).
[Crossref]

Chandrasoma, P. T.

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
[Crossref] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Chee, A.

Chen, C. W.

S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
[Crossref] [PubMed]

Chen, Y.

Cheung, E. L. M.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Choi, E. S.

Choi, H. Y.

Choi, M.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Choyke, P. L.

H. Kobayashi and P. L. Choyke, “Target-cancer-cell-specific activatable fluorescence imaging probes: Rational design and in vivo applications,” Acc. Chem. Res. 44(2), 83–90 (2011).
[Crossref] [PubMed]

T. Barrett, Y. Koyama, Y. Hama, G. Ravizzini, I. S. Shin, B. S. Jang, C. H. Paik, Y. Urano, P. L. Choyke, and H. Kobayashi, “In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies,” Clin. Cancer Res. 13(22), 6639–6648 (2007).
[Crossref] [PubMed]

Chudoba, C.

Chung, E.

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19(6), 760–771 (2013).
[Crossref]

Cocker, E. D.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Contag, C. H.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
[Crossref] [PubMed]

Cragg, J.

R. Nandhagopal, L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, C. S. Lee, J. McKenzie, S. McCormick, A. Samii, A. Troiano, T. J. Ruth, V. Sossi, R. de la Fuente-Fernandez, D. B. Calne, and A. J. Stoessl, “Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study,” Brain 132(11), 2970–2979 (2009).
[Crossref] [PubMed]

Curatolo, A.

R. A. McLaughlin, B. C. Quirk, A. Curatolo, R. W. Kirk, L. Scolaro, D. Lorenser, P. D. Robbins, B. A. Wood, C. M. Saunders, and D. D. Sampson, “Imaging of breast cancer with optical coherence tomography needle probes: Feasibility and initial results,” IEEE J. Sel. Top. Quantum Electron. 18(3), 1184–1191 (2012).
[Crossref]

B. C. Quirk, R. A. McLaughlin, A. Curatolo, R. W. Kirk, P. B. Noble, and D. D. Sampson, “In situ imaging of lung alveoli with an optical coherence tomography needle probe,” J. Biomed. Opt. 16(3), 036009 (2011).
[Crossref] [PubMed]

Daly, C. J.

C. J. Daly and J. C. McGrath, “Fluorescent ligands, antibodies, and proteins for the study of receptors,” Pharmacol. Ther. 100(2), 101–118 (2003).
[Crossref] [PubMed]

Davis, S. C.

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B-Biol. 98(1), 77–94 (2010).

Daxhelet, X.

de la Fuente-Fernandez, R.

R. Nandhagopal, L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, C. S. Lee, J. McKenzie, S. McCormick, A. Samii, A. Troiano, T. J. Ruth, V. Sossi, R. de la Fuente-Fernandez, D. B. Calne, and A. J. Stoessl, “Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study,” Brain 132(11), 2970–2979 (2009).
[Crossref] [PubMed]

De Montigny, E.

Delp, S. L.

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[PubMed]

Dombeck, D. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

Dragulescu-Andrasi, A.

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: Recent advances,” Curr. Opin. Biotechnol. 18(1), 17–25 (2007).
[Crossref] [PubMed]

Du, C. W.

Edmond, M.

Engelbrecht, C. J.

C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, and E. J. Seibel, “Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging,” J. Biophotonics 3(5-6), 385–407 (2010).
[Crossref] [PubMed]

C. J. Engelbrecht, R. S. Johnston, E. J. Seibel, and F. Helmchen, “Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo,” Opt. Express 16(8), 5556–5564 (2008).
[Crossref] [PubMed]

Feldwisch, J.

R. P. Baum, V. Prasad, D. Müller, C. Schuchardt, A. Orlova, A. Wennborg, V. Tolmachev, and J. Feldwisch, “Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules,” J. Nucl. Med. 51(6), 892–897 (2010).
[Crossref] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Flusberg, B. A.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

Frangioni, J. V.

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol. 7(5), 626–634 (2003).
[Crossref] [PubMed]

Friedland, S.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
[Crossref] [PubMed]

Fujimoto, J. G.

X. Li, C. Chudoba, T. Ko, C. Pitris, and J. G. Fujimoto, “Imaging needle for optical coherence tomography,” Opt. Lett. 25(20), 1520–1522 (2000).
[Crossref] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Gambhir, S. S.

T. F. Massoud and S. S. Gambhir, “Molecular imaging in living subjects: Seeing fundamental biological processes in a new light,” Genes Dev. 17(5), 545–580 (2003).
[Crossref] [PubMed]

S. S. Gambhir, “Molecular imaging of cancer with positron emission tomography,” Nat. Rev. Cancer 2(9), 683–693 (2002).
[Crossref] [PubMed]

Gardecki, J. A.

Giday, S. A.

Y. C. Wu, J. F. Xi, L. Huo, J. Padvorac, E. J. Shin, S. A. Giday, A. M. Lennon, M. I. F. Canto, J. H. Hwang, and X. D. Li, “Robust high-resolution fine OCT needle for side-viewing interstitial tissue imaging,” IEEE J. Sel. Top. Quantum Electron. 16(4), 863–869 (2010).
[Crossref]

Gillenwater, A.

Godbout, N.

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Griffiths, G.

S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
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Grounds, M. D.

Haase, M.

M. Haase and H. Schäfer, “Upconverting nanoparticles,” Angew. Chem. Int. Ed. Engl. 50(26), 5808–5829 (2011).
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Hama, Y.

T. Barrett, Y. Koyama, Y. Hama, G. Ravizzini, I. S. Shin, B. S. Jang, C. H. Paik, Y. Urano, P. L. Choyke, and H. Kobayashi, “In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies,” Clin. Cancer Res. 13(22), 6639–6648 (2007).
[Crossref] [PubMed]

Hamidi, E.

Hasegawa, K.

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
[Crossref] [PubMed]

Hawes, S. M.

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
[Crossref] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Hellebust, A.

A. Hellebust and R. Richards-Kortum, “Advances in molecular imaging: Targeted optical contrast agents for cancer diagnostics,” Nanomedicine (Lond) 7(3), 429–445 (2012).
[Crossref] [PubMed]

Helmchen, F.

C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, and E. J. Seibel, “Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging,” J. Biophotonics 3(5-6), 385–407 (2010).
[Crossref] [PubMed]

C. J. Engelbrecht, R. S. Johnston, E. J. Seibel, and F. Helmchen, “Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo,” Opt. Express 16(8), 5556–5564 (2008).
[Crossref] [PubMed]

Hilderbrand, S. A.

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, “Upconverting luminescent nanomaterials: Application to in vivo bioimaging,” Chem. Commun. (Camb.) (28), 4188–4190 (2009).
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Hohert, G.

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Huo, L.

Y. C. Wu, J. F. Xi, L. Huo, J. Padvorac, E. J. Shin, S. A. Giday, A. M. Lennon, M. I. F. Canto, J. H. Hwang, and X. D. Li, “Robust high-resolution fine OCT needle for side-viewing interstitial tissue imaging,” IEEE J. Sel. Top. Quantum Electron. 16(4), 863–869 (2010).
[Crossref]

Hwang, J. H.

Y. C. Wu, J. F. Xi, L. Huo, J. Padvorac, E. J. Shin, S. A. Giday, A. M. Lennon, M. I. F. Canto, J. H. Hwang, and X. D. Li, “Robust high-resolution fine OCT needle for side-viewing interstitial tissue imaging,” IEEE J. Sel. Top. Quantum Electron. 16(4), 863–869 (2010).
[Crossref]

Jacobs, A.

K. Shah, A. Jacobs, X. O. Breakefield, and R. Weissleder, “Molecular imaging of gene therapy for cancer,” Gene Ther. 11(15), 1175–1187 (2004).
[Crossref] [PubMed]

Jacques, P. V.

Jaffer, F. A.

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
[Crossref] [PubMed]

Jang, B. S.

T. Barrett, Y. Koyama, Y. Hama, G. Ravizzini, I. S. Shin, B. S. Jang, C. H. Paik, Y. Urano, P. L. Choyke, and H. Kobayashi, “In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies,” Clin. Cancer Res. 13(22), 6639–6648 (2007).
[Crossref] [PubMed]

Jiang, J.

S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
[Crossref] [PubMed]

Johnston, R. S.

Jung, J. C.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[Crossref] [PubMed]

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Jung, K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kadir, A.

A. Nordberg, J. O. Rinne, A. Kadir, and B. Långström, “The use of PET in Alzheimer disease,” Nat. Rev. Neurol. 6(2), 78–87 (2010).
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Kasischke, K. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

Kim, J. K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kim, J. W.

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
[Crossref] [PubMed]

Kim, P.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

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J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
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R. A. McLaughlin, X. Yang, B. C. Quirk, D. Lorenser, R. W. Kirk, P. B. Noble, and D. D. Sampson, “Static and dynamic imaging of alveoli using optical coherence tomography needle probes,” J. Appl. Physiol. 113(6), 967–974 (2012).
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S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
[Crossref] [PubMed]

Yun, S. H.

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19(6), 760–771 (2013).
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J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
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Zeidel, M. L.

Zhang, Y.

Acc. Chem. Res. (1)

H. Kobayashi and P. L. Choyke, “Target-cancer-cell-specific activatable fluorescence imaging probes: Rational design and in vivo applications,” Acc. Chem. Res. 44(2), 83–90 (2011).
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Angew. Chem. Int. Ed. Engl. (1)

M. Haase and H. Schäfer, “Upconverting nanoparticles,” Angew. Chem. Int. Ed. Engl. 50(26), 5808–5829 (2011).
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Biomed. Opt. Express (5)

Brain (1)

R. Nandhagopal, L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, C. S. Lee, J. McKenzie, S. McCormick, A. Samii, A. Troiano, T. J. Ruth, V. Sossi, R. de la Fuente-Fernandez, D. B. Calne, and A. J. Stoessl, “Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study,” Brain 132(11), 2970–2979 (2009).
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Clin. Cancer Res. (1)

T. Barrett, Y. Koyama, Y. Hama, G. Ravizzini, I. S. Shin, B. S. Jang, C. H. Paik, Y. Urano, P. L. Choyke, and H. Kobayashi, “In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies,” Clin. Cancer Res. 13(22), 6639–6648 (2007).
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Curr. Opin. Biotechnol. (1)

J. Rao, A. Dragulescu-Andrasi, and H. Yao, “Fluorescence imaging in vivo: Recent advances,” Curr. Opin. Biotechnol. 18(1), 17–25 (2007).
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Curr. Opin. Chem. Biol. (1)

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol. 7(5), 626–634 (2003).
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Eur. J. Surg. Oncol. (1)

E. A. te Velde, T. Veerman, V. Subramaniam, and T. Ruers, “The use of fluorescent dyes and probes in surgical oncology,” Eur. J. Surg. Oncol. 36(1), 6–15 (2010).
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Eur. Radiol. (1)

V. Ntziachristos, C. Bremer, and R. Weissleder, “Fluorescence imaging with near-infrared light: New technological advances that enable in vivo molecular imaging,” Eur. Radiol. 13(1), 195–208 (2003).
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Gene Ther. (1)

K. Shah, A. Jacobs, X. O. Breakefield, and R. Weissleder, “Molecular imaging of gene therapy for cancer,” Gene Ther. 11(15), 1175–1187 (2004).
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Genes Dev. (1)

T. F. Massoud and S. S. Gambhir, “Molecular imaging in living subjects: Seeing fundamental biological processes in a new light,” Genes Dev. 17(5), 545–580 (2003).
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IEEE J. Sel. Top. Quantum Electron. (2)

R. A. McLaughlin, B. C. Quirk, A. Curatolo, R. W. Kirk, L. Scolaro, D. Lorenser, P. D. Robbins, B. A. Wood, C. M. Saunders, and D. D. Sampson, “Imaging of breast cancer with optical coherence tomography needle probes: Feasibility and initial results,” IEEE J. Sel. Top. Quantum Electron. 18(3), 1184–1191 (2012).
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Y. C. Wu, J. F. Xi, L. Huo, J. Padvorac, E. J. Shin, S. A. Giday, A. M. Lennon, M. I. F. Canto, J. H. Hwang, and X. D. Li, “Robust high-resolution fine OCT needle for side-viewing interstitial tissue imaging,” IEEE J. Sel. Top. Quantum Electron. 16(4), 863–869 (2010).
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J. Appl. Physiol. (2)

R. A. McLaughlin, X. Yang, B. C. Quirk, D. Lorenser, R. W. Kirk, P. B. Noble, and D. D. Sampson, “Static and dynamic imaging of alveoli using optical coherence tomography needle probes,” J. Appl. Physiol. 113(6), 967–974 (2012).
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W. M. Kuebler, K. Parthasarathi, J. Lindert, and J. Bhattacharya, “Real-time lung microscopy,” J. Appl. Physiol. 102(3), 1255–1264 (2006).
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J. Biomed. Opt. (2)

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
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B. C. Quirk, R. A. McLaughlin, A. Curatolo, R. W. Kirk, P. B. Noble, and D. D. Sampson, “In situ imaging of lung alveoli with an optical coherence tomography needle probe,” J. Biomed. Opt. 16(3), 036009 (2011).
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J. Biophotonics (1)

C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, and E. J. Seibel, “Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging,” J. Biophotonics 3(5-6), 385–407 (2010).
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J. Neurophysiol. (2)

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
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M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
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J. Nucl. Med. (1)

R. P. Baum, V. Prasad, D. Müller, C. Schuchardt, A. Orlova, A. Wennborg, V. Tolmachev, and J. Feldwisch, “Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules,” J. Nucl. Med. 51(6), 892–897 (2010).
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J. Photochem. Photobiol. B-Biol. (1)

F. Leblond, S. C. Davis, P. A. Valdes, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol. B-Biol. 98(1), 77–94 (2010).

Nanomedicine (Lond) (1)

A. Hellebust and R. Richards-Kortum, “Advances in molecular imaging: Targeted optical contrast agents for cancer diagnostics,” Nanomedicine (Lond) 7(3), 429–445 (2012).
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Nat. Med. (1)

H. Yoo, J. W. Kim, M. Shishkov, E. Namati, T. Morse, R. Shubochkin, J. R. McCarthy, V. Ntziachristos, B. E. Bouma, F. A. Jaffer, and G. J. Tearney, “Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo,” Nat. Med. 17(12), 1680–1684 (2011).
[Crossref] [PubMed]

Nat. Methods (1)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
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Nat. Protoc. (1)

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
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Nat. Rev. Cancer (1)

S. S. Gambhir, “Molecular imaging of cancer with positron emission tomography,” Nat. Rev. Cancer 2(9), 683–693 (2002).
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Nat. Rev. Neurol. (1)

A. Nordberg, J. O. Rinne, A. Kadir, and B. Långström, “The use of PET in Alzheimer disease,” Nat. Rev. Neurol. 6(2), 78–87 (2010).
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Nature (2)

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452(7187), 580–589 (2008).
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M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[PubMed]

Opt. Express (4)

Opt. Fiber Technol. (1)

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19(6), 760–771 (2013).
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Opt. Lett. (8)

Y. T. Pan, T. Q. Xie, C. W. Du, S. Bastacky, S. Meyers, and M. L. Zeidel, “Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography,” Opt. Lett. 28(24), 2485–2487 (2003).
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W. J. Madore, E. De Montigny, O. Ouellette, S. Lemire-Renaud, M. Leduc, X. Daxhelet, N. Godbout, and C. Boudoux, “Asymmetric double-clad fiber couplers for endoscopy,” Opt. Lett. 38(21), 4514–4517 (2013).
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J. Xi, Y. Chen, Y. Zhang, K. Murari, M. J. Li, and X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
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D. Lorenser, B. C. Quirk, M. Auger, W. J. Madore, R. W. Kirk, N. Godbout, D. D. Sampson, C. Boudoux, and R. A. McLaughlin, “Dual-modality needle probe for combined fluorescence imaging and three-dimensional optical coherence tomography,” Opt. Lett. 38(3), 266–268 (2013).
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L. Scolaro, D. Lorenser, R. A. McLaughlin, B. C. Quirk, R. W. Kirk, and D. D. Sampson, “High-sensitivity anastigmatic imaging needle for optical coherence tomography,” Opt. Lett. 37(24), 5247–5249 (2012).
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D. Lorenser, X. Yang, R. W. Kirk, B. C. Quirk, R. A. McLaughlin, and D. D. Sampson, “Ultrathin side-viewing needle probe for optical coherence tomography,” Opt. Lett. 36(19), 3894–3896 (2011).
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S. Y. Ryu, H. Y. Choi, J. Na, E. S. Choi, and B. H. Lee, “Combined system of optical coherence tomography and fluorescence spectroscopy based on double-cladding fiber,” Opt. Lett. 33(20), 2347–2349 (2008).
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Pharmacol. Ther. (1)

C. J. Daly and J. C. McGrath, “Fluorescent ligands, antibodies, and proteins for the study of receptors,” Pharmacol. Ther. 100(2), 101–118 (2003).
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Phys. Med. Biol. (1)

S. Yuan, C. A. Roney, J. Wierwille, C. W. Chen, B. Xu, G. Griffiths, J. Jiang, H. Ma, A. Cable, R. M. Summers, and Y. Chen, “Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging,” Phys. Med. Biol. 55(1), 191–206 (2010).
[Crossref] [PubMed]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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Stem Cells (1)

L. A. Stamp, D. R. Braxton, J. Wu, V. Akopian, K. Hasegawa, P. T. Chandrasoma, S. M. Hawes, C. McLean, L. M. Petrovic, K. Wang, and M. F. Pera, “The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin,” Stem Cells 30(9), 1999–2009 (2012).
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Other (1)

S. A. Hilderbrand, F. Shao, C. Salthouse, U. Mahmood, and R. Weissleder, “Upconverting luminescent nanomaterials: Application to in vivo bioimaging,” Chem. Commun. (Camb.) (28), 4188–4190 (2009).
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Figures (10)

Fig. 1
Fig. 1 Schematic of the dual-modality OCT + fluorescence imaging system with asymmetric double-clad fiber coupler and MI needle (inset). SS, swept source; WDM, wavelength-division multiplexing coupler; SMF-28, single-mode fiber; MMF, multimode fiber; DCF, double-clad fiber; DCFC, double-clad fiber coupler; EF, long-pass emission filter; BF, blocking filter; PMT, photomultiplier tube; SIF, step-index fiber; GRIN, gradient-index fiber; NCF, no-core fiber; VOA, variable optical attenuator; BD, balanced photodetector; DAQ, data acquisition.
Fig. 2
Fig. 2 The fabricated MI needle. (a) Angle-polished all-fiber probe with cross-sectional schematics of each of the fibers used in the final design. (b) Capillary encased probe with total internal reflection (TIR) for side-viewing. (c) Final 24-gauge molecular imaging needle.
Fig. 3
Fig. 3 Schematic of the tissue-mimicking, scattering and fluorescent phantom. (a) 3D view. (b) Cross-sectional radial view showing the dimensions and positions of the three nylon monofilament lines relative to the needle hole in the center. Lines 2 and 3 are fluorescent; whereas, line 1 is non-fluorescent.
Fig. 4
Fig. 4 Side-viewing needle scanning configuration for imaging prepared liver sections using x-y raster scanning stage (water immersion not shown).
Fig. 5
Fig. 5 Output beam profiles (using FWHM beam diameters) at 1310 nm wavelength. (a) Measured output beam diameters for the fabricated side-viewing MI needle in air (squares and circles) with corresponding simulated diameters obtained from ray-matrix transformations (Solid and dashed lines). (b) Simulated beam diameters calculated from (a) for the side-viewing MI needle in water.
Fig. 6
Fig. 6 Fluorescence PSF measured using a fluorescent bead in water. (a) and (c) 2D fluorescence image (raster scanned) of a bead at 300 µm and 1050 µm from the needle, respectively. (b) and (d) Corresponding fluorescence cross-sectional profiles (blue lines) and Gaussian curve fitting (red dashed lines) along x-axis (top panel) and y-axis (bottom panel) for a bead at 300 µm and 1050 µm from the needle, respectively. (e) FWHM diameters of the fluorescence PSF in x- and y-axes as a function of depth through water, obtained from Gaussian fitting. (f) Normalized amplitude of the fluorescence PSF as a function of depth in water. (g) Log (dB) normalized amplitude of the fluorescence PSF as a function of depth in water, with line of best fit (red line) showing rate of decay of fluorescence efficiency.
Fig. 7
Fig. 7 Fluorescence sensitivity measured using fluorescein at pH 9.5. (a) Measured fluorescence signal (upper panel) with log-scaled fluorescence image (lower panel) of four glass capillary tubes filled with decreasing concentrations of fluorescein. Inset: magnified plot of signal from 10 nM and 5 nM fluorescein filled tubes (blue line) compared to the same tubes with no fluorescein (black line). In the fluorescence colourbar, dB is measured relative to maximum measured fluorescence signal. (b) Plot of maximum fluorescence signal from each tube (blue circles) with line of best fit (blue line) compared to the RMS noise floor (red dashed line).
Fig. 8
Fig. 8 Dual-modality images obtained for the scattering and fluorescent tissue-mimicking phantom using the side-viewing needle with rotation and translational scanning. (a) A cutaway view of the 3D OCT image with the measured fluorescence signal for each radial location projected onto the surface of the cutaway plane. (b) A cross-sectional radial view showing the image of the three lines with the measured fluorescence signal for each radial position projected onto the circumference of the radial image. In the fluorescent colourbar, dB is measured relative to maximum measured fluorescence signal.
Fig. 9
Fig. 9 Side-viewing MI needle images obtained for a section of normal human liver, showing labeled biliary ducts and liver progenitor cells. (a) En face OCT needle image obtained after averaging 4 co-located OCT A-scans at each radial position. (b) Corresponding fluorescence needle image. (c) Magnified OCT image of selected region indicated by dashed box in a. (d) Corresponding magnified fluorescence needle image of selected region indicated by dashed box in b. (e) OCT + fluorescence magnified image of selected region. Inset: Magnified view of region indicated by small pink box. (f) Corresponding standard wide-field fluorescence microscopy image for selected region. Inset: High magnification (10 × objective) image of region indicated by pink box confirming liver progenitor cells (LPCs).
Fig. 10
Fig. 10 Radial images obtained at two pullback locations using the MI needle deep within a whole mouse liver. The fluorescence signal for each radial position is projected onto the circumference. Fluorescently labeled epithelial cells are visible in each image. OCT images show corresponding ductal structures surrounding low backscattering lumen. The vertical black line at the 6 o’clock position marks the start and end location of the needle rotation. Fluorescent signal (in dB) is measured relative to maximum measured fluorescence signal.

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