Simultaneous decomposition of multiple hyperspectral data sets: signal recovery of unknown fluorophores in the retinal pigment epithelium

R. Theodore Smith; Robert Post; Ansh Johri; Michele D. Lee; Zsolt Ablonczy; Christine A. Curcio; Thomas Ach; Paul Sajda

doi:10.1364/BOE.5.004171

Simultaneous decomposition of multiple hyperspectral data sets: signal recovery of unknown fluorophores in the retinal pigment epithelium

R. Theodore Smith, Robert Post, Ansh Johri, Michele D. Lee, Zsolt Ablonczy, Christine A. Curcio, Thomas Ach, and Paul Sajda

Biomedical Optics Express
Vol. 5,
Issue 12,
pp. 4171-4185
(2014)
•https://doi.org/10.1364/BOE.5.004171

Get Citation
Copy Citation Text
R. Theodore Smith, Robert Post, Ansh Johri, Michele D. Lee, Zsolt Ablonczy, Christine A. Curcio, Thomas Ach, and Paul Sajda, "Simultaneous decomposition of multiple hyperspectral data sets: signal recovery of unknown fluorophores in the retinal pigment epithelium," Biomed. Opt. Express 5, 4171-4185 (2014)

Export Citation
- BibTex
- Endnote (RIS)
- HTML
- Plain Text
Get PDF (9254 KB)
Set citation alerts
Save article

Related Topics
Table of Contents Category
- Spectroscopic Diagnostics
Optics & Photonics Topics
?

The topics in this list come from the OSA Optics and Photonics Topics applied to this article.
Previously assigned OCIS codes
- Image analysis (100.2960)
- Motion, hyperspectral image processing (100.4145)
- Multispectral and hyperspectral imaging (110.4234)
- Ophthalmology (170.4470)
- Spectroscopy, fluorescence and luminescence (170.6280)
- Spectroscopy, tissue diagnostics (170.6510)

About this Article
History
- Original Manuscript: June 17, 2014
- Revised Manuscript: August 17, 2014
- Manuscript Accepted: November 1, 2014
- Published: November 6, 2014

Accessible

Open Access

Abstract

Upon excitation with different wavelengths of light, biological tissues emit distinct but related autofluorescence signals. We used non-negative matrix factorization (NMF) to simultaneously decompose co-registered hyperspectral emission data from human retinal pigment epithelium/Bruch’s membrane specimens illuminated with 436 and 480 nm light. NMF analysis was initialized with Gaussian mixture model fits and constrained to provide identical abundance images for the two excitation wavelengths. Spectra recovered this way were smoother than those obtained separately; fluorophore abundances more clearly localized within tissue compartments. These studies provide evidence that leveraging multiple co-registered hyperspectral emission data sets is preferential for identifying biologically relevant fluorophore information.

Full Article | PDF Article

OSA Recommended Articles

Quantifying melanin concentration in retinal pigment epithelium using broadband photoacoustic microscopy

Xiao Shu, Hao Li, Biqin Dong, Cheng Sun, and Hao F. Zhang
Biomed. Opt. Express 8(6) 2851-2865 (2017)

In vivo imaging of retinal pigment epithelium cells in age related macular degeneration

Ethan A. Rossi, Piero Rangel-Fonseca, Keith Parkins, William Fischer, Lisa R. Latchney, Margaret A. Folwell, David R. Williams, Alfredo Dubra, and Mina M. Chung
Biomed. Opt. Express 4(11) 2527-2539 (2013)

Tensor methods for hyperspectral data analysis: a space object material identification study

Qiang Zhang, Han Wang, Robert J. Plemmons, and V. Pau'l Pauca
J. Opt. Soc. Am. A 25(12) 3001-3012 (2008)

References

View by:
Article Order
|
Year
|
Author
|
Publication

N. Lee, J. Wielaard, A. A. Fawzi, P. Sajda, A. F. Laine, G. Martin, M. S. Humayun, and R. T. Smith, “In vivo snapshot hyperspectral image analysis of age-related macular degeneration,” in Engineering in Medicine and Biology Society (EMBC),2010Annual International Conference of the IEEE (IEEE, 2010), pp. 5363–5366.
[Crossref]
P. Sajda, “Machine learning for detection and diagnosis of disease,” Annu. Rev. Biomed. Eng. 8(1), 537–565 (2006).
[Crossref] [PubMed]
P. Sajda, S. Du, T. R. Brown, R. Stoyanova, D. C. Shungu, X. Mao, and L. C. Parra, “Nonnegative matrix factorization for rapid recovery of constituent spectra in magnetic resonance chemical shift imaging of the brain,” IEEE Trans. Med. Imaging 23(12), 1453–1465 (2004).
[Crossref] [PubMed]
P. Sajda, S. Du, and L. C. Parra, “Recovery of constituent spectra using non-negative matrix factorization,” in Proceedings of SPIEVol. 5207, Wavelets: Applications in Signal and Image Processing X, M. A. Unser, A. Aldroubi, and A. F. Laine, eds. (SPIE, 2003), pp. 321–331.
C. A. Curcio and M. Johnson, “Structure, function, and pathology of Bruch's membrane,” in Retina Vol. 1, Fifth ed., S. J. Ryan, A. P. Schachat, C. P. Wilkinson, D. R. Hinton, S. Sadda, and P. Wiedemann, eds. (Elsevier, 2013).
A. Shashua and T. Hazan, “Non-negative tensor factorization with applications to statistics and computer vision,” in Proceedings of the 22nd International Conference on Machine Learning (ACM, 2005), pp. 792–799.
[Crossref]
R. A. Neher, M. Mitkovski, F. Kirchhoff, E. Neher, F. J. Theis, and A. Zeug, “Blind source separation techniques for the decomposition of multiply labeled fluorescence images,” Biophys. J. 96(9), 3791–3800 (2009).
[Crossref] [PubMed]
A. Cichocki, R. Zdunek, A. H. Phan, and S. Amari, Nonnegative Matrix and Tensor Factorizations: Applications to Exploratory Multi-Way Data Analysis and Blind Source Separation (John Wiley & Sons, 2009).
J. R. Sparrow, E. Gregory-Roberts, K. Yamamoto, A. Blonska, S. K. Ghosh, K. Ueda, and J. Zhou, “The bisretinoids of retinal pigment epithelium,” Prog. Retin. Eye Res. 31(2), 121–135 (2012).
[Crossref] [PubMed]
O. Strauss, “The retinal pigment epithelium in visual function,” Physiol. Rev. 85(3), 845–881 (2005).
[Crossref] [PubMed]
M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. I. Comparative histology,” Arch. Ophthalmol. 78(5), 641–649 (1967).
[Crossref] [PubMed]
J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]
L. Feeney, “Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies,” Invest. Ophthalmol. Vis. Sci. 17(7), 583–600 (1978).
[PubMed]
K. P. Ng, B. Gugiu, K. Renganathan, M. W. Davies, X. Gu, J. S. Crabb, S. R. Kim, M. B. Rózanowska, V. L. Bonilha, M. E. Rayborn, R. G. Salomon, J. R. Sparrow, M. E. Boulton, J. G. Hollyfield, and J. W. Crabb, “Retinal pigment epithelium lipofuscin proteomics,” Mol. Cell. Proteomics 7(7), 1397–1405 (2008).
[Crossref] [PubMed]
P. H. Tang, M. Kono, Y. Koutalos, Z. Ablonczy, and R. K. Crouch, “New insights into retinoid metabolism and cycling within the retina,” Prog. Retin. Eye Res. 32, 48–63 (2013).
[Crossref] [PubMed]
J. C. Hwang, J. W. Chan, S. Chang, and R. T. Smith, “Predictive value of fundus autofluorescence for development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(6), 2655–2661 (2006).
[Crossref] [PubMed]
J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]
Z. Ablonczy, D. Higbee, D. M. Anderson, M. Dahrouj, A. C. Grey, D. Gutierrez, Y. Koutalos, K. L. Schey, A. Hanneken, and R. K. Crouch, “Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 54(8), 5535–5542 (2013).
[Crossref] [PubMed]
L. Feeney-Burns, E. R. Berman, and H. Rothman, “Lipofuscin of human retinal pigment epithelium,” Am. J. Ophthalmol. 90(6), 783–791 (1980).
[Crossref] [PubMed]
G. E. Eldred and M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]
Y. Wu, N. E. Fishkin, A. Pande, J. Pande, and J. R. Sparrow, “Novel lipofuscin bisretinoids prominent in human retina and in a model of recessive Stargardt disease,” J. Biol. Chem. 284(30), 20155–20166 (2009).
[Crossref] [PubMed]
K. Yamamoto, K. D. Yoon, K. Ueda, M. Hashimoto, and J. R. Sparrow, “A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine,” Invest. Ophthalmol. Vis. Sci. 52(12), 9084–9090 (2011).
[Crossref] [PubMed]
Y. P. Jang, H. Matsuda, Y. Itagaki, K. Nakanishi, and J. R. Sparrow, “Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin,” J. Biol. Chem. 280(48), 39732–39739 (2005).
[Crossref] [PubMed]
S. R. Kim, Y. P. Jang, S. Jockusch, N. E. Fishkin, N. J. Turro, and J. R. Sparrow, “The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19273–19278 (2007).
[Crossref] [PubMed]
Z. Ablonczy, N. Smith, D. M. Anderson, A. C. Grey, J. Spraggins, Y. Koutalos, K. L. Schey, and R. K. Crouch, “The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry,” Proteomics 14(7-8), 936–944 (2014).
[Crossref] [PubMed]
Z. Ablonczy, D. Higbee, A. C. Grey, Y. Koutalos, K. L. Schey, and R. K. Crouch, “Similar molecules spatially correlate with lipofuscin and N-retinylidene-N-retinylethanolamine in the mouse but not in the human retinal pigment epithelium,” Arch. Biochem. Biophys. 539(2), 196–202 (2013).
[Crossref] [PubMed]
T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]
J. J. Weiter, F. C. Delori, G. L. Wing, and K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Vis. Sci. 27(2), 145–152 (1986).
[PubMed]
V. P. Gabel, R. Birngruber, and F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in Proceedings of the 23rd International Congress of Ophthalmology, K. Shimizu and J. A. Oosterhuis, eds. (Exerpta Medica, 1979), pp. 658–662.
T. Ach, G. Best, S. Rossberger, R. Heintzmann, C. Cremer, and S. Dithmar, “Autofluorescence imaging of human RPE cell granules using structured illumination microscopy,” Br. J. Ophthalmol. 96(8), 1141–1144 (2012).
[Crossref] [PubMed]
T. Pengo, A. Muñoz-Barrutia, I. Zudaire, and C. Ortiz-de-Solorzano, “Efficient blind spectral unmixing of fluorescently labeled samples using multi-layer non-negative matrix factorization,” PLoS ONE 8(11), e78504 (2013).
[Crossref] [PubMed]

2014 (2)

Z. Ablonczy, N. Smith, D. M. Anderson, A. C. Grey, J. Spraggins, Y. Koutalos, K. L. Schey, and R. K. Crouch, “The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry,” Proteomics 14(7-8), 936–944 (2014).
[Crossref] [PubMed]

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

2013 (4)

Z. Ablonczy, D. Higbee, A. C. Grey, Y. Koutalos, K. L. Schey, and R. K. Crouch, “Similar molecules spatially correlate with lipofuscin and N-retinylidene-N-retinylethanolamine in the mouse but not in the human retinal pigment epithelium,” Arch. Biochem. Biophys. 539(2), 196–202 (2013).
[Crossref] [PubMed]

T. Pengo, A. Muñoz-Barrutia, I. Zudaire, and C. Ortiz-de-Solorzano, “Efficient blind spectral unmixing of fluorescently labeled samples using multi-layer non-negative matrix factorization,” PLoS ONE 8(11), e78504 (2013).
[Crossref] [PubMed]

P. H. Tang, M. Kono, Y. Koutalos, Z. Ablonczy, and R. K. Crouch, “New insights into retinoid metabolism and cycling within the retina,” Prog. Retin. Eye Res. 32, 48–63 (2013).
[Crossref] [PubMed]

Z. Ablonczy, D. Higbee, D. M. Anderson, M. Dahrouj, A. C. Grey, D. Gutierrez, Y. Koutalos, K. L. Schey, A. Hanneken, and R. K. Crouch, “Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 54(8), 5535–5542 (2013).
[Crossref] [PubMed]

2012 (2)

J. R. Sparrow, E. Gregory-Roberts, K. Yamamoto, A. Blonska, S. K. Ghosh, K. Ueda, and J. Zhou, “The bisretinoids of retinal pigment epithelium,” Prog. Retin. Eye Res. 31(2), 121–135 (2012).
[Crossref] [PubMed]

T. Ach, G. Best, S. Rossberger, R. Heintzmann, C. Cremer, and S. Dithmar, “Autofluorescence imaging of human RPE cell granules using structured illumination microscopy,” Br. J. Ophthalmol. 96(8), 1141–1144 (2012).
[Crossref] [PubMed]

2011 (1)

K. Yamamoto, K. D. Yoon, K. Ueda, M. Hashimoto, and J. R. Sparrow, “A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine,” Invest. Ophthalmol. Vis. Sci. 52(12), 9084–9090 (2011).
[Crossref] [PubMed]

2010 (1)

J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]

2009 (2)

R. A. Neher, M. Mitkovski, F. Kirchhoff, E. Neher, F. J. Theis, and A. Zeug, “Blind source separation techniques for the decomposition of multiply labeled fluorescence images,” Biophys. J. 96(9), 3791–3800 (2009).
[Crossref] [PubMed]

Y. Wu, N. E. Fishkin, A. Pande, J. Pande, and J. R. Sparrow, “Novel lipofuscin bisretinoids prominent in human retina and in a model of recessive Stargardt disease,” J. Biol. Chem. 284(30), 20155–20166 (2009).
[Crossref] [PubMed]

2008 (1)

K. P. Ng, B. Gugiu, K. Renganathan, M. W. Davies, X. Gu, J. S. Crabb, S. R. Kim, M. B. Rózanowska, V. L. Bonilha, M. E. Rayborn, R. G. Salomon, J. R. Sparrow, M. E. Boulton, J. G. Hollyfield, and J. W. Crabb, “Retinal pigment epithelium lipofuscin proteomics,” Mol. Cell. Proteomics 7(7), 1397–1405 (2008).
[Crossref] [PubMed]

2007 (1)

S. R. Kim, Y. P. Jang, S. Jockusch, N. E. Fishkin, N. J. Turro, and J. R. Sparrow, “The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19273–19278 (2007).
[Crossref] [PubMed]

2006 (2)

P. Sajda, “Machine learning for detection and diagnosis of disease,” Annu. Rev. Biomed. Eng. 8(1), 537–565 (2006).
[Crossref] [PubMed]

J. C. Hwang, J. W. Chan, S. Chang, and R. T. Smith, “Predictive value of fundus autofluorescence for development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(6), 2655–2661 (2006).
[Crossref] [PubMed]

2005 (2)

Y. P. Jang, H. Matsuda, Y. Itagaki, K. Nakanishi, and J. R. Sparrow, “Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin,” J. Biol. Chem. 280(48), 39732–39739 (2005).
[Crossref] [PubMed]

O. Strauss, “The retinal pigment epithelium in visual function,” Physiol. Rev. 85(3), 845–881 (2005).
[Crossref] [PubMed]

2004 (1)

P. Sajda, S. Du, T. R. Brown, R. Stoyanova, D. C. Shungu, X. Mao, and L. C. Parra, “Nonnegative matrix factorization for rapid recovery of constituent spectra in magnetic resonance chemical shift imaging of the brain,” IEEE Trans. Med. Imaging 23(12), 1453–1465 (2004).
[Crossref] [PubMed]

2003 (1)

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

1988 (1)

G. E. Eldred and M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

1986 (1)

J. J. Weiter, F. C. Delori, G. L. Wing, and K. A. Fitch, “Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes,” Invest. Ophthalmol. Vis. Sci. 27(2), 145–152 (1986).
[PubMed]

1980 (1)

L. Feeney-Burns, E. R. Berman, and H. Rothman, “Lipofuscin of human retinal pigment epithelium,” Am. J. Ophthalmol. 90(6), 783–791 (1980).
[Crossref] [PubMed]

1978 (1)

L. Feeney, “Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies,” Invest. Ophthalmol. Vis. Sci. 17(7), 583–600 (1978).
[PubMed]

1967 (1)

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. I. Comparative histology,” Arch. Ophthalmol. 78(5), 641–649 (1967).
[Crossref] [PubMed]

Ablonczy, Z.

Ach, T.

Anderson, D. M.

Bentley, M. J.

Berman, E. R.

L. Feeney-Burns, E. R. Berman, and H. Rothman, “Lipofuscin of human retinal pigment epithelium,” Am. J. Ophthalmol. 90(6), 783–791 (1980).
[Crossref] [PubMed]

Best, G.

Blonska, A.

Bonilha, V. L.

Boulton, M. E.

Brown, T. R.

Cai, B.

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Chan, J. W.

Chang, S.

Crabb, J. S.

Crabb, J. W.

Cremer, C.

Crouch, R. K.

Curcio, C. A.

Dahrouj, M.

Davies, M. W.

Delori, F. C.

Dithmar, S.

Du, S.

Eldred, G. E.

G. E. Eldred and M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

Feeney, L.

Feeney-Burns, L.

L. Feeney-Burns, E. R. Berman, and H. Rothman, “Lipofuscin of human retinal pigment epithelium,” Am. J. Ophthalmol. 90(6), 783–791 (1980).
[Crossref] [PubMed]

Fishkin, N.

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Fishkin, N. E.

Fitch, K. A.

Friedman, E.

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. I. Comparative histology,” Arch. Ophthalmol. 78(5), 641–649 (1967).
[Crossref] [PubMed]

Ghosh, S. K.

Gregory-Roberts, E.

Grey, A. C.

Gu, X.

Gugiu, B.

Gutierrez, D.

Gutierrez, D. B.

Hanneken, A.

Hashimoto, M.

Hazan, T.

A. Shashua and T. Hazan, “Non-negative tensor factorization with applications to statistics and computer vision,” in Proceedings of the 22nd International Conference on Machine Learning (ACM, 2005), pp. 792–799.
[Crossref]

Heintzmann, R.

Higbee, D.

Hollyfield, J. G.

Huisingh, C.

Hwang, J. C.

Itagaki, Y.

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Jang, Y. P.

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Jockusch, S.

Katz, M. L.

G. E. Eldred and M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

Kim, C. Y.

J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]

Kim, S. R.

Kirchhoff, F.

Kono, M.

Koutalos, Y.

Krane, S.

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Mao, X.

Matsuda, H.

McGwin, G.

Messinger, J. D.

Mitkovski, M.

Muñoz-Barrutia, A.

Nakanishi, K.

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Neher, E.

Neher, R. A.

Ng, K. P.

Ortiz-de-Solorzano, C.

Pande, A.

Pande, J.

Parra, L. C.

Pengo, T.

Rayborn, M. E.

Renganathan, K.

Rossberger, S.

Rothman, H.

L. Feeney-Burns, E. R. Berman, and H. Rothman, “Lipofuscin of human retinal pigment epithelium,” Am. J. Ophthalmol. 90(6), 783–791 (1980).
[Crossref] [PubMed]

Rózanowska, M. B.

Sajda, P.

P. Sajda, “Machine learning for detection and diagnosis of disease,” Annu. Rev. Biomed. Eng. 8(1), 537–565 (2006).
[Crossref] [PubMed]

Salomon, R. G.

Schey, K. L.

Shashua, A.

Shungu, D. C.

Sloan, K. R.

Smith, N.

Smith, R. T.

Sparrow, J. R.

J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Spraggins, J.

Stoyanova, R.

Strauss, O.

O. Strauss, “The retinal pigment epithelium in visual function,” Physiol. Rev. 85(3), 845–881 (2005).
[Crossref] [PubMed]

Tang, P. H.

Theis, F. J.

Ts’o, M. O.

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. I. Comparative histology,” Arch. Ophthalmol. 78(5), 641–649 (1967).
[Crossref] [PubMed]

Turro, N. J.

Ueda, K.

Weiter, J. J.

Wing, G. L.

Wu, Y.

J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]

Yamamoto, K.

Yoon, K. D.

Zeug, A.

Zhang, T.

Zhou, J.

J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Zudaire, I.

Am. J. Ophthalmol. (1)

L. Feeney-Burns, E. R. Berman, and H. Rothman, “Lipofuscin of human retinal pigment epithelium,” Am. J. Ophthalmol. 90(6), 783–791 (1980).
[Crossref] [PubMed]

Annu. Rev. Biomed. Eng. (1)

P. Sajda, “Machine learning for detection and diagnosis of disease,” Annu. Rev. Biomed. Eng. 8(1), 537–565 (2006).
[Crossref] [PubMed]

Arch. Biochem. Biophys. (1)

Arch. Ophthalmol. (1)

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. I. Comparative histology,” Arch. Ophthalmol. 78(5), 641–649 (1967).
[Crossref] [PubMed]

Biophys. J. (1)

Br. J. Ophthalmol. (1)

Exp. Eye Res. (1)

G. E. Eldred and M. L. Katz, “Fluorophores of the human retinal pigment epithelium: separation and spectral characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

IEEE Trans. Med. Imaging (1)

Invest. Ophthalmol. Vis. Sci. (6)

J. Biol. Chem. (2)

J. Lipid Res. (1)

J. R. Sparrow, Y. Wu, C. Y. Kim, and J. Zhou, “Phospholipid meets all-trans-retinal: the making of RPE bisretinoids,” J. Lipid Res. 51(2), 247–261 (2010).
[Crossref] [PubMed]

Mol. Cell. Proteomics (1)

Physiol. Rev. (1)

O. Strauss, “The retinal pigment epithelium in visual function,” Physiol. Rev. 85(3), 845–881 (2005).
[Crossref] [PubMed]

PLoS ONE (1)

Proc. Natl. Acad. Sci. U.S.A. (1)

Prog. Retin. Eye Res. (2)

Proteomics (1)

Vision Res. (1)

J. R. Sparrow, N. Fishkin, J. Zhou, B. Cai, Y. P. Jang, S. Krane, Y. Itagaki, and K. Nakanishi, “A2E, a byproduct of the visual cycle,” Vision Res. 43(28), 2983–2990 (2003).
[Crossref] [PubMed]

Other (6)

N. Lee, J. Wielaard, A. A. Fawzi, P. Sajda, A. F. Laine, G. Martin, M. S. Humayun, and R. T. Smith, “In vivo snapshot hyperspectral image analysis of age-related macular degeneration,” in Engineering in Medicine and Biology Society (EMBC),2010Annual International Conference of the IEEE (IEEE, 2010), pp. 5363–5366.
[Crossref]

A. Cichocki, R. Zdunek, A. H. Phan, and S. Amari, Nonnegative Matrix and Tensor Factorizations: Applications to Exploratory Multi-Way Data Analysis and Blind Source Separation (John Wiley & Sons, 2009).

P. Sajda, S. Du, and L. C. Parra, “Recovery of constituent spectra using non-negative matrix factorization,” in Proceedings of SPIEVol. 5207, Wavelets: Applications in Signal and Image Processing X, M. A. Unser, A. Aldroubi, and A. F. Laine, eds. (SPIE, 2003), pp. 321–331.

C. A. Curcio and M. Johnson, “Structure, function, and pathology of Bruch's membrane,” in Retina Vol. 1, Fifth ed., S. J. Ryan, A. P. Schachat, C. P. Wilkinson, D. R. Hinton, S. Sadda, and P. Wiedemann, eds. (Elsevier, 2013).

V. P. Gabel, R. Birngruber, and F. Hillenkamp, “Visible and near infrared light absorption in pigment epithelium and choroid,” in Proceedings of the 23rd International Congress of Ophthalmology, K. Shimizu and J. A. Oosterhuis, eds. (Exerpta Medica, 1979), pp. 658–662.

Cited By

OSA participates in Crossref's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.

Click here to see a list of articles that cite this paper

Fig. 1 Quantum efficiency (QE) of the Nuance camera spectral detector (arbitrary units) supplied by the manufacturer (Caliper Life Sciences). The QE is approximately linear from 400 to 700 nm, with some small shoulders, and then drops at 700 nm. Since both RPE and BrM have intrinsic autofluorescence properties, and RPE anatomically overlies BrM, the hyperspectral data cubes captured the sum of the RPE signal and a portion of that from the underlying BrM. Hence, to assist in identifying the pure RPE spectrum at each location, a pure BrM signal without overlying RPE cells was also recorded separately from areas where a few RPE cells were dislodged during preparation. For locations at which the RPE monolayer was completely intact, a pure BrM signal was separately imaged at an adjacent area.

Download Full Size | PPT Slide | PDF

Fig. 2 The pure spectrum of the RPE. Left: RGB composite AF image from a 47-year-old female donor, excitation 480 nm, perifovea. Sample raw spectral data (photon counts) were acquired in regions marked. Green mark: BrM in isolation. Red marks: RPE cells containing lipofuscin overlying BrM. Right: Separated emission curves. Green: isolated BrM. Red: RPE overlying BrM, which includes 25% of the pure BrM signal. Magenta: pure RPE signal (after subtraction of 25% of the BrM signal).

Download Full Size | PPT Slide | PDF

Fig. 3 Gaussian fits to a sample RPE spectrum. The pure RPE hyperspectral data from Fig. 2 (black line) were calibrated to the acquisition time of 18 ms and instrument gain of 3 to yield spectral intensity in units of photons/sec and then fit to the four Gaussian components of the mixture model. The arrows indicate two peaks and two slight shoulders in the original spectrum. The mixture model (sum of four Gaussians) is the solid magenta line and largely overlies the original RPE data (an overall excellent fit). Note that the centers of the Gaussians, especially Gaussian 3 (red), do not necessarily coincide with the original peaks in the RPE data. The dotted magenta lines are the 95% confidence prediction bounds of the model under the assumption of 5% random error in the original RPE spectrum.

Download Full Size | PPT Slide | PDF

Fig. 4 RPE flatmount, 90-year-old female donor, perifovea. A, (B), spectra recovered from 436 nm excitation; (C), (D), spectra recovered from 480 nm excitation. (A), (C), decomposed spectra from individual excitation data sets; (B), (D), spectra from simultaneous solution of both excitation data sets. The tissue image is a full 40X field. The five individual spectra in each set are labeled C1 to C5. The corresponding abundance images are also labeled C1 to C5, with false coloring to indicate the relative signal intensities. The spectra in (A), (C) have multiple subsidiary peaks, suggesting contributions from multiple sources. Those from 480 nm excitation are particularly jagged, while two signals from 436 nm excitation are nearly degenerate (C4, C5). The spectra in (B), (D) are all broad, as expected from known fluorophore data, and can be paired by shape and location. In particular, there are no degenerate solutions in the simultaneous solutions. The recovered paired spectra are smoother than either spectrum recovered separately, with more congruent shapes. The lower right element of each panel is the composite RGB image from the total AF signal for that excitation. The constrained identical abundance images on the right for each pair of spectra show precise anatomic detail and are more clearly defined than the abundances recovered individually; hence they are more consistent with well-defined species of emitter. For example, C3 is more specifically localized to isolated BrM than its counterparts in the individual cases, at both excitation wavelengths. Signals from RPE cells (C1, C2, C4, and C5) can be distinguished from each other by the relative size of the signal-poor region (blue) in the center of each hexagonal RPE cell in the concatenated solutions, whereas such distinctions between the abundances in the individual solutions are slight. C1-436 and C2-480, similarly shaped, are linked, initialized with Gaussians at 600 nm; C3 is BrM in each; C4 and C5 are linked in each; C1-480 is linked to, and red-shifted from, C2-436.

Download Full Size | PPT Slide | PDF

Fig. 5 Graded improvement in spectral recovery. Top: Moderate improvement in spectral recovery with concatenated NMF. Jagged C2 and C3 are replaced by smoother C3 and C4, both significantly improved. The other signals are not improved. NTF improvement is graded moderate. Bottom: No improvement. C5, almost degenerate, regains amplitude with NTF, but C4 changes from a single peak to two. Net improvement is graded none.

Download Full Size | PPT Slide | PDF

Fig. 6 BrM total emission spectra; perifovea of a 78-year-old female donor; excitations at 436 and 480 nm. Each signal was fit with three approximately evenly spaced Gaussians (not shown) in a manner similar to that in Fig. 3.

Download Full Size | PPT Slide | PDF

Fig. 7 Isolated BrM; perifovea of 78-year-old female donor. (A), (B), spectra recovered from 436 nm excitation; (C), (D), spectra recovered from 480 nm excitation. (A), (C), decomposed spectra from individual excitation data sets; (B), (D), spectra from NTF, simultaneous solution of all three concatenated excitation data sets. Three abundant signals are recovered with NMF decomposition of each individual excitation data set and with the concatenated solution. The corresponding abundance images are C1, C2, and C3 in each set. False coloring indicates the relative intensities of the signals. The lower right panel in each set is the composite RGB image from the total AF signal for that excitation.

Download Full Size | PPT Slide | PDF

Equations (2)

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

X_{λ} = A_{λ} S_{λ}

[X_{λ_{1}} X_{λ_{2}} \dots X_{λ_{n}}] = A [S_{λ_{1}} S_{λ_{2}} \dots S_{λ_{n}}]