Abstract

Clinical use of laser Doppler velocimetry of absolute red blood cell velocity Vmax in the center of major retinal vessels becomes possible with recent advances in microcomputer technology. Speed and automation of Doppler photocurrent analysis and identification of proper laser beam positioning are the major requirements in making direct quantitative assessment of retinal hemodynamics a routine diagnostic tool. We discuss our efforts toward achieving this goal and illustrate our current capabilities with examples of changes in retinal blood flow in response to physiologic maneuvers. In veins, Vmax can now be determined on-line. In arteries, current computing speed only supports intermittent on-line data acquisition.

© 1988 Optical Society of America

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  1. C. E. Riva, G. T. Feke, B. Eberli, V. Benary, “Bidirectional LDV System for Absolute Measurement of Blood Speed in Retinal Vessels,” Appl. Opt. 18, 2301 (1979).
    [Crossref] [PubMed]
  2. C. E. Riva, G. T. Feke, “Laser Doppler Velocimetry in the Measurement of Retinal Blood Flow,” in The Biomedical Laser: Technology and Clinical Application, L. Goldmann, Ed. (Springer-Verlag, New York, 1981), pp. 135–161.
  3. C. E. Riva, J. E. Grunwald, S. H. Sinclair, K. O’Keefe, “Fundus Camera Based Retinal LDV,” Appl. Opt. 20, 117 (1981).
    [Crossref] [PubMed]
  4. C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
    [PubMed]
  5. D. U. Fluckiger, R. J. Keyes, J. H. Shapiro, “Optical Autodyne Detection: Theory and Experiment,” Appl. Opt. 26, 318 (1987).
    [Crossref] [PubMed]
  6. We now use the term autodyne detection rather than heterodyne detection to describe our technique. In heterodyne detection, light scattered by moving targets is mixed with a local oscillator most often derived directly from the same laser source. The disadvantage is that the matching of polarization and spatial mode character between these two laser beams is very critical, especially when dealing with a signal beam coming from a human eye. Autodyne detection does not depend on a local oscillator. Rather it is a direct detection scheme involving self-beating between the various frequency components of the received signal beam. In this application a relatively large portion of the signal beam originates from light scattered by the vessel wall and surrounding quasi-stationary tissue and is mixed with the signal light scattered by the red cells.
  7. B. L. Petrig, C. E. Riva, J. E. Grunwald, “Computer Analysis of Laser Doppler Measurements in Retinal Blood Vessels,” Invest. Ophthalmol. Vis. Sci. 25 (Suppl.), 7 (1984).
  8. C. E. Riva, J. E. Grunwald, B. L. Petrig, “Laser Doppler Measurement of Retinal Blood Velocity: Validity of the Single Scattering Model,” Appl. Opt. 24, 605 (1985).
    [Crossref] [PubMed]
  9. C. E. Riva, J. E. Grunwald, S. H. Sinclair, “Laser Doppler Velocimetry Study of the Effect of Pure Oxygen Breathing on Retinal Blood Flow,” Invest. Ophthalmol. Vis. Sci. 24, 47 (1983).
    [PubMed]
  10. C. E. Riva, B. L. Petrig, J. E. Grunwald, “Near Infrared Retinal Laser Doppler Velocimetry,” Lasers Ophthalmol. 1, 211 (1987).
  11. C. E. Riva, J. E. Grunwald, B. L. Petrig, “Autoregulation of Human Retinal Blood Flow: an Investigation with Laser Doppler Velocimetry,” Invest. Ophthalmol. Vis. Sci. 27, 1706 (1986).
    [PubMed]
  12. B. Petrig, E. B. Werner, C. E. Riva, J. E. Grunwald, “Response of Macular Capillary Blood Flow to Changes in Intraocular Pressure as Measured by the Blue Field Simulation Technique,” in Proceedings, Sixth International Visual Field Symposium, A. Heijl, E. L. Greve, Eds. (Dr. W. Junk Publishers, Dordrecht, The Netherlands, 1985), pp. 447–451.
    [Crossref]

1987 (2)

D. U. Fluckiger, R. J. Keyes, J. H. Shapiro, “Optical Autodyne Detection: Theory and Experiment,” Appl. Opt. 26, 318 (1987).
[Crossref] [PubMed]

C. E. Riva, B. L. Petrig, J. E. Grunwald, “Near Infrared Retinal Laser Doppler Velocimetry,” Lasers Ophthalmol. 1, 211 (1987).

1986 (1)

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Autoregulation of Human Retinal Blood Flow: an Investigation with Laser Doppler Velocimetry,” Invest. Ophthalmol. Vis. Sci. 27, 1706 (1986).
[PubMed]

1985 (2)

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Laser Doppler Measurement of Retinal Blood Velocity: Validity of the Single Scattering Model,” Appl. Opt. 24, 605 (1985).
[Crossref] [PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
[PubMed]

1984 (1)

B. L. Petrig, C. E. Riva, J. E. Grunwald, “Computer Analysis of Laser Doppler Measurements in Retinal Blood Vessels,” Invest. Ophthalmol. Vis. Sci. 25 (Suppl.), 7 (1984).

1983 (1)

C. E. Riva, J. E. Grunwald, S. H. Sinclair, “Laser Doppler Velocimetry Study of the Effect of Pure Oxygen Breathing on Retinal Blood Flow,” Invest. Ophthalmol. Vis. Sci. 24, 47 (1983).
[PubMed]

1981 (1)

1979 (1)

Benary, V.

Eberli, B.

Feke, G. T.

C. E. Riva, G. T. Feke, B. Eberli, V. Benary, “Bidirectional LDV System for Absolute Measurement of Blood Speed in Retinal Vessels,” Appl. Opt. 18, 2301 (1979).
[Crossref] [PubMed]

C. E. Riva, G. T. Feke, “Laser Doppler Velocimetry in the Measurement of Retinal Blood Flow,” in The Biomedical Laser: Technology and Clinical Application, L. Goldmann, Ed. (Springer-Verlag, New York, 1981), pp. 135–161.

Fluckiger, D. U.

Grunwald, J. E.

C. E. Riva, B. L. Petrig, J. E. Grunwald, “Near Infrared Retinal Laser Doppler Velocimetry,” Lasers Ophthalmol. 1, 211 (1987).

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Autoregulation of Human Retinal Blood Flow: an Investigation with Laser Doppler Velocimetry,” Invest. Ophthalmol. Vis. Sci. 27, 1706 (1986).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
[PubMed]

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Laser Doppler Measurement of Retinal Blood Velocity: Validity of the Single Scattering Model,” Appl. Opt. 24, 605 (1985).
[Crossref] [PubMed]

B. L. Petrig, C. E. Riva, J. E. Grunwald, “Computer Analysis of Laser Doppler Measurements in Retinal Blood Vessels,” Invest. Ophthalmol. Vis. Sci. 25 (Suppl.), 7 (1984).

C. E. Riva, J. E. Grunwald, S. H. Sinclair, “Laser Doppler Velocimetry Study of the Effect of Pure Oxygen Breathing on Retinal Blood Flow,” Invest. Ophthalmol. Vis. Sci. 24, 47 (1983).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, K. O’Keefe, “Fundus Camera Based Retinal LDV,” Appl. Opt. 20, 117 (1981).
[Crossref] [PubMed]

B. Petrig, E. B. Werner, C. E. Riva, J. E. Grunwald, “Response of Macular Capillary Blood Flow to Changes in Intraocular Pressure as Measured by the Blue Field Simulation Technique,” in Proceedings, Sixth International Visual Field Symposium, A. Heijl, E. L. Greve, Eds. (Dr. W. Junk Publishers, Dordrecht, The Netherlands, 1985), pp. 447–451.
[Crossref]

Keyes, R. J.

O’Keefe, K.

Petrig, B.

B. Petrig, E. B. Werner, C. E. Riva, J. E. Grunwald, “Response of Macular Capillary Blood Flow to Changes in Intraocular Pressure as Measured by the Blue Field Simulation Technique,” in Proceedings, Sixth International Visual Field Symposium, A. Heijl, E. L. Greve, Eds. (Dr. W. Junk Publishers, Dordrecht, The Netherlands, 1985), pp. 447–451.
[Crossref]

Petrig, B. L.

C. E. Riva, B. L. Petrig, J. E. Grunwald, “Near Infrared Retinal Laser Doppler Velocimetry,” Lasers Ophthalmol. 1, 211 (1987).

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Autoregulation of Human Retinal Blood Flow: an Investigation with Laser Doppler Velocimetry,” Invest. Ophthalmol. Vis. Sci. 27, 1706 (1986).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
[PubMed]

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Laser Doppler Measurement of Retinal Blood Velocity: Validity of the Single Scattering Model,” Appl. Opt. 24, 605 (1985).
[Crossref] [PubMed]

B. L. Petrig, C. E. Riva, J. E. Grunwald, “Computer Analysis of Laser Doppler Measurements in Retinal Blood Vessels,” Invest. Ophthalmol. Vis. Sci. 25 (Suppl.), 7 (1984).

Riva, C. E.

C. E. Riva, B. L. Petrig, J. E. Grunwald, “Near Infrared Retinal Laser Doppler Velocimetry,” Lasers Ophthalmol. 1, 211 (1987).

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Autoregulation of Human Retinal Blood Flow: an Investigation with Laser Doppler Velocimetry,” Invest. Ophthalmol. Vis. Sci. 27, 1706 (1986).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
[PubMed]

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Laser Doppler Measurement of Retinal Blood Velocity: Validity of the Single Scattering Model,” Appl. Opt. 24, 605 (1985).
[Crossref] [PubMed]

B. L. Petrig, C. E. Riva, J. E. Grunwald, “Computer Analysis of Laser Doppler Measurements in Retinal Blood Vessels,” Invest. Ophthalmol. Vis. Sci. 25 (Suppl.), 7 (1984).

C. E. Riva, J. E. Grunwald, S. H. Sinclair, “Laser Doppler Velocimetry Study of the Effect of Pure Oxygen Breathing on Retinal Blood Flow,” Invest. Ophthalmol. Vis. Sci. 24, 47 (1983).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, K. O’Keefe, “Fundus Camera Based Retinal LDV,” Appl. Opt. 20, 117 (1981).
[Crossref] [PubMed]

C. E. Riva, G. T. Feke, B. Eberli, V. Benary, “Bidirectional LDV System for Absolute Measurement of Blood Speed in Retinal Vessels,” Appl. Opt. 18, 2301 (1979).
[Crossref] [PubMed]

B. Petrig, E. B. Werner, C. E. Riva, J. E. Grunwald, “Response of Macular Capillary Blood Flow to Changes in Intraocular Pressure as Measured by the Blue Field Simulation Technique,” in Proceedings, Sixth International Visual Field Symposium, A. Heijl, E. L. Greve, Eds. (Dr. W. Junk Publishers, Dordrecht, The Netherlands, 1985), pp. 447–451.
[Crossref]

C. E. Riva, G. T. Feke, “Laser Doppler Velocimetry in the Measurement of Retinal Blood Flow,” in The Biomedical Laser: Technology and Clinical Application, L. Goldmann, Ed. (Springer-Verlag, New York, 1981), pp. 135–161.

Shapiro, J. H.

Sinclair, S. H.

C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, “Laser Doppler Velocimetry Study of the Effect of Pure Oxygen Breathing on Retinal Blood Flow,” Invest. Ophthalmol. Vis. Sci. 24, 47 (1983).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, K. O’Keefe, “Fundus Camera Based Retinal LDV,” Appl. Opt. 20, 117 (1981).
[Crossref] [PubMed]

Werner, E. B.

B. Petrig, E. B. Werner, C. E. Riva, J. E. Grunwald, “Response of Macular Capillary Blood Flow to Changes in Intraocular Pressure as Measured by the Blue Field Simulation Technique,” in Proceedings, Sixth International Visual Field Symposium, A. Heijl, E. L. Greve, Eds. (Dr. W. Junk Publishers, Dordrecht, The Netherlands, 1985), pp. 447–451.
[Crossref]

Appl. Opt. (4)

Invest. Ophthalmol. Vis. Sci. (4)

C. E. Riva, J. E. Grunwald, S. H. Sinclair, “Laser Doppler Velocimetry Study of the Effect of Pure Oxygen Breathing on Retinal Blood Flow,” Invest. Ophthalmol. Vis. Sci. 24, 47 (1983).
[PubMed]

C. E. Riva, J. E. Grunwald, S. H. Sinclair, B. L. Petrig, “Blood Flow Velocity and Volumetric Flow Rate in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci. 26, 1124 (1985).
[PubMed]

C. E. Riva, J. E. Grunwald, B. L. Petrig, “Autoregulation of Human Retinal Blood Flow: an Investigation with Laser Doppler Velocimetry,” Invest. Ophthalmol. Vis. Sci. 27, 1706 (1986).
[PubMed]

B. L. Petrig, C. E. Riva, J. E. Grunwald, “Computer Analysis of Laser Doppler Measurements in Retinal Blood Vessels,” Invest. Ophthalmol. Vis. Sci. 25 (Suppl.), 7 (1984).

Lasers Ophthalmol. (1)

C. E. Riva, B. L. Petrig, J. E. Grunwald, “Near Infrared Retinal Laser Doppler Velocimetry,” Lasers Ophthalmol. 1, 211 (1987).

Other (3)

We now use the term autodyne detection rather than heterodyne detection to describe our technique. In heterodyne detection, light scattered by moving targets is mixed with a local oscillator most often derived directly from the same laser source. The disadvantage is that the matching of polarization and spatial mode character between these two laser beams is very critical, especially when dealing with a signal beam coming from a human eye. Autodyne detection does not depend on a local oscillator. Rather it is a direct detection scheme involving self-beating between the various frequency components of the received signal beam. In this application a relatively large portion of the signal beam originates from light scattered by the vessel wall and surrounding quasi-stationary tissue and is mixed with the signal light scattered by the red cells.

C. E. Riva, G. T. Feke, “Laser Doppler Velocimetry in the Measurement of Retinal Blood Flow,” in The Biomedical Laser: Technology and Clinical Application, L. Goldmann, Ed. (Springer-Verlag, New York, 1981), pp. 135–161.

B. Petrig, E. B. Werner, C. E. Riva, J. E. Grunwald, “Response of Macular Capillary Blood Flow to Changes in Intraocular Pressure as Measured by the Blue Field Simulation Technique,” in Proceedings, Sixth International Visual Field Symposium, A. Heijl, E. L. Greve, Eds. (Dr. W. Junk Publishers, Dordrecht, The Netherlands, 1985), pp. 447–451.
[Crossref]

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Figures (9)

Fig. 1
Fig. 1

Block diagram of MCS-561 computer system. The main CPU (Motorola 68010) controls three slave processors (dashed lines). The data acquisition processor handles A–D conversion of photocurrent and pulse signals. It also makes the time course of selected parameters available through D–A converters for hard copy recording. The data path is indicated by wide arrows. The array processor takes the signal from main memory buffers, calculates FFT, power spectrum, and cutoff frequency for each channel, and returns results to main memory. The display processor plots power spectra and time course of results on-line on a graphics monitor.

Fig. 2
Fig. 2

Partial view of the graphics monitor during measurements in a human retinal vein. The upper two panels show the instantaneous unaveraged power spectrum in each channel. The x axes are scaled according to the selected photocurrent signal bandwidth. In this case, horizontal divisions represent 2.5 kHz. The y axes are adjusted to show the maximum power spectral density of each channel at full scale. The vertical and horizontal lines drawn on top of the spectra show the automatically determined cutoff frequency and the linear fit of the data below the cutoff, respectively. The lower panel shows a wraparound trace of the 512 most recent values of the average center line red cell velocity 〈Vmax〉 as a function of time. 〈Vmax〉 is calculated as the running average of the eight most recent values of Vmax derived from single pairs of power spectra. The x-axis scale depends on the frequency of Vmax analysis (6.4 s, full scale); the y axis is calibrated in cm/s/div.

Fig. 3
Fig. 3

Partial view of the graphics monitor during measurements in a human retinal artery as seen at the systolic (A) and diastolic (B) phase of the cardiac cycle. Similar to Fig. 2, panels show instantaneous power spectra (5 kHz/horizontal division) and 〈Vmax〉. An additional panel on the bottom shows a trace of the pulse wave. The signal saturated while it was recorded but still indicates the systolic and diastolic phases. Blinks or inappropriate fixation cause a disturbance of Vmax during the latter portion of (B).

Fig. 4
Fig. 4

Effect of oxygen breathing on retinal blood flow in the miniature pig. Relative red cell velocity (given by the cutoff frequency fmax measured with a unidirectional system) is shown in an anesthetized animal going from air to 100% oxygen breathing. The diastolic and systolic limits (A) and the time average (B) of fmax are presented. After ~2 min of inhaling pure oxygen a new equilibrium is reached between 60 and 72% below the base line value.

Fig. 5
Fig. 5

Portions of Vmax redrawn from Fig. 4 on an expanded time scale to illustrate the waveform at base line (A) and at 5 min of O2 breathing (B). These data demonstrate the regularity of Vmax measurements in the well-stabilized conditions of an animal experiment as opposed to those in a human subject shown in Fig. 6.

Fig. 6
Fig. 6

Effect of oxygen breathing on blood flow in the normal human retina. Arterial Vmax is shown during air breathing (A) and at 5 min of 100% O2 breathing. A decrease of ~40% can be noted.

Fig. 7
Fig. 7

Effect of acute elevation of intraocular pressure on blood flow in the normal human retinal artery. Relative red cell velocity fmax is plotted at rest (A) and at an intraocular pressure elevated to diastolic retinal artery pressure (B) by means of a scleral suction cup. The cutoff frequency at diastole is reduced to about zero, while the same at systole is increased over its base line value, suggesting that the retinal vasculature is counteracting the change in perfusion pressure. Nevertheless, time-averaged velocity is decreased. Note that the effect of blinks lasts only for a short time.

Fig. 8
Fig. 8

Effect of acute elevation of intraocular pressure on blood flow in a normal human retinal vein. On-line absolute Vmax measurements are shown before and after an acute increase induced by suction cup (A) and before and after releasing the suction (B). Vmax decreases from ~1.5 to 0.5 cm/s after pressure elevation to 38 mm Hg (A). Raising the pressure to diastolic (B) causes Vmax to approach zero. After the cup is released Vmax quickly increases to 2.5 cm/s and returns to base line after ~1 min.

Fig. 9
Fig. 9

Effect of chronic decrease in perfusion pressure on retinal blood flow. Arterial Vmax (top trace), pulse pressure (middle), and the goodness of fit parameter q (bottom) are shown for a patient with carotid occlusion. The horizontal divisions of the chart paper do not align in all traces because these were combined from two sequential strips of a two-channel chart recorder, but all signals are aligned in time. On the left, Vmax follows a regular waveform over several cardiac cycles. Parameter q (see text) rises periodically during diastole. On the right, when fixation is no longer maintained as indicated by the arrow, the q value remains low over several pulses providing an objective means to determine those time periods when signal is recorded from a well-centered laser beam.

Tables (3)

Tables Icon

Table I Theoretical Constraints on Maximum Rate of Cutoff Analysis

Tables Icon

Table II Computational Constraints on Maximum Rate of Cutoff Analysis

Tables Icon

Table III Data Storage Requirements for 5 s of Signal (All Channels)

Equations (13)

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

V max = k | f max , 1 f max , 2 | .
q j = 1 1 + ( M 1 1 ) · s 1 2 + ( M 2 1 ) · s 2 2 M 1 · d 1 2 + M 2 · d 2 2 , j = 1 , 2 ,
q = q 1 · q 2
g j = X model 2 X norm 2 .
{ x i } , 0 i < N
{ m i } = { A , 0 i < M , B , M i < N ,
A = 1 M 0 M 1 x i
B = 1 N M M N 1 x i
g j = 0 M 1 ( x i A ) 2 + M N 1 ( x i B ) 2 0 N 1 ( x i C ) 2 ,
C = 1 N 0 N 1 x i .
s 1 2 = 1 M 1 0 M 1 ( x i A ) 2 and s 2 2 = 1 N M 1 M N 1 ( x i B ) 2 ,
g j = ( M 1 ) s 1 2 + ( N M 1 ) s 2 2 ( M 1 ) s 1 2 + M d 1 2 + ( N M 1 ) s 2 2 + ( N M ) d 2 2 ·
q j = 1 g j ,

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