Abstract

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX sensitivity in wide-field fluorescence imaging may improve the residual tumor detection during surgery with consequent impact on survival.

© 2015 Optical Society of America

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References

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2015 (2)

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

T. Hollon, S. L. Hervey-Jumper, O. Sagher, and D. A. Orringer, “Advances in the Surgical Management of Low-Grade Glioma,” Semin. Radiat. Oncol. 25(3), 181–188 (2015).
[Crossref] [PubMed]

2014 (1)

X. Zhang, “Instrumentation in Diffuse Optical Imaging,” Photonics 1(1), 9–32 (2014).
[Crossref] [PubMed]

2013 (3)

P. A. Valdes, V. L. Jacobs, B. C. Wilson, F. Leblond, D. W. Roberts, and K. D. Paulsen, “System and methods for wide-field quantitative fluorescence imaging during neurosurgery,” Opt. Lett. 38(15), 2786–2788 (2013).
[Crossref] [PubMed]

K. Petrecca, M.-C. Guiot, V. Panet-Raymond, and L. Souhami, “Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma,” J. Neurooncol. 111(1), 19–23 (2013).
[Crossref] [PubMed]

Q. T. Nguyen and R. Y. Tsien, “Fluorescence-guided surgery with live molecular navigation--a new cutting edge,” Nat. Rev. Cancer 13(9), 653–662 (2013).
[Crossref] [PubMed]

2012 (4)

P. Valdes, F. Leblond, and V. L. Jacobs, “Fluorescence detection in the operating room: a review of principles, methods, and applications,” Curr. Med. Imaging Rev. 8, 211–232 (2012).
[Crossref]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci. Rep. 2, 798 (2012).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery,” Opt. Lett. 37(11), 1817–1819 (2012).
[Crossref] [PubMed]

K. Roessler, A. Becherer, M. Donat, M. Cejna, and I. Zachenhofer, “Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography ((18)F-FET PET) in glioblastoma surgery,” Neurol. Res. 34(3), 314–317 (2012).
[PubMed]

2011 (4)

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

2010 (3)

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

F. Bestvater, Z. Seghiri, M. S. Kang, N. Gröner, J. Y. Lee, K.-B. Im, and M. Wachsmuth, “EMCCD-based spectrally resolved fluorescence correlation spectroscopy,” Opt. Express 18(23), 23818–23828 (2010).
[Crossref] [PubMed]

2009 (2)

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

C. Li, G. S. Mitchell, J. Dutta, S. Ahn, R. M. Leahy, and S. R. Cherry, “A three-dimensional multispectral fluorescence optical tomography imaging system for small animals based on a conical mirror design,” Opt. Express 17(9), 7571–7585 (2009).
[Crossref] [PubMed]

2008 (2)

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (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]

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

2006 (2)

W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, and ALA-Glioma Study Group, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol. 7(5), 392–401 (2006).
[Crossref] [PubMed]

M. Burkhardt and P. Schwille, “Electron multiplying CCD based detection for spatially resolved fluorescence correlation spectroscopy,” Opt. Express 14(12), 5013–5020 (2006).
[Crossref] [PubMed]

2004 (1)

C. Nimsky, A. Fujita, O. Ganslandt, B. Von Keller, and R. Fahlbusch, “Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging,” Neurosurgery 55(2), 358–371 (2004).
[Crossref] [PubMed]

2001 (2)

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

G. E. Keles, K. R. Lamborn, and M. S. Berger, “Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome,” J. Neurosurg. 95(5), 735–745 (2001).
[Crossref] [PubMed]

1998 (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]

1994 (1)

M. S. Berger, A. V. Deliganis, J. Dobbins, and G. E. Keles, “The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas,” Cancer 74(6), 1784–1791 (1994).
[Crossref] [PubMed]

Abi-Said, D.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Ahn, S.

Asenbaum, S.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Attenello, F. J.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Becherer, A.

K. Roessler, A. Becherer, M. Donat, M. Cejna, and I. Zachenhofer, “Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography ((18)F-FET PET) in glioblastoma surgery,” Neurol. Res. 34(3), 314–317 (2012).
[PubMed]

Bekelis, K.

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

Berger, M. S.

G. E. Keles, K. R. Lamborn, and M. S. Berger, “Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome,” J. Neurosurg. 95(5), 735–745 (2001).
[Crossref] [PubMed]

M. S. Berger, A. V. Deliganis, J. Dobbins, and G. E. Keles, “The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas,” Cancer 74(6), 1784–1791 (1994).
[Crossref] [PubMed]

Bestvater, F.

Blais-Ouellette, S.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

Brem, H.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Burger, P. C.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

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]

Burkhardt, M.

Carignan, C.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

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]

Cejna, M.

K. Roessler, A. Becherer, M. Donat, M. Cejna, and I. Zachenhofer, “Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography ((18)F-FET PET) in glioblastoma surgery,” Neurol. Res. 34(3), 314–317 (2012).
[PubMed]

Chaichana, K. L.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Cherry, S. R.

Conde, O. M.

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

Coons, S. W.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Czech, T.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Daigle, O.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

Deliganis, A. V.

M. S. Berger, A. V. Deliganis, J. Dobbins, and G. E. Keles, “The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas,” Cancer 74(6), 1784–1791 (1994).
[Crossref] [PubMed]

DeMonte, F.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Dobbins, J.

M. S. Berger, A. V. Deliganis, J. Dobbins, and G. E. Keles, “The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas,” Cancer 74(6), 1784–1791 (1994).
[Crossref] [PubMed]

Donat, M.

K. Roessler, A. Becherer, M. Donat, M. Cejna, and I. Zachenhofer, “Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography ((18)F-FET PET) in glioblastoma surgery,” Neurol. Res. 34(3), 314–317 (2012).
[PubMed]

Dutta, J.

Ehrhardt, A.

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]

Erkmen, K.

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Eschbacher, J. M.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Fahlbusch, R.

C. Nimsky, A. Fujita, O. Ganslandt, B. Von Keller, and R. Fahlbusch, “Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging,” Neurosurgery 55(2), 358–371 (2004).
[Crossref] [PubMed]

Fan, X.

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Fortin, C.-A.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

Fourney, D. R.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Franz, K.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Fujita, A.

C. Nimsky, A. Fujita, O. Ganslandt, B. Von Keller, and R. Fahlbusch, “Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging,” Neurosurgery 55(2), 358–371 (2004).
[Crossref] [PubMed]

Gach, J.-L.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

Ganslandt, O.

C. Nimsky, A. Fujita, O. Ganslandt, B. Von Keller, and R. Fahlbusch, “Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging,” Neurosurgery 55(2), 358–371 (2004).
[Crossref] [PubMed]

Gokaslan, Z. L.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Gröner, N.

Guillaume, C.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

Guiot, M.-C.

K. Petrecca, M.-C. Guiot, V. Panet-Raymond, and L. Souhami, “Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma,” J. Neurooncol. 111(1), 19–23 (2013).
[Crossref] [PubMed]

Hainfellner, J. A.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Harris, B. T.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

Hartov, A.

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Hassenbusch, S. J.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Hervey-Jumper, S. L.

T. Hollon, S. L. Hervey-Jumper, O. Sagher, and D. A. Orringer, “Advances in the Surgical Management of Low-Grade Glioma,” Semin. Radiat. Oncol. 25(3), 181–188 (2015).
[Crossref] [PubMed]

Hess, K.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Holland, E.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Hollon, T.

T. Hollon, S. L. Hervey-Jumper, O. Sagher, and D. A. Orringer, “Advances in the Surgical Management of Low-Grade Glioma,” Semin. Radiat. Oncol. 25(3), 181–188 (2015).
[Crossref] [PubMed]

Honea, N. J.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Ichioka, T.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

Im, K.-B.

Jacobs, V.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

Jacobs, V. L.

P. A. Valdes, V. L. Jacobs, B. C. Wilson, F. Leblond, D. W. Roberts, and K. D. Paulsen, “System and methods for wide-field quantitative fluorescence imaging during neurosurgery,” Opt. Lett. 38(15), 2786–2788 (2013).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci. Rep. 2, 798 (2012).
[Crossref] [PubMed]

P. Valdes, F. Leblond, and V. L. Jacobs, “Fluorescence detection in the operating room: a review of principles, methods, and applications,” Curr. Med. Imaging Rev. 8, 211–232 (2012).
[Crossref]

Ji, S.

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[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]

Kajimoto, Y.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

Kang, M. S.

Keles, G. E.

G. E. Keles, K. R. Lamborn, and M. S. Berger, “Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome,” J. Neurosurg. 95(5), 735–745 (2001).
[Crossref] [PubMed]

M. S. Berger, A. V. Deliganis, J. Dobbins, and G. E. Keles, “The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas,” Cancer 74(6), 1784–1791 (1994).
[Crossref] [PubMed]

Khurana, M.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

Kim, A.

P. A. Valdés, F. Leblond, A. Kim, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery,” Opt. Lett. 37(11), 1817–1819 (2012).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[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]

Knosp, E.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Krssak, M.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Kuroiwa, T.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

Lacroix, M.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Lamborn, K. R.

G. E. Keles, K. R. Lamborn, and M. S. Berger, “Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome,” J. Neurosurg. 95(5), 735–745 (2001).
[Crossref] [PubMed]

Lang, F. F.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Leahy, R. M.

Leblond, F.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

P. A. Valdes, V. L. Jacobs, B. C. Wilson, F. Leblond, D. W. Roberts, and K. D. Paulsen, “System and methods for wide-field quantitative fluorescence imaging during neurosurgery,” Opt. Lett. 38(15), 2786–2788 (2013).
[Crossref] [PubMed]

P. Valdes, F. Leblond, and V. L. Jacobs, “Fluorescence detection in the operating room: a review of principles, methods, and applications,” Curr. Med. Imaging Rev. 8, 211–232 (2012).
[Crossref]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci. Rep. 2, 798 (2012).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery,” Opt. Lett. 37(11), 1817–1819 (2012).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Lee, J. Y.

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]

Lessard, S.

O. Daigle, C. Carignan, J.-L. Gach, C. Guillaume, S. Lessard, C.-A. Fortin, and S. Blais-Ouellette, “Extreme faint flux imaging with an EMCCD,” Publ. Astron. Soc. Pac. 121(882), 866–884 (2009).
[Crossref]

Li, 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]

McCutcheon, I. E.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

McGirt, M. J.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Meinel, T.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, and ALA-Glioma Study Group, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol. 7(5), 392–401 (2006).
[Crossref] [PubMed]

Michael, C.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Miller, D.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Minchev, G.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Mitchell, G. S.

Miyashita, M.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

Miyatake, S.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[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]

Moriyama, Y.

A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt. 15(6), 067006 (2010).
[Crossref] [PubMed]

Nguyen, Q. T.

Q. T. Nguyen and R. Y. Tsien, “Fluorescence-guided surgery with live molecular navigation--a new cutting edge,” Nat. Rev. Cancer 13(9), 653–662 (2013).
[Crossref] [PubMed]

Nimsky, C.

C. Nimsky, A. Fujita, O. Ganslandt, B. Von Keller, and R. Fahlbusch, “Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging,” Neurosurgery 55(2), 358–371 (2004).
[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]

Olivi, A.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Oppel, F.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Orringer, D. A.

T. Hollon, S. L. Hervey-Jumper, O. Sagher, and D. A. Orringer, “Advances in the Surgical Management of Low-Grade Glioma,” Semin. Radiat. Oncol. 25(3), 181–188 (2015).
[Crossref] [PubMed]

Panet-Raymond, V.

K. Petrecca, M.-C. Guiot, V. Panet-Raymond, and L. Souhami, “Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma,” J. Neurooncol. 111(1), 19–23 (2013).
[Crossref] [PubMed]

Paulsen, K. D.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

P. A. Valdes, V. L. Jacobs, B. C. Wilson, F. Leblond, D. W. Roberts, and K. D. Paulsen, “System and methods for wide-field quantitative fluorescence imaging during neurosurgery,” Opt. Lett. 38(15), 2786–2788 (2013).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci. Rep. 2, 798 (2012).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery,” Opt. Lett. 37(11), 1817–1819 (2012).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Petrecca, K.

K. Petrecca, M.-C. Guiot, V. Panet-Raymond, and L. Souhami, “Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma,” J. Neurooncol. 111(1), 19–23 (2013).
[Crossref] [PubMed]

Pichlmeier, U.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, and ALA-Glioma Study Group, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol. 7(5), 392–401 (2006).
[Crossref] [PubMed]

Pietsch, T.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Prayer, D.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[Crossref] [PubMed]

Quinoñes-Hinojosa, A.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[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]

Reulen, H.-J.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, and ALA-Glioma Study Group, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol. 7(5), 392–401 (2006).
[Crossref] [PubMed]

Roberts, D. W.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

P. A. Valdes, V. L. Jacobs, B. C. Wilson, F. Leblond, D. W. Roberts, and K. D. Paulsen, “System and methods for wide-field quantitative fluorescence imaging during neurosurgery,” Opt. Lett. 38(15), 2786–2788 (2013).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci. Rep. 2, 798 (2012).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery,” Opt. Lett. 37(11), 1817–1819 (2012).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Roessler, K.

K. Roessler, A. Becherer, M. Donat, M. Cejna, and I. Zachenhofer, “Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography ((18)F-FET PET) in glioblastoma surgery,” Neurol. Res. 34(3), 314–317 (2012).
[PubMed]

Rohde, V.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Sagher, O.

T. Hollon, S. L. Hervey-Jumper, O. Sagher, and D. A. Orringer, “Advances in the Surgical Management of Low-Grade Glioma,” Semin. Radiat. Oncol. 25(3), 181–188 (2015).
[Crossref] [PubMed]

Sanai, N.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Sawaya, R.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

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]

Schumacher, W.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Schwille, P.

Seghiri, Z.

Shi, W.

M. Lacroix, D. Abi-Said, D. R. Fourney, Z. L. Gokaslan, W. Shi, F. DeMonte, F. F. Lang, I. E. McCutcheon, S. J. Hassenbusch, E. Holland, K. Hess, C. Michael, D. Miller, and R. Sawaya, “A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival,” J. Neurosurg. 95(2), 190–198 (2001).
[Crossref] [PubMed]

Simmons, N. E.

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Smith, K. A.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Snyder, L. A.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Souhami, L.

K. Petrecca, M.-C. Guiot, V. Panet-Raymond, and L. Souhami, “Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma,” J. Neurooncol. 111(1), 19–23 (2013).
[Crossref] [PubMed]

Spetzler, R. F.

N. Sanai, L. A. Snyder, N. J. Honea, S. W. Coons, J. M. Eschbacher, K. A. Smith, and R. F. Spetzler, “Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas,” J. Neurosurg. 115(4), 740–748 (2011).
[Crossref] [PubMed]

Stepp, H.

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.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, and ALA-Glioma Study Group, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol. 7(5), 392–401 (2006).
[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]

Tanaka, H.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

Than, K.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Tonn, J.-C.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Tosteson, T. D.

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Tsien, R. Y.

Q. T. Nguyen and R. Y. Tsien, “Fluorescence-guided surgery with live molecular navigation--a new cutting edge,” Nat. Rev. Cancer 13(9), 653–662 (2013).
[Crossref] [PubMed]

Tsuji, M.

Y. Kajimoto, T. Kuroiwa, S. Miyatake, T. Ichioka, M. Miyashita, H. Tanaka, and M. Tsuji, “Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence,” J. Neurosurg. 106(6), 1070–1074 (2007).
[Crossref] [PubMed]

Turowski, B.

W. Stummer, H.-J. Reulen, T. Meinel, U. Pichlmeier, W. Schumacher, J.-C. Tonn, V. Rohde, F. Oppel, B. Turowski, C. Woiciechowsky, K. Franz, T. Pietsch, and ALA-Glioma Study Group, “Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias,” Neurosurgery 62(3), 564–576 (2008).
[Crossref] [PubMed]

Valdes, P.

P. Valdes, F. Leblond, and V. L. Jacobs, “Fluorescence detection in the operating room: a review of principles, methods, and applications,” Curr. Med. Imaging Rev. 8, 211–232 (2012).
[Crossref]

Valdes, P. A.

Valdés, P. A.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, V. L. Jacobs, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “Quantitative, spectrally-resolved intraoperative fluorescence imaging,” Sci. Rep. 2, 798 (2012).
[Crossref] [PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. C. Wilson, K. D. Paulsen, and D. W. Roberts, “A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery,” Opt. Lett. 37(11), 1817–1819 (2012).
[Crossref] [PubMed]

P. A. Valdés, A. Kim, F. Leblond, O. M. Conde, B. T. Harris, K. D. Paulsen, B. C. Wilson, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref] [PubMed]

K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus 30(5), E8 (2011).
[PubMed]

P. A. Valdés, F. Leblond, A. Kim, B. T. Harris, B. C. Wilson, X. Fan, T. D. Tosteson, A. Hartov, S. Ji, K. Erkmen, N. E. Simmons, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker,” J. Neurosurg. 115(1), 11–17 (2011).
[Crossref] [PubMed]

Von Keller, B.

C. Nimsky, A. Fujita, O. Ganslandt, B. Von Keller, and R. Fahlbusch, “Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging,” Neurosurgery 55(2), 358–371 (2004).
[Crossref] [PubMed]

Wachsmuth, M.

Weingart, J. D.

M. J. McGirt, K. L. Chaichana, F. J. Attenello, J. D. Weingart, K. Than, P. C. Burger, A. Olivi, H. Brem, and A. Quinoñes-Hinojosa, “Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas,” Neurosurgery 63(4), 700–708 (2008).
[Crossref] [PubMed]

Widhalm, G.

G. Widhalm, S. Wolfsberger, G. Minchev, A. Woehrer, M. Krssak, T. Czech, D. Prayer, S. Asenbaum, J. A. Hainfellner, and E. Knosp, “5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement,” Cancer 116(6), 1545–1552 (2010).
[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]

W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, and ALA-Glioma Study Group, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol. 7(5), 392–401 (2006).
[Crossref] [PubMed]

Wilson, B. C.

P. A. Valdés, V. Jacobs, B. T. Harris, B. C. Wilson, F. Leblond, K. D. Paulsen, and D. W. Roberts, “Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery,” J. Neurosurg. 123(3), 771–780 (2015).
[Crossref] [PubMed]

P. A. Valdes, V. L. Jacobs, B. C. Wilson, F. Leblond, D. W. Roberts, and K. D. Paulsen, “System and methods for wide-field quantitative fluorescence imaging during neurosurgery,” Opt. Lett. 38(15), 2786–2788 (2013).
[Crossref] [PubMed]

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Figures (5)

Fig. 1
Fig. 1 Schematic of the imaging set up used to evaluate the performance of the EMCCD- and CMOS-based spectral imaging systems connected to different ports on a commercial neuroscurgical microscope. The photograph shows the EMCCD system, including the coherent imaging bundle used for remote light detection.
Fig. 2
Fig. 2 Recovered values of PpIX concentration versus the known PpIX values in the different tissue-simulating phantoms for both the CMOS (a,c) and EMCCD systems (b,d) with integration times of 5 ms per wavelength (a,b) and 20 ms per wavelength (c,d). Measurements were averaged over a 5 by 5 pixel window in the center of the inclusion. Measurements at each PpIX concentration correspond to 9 phantoms with different absorption-scattering combinations at 600 nm ranging from μa = 0.02 to 0.06 cm−1 and μs’ = 8.7 to 14.5 cm−1. The lines of fit are in red.
Fig. 3
Fig. 3 Examples of fluorescence spectra acquired with both imaging systems for 20 ms exposure at PpIX concentrations of 40 and 200 ng/ml and with optical properites μa = 0.03 cm−1 and μs’ = 14.5 cm−1. The measurements were averaged over a 5 by 5 pixel window at the center of the inclusion, and the spectra are normalized by reflectance data.
Fig. 4
Fig. 4 (a,c) Two ex vivo brain tissue samples containing glioma, as viewed through the neurosurgical microscope under violet light excitation. (b,d) show the corresponding images for the derived quantitative fluorescence using the EMCCD system. Representative contrast ratios (CR) are shown within the tumor. The images have been cropped to highlight the tissue samples.
Fig. 5
Fig. 5 Correlation between the quantatitive PpIX fluorescence measured with the EMCCD system at 7 different locations (averaged over 5 by 5 pixel regions) and the corresponding quantitative point probe measurements. The linear regression line is also shown.

Tables (2)

Tables Icon

Table 1 Descriptions of the parameters used in Eq. (1), with the relevant values for the EMCCD and sCMOS systems.

Tables Icon

Table 2 R2 values for the fit of quantified PpIX concentration (log) vs true PpIX concentration (log) for the CMOS and EMCCD systems at different exposure times.

Equations (2)

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SNR= QE×( I PpIX + I Bkg ) F 2 [ ( I PpIX + I Bkg )×QE×T+D×T+C ]+ σ 2 G 2 ,
I m = 299R+587G+114B 1000

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