Abstract

Proper treatment of deep seated brain tumors requires correct histological diagnosis which unambiguously necessitates biopsy sampling. Stereotactically guided sampling of biopsies is widely used but bears the danger of incorrect sampling locations and damage to intracerebral blood vessels. Here, we present a minimally invasive contact endoscopic probe that can be inserted into the tissue inside a standard biopsy needle and allows for fluorescence detection of both tumorous tissue and intracerebral blood vessels. Outer diameter of our contact probe is smaller than 1.5 mm, field-of-view in the range of several hundred microns; the optical design allows for simultaneous detection and visualization of tissue autofluorescence and selective fluorescence signals from deep seated brain tumors and vasculature as shown on in vivo animal models. We demonstrate the tumor detection capability during stereotactic needle insertion in a clinical pilot trial. Using our probe, we expect stereotactic interventions to become safer and more precise and the technology might ultimately be used also for various other kinds of applications.

© 2012 OSA

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2012 (2)

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

2011 (4)

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

2010 (4)

K. J. Rosbach, D. Shin, T. J. Muldoon, M. A. Quraishi, L. P. Middleton, K. K. Hunt, F. Meric-Bernstam, T. K. Yu, R. R. Richards-Kortum, and W. Yang, “High-resolution fiber optic microscopy with fluorescent contrast enhancement for the identification of axillary lymph node metastases in breast cancer: a pilot study,” Biomed. Opt. Express1(3), 911–922 (2010).
[CrossRef] [PubMed]

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

S. M. Landau, C. Liang, R. T. Kester, T. S. Tkaczyk, and M. R. Descour, “Design and evaluation of an ultra-slim objective for in-vivo deep optical biopsy,” Opt. Express18(5), 4758–4775 (2010).
[CrossRef] [PubMed]

2009 (3)

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

2008 (2)

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

2007 (2)

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

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. Express15(25), 16413–16423 (2007).
[CrossRef] [PubMed]

2005 (1)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

2004 (1)

2003 (2)

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

2002 (1)

F. Helmchen, “Miniaturization of fluorescence microscopes using fibre optics,” Exp. Physiol.87(6), 737–745 (2002).
[CrossRef] [PubMed]

2001 (2)

T. Kuroiwa, Y. Kajimoto, and T. Ohta, “Development and clinical application of near-infrared surgical microscope: preliminary report,” Minim. Invasive Neurosurg.44(4), 240–242 (2001).
[CrossRef] [PubMed]

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

1998 (3)

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

D. Kondziolka, A. D. Firlik, and L. D. Lunsford, “Complications of stereotactic brain surgery,” Neurol. Clin.16(1), 35–54 (1998).
[CrossRef] [PubMed]

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Anandasabapathy, S.

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

Attardo, A.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Barretto, R. P.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

Baumgartner, R.

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

Beck, J.

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

Bornemann, A.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Burger, P. C.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Burgold, S.

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Burns, L. D.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

Capps, G.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Cavenee, W. K.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Cheung, E. L.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Choi, C.

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Choi, M.

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Cocker, E. D.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Danz, S.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Dehara, M.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Descour, M. R.

Ehrhardt, A.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Feigl, G. C.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Firlik, A. D.

D. Kondziolka, A. D. Firlik, and L. D. Lunsford, “Complications of stereotactic brain surgery,” Neurol. Clin.16(1), 35–54 (1998).
[CrossRef] [PubMed]

Flusberg, B. A.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Fuhrmann, M.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Furtner, J.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Gerlach, R.

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

Germer, C. T.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Gibbs-Strauss, S. L.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

Gillenwater, A.

Gillenwater, A. M.

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

Göbel, W.

Goldbrunner, R.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

Hainfellner, J. A.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Hasan, T.

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

Helmchen, F.

Herms, J.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Hofstetter, A.

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

Hoopes, P. J.

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

Hunt, K. K.

Ieva, A.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Imakita, M.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Irion, K. M.

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

Isbert, C.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Jack Hoopes, P.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

Johansson, A.

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

Jouvet, A.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Jung, J. C.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Kajimoto, Y.

T. Kuroiwa, Y. Kajimoto, and T. Ohta, “Development and clinical application of near-infrared surgical microscope: preliminary report,” Minim. Invasive Neurosurg.44(4), 240–242 (2001).
[CrossRef] [PubMed]

Kang, Y.

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Kauppinen, R. A.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

Kerr, J. N.

Kester, R. T.

Khan Hekmatyar, S.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

Kienast, Y.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Kiesel, B.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Kleihues, P.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Klinkert, W. E.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

Knappe, V.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Knosp, E.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Ko, T. H.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

Koh, G. Y.

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Kondziolka, D.

D. Kondziolka, A. D. Firlik, and L. D. Lunsford, “Complications of stereotactic brain surgery,” Neurol. Clin.16(1), 35–54 (1998).
[CrossRef] [PubMed]

Kretzschmar, H.

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Kuroiwa, T.

T. Kuroiwa, Y. Kajimoto, and T. Ohta, “Development and clinical application of near-infrared surgical microscope: preliminary report,” Minim. Invasive Neurosurg.44(4), 240–242 (2001).
[CrossRef] [PubMed]

Kwon, K.

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Landau, S. M.

Lee, J.

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Leonhard, M.

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Liang, C.

Louis, D. N.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Lunsford, L. D.

D. Kondziolka, A. D. Firlik, and L. D. Lunsford, “Complications of stereotactic brain surgery,” Neurol. Clin.16(1), 35–54 (1998).
[CrossRef] [PubMed]

Marosi, C.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Maru, D.

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

Meric-Bernstam, F.

Mert, A.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Middleton, L. P.

Minchev, G.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Mitteregger, G.

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Möller, G.

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Moriuchi, S.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Mukamel, E. A.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

Muldoon, T. J.

Müller, G.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Nida, D. L.

Nimmerjahn, A.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

W. Göbel, J. N. Kerr, A. Nimmerjahn, and F. Helmchen, “Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective,” Opt. Lett.29(21), 2521–2523 (2004).
[CrossRef] [PubMed]

Noell, S.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

O’Hara, J. A.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

Ohgaki, H.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Ohta, T.

T. Kuroiwa, Y. Kajimoto, and T. Ohta, “Development and clinical application of near-infrared surgical microscope: preliminary report,” Minim. Invasive Neurosurg.44(4), 240–242 (2001).
[CrossRef] [PubMed]

Palte, G.

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

Pierce, M. C.

Piyawattanametha, W.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Pogue, B. W.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

Prayer, D.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Preusser, M.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Quraishi, M. A.

Raabe, A.

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

Recht, L.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Reulen, H. J.

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Richards-Kortum, R.

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

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. Express15(25), 16413–16423 (2007).
[CrossRef] [PubMed]

Richards-Kortum, R. R.

Ritz, J. P.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Ritz, R.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Roblyer, D.

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

Roggan, A.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Rosbach, K. J.

Samkoe, K. S.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

Schädel, D.

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Scheithauer, B. W.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Schnell, O.

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

Schnitzer, M. J.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

Schuhmann, M. U.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Seifert, V.

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

Shin, D.

Soda, T.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Star, W. M.

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

Stepanek, V. M.

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

Stepp, H.

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Stummer, W.

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Taneda, M.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Tatagiba, M. S.

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Teramoto, Y.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Tkaczyk, T. S.

Tomanek, B.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Tonn, J. C.

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

von Baumgarten, L.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Wagnières, G. A.

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

Wang, T. J.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Waters, A. C.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Widhalm, G.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Wiestler, O. D.

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Williams, M. D.

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

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. Express15(25), 16413–16423 (2007).
[CrossRef] [PubMed]

Wilson, B. C.

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

Winkler, F.

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Woehrer, A.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Wolfsberger, S.

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Yamada, K.

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

Yang, H. H.

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

Yang, W.

Yu, T. K.

Zaak, D.

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

Zimmermann, M.

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

Ziv, Y.

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Acta Neurochir. (Wien) (1)

W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. J. Reulen, “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien)140(10), 995–1000 (1998).
[CrossRef] [PubMed]

Acta Neuropathol. (1)

D. N. Louis, H. Ohgaki, O. D. Wiestler, W. K. Cavenee, P. C. Burger, A. Jouvet, B. W. Scheithauer, and P. Kleihues, “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathol.114(2), 97–109 (2007).
[CrossRef] [PubMed]

Biomed. Opt. Express (1)

Exp. Physiol. (1)

F. Helmchen, “Miniaturization of fluorescence microscopes using fibre optics,” Exp. Physiol.87(6), 737–745 (2002).
[CrossRef] [PubMed]

Gastrointest. Endosc. (1)

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

Glia (1)

F. Winkler, Y. Kienast, M. Fuhrmann, L. Von Baumgarten, S. Burgold, G. Mitteregger, H. Kretzschmar, and J. Herms, “Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis,” Glia57(12), 1306–1315 (2009).
[CrossRef] [PubMed]

Head Neck (1)

T. J. Muldoon, D. Roblyer, M. D. Williams, V. M. Stepanek, R. Richards-Kortum, and A. M. Gillenwater, “Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope,” Head Neck34(3), 305–312 (2012).
[CrossRef] [PubMed]

J. Biomed. Opt. (2)

S. L. Gibbs-Strauss, J. A. O’Hara, P. J. Hoopes, T. Hasan, and B. W. Pogue, “Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo,” J. Biomed. Opt.14(1), 014007 (2009).
[CrossRef] [PubMed]

K. S. Samkoe, S. L. Gibbs-Strauss, H. H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, J. A. O’Hara, R. A. Kauppinen, and B. W. Pogue, “Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy,” J. Biomed. Opt.16(9), 096008 (2011).
[CrossRef] [PubMed]

J. Neurosurg. (2)

S. Moriuchi, K. Yamada, M. Dehara, Y. Teramoto, T. Soda, M. Imakita, and M. Taneda, “Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy,” J. Neurosurg.115(2), 278–280 (2011).
[CrossRef] [PubMed]

R. Ritz, G. C. Feigl, M. U. Schuhmann, A. Ehrhardt, S. Danz, S. Noell, A. Bornemann, and M. S. Tatagiba, “Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor,” J. Neurosurg.114(5), 1410–1413 (2011).
[PubMed]

Med. Laser Appl. (2)

A. Ehrhardt, H. Stepp, K. M. Irion, W. Stummer, D. Zaak, R. Baumgartner, and A. Hofstetter, “Fluorescence detection of human malignancies using incoherent light systems,” Med. Laser Appl.18(1), 27–35 (2003).
[CrossRef]

A. Roggan, J. P. Ritz, V. Knappe, C. T. Germer, C. Isbert, D. Schädel, and G. Müller, “Radiation planning for thermal laser treatment,” Med. Laser Appl.16(2), 65–72 (2001).
[CrossRef]

Minim. Invasive Neurosurg. (1)

T. Kuroiwa, Y. Kajimoto, and T. Ohta, “Development and clinical application of near-infrared surgical microscope: preliminary report,” Minim. Invasive Neurosurg.44(4), 240–242 (2001).
[CrossRef] [PubMed]

Nat. Med. (2)

R. P. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Y. Kienast, L. von Baumgarten, M. Fuhrmann, W. E. Klinkert, R. Goldbrunner, J. Herms, and F. Winkler, “Real-time imaging reveals the single steps of brain metastasis formation,” Nat. Med.16(1), 116–122 (2010).
[CrossRef] [PubMed]

Nat. Methods (2)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods5(11), 935–938 (2008).
[CrossRef] [PubMed]

Neurol. Clin. (1)

D. Kondziolka, A. D. Firlik, and L. D. Lunsford, “Complications of stereotactic brain surgery,” Neurol. Clin.16(1), 35–54 (1998).
[CrossRef] [PubMed]

Neurosurg. Rev. (1)

G. Widhalm, G. Minchev, A. Woehrer, M. Preusser, B. Kiesel, J. Furtner, A. Mert, A. Ieva, B. Tomanek, D. Prayer, C. Marosi, J. A. Hainfellner, E. Knosp, and S. Wolfsberger, “Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies,” Neurosurg. Rev.35(3), 381–391, discussion 391 (2012).
[CrossRef] [PubMed]

Neurosurgery (1)

A. Raabe, J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert, “Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow,” Neurosurgery52(1), 132–139, discussion 139 (2003).
[PubMed]

Opt. Express (2)

Opt. Lett. (1)

Photochem. Photobiol. (2)

A. Johansson, G. Palte, O. Schnell, J. C. Tonn, J. Herms, and H. Stepp, “5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors,” Photochem. Photobiol.86(6), 1373–1378 (2010).
[CrossRef] [PubMed]

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

PLoS ONE (1)

Y. Kang, M. Choi, J. Lee, G. Y. Koh, K. Kwon, and C. Choi, “Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics,” PLoS ONE4(1), e4275 (2009).
[CrossRef] [PubMed]

Other (4)

S. Eigenbrod, Department of Neuropathology, Ludwig-Maximilians-University Munich, R. Trabold, D. Brucker, C. Erös, B. Suchorska, R. Egensperger, G. Pöpperl, A. Rühm, W. Göbel, H. Kretzschmar, J. C. Tonn, J. Herms, A. Giese, and F. W. Kreth are preparing a manuscript to be called “Molecular stereotactic biopsy technique improves tumor classification in glioma patients.”

A. Rühm, Laser-Research-Laboratory, Ludwig-Maximilians-University Munich, W. Göbel, and H. Stepp are preparing a manuscript to be called “Fiber baser fluorescence diagnosis based on PpIX and ICG – Excitation power limitations due to thermal effects in human brain tissue.”

K. Irion, “US 7,662,095 (B2) - Endoscope provided with a lighting system and a combined image transmission,” (2010).

Brain Tumor Primer - a comprehensive introduction to brain tumors (American Brain Tumor Association, 2010).

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Figures (6)

Fig. 1
Fig. 1

Stereotactically guided biopsy sampling in neurosurgery. A hollow stereotactic needle is attached to the stereotactic frame firmly connected to the patient’s skull and inserted into the brain along a predefined trajectory. The distal tip is positioned within the putative tumor region. Damage to blood vessels is to be unambiguously avoided.

Fig. 2
Fig. 2

Scheme of setup and optical layout for minimally invasive tumor biopsy needle endoscope. (a) Schematic view of the entire system. Light from two laser diodes emitting at 405 nm and 785 nm wavelength is combined with a dichroic mirror and coupled into a coherent image guide using a dual-band dichroic mirror and an eye piece lens. Fluorescence is separated by the dual-band dichroic mirror and imaged onto a 3-chip CCD camera. Two emission filters selectively block excitation wavelengths 405 nm and 785 nm. (b) Filter characteristics of the excitation wavelengths (blue and dark brown curves), dichroic mirrors (green curve) and emission filters (red curve). Expected fluorescence modalities are indicated (PpIX, ICG - external marker fluorescence; AF - autofluorescence). (c) Spectral characteristics of the 3-chip camera system. Interestingly, near infrared fluorescence light is visualized in the blue color channel due to a second sensitivity maximum of the blue-channel CCD chip in the near infrared region. (d) Example autofluorescence contact images of felt (top) and skin with sweat duct (bottom). (e) Example image of near-infrared ICG fluorescence at edge of a fluorescing region of an ICG test object.

Fig. 3
Fig. 3

In vivo fluorescence visualization of superficial tumors and blood vessels. (a) Fluorescence images of healthy tissue (top), tumor center with bright red PpIX fluorescence (middle), and tumor margin (bottom). (b) Bleaching of PpIX fluorescence signal over time. Top: exemplary decay of red fluorescence over time; bottom: example images at beginning and end of recording at time points indicated as red vertical lines in the decay graph. (c) Blood vessel visualization in pure ICG mode at 785 nm excitation (top), in pure autofluorescence mode at 405 nm excitation (middle), and simultaneous autofluorescence and ICG visualization (bottom).

Fig. 4
Fig. 4

Detection of blood vessels inside tissue. (a) Photo of artificial blood vessels filled with blood/ICG solution and embedded into brain tissue for simulating blood vessel detection. The black-coated bare fiber probe is also visible. (b) Signal decay in the blue/infrared camera channel as a function of distance of the distal probe tip from the blood vessel dummy for three different light intensities. The remaining signal at distances above 2000 µm results from scattered excitation light detection. Signals were analyzed across the active area of the image guide and normalized to the maximum intensity value of 255. Intensity levels between 1 – 5 mW seem optimal for blood vessel detection. (c) ICG fluorescence images at various distances from the blood vessel dummy (top: direct contact; middle: 750µm distance; bottom: 1500µm distance). Bluish ICG fluorescence was detectable at a distance of ~1 mm before touching the artificial vessel.

Fig. 5
Fig. 5

Images obtained during probe insertion towards, into and through deep seated brain tumors based on red PpIX fluorescence. The image series demonstrate the probe’s ability to detect tumor margins. (a) Series of 4 consecutive images obtained during 5 probe insertions through a tumorous region. Top row: pial surface; second row: autofluorescence during insertion before reaching tumor region (note pial blood vessels being dragged until pial rupture during some of the insertion trials); third row: vital tumor region as indicated by strong red PpIX fluorescence; fourth row: autofluorescence below/behind tumor. (b) Series of 4 consecutive images as in (a), but obtained on a control animal with previous 5-ALA administration but without implanted tumor. Image series at same depth regimes as in (a). The bluish background seen in many images in the left panel is due to ICG leakage from damaged blood vessels into the tissue, which occurred during consecutive trials to hit the vital, deep seated tumor region.

Fig. 6
Fig. 6

Probe design and imaging results obtained during a clinical pilot trial. (a) Photograph of the optical probe in comparison to the conventional mandrin and the hollow needle. Mandrin and optical needle’s end tip share nearly identical mechanical properties (see Fig. 4(a) for comparison with a bare optical fiber bundle). (b) Example images (left) from putative necrotic (top panels) and vital tumor region (bottom panels), respectively. The two images on the left were acquired at different depths along the axial position of the biopsy channel during probe propulsion. Histological sections of biopsies from the same tissue locations are shown on the right, correlating well with the imaging results. Scale bar, 50 µm.

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