Abstract

In this study the first results on evaluation and assessment of grafted bioengineered skin substitutes using an optical Diffuse Reflectance Spectroscopy (DRS) system with a remote optical probe are shown. The proposed system is able to detect early vascularization of skin substitutes expressing the Vascular Endothelial Growth Factor (VEGF) protein compared to normal grafts, even though devitalized skin is used to protect the grafts. Given the particularities of the biological problem, data analysis is performed using two Blind Signal Separation (BSS) methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). These preliminary results are the first step towards point-of-care diagnostics for skin implants early assessment.

© 2014 Optical Society of America

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References

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  1. S. MacNeil, “Progress and opportunities for tissue-engineered skin,” Nature 445(7130), 874–880 (2007).
    [Crossref] [PubMed]
  2. M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
    [Crossref] [PubMed]
  3. L. Martínez-Santamaría, S. Guerrero-Aspizua, and M. Del Río, “Skin bioengineering: preclinical and clinical applications,” Actas Dermosifiliogr. 103(1), 5–11 (2012).
  4. A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
    [Crossref] [PubMed]
  5. A. Eguizabal, A. M. Laughney, P. B. García-Allende, V. Krishnaswamy, W. A. Wells, K. D. Paulsen, B. W. Pogue, J. M. Lopez-Higuera, and O. M. Conde, “Direct identification of breast cancer pathologies using blind separation of label-free localized reflectance measurements,” Biomed. Opt. Express 4(7), 1104–1118 (2013).
    [Crossref] [PubMed]
  6. J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
    [Crossref] [PubMed]
  7. A. Hyvärinen and E. Oja, “Independent component analysis: algorithms and applications,” Neural Netw. 13(4-5), 411–430 (2000).
    [Crossref] [PubMed]
  8. J. Chen and X. Z. Wang, “A new approach to near-infrared spectral data analysis using independent component analysis,” J. Chem. Inf. Comput. Sci. 41(4), 992–1001 (2001).
    [Crossref] [PubMed]
  9. A. Croitor Sava, D. M. Sima, M. C. Martinez-Bisbal, B. Celda, and S. Van Huffel, “Non-negative blind source separation techniques for tumor tissue typing using HR-MAS signals,” in Proceedings of IEEE Conference on Engineering in Medicine and Biology Society (EMBC) (IEEE, 2010) pp. 3658–3661.
    [Crossref]
  10. A. Hyvärinen, “Fast and robust fixed-point algorithms for Independent Component Analysis,” IEEE Trans. Neural Netw. 10(3), 626–634 (1999).
    [Crossref] [PubMed]

2013 (1)

2012 (1)

L. Martínez-Santamaría, S. Guerrero-Aspizua, and M. Del Río, “Skin bioengineering: preclinical and clinical applications,” Actas Dermosifiliogr. 103(1), 5–11 (2012).

2010 (1)

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

2007 (2)

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

S. MacNeil, “Progress and opportunities for tissue-engineered skin,” Nature 445(7130), 874–880 (2007).
[Crossref] [PubMed]

2004 (1)

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

2001 (1)

J. Chen and X. Z. Wang, “A new approach to near-infrared spectral data analysis using independent component analysis,” J. Chem. Inf. Comput. Sci. 41(4), 992–1001 (2001).
[Crossref] [PubMed]

2000 (1)

A. Hyvärinen and E. Oja, “Independent component analysis: algorithms and applications,” Neural Netw. 13(4-5), 411–430 (2000).
[Crossref] [PubMed]

1999 (1)

A. Hyvärinen, “Fast and robust fixed-point algorithms for Independent Component Analysis,” IEEE Trans. Neural Netw. 10(3), 626–634 (1999).
[Crossref] [PubMed]

Amyot, F.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Chen, J.

J. Chen and X. Z. Wang, “A new approach to near-infrared spectral data analysis using independent component analysis,” J. Chem. Inf. Comput. Sci. 41(4), 992–1001 (2001).
[Crossref] [PubMed]

Chernomordik, V.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

Chernomordik, V. V.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Conde, O. M.

Dasgeb, B.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Del Río, M.

L. Martínez-Santamaría, S. Guerrero-Aspizua, and M. Del Río, “Skin bioengineering: preclinical and clinical applications,” Actas Dermosifiliogr. 103(1), 5–11 (2012).

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Demos, S. G.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Eguizabal, A.

Ehler, M.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

Escámez, M. J.

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Gandjbakhche, A. H.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

García, M.

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

García-Allende, P. B.

Guerrero-Aspizua, S.

L. Martínez-Santamaría, S. Guerrero-Aspizua, and M. Del Río, “Skin bioengineering: preclinical and clinical applications,” Actas Dermosifiliogr. 103(1), 5–11 (2012).

Hassan, M.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Hitzenberger, C. K.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

Hyvärinen, A.

A. Hyvärinen and E. Oja, “Independent component analysis: algorithms and applications,” Neural Netw. 13(4-5), 411–430 (2000).
[Crossref] [PubMed]

A. Hyvärinen, “Fast and robust fixed-point algorithms for Independent Component Analysis,” IEEE Trans. Neural Netw. 10(3), 626–634 (1999).
[Crossref] [PubMed]

Jorcano, J. L.

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Kainerstorfer, J. M.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

Krishnaswamy, V.

Larcher, F.

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Laughney, A. M.

Little, R. F.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Lopez-Higuera, J. M.

MacNeil, S.

S. MacNeil, “Progress and opportunities for tissue-engineered skin,” Nature 445(7130), 874–880 (2007).
[Crossref] [PubMed]

Martínez-Santamaría, L.

L. Martínez-Santamaría, S. Guerrero-Aspizua, and M. Del Río, “Skin bioengineering: preclinical and clinical applications,” Actas Dermosifiliogr. 103(1), 5–11 (2012).

Meana, A.

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Muñoz, E.

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Oja, E.

A. Hyvärinen and E. Oja, “Independent component analysis: algorithms and applications,” Neural Netw. 13(4-5), 411–430 (2000).
[Crossref] [PubMed]

Paulsen, K. D.

Pogue, B. W.

Pursley, R.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Riley, J. D.

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Tao, Y.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Vogel, A.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Wang, X. Z.

J. Chen and X. Z. Wang, “A new approach to near-infrared spectral data analysis using independent component analysis,” J. Chem. Inf. Comput. Sci. 41(4), 992–1001 (2001).
[Crossref] [PubMed]

Wells, W. A.

Yarchoan, R.

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

Actas Dermosifiliogr. (1)

L. Martínez-Santamaría, S. Guerrero-Aspizua, and M. Del Río, “Skin bioengineering: preclinical and clinical applications,” Actas Dermosifiliogr. 103(1), 5–11 (2012).

Biomed. Opt. Express (1)

IEEE Trans. Neural Netw. (1)

A. Hyvärinen, “Fast and robust fixed-point algorithms for Independent Component Analysis,” IEEE Trans. Neural Netw. 10(3), 626–634 (1999).
[Crossref] [PubMed]

J. Biomed. Opt. (2)

J. M. Kainerstorfer, M. Ehler, F. Amyot, M. Hassan, S. G. Demos, V. Chernomordik, C. K. Hitzenberger, A. H. Gandjbakhche, and J. D. Riley, “Principal component model of multispectral data for near real-time skin chromophore mapping,” J. Biomed. Opt. 15(4), 046007 (2010).
[Crossref] [PubMed]

A. Vogel, V. V. Chernomordik, J. D. Riley, M. Hassan, F. Amyot, B. Dasgeb, S. G. Demos, R. Pursley, R. F. Little, R. Yarchoan, Y. Tao, and A. H. Gandjbakhche, “Using noninvasive multispectral imaging to quantitatively assess tissue vasculature,” J. Biomed. Opt. 12(5), 051604 (2007).
[Crossref] [PubMed]

J. Chem. Inf. Comput. Sci. (1)

J. Chen and X. Z. Wang, “A new approach to near-infrared spectral data analysis using independent component analysis,” J. Chem. Inf. Comput. Sci. 41(4), 992–1001 (2001).
[Crossref] [PubMed]

J. Invest. Dermatol. (1)

M. J. Escámez, M. García, F. Larcher, A. Meana, E. Muñoz, J. L. Jorcano, and M. Del Río, “An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice,” J. Invest. Dermatol. 123(6), 1182–1191 (2004).
[Crossref] [PubMed]

Nature (1)

S. MacNeil, “Progress and opportunities for tissue-engineered skin,” Nature 445(7130), 874–880 (2007).
[Crossref] [PubMed]

Neural Netw. (1)

A. Hyvärinen and E. Oja, “Independent component analysis: algorithms and applications,” Neural Netw. 13(4-5), 411–430 (2000).
[Crossref] [PubMed]

Other (1)

A. Croitor Sava, D. M. Sima, M. C. Martinez-Bisbal, B. Celda, and S. Van Huffel, “Non-negative blind source separation techniques for tumor tissue typing using HR-MAS signals,” in Proceedings of IEEE Conference on Engineering in Medicine and Biology Society (EMBC) (IEEE, 2010) pp. 3658–3661.
[Crossref]

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Figures (5)

Fig. 1
Fig. 1 a) Photograph of a mouse several days after engraftment. Note the devitalized skin on top on the engraftment, avoiding direct optical access to it. b) Detail of the optical remote probe performing a measurement on a fresh engraftment.
Fig. 2
Fig. 2 Block diagram of the sensor.
Fig. 3
Fig. 3 Histological appearance of engrafted bioengineered skins seven days after grafting. a) Control graft. b) VEGF-producing graft. Note the hemorrhagic blood vessels (H) invading the fibrin dermal matrix (FM).
Fig. 4
Fig. 4 a) PCA coordinates for each engraftment on day 6. Note the clear differentiation between graft types for the first principal component. b) Concentration obtained in the ICA analysis for the three constituent components. It is possible to clearly differentiate between graft types for the constituent component 1.
Fig. 5
Fig. 5 a) Evolution of the coordinates of the first principal component of the PCA analysis for each mouse for days 2 and 6. b) Evolution of the concentration for the constituent component 1 obtained in the ICA analysis for days 2 and 6.

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