Abstract

The molecular bases of Alzheimer disease and related neurodegenerative disorders are becoming better understood, but the means for definitive diagnosis and monitoring in vivo remain lacking. Near-infrared optical spectroscopy offers a potential solution. We acquired transmission and reflectance spectra of thin brain tissue slabs, from which we calculated wavelength-dependent absorption and reduced scattering coefficients from 4701000nm. The reduced scattering coefficients in the near infrared clearly differentiated Alzheimer from control specimens. Diffuse reflectance spectra of gross brain tissue in vitro confirmed this observation. These results suggest a means for diagnosing and monitoring Alzheimer disease in vivo, using near-infrared optical spectroscopy.

© 2008 Optical Society of America

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    [PubMed]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [PubMed]

2006

A. Coimbra, D. S. Williams, and E. D. Hostetler, Curr. Top Med. Chem. 6, 629 (2006).
[CrossRef] [PubMed]

2005

C. R. Jack, M. M. Shiung, S. D. Weigand, P. C. O'Brien, J. L. Gunter, B. F. Boeve, D. S. Knopman, G. E. Smith, R. J. Ivnik, E. G. Tangalos, and R. C. Petersen, Neurology 65, 27 (2005).
[CrossRef]

M. Hintersteiner, A. Enz, P. Frey, A. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. Wiederhold, and H. Gremlich, Nat. Biotechnol. 23, 577 (2005).
[CrossRef] [PubMed]

H. Braak and E. Braak, Acta Neuropathol. (Berl) 82, 239 (2005).
[CrossRef]

2004

C. A. Mathis, Y. Wang, and W. E. Klunk, Curr. Pharm. Des. 10, 1469 (2004).
[CrossRef] [PubMed]

2003

M. M. Machulda, H. A. Ward, B. Borowski, J. L. Gunter, R. H. Cha, P. C. O'Brien, R. C. Petersen, B. F. Boeve, D. Knopman, D. F. Tang-Wai, R. J. Ivnik, G. E. Smith, E. G. Tangalos, and C. R. Jack, Neurology 61, 500 (2003).
[PubMed]

2002

G. Strangman, J. P. Culver, J. H. Thompson, and D. A. Boas, Neuroimage 17, 719 (2002).
[CrossRef] [PubMed]

2001

M. C. Irizarry and B. T. Hyman, J. Neuropathol. Exp. Neurol. 60, 923 (2001).
[PubMed]

1999

E. B. Hanlon, I. Itzkan, R. R. Dasari, M. S. Feld, R. J. Ferrante, A. C. McKee, D. Lathi, and N. W. Kowall, Photochem. Photobiol. 70, 236 (1999).
[PubMed]

1998

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

1997

C. Hock, K. Villringer, F. Muller-Spahn, R. Wenzel, H. Heekeren, S. Schuh-Hofer, M. Hofmann, S. Minoshima, M. Schwaiger, U. Dirnagl, and A. Villringer, Brain Res. 755, 293 (1997).
[CrossRef] [PubMed]

1993

P. Van der Zee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

1990

W. F. Cheong, S. A. Prahl, and A. J. Welch, IEEE J. Quantum Electron. 26, 2166 (1990).
[CrossRef]

Acta Neuropathol. (Berl)

H. Braak and E. Braak, Acta Neuropathol. (Berl) 82, 239 (2005).
[CrossRef]

Brain Res.

C. Hock, K. Villringer, F. Muller-Spahn, R. Wenzel, H. Heekeren, S. Schuh-Hofer, M. Hofmann, S. Minoshima, M. Schwaiger, U. Dirnagl, and A. Villringer, Brain Res. 755, 293 (1997).
[CrossRef] [PubMed]

Curr. Pharm. Des.

C. A. Mathis, Y. Wang, and W. E. Klunk, Curr. Pharm. Des. 10, 1469 (2004).
[CrossRef] [PubMed]

Curr. Top Med. Chem.

A. Coimbra, D. S. Williams, and E. D. Hostetler, Curr. Top Med. Chem. 6, 629 (2006).
[CrossRef] [PubMed]

IEEE J. Quantum Electron.

W. F. Cheong, S. A. Prahl, and A. J. Welch, IEEE J. Quantum Electron. 26, 2166 (1990).
[CrossRef]

J. Neuropathol. Exp. Neurol.

M. C. Irizarry and B. T. Hyman, J. Neuropathol. Exp. Neurol. 60, 923 (2001).
[PubMed]

Nat. Biotechnol.

M. Hintersteiner, A. Enz, P. Frey, A. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. Wiederhold, and H. Gremlich, Nat. Biotechnol. 23, 577 (2005).
[CrossRef] [PubMed]

Neuroimage

G. Strangman, J. P. Culver, J. H. Thompson, and D. A. Boas, Neuroimage 17, 719 (2002).
[CrossRef] [PubMed]

Neurology

M. M. Machulda, H. A. Ward, B. Borowski, J. L. Gunter, R. H. Cha, P. C. O'Brien, R. C. Petersen, B. F. Boeve, D. Knopman, D. F. Tang-Wai, R. J. Ivnik, G. E. Smith, E. G. Tangalos, and C. R. Jack, Neurology 61, 500 (2003).
[PubMed]

C. R. Jack, M. M. Shiung, S. D. Weigand, P. C. O'Brien, J. L. Gunter, B. F. Boeve, D. S. Knopman, G. E. Smith, R. J. Ivnik, E. G. Tangalos, and R. C. Petersen, Neurology 65, 27 (2005).
[CrossRef]

Photochem. Photobiol.

E. B. Hanlon, I. Itzkan, R. R. Dasari, M. S. Feld, R. J. Ferrante, A. C. McKee, D. Lathi, and N. W. Kowall, Photochem. Photobiol. 70, 236 (1999).
[PubMed]

Phys. Rev. Lett.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Proc. SPIE

P. Van der Zee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

Other

E. P. Zede, A. P. Ivanov, and I. L. Katsev, Image Transfer Through a Scattering Medium (Springer-Verlag, 1991).

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Figures (4)

Fig. 1
Fig. 1

Total reflectance ( R ) and transmission ( T ) spectra, acquired with an integrating sphere, of 1 mm thick brain tissue slabs from confirmed AD (broken curve) and non-AD (solid curve) cases.

Fig. 2
Fig. 2

Reflectance and transmission (R, T) calculated for a turbid slab of 1 mm thickness using Eqs. (1, 2) (solid curve) and Monte Carlo simulations (symbols) over a range of 0.01 μ a 10.0 ( cm 1 ) and 1 μ s 100 ( cm 1 ) . Open symbols indicate reflectance; solid symbols indicate transmission. Triangles, μ s = 100 cm 1 ; circles, μ s = 10 cm 1 ; diamonds, μ s = 1 cm 1 .

Fig. 3
Fig. 3

Absorption ( μ a ) and reduced scattering ( μ s ) coefficients for non-AD and AD brain tissue obtained by fitting Eqs. (1, 2) to experiment (Fig. 1).

Fig. 4
Fig. 4

Mean diffuse reflectance spectra of intact temporal pole specimens from neuropathologically confirmed AD cases (AD), n = 5 , and control cases (non-AD), n = 4 . Error bars indicate the standard error of the mean for the AD and non-AD populations based on the spectra measured for each group.

Equations (4)

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R = 1 r 2 r C ,
T = [ C r Λ 2 ( 1 r ) ( 1 + γ ) ( 1 exp [ 1 ( 1 + λ ) τ ] ) ] exp ( γ τ ) + [ C + Λ 2 ( 1 r ) ( 1 + γ ) ( 1 exp [ 1 ( 1 λ ) τ ] ) ] exp ( γ τ ) ,
C = r Λ / 2 ( 1 r ) ( 1 + γ ) ( 1 r 2 exp ( 2 γ τ ) ) [ 1 r ( ( 1 + γ ) / ( 1 γ ) ) exp ( 2 γ τ ) + ( r ( ( 1 + γ ) / ( 1 γ ) ) 1 ) exp ( ( 1 + γ ) τ ) ]
r = [ ( a ( 1 Λ ) γ / b Λ ] 1 ,

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