Abstract

Several investigators have demonstrated techniques for noninvasive measurement of the oxygen saturation of blood in retinal arteries and veins. These techniques have been based on measuring the optical density of a retinal vessel at multiple wavelengths and on calculating the oxygen saturation on the basis of the known absorption coefficients of hemoglobin and oxyhemoglobin. A technique is presented for determining the optimum wavelengths for retinal oximetry measurements. What is believed to be a novel wavelength combination of 488, 635, and 905 nm is found to provide excellent oxygen sensitivity across a broad range of typical vessel diameters and saturations. The use of this wavelength combination should allow for the most accurate retinal saturation measurements made to date.

© 1999 Optical Society of America

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References

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  1. J. B. Hickam, R. Frayser, J. C. Ross, “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation 27, 375–385 (1963).
    [CrossRef] [PubMed]
  2. A. J. Cohen, R. A. Laing, “Multiple scattering analysis of retinal blood oximetry,” IEEE Trans. Biomed. Eng. 23, 391–400 (1976).
    [CrossRef] [PubMed]
  3. F. C. Delori, “Noninvasive technique for oximetry of blood in retinal vessels,” Appl. Opt. 27, 1113–1125 (1988).
    [CrossRef] [PubMed]
  4. D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
    [CrossRef]
  5. J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
    [CrossRef] [PubMed]
  6. M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
    [CrossRef] [PubMed]
  7. K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
    [CrossRef] [PubMed]
  8. O. W. Van Assendelft, Spectrophotometry of Haemoglobin Derivatives (Thomas, Springfield, Ill., 1970).
  9. V. Twersky, “Multiple scattering of waves and optical phenomena,” J. Opt. Soc. Am. 52, 145–171 (1962).
    [CrossRef] [PubMed]
  10. V. Twersky, “Absorption and multiple scattering by biological suspensions,” J. Opt. Soc. Am. 60, 1084–1093 (1970).
    [CrossRef] [PubMed]
  11. R. N. Pittman, B. R. Duling, “A new method for the measurement of percent oxyhemoglobin,” J. Appl. Phys. 38, 315–320 (1975).
  12. A. L. Lehninger, Biochemistry (Worth, New York, 1975).
  13. W. J. Geeraets, E. R. Berry, “Ocular spectral characteristics as related to hazards from lasers and other light sources,” Am. J. Ophthalmol. 66, 15–20 (1968).
    [PubMed]

1998 (2)

J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
[CrossRef] [PubMed]

M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
[CrossRef] [PubMed]

1997 (1)

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

1988 (1)

1976 (1)

A. J. Cohen, R. A. Laing, “Multiple scattering analysis of retinal blood oximetry,” IEEE Trans. Biomed. Eng. 23, 391–400 (1976).
[CrossRef] [PubMed]

1975 (1)

R. N. Pittman, B. R. Duling, “A new method for the measurement of percent oxyhemoglobin,” J. Appl. Phys. 38, 315–320 (1975).

1970 (1)

1968 (1)

W. J. Geeraets, E. R. Berry, “Ocular spectral characteristics as related to hazards from lasers and other light sources,” Am. J. Ophthalmol. 66, 15–20 (1968).
[PubMed]

1963 (1)

J. B. Hickam, R. Frayser, J. C. Ross, “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation 27, 375–385 (1963).
[CrossRef] [PubMed]

1962 (1)

Bartsch, U.

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

Beach, J. M.

J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
[CrossRef] [PubMed]

Berry, E. R.

W. J. Geeraets, E. R. Berry, “Ocular spectral characteristics as related to hazards from lasers and other light sources,” Am. J. Ophthalmol. 66, 15–20 (1968).
[PubMed]

Chipman, R. A.

M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
[CrossRef] [PubMed]

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Cohen, A. J.

A. J. Cohen, R. A. Laing, “Multiple scattering analysis of retinal blood oximetry,” IEEE Trans. Biomed. Eng. 23, 391–400 (1976).
[CrossRef] [PubMed]

Delori, F. C.

Denninghoff, K. R.

M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
[CrossRef] [PubMed]

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Duling, B. R.

R. N. Pittman, B. R. Duling, “A new method for the measurement of percent oxyhemoglobin,” J. Appl. Phys. 38, 315–320 (1975).

Frayser, R.

J. B. Hickam, R. Frayser, J. C. Ross, “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation 27, 375–385 (1963).
[CrossRef] [PubMed]

Geeraets, W. J.

W. J. Geeraets, E. R. Berry, “Ocular spectral characteristics as related to hazards from lasers and other light sources,” Am. J. Ophthalmol. 66, 15–20 (1968).
[PubMed]

Hammer, M.

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

Hickam, J. B.

J. B. Hickam, R. Frayser, J. C. Ross, “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation 27, 375–385 (1963).
[CrossRef] [PubMed]

Hillman, L. W.

M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
[CrossRef] [PubMed]

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Hughes, C. E.

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Jester, P. M.

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Kirk, S. E.

J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
[CrossRef] [PubMed]

Kuhn, F.

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Laing, R. A.

A. J. Cohen, R. A. Laing, “Multiple scattering analysis of retinal blood oximetry,” IEEE Trans. Biomed. Eng. 23, 391–400 (1976).
[CrossRef] [PubMed]

Lehninger, A. L.

A. L. Lehninger, Biochemistry (Worth, New York, 1975).

Leistritz, L.

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

Pittman, R. N.

R. N. Pittman, B. R. Duling, “A new method for the measurement of percent oxyhemoglobin,” J. Appl. Phys. 38, 315–320 (1975).

Ross, J. C.

J. B. Hickam, R. Frayser, J. C. Ross, “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation 27, 375–385 (1963).
[CrossRef] [PubMed]

Rue, L. W.

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Schweitzer, D.

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

Scibor, M.

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

Smith, M. H.

M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
[CrossRef] [PubMed]

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Srinivas, S.

J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
[CrossRef] [PubMed]

Strobel, J.

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

Tiedeman, J. S.

J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
[CrossRef] [PubMed]

Twersky, V.

Van Assendelft, O. W.

O. W. Van Assendelft, Spectrophotometry of Haemoglobin Derivatives (Thomas, Springfield, Ill., 1970).

Am. J. Ophthalmol. (1)

W. J. Geeraets, E. R. Berry, “Ocular spectral characteristics as related to hazards from lasers and other light sources,” Am. J. Ophthalmol. 66, 15–20 (1968).
[PubMed]

Appl. Opt. (1)

Circulation (1)

J. B. Hickam, R. Frayser, J. C. Ross, “A study of retinal venous blood oxygen saturation in human subjects by photographic means,” Circulation 27, 375–385 (1963).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Eng. (1)

A. J. Cohen, R. A. Laing, “Multiple scattering analysis of retinal blood oximetry,” IEEE Trans. Biomed. Eng. 23, 391–400 (1976).
[CrossRef] [PubMed]

J. Appl. Phys. (1)

R. N. Pittman, B. R. Duling, “A new method for the measurement of percent oxyhemoglobin,” J. Appl. Phys. 38, 315–320 (1975).

J. Biomed. Opt. (1)

M. H. Smith, K. R. Denninghoff, L. W. Hillman, R. A. Chipman, “Oxygen saturation measurements of blood in retinal vessels during blood loss,” J. Biomed. Opt. 3, 296–303 (1998).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (2)

J. Trauma (1)

K. R. Denninghoff, M. H. Smith, R. A. Chipman, L. W. Hillman, P. M. Jester, C. E. Hughes, F. Kuhn, L. W. Rue, “Retinal large vessel oxygen saturation correlates with early blood loss and hypoxia in anesthetized swine,” J. Trauma 43, 29–34 (1997).
[CrossRef] [PubMed]

Ophthalmology (1)

J. S. Tiedeman, S. E. Kirk, S. Srinivas, J. M. Beach, “Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy,” Ophthalmology 105, 31–36 (1998).
[CrossRef] [PubMed]

Other (3)

A. L. Lehninger, Biochemistry (Worth, New York, 1975).

O. W. Van Assendelft, Spectrophotometry of Haemoglobin Derivatives (Thomas, Springfield, Ill., 1970).

D. Schweitzer, L. Leistritz, M. Hammer, M. Scibor, U. Bartsch, J. Strobel, “Calibration-free measurement of the oxygen saturation in retinal vessels of men,” in Ophthalmic Technologies V, J.-M. Parel, Q. Ren, K. M. Joos, eds., Proc. SPIE2393, 210–218 (1995).
[CrossRef]

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Figures (8)

Fig. 1
Fig. 1

Millimolar extinction coefficients of Hb and HbO2 (data from Ref. 8).

Fig. 2
Fig. 2

Relative error in the two-wavelength saturation calculation. Light areas correspond to wavelength pairs with low associated error; dark areas correspond to high error. The error for typical (a) retinal veins and (b) arteries are plotted separately.

Fig. 3
Fig. 3

Variation in the two-wavelength saturation error for the 635- and 960-nm wavelength pair. A Hb concentration of 15 g/100 ml is assumed, and vessel diameter is indicated in the legend.

Fig. 4
Fig. 4

Wavelength triads yielding saturation errors less than 5%O2Sat., owing to transmittance measurement errors of ΔT = 0.01, are plotted. Results are displayed separately for typical retinal (a) veins and (b) arteries.

Fig. 5
Fig. 5

Relative error in the three-wavelength saturation calculation for 635 nm and two other wavelengths. Light areas correspond to wavelengths with low associated error; dark areas correspond to high error. The error for typical retinal (a) veins and (b) arteries are plotted separately.

Fig. 6
Fig. 6

Error in the three-wavelength saturation equation with 635 nm, 960 nm, and a third wavelength (x axis). Error is calculated for typical retinal veins and arteries.

Fig. 7
Fig. 7

Variation in the three-wavelength saturation error for three different wavelength triads. Vessel diameters are listed in the legends, and the Hb concentration is assumed to be 15 g/100 ml.

Fig. 8
Fig. 8

Error in the three-wavelength saturation calculation for the 488-, 635-, and 905-nm wavelength triad, assuming a 25% scattering loss by the blood vessel. Vessel diameter is indicated in the legend, and the Hb concentration is assumed to be 15 g/100 ml.

Tables (2)

Tables Icon

Table 1 Target Values Chosen for Wavelength Optimization

Tables Icon

Table 2 Calculated Saturation Error Due to 0.01 Error in T for the Wavelength Combinations Used by Various Investigatorsa

Equations (24)

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D=1c1l+2c2l++ncnl,
D=HbcHbl+HbO2cHbO2l.
s=cHbO2cHbO2+cHb=cHbO2cHbTOTAL,
D=sHbO2cHbTOTALl+1-sHbcHbTOTALl
D=sHbO2-HbcHbTOTALl+HbcHbTOTALl.
Dλ1=msHbO2λ1-Hbλ1+Hbλ1, Dλ2=msHbO2λ2-Hbλ2+Hbλ2,
s=Dλ2Hbλ1-Dλ1Hbλ2Dλ1HbO2λ2-Hbλ2-Dλ2HbO2λ1-Hbλ1.
D=cl+Bλ,
Dλ1=msHbO2λ1-Hbλ1+Hbλ1+B, Dλ2=msHbO2λ2-Hbλ2+Hbλ2+B, Dλ3=msHbO2λ3-Hbλ3+Hbλ3+B,
s=Dλ1Hbλ3-Hbλ2+Dλ2Hbλ1-Hbλ3+Dλ3Hbλ2-Hbλ1Dλ1Hbλ3-HbO2λ3-Hbλ2-HbO2λ2+Dλ2Hbλ1-HbO2λ1-Hbλ3-HbO2λ3+Dλ3Hbλ2-HbO2λ2-Hbλ1-HbO2λ1.
HbO2λ2=Hbλ2,  HbO2λ3=Hbλ3.
s=Dλ1Hbλ3-Hbλ2+Dλ2Hbλ1-Hbλ3+Dλ3Hbλ2-Hbλ1Dλ2-Dλ3Hbλ1-HbO2λ1.
D=-logT=-lnTln10.
ΔD=dDdT ΔT=-ΔTln101T,
ΔDD=ΔTT lnT.
dΔD/DdT=-lnT+1T lnT2 ΔT=0.
T=1/e=36.8%, D=0.434.
s=a+bDλ1/Dλ2.
Δs=sTλ1 ΔTλ12+sTλ2 ΔTλ22++sTλn ΔTλn21/2,
s=logTλ2Hbλ1-logTλ1Hbλ2logTλ1HbO2λ2-Hbλ2-logTλ2HbO2λ1-Hbλ1.
Δs=sTλ1 ΔTλ12+sTλ2 ΔTλ221/2.
sTλ1=-logTλ2Tλ1Hbλ1HbO2λ2-Hbλ2HbO2λ1logTλ1HbO2λ2-Hbλ2-logTλ2HbO2λ1-Hbλ12
Tλ=10-clsHbO2λ+1-sHbλ,
Tλ=Ts10-clsHbO2λ+1-sHbλ.

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