A laser Doppler scanner for imaging blood flow in skin T.J.H. Essex and P.O. Byrne Northern Regional Medical Physics Department,
Newcastle
General
Hospital,
Newcastle
upon Tyne, NE4 6BE, UK ABSTRACT This paper describes a novel medical instrument that produces an image of bloodfl ow in the capillaries under the skin surjaa. A laser beam is used to detect blood cell motion from the Doppler broadening of the laser light scatteredfiom the skin. The image is generated by scanning the t&r beam in a raster. The design of a practical clinical instrument is outlined and some preliminary results are presented. Keywords:
Blood flow, imaging, laser Doppler scanner, skin
INTRODUCTION
Scanner
Knowledge of blood flow in the skin is important in many areas of medicine, such as plastic surgery, bum management, dermatology and vascular medicine. Experience from skin blood flow measurement suggests there is a clinical need for an instrument that provides a measurement of skin blood flow in the form of an image of the area of skin being studied. An instrument has been developed to do this using a scanning laser Doppler techni ue. Unlike existing instruments, which use optical fiB re probes at fixed sites, this instrument scans a laser beam in a raster pattern over the skin to build up a laser Doppler image. It is able to produce an image of an area of skin in terms of the movement of blood cells under the skin surface. An area of up to 500 x 700 mm can be scanned in 6 min. The spatial resolution at the skin surface is about 3 mm, which is sufficient for clinical diagnosis. Trials of the scanner have indicated that it detects blood cell movement and artefact caused by the scanning motion is minimal. Fijpre 7 shows a typical clinical arrangement with the scanner mounted over a couch. The patient lies on the couch and simply remains still while the scan is made. Normal small movements caused by breathing, for example, do not affect the scan. The fact that the scanner itself does not come near the patient has some incidental advantages: there is no risk of contact with open wounds, and the scanner cannot influence the blood flow, which can happen with a probe-based instrument. by an IBM-AT-type The scanner is controlled computer which is also used for image display and storage. The images are displayed with colours representing a scale of blood flow. Image processing and analysis software is now being developed in conjunction with the clinical evaluation of the instrument. Clinical trials are in progress in various areas of Correspondence
to: T.J.H. Essex
0 1991 Butterworth-Heinemann 0 14 I -.532.5/9 I /O:iO1X9-06
unit
Ia
\ Operator
\,
position :-3
/
/
Figure 1 Typical clinical arrangement of the laser Doppler scanner positioned about 1.6 m above the couch
medicine, including dermatology, vascular disorders and bum assessment, with pro’ected work in breast tumour detection, and study o 1 pressure sore formation. The scanner has been patented by British Technology Group (London, UK)‘.
LASER DOPPLER AND SKIN BLOOD FLOW Conventional laser Doppler blood flowmeters”‘” use optical fibres to carry light from a laser (usually helium-neon) to the skin. The light is scattered in the skin tissue and that which is scattered from moving blood cells experiences a Doppler frequency shift (Figure 2). Optical fibres collect some of this light at the skin surface and return it to the photodetectors. Typical blood cell velocities are of the order of 1 mm s-’ in the capillary loops, giving rise to Doppler frequency shifts of u to 3 kHz, though scattering by faster moving bloo B in deeper vessels extends the spectrum to above 10 kHz. Optical frequency shifts of this magnitude are too small to detect directly, but
for BES J. Biomed. Eng. 1991, Vol. 13, May
189
Laser Doppler blood flow imaging: T.J.H. Fsex and P.O. Byrne Photodiodes
Transmitting
optical fibre
Collecting optical
Laser
fibre
Figure Figure 2 Simplified cross-section of skin. Laser light is scattered the skin tissue and by blood cells in the capillary loops
Lenses k+
mirror
system, and the output is in the form of an image on a computer display rather than a continuous reading. ‘IWE SCANNER Optical and mechanical
considerations
F&we 4 is a representation of the layout of the scanner. The 2mW helium-neon laser is mounted behind the array of four photodiodes and lenses, and the beam passes coaxially through this assembly onto the centre of the 250mm diameter plane-scanning mirror, which directs the beam onto the target. Light scattered from the target is collected by the same mirror and focused by the lenses (50mm diameter, f = 100 mm) onto the four photodiodes (BPW34). The function of the lenses is simply to increase the light collecting area, the spatial resolution being determined by the laser beam diameter, as in the early flying-spot television systems. This has the convenient effect of giving the scanner a great depth of field. The scanning mirror is driven horizontally by a DC motor, gearbox and crank arrangement. This provides smooth continuous motion and the crank is arranged to maintain a constant angular velocity of the mirror during each line of the scan. Between lines the mirror is incremented vertically by a stepper motor. Mirror position information is derived from an optical encoder on the gearbox shaft and by counting pulses sent to the stepper motor. A dedicated microprocessor controls the motors and sends the mirror position signals to the corn uter to enable it to assemble the processed Dopp Per information into an image. The use of a single plane mirror for scanning the laser beam and collecting the scattered light has the advantage that the image of the laser spot on the photodiodes remains stationary as the mirror scans. Ideally the laser beam and collecting lens should be coaxial, but the only disadvantage of using off-axis lenses is that the image of the spot moves over the photodiode depending on the target distance. Using a 5mm square photodiode keeps the image on the active surface for a sufficient range of target distance (0.6-2 m). Studies with different lens configurations showed that the total collecting area is the most important factor for improving the signal-to-noise ratio with no significant disadvantage of using multiple lenses.
Z)oppkr blood flow imaging: T2.H. Fsex and P.O. Byrne
her
The arrangement of four lenses that was finally used makes the best use of the circular mirror area and by summing the photodiodes in two pairs it is possible to use a differential input amplifier. The completed optical assembly is rugged and easy to align.
displayed image 16 colours are assigned to this scale. Some image processing is possible, such as spatial averaging, contrast manipulation and measurement of areas of raised flow. Further processing developments are being made as clinical work progresses.
Scan size and acquisition
SCANNING
speeds
A continuous scanning motion was used to avoid the need for a mirror settling time, which would have been necessary with a stepping scan method before making each pixel measurement. Continuous motion decreases the total scan time but there is then the risk of artefacts due to the movement of the beam (see the Beam movement section). The lowest frequency of interest in the Doppler spectrum is 250Hz, this being a result of filtering to limit artefacts at lower fre uencies. This requires a sample time per pixel of at 8 east 4ms to estimate the power in the spectrum. Using a continuous smooth scanning motion at this rate, the line time is 1 s, and allowing for turnround at the end of lines the total scan time is 6 min, which is quite convenient for clinical use. The outputs of the analogue processor are low-pass filtered at 160 Hz to optimize performance at this pixel rate. Doppler
signal processing
The analogue processing circuit used in the scanner is based on one developed previously for a conventional type of laser Doppler flowmeter and validated against radioisotope-labelled microspheres in cerebral tissue7. (The detailed design of a Doppler signal processor is not the subject of this work.) The analogue processor sends two output signals to the computer’s A/D converter. One is a light intensity signal, formed by summing the outputs of the four photodiodes, the other is the flow-related signal derived from the Doppler spectrum. The Do pler spectrum is the AC component of the photodio dp es’ outputs. The top two photodiodes are summed into one side of an AC-coupled differential amplifier and the bottom two into the other side. This provides rejection of any common mode signals.
Patient
ARTEFACTS
movement
The Doppler spectrum from the photodiodes results from the mixing of the various Doppler-shifted and -unshifted components from the skin, and therefore represents movement of blood cells relative to the static skin tissue. Small movements of the patient, such as those caused by breathing, will therefore not cause additional spectral components affecting the measurement. It is necessary, however, to avoid gross movements of the patient which would distort the image obtained. Beam movement An important source of artefact arises from the laser scanning regions of different reflectivities. This results in a large AC component in the received light intensity. The differential input to the Doppler processor virtually eliminates this. The intensity variations appear as a common mode signal to the photodiodes, i.e. they are highly correlated. The Doppler spectra at each photodiode are not significantly correlated and the differential input allows these signals to pass through to the Doppler processor without the intensity variations. The differential input also rejects other common mode signals, such as laser noise and mains frequency harmonics from room lighting. Spectra were obtained from skin at the normal scanning speed (1 s per line) and a low scanning speed (9s per line), the lower bandwidth limit being 5OHz (Figure 5). Additional spectral components at the higher speed are visible, mainly below 300 Hz, with minimal difference above this frequency. This Range.-51
dBV
B: Stored
Computer
processing
The computer receives the light intensity and blood flux signals from the Doppler processor via an A/D converter, and the mirror position information signals from the motor control microprocessor. Before this information is used to assemble the image, the blood flux signal is compensated for noise effects. Circuit noise and shot noise from the photodiodes appear at the flux output as an offset whose value depends on the received light intensity. This offset increases the effective flux reading. To compensate for this a variable offset is subtracted from the flux value and is obtained from a look-up table of the noise-intensity relationship of the scanner. The intensity output from the Doppler processor is used to index the look-up table. The compensated flux values are represented on a scale of O-255 arbitrary blood flux units. In the
100 mVrs
Status Paused RMS: 250
II
I
I
Ii
ll
I
10 mVrs /DIV
0
vrmsA-stop
Start.
OHz
Frequency (Hz)
spectra from skin, showing addItIona spectral due to scannmg. The lower trace was recorded at a very low scanning speed. the upper a! normal scanning speed Figure 5
Doppler
components
at low
frequencies
J. Biomed. Eng. 1991, Vol. 13, May
191
Lam Doppler bloodjow imaging: TJ,H. Essex and P.O. Byrne
relationship between the spectra obtained is highly repeatable, suggesting that the changes are not due to blood flow variations. The range of frequencies of the additional spectral components suggests that they are the residual effects of the reflectance variations mentioned above not being completely rejected by the differential amplifier. It is therefore necessary to filter the low frequency end of the Doppler spectrum to attenuate these artefact components. A second-order high-pass filter with a cut-off frequency of 250 Hz is used for this purpose. Some residual corn onents remain after filtering, but the nature of the g oppler signal processing is such that lower frequencies carry little weight in the computed flux value. These scanning artefacts and the filtering necessary have an effect on the scanner’s measurements. EVALUATION Flow tests The scanner’s response to changes in flow was evaluated using a suspension of 15pm nylon particles in water, pumped through a test cell. There was no attempt to mimic skin tissue with the set-up, although the reflectance and Doppler spectra were similar to those of skin. The cell consisted of two microscope slides, their faces separated by 0.12 mm, sealed down their long sides, forming a channel of 20 X 0.12 mm. The assembly was sandwiched between two 1 mm thick pieces of silicone rubber acting as diffusers. The stationary laser beam from the scanner was aimed perpendicularly at one of the cell faces. The nylon particle suspensions were pumped through the channel between the slides. Figure 6 shows the scanner outputs obtained for various flow rates. These measurements were made at a fixed particle concentration of 0.2% v/v, and hence represent a velocity relationship. The particle concentration and flow rates chosen were such that the resulting Doppler signals were similar in spectral shape and amplitude to those obtained from normal skin, giving similar output values from the processor. The actual velocities in the cell do not relate directly to those of blood cells in skin, however, because of the transverse cell flow and the different scattering properties of the cell compared with skin.
0
2
4
6
8
Flow through
10
12
14
16
18
20
test rig (p\ s-‘1
Figure 6 Relationship between the scanner processor output and flow through a test rig. Bars show 1 standard deviation from the mean. The processor output is in arbitrary flux units
192
J. Biomed. Eng. 1991, Vol. 13, May
At high flow rates, 14-20 ~1 s-’ and above, the relationship in Figure 6 is a straight line that would intercept the origin, as expected. The dip in the line at lower flows is a result of the filtering at low frequencies to limit scanning artefact. This reduces the sensitivity of the scanner to low blood velocities. Scan speed artefacts Sixty pairs of blood flux values were obtained, each pair being of an identical area of skin scanned at the normal and low scan speeds used to obtain Figure 5. The 250Hz filter was in place for these measurements. Each flux value was the mean of 96 pixel measurements. The difference within each pair was calculated, as well as the mean and standard deviation of all the differences. The same calculations were made for 60 pairs of flux values recorded both at the lower scan speed, representing the variability due to blood flow changes and the measurement technique. The mean change in the flux between low and normal scanning speeds was -0.1 (k8.6) flux units at a mean flux for all points of 82.5 units. In the group of airs at the low speed, the mean change was -2.5 56.6) units and the mean flux for all pints 8 1.8 units. P These results seem to indicate that any error in the flux measurement due to the beam scanning is not significant compared with the variability in the measurement itself. It would be necessary to take a much larger set of readings to extract any systematic error due to the scanning motion.
Clinical
results
Examples of images obtained from the laser Doppler scanner are shown in Figures 7-77. In F&we 7, the dorsal surface of a hand is seen, where the blood flow to one finger was interrupted using an elastic band. There is clearly no flux visible on the scan in this finger. Figure 8 is the chest of a normal subject after he had made a scratch on the skin with his fingernails. No visible changes were apparent on the skin, but the area affected by the scratch is visible as an area of raised blood flux. The increase in area covered by the scan compared with Figure 7 is achieved by placing the subject further from the scanner (1.6 m compared with 600 mm). The subject in Figure 9 had a skin graft performed as a child, about 20 years ago. This area shows a reduced blood flux in the skin. Figure 70 is the result of a series of tests to obtain a dose-response curve for a skin irritant. The patches of raised blood flux are due to various doses of the irritant and the black square is a known reference area. Software is being developed to anal se the dose response in terms of increase in blood Kux and the size of the area affected. The method is quick and convenient compared with methods currentIy in use. Finally, Figure 11 is a scan of a pair of hands, again the dorsal surface. The point of interest on this scan is on the right hand, where there was some inflammation of the tendon of the first finger. This is reflected as an increase in the blood flux in the skin overlying the tendon.
Laser Doppler bloodflow
Relative
perfusion
imaging: i?JH. Fsex and P.O. Byrne
sCOle
Figure 7 her Doppler scan of the dorsal blood flow to one finger interrupted
surface
of a hand
with
2, 2: 5: 7;
100 *
125 h
150 ?I
175 n
Relative perfusion Figure
10
Laser Doppler
scans of responses
ii k
2;
5;
7;
100
A
A
125 Relative
l:O
175
perfusion
200 n
225 A
250 A
to doses of skin irritant
n 200
n 225
A
250
Units
scale
Figure 11 hands;
Units
scale
Laser Doppler scan of the dorsal surface of a pair the tendon of the first finger of the right hand is inflamed.
of
CONCLUSION
;
2:
5;
7;
to”0
125 A
Relative Figure 8 Laser Doppler had scratched his skin
150 A perfusion
175 n
200 A
225 A
250 h
Units
scale
scan of the chest of a normal
subject
who
A scanning laser Doppler instrument has been developed that is able to generate an image of blood flux in the capllaries under the surface of the skin. It has been demonstrated to detect changes in blood flux resulting from injury, disease and temperature. Although it is not possible to calibrate the instrument directly, in most cases a comparison can be made between the area being studied and an adjacent or symmetrically opposite part of the body. Clinical studies are in progress to evaluate the scanner in various areas of medicine.
J. Biomed.
Eng. 1991, Vol. 13, May
193
Laser Doppler blood flow imaging: TJH. Essex and P.O. Byrne
ACKNOWLEDGEMENTS The authors are indebted to the numerous clinicians in the Newcastle hospitals who have contributed advice and effort to this work, and from the Medical Physics Department, Mr E. Horsefield for the mechanical fabrication of the instrument and Professor Boddy for supporting the project. REFERENCES 1. British Technology Group UK Patent Nos GB 2 23 1742 A and WO 90/ 11044. 2. Watkins D, Holloway GA. An instrument to measure cutaneous blood flow using the Doppler shift of laser light. IlL!!X Trans Biomed Eng 1978; BME-25: 28-33.
194 J. Biomed. Eng. 1991, Vol. 13, May
3. Nilsson GE, Tenland T, oberg PA. A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy. IEEE Trans Biomed Eng 1980; BME-27: 12-9. 4. Bonner R, Nossal R. Model for laser Doppler measurements in tissue. A# Opt 1981; 20: 2097-107. 5. Jentink HW, de Mu1 FFM, Hermsen RGAM, Graaff R, Greve J. Monte Carlo simulations of laser Doppler blood flow measurements in tissue. Appl Opt 1990; 29: 2371-81. 6. Nilsson GE. Signal processor for laser Doppler flowmeters. Med Biol Eng Comput 1984; 22: 343-8. 7. Eyre JA, Essex TJH, Flecknell PA, Bartholomew PH, SinclairJI. A comparison of measurement of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres. Clin Phys Physiol Meas 1988; 9: 65-74.
Newcastle
General
Hospital,
Newcastle
upon Tyne, NE4 6BE, UK ABSTRACT This paper describes a novel medical instrument that produces an image of bloodfl ow in the capillaries under the skin surjaa. A laser beam is used to detect blood cell motion from the Doppler broadening of the laser light scatteredfiom the skin. The image is generated by scanning the t&r beam in a raster. The design of a practical clinical instrument is outlined and some preliminary results are presented. Keywords:
Blood flow, imaging, laser Doppler scanner, skin
INTRODUCTION
Scanner
Knowledge of blood flow in the skin is important in many areas of medicine, such as plastic surgery, bum management, dermatology and vascular medicine. Experience from skin blood flow measurement suggests there is a clinical need for an instrument that provides a measurement of skin blood flow in the form of an image of the area of skin being studied. An instrument has been developed to do this using a scanning laser Doppler techni ue. Unlike existing instruments, which use optical fiB re probes at fixed sites, this instrument scans a laser beam in a raster pattern over the skin to build up a laser Doppler image. It is able to produce an image of an area of skin in terms of the movement of blood cells under the skin surface. An area of up to 500 x 700 mm can be scanned in 6 min. The spatial resolution at the skin surface is about 3 mm, which is sufficient for clinical diagnosis. Trials of the scanner have indicated that it detects blood cell movement and artefact caused by the scanning motion is minimal. Fijpre 7 shows a typical clinical arrangement with the scanner mounted over a couch. The patient lies on the couch and simply remains still while the scan is made. Normal small movements caused by breathing, for example, do not affect the scan. The fact that the scanner itself does not come near the patient has some incidental advantages: there is no risk of contact with open wounds, and the scanner cannot influence the blood flow, which can happen with a probe-based instrument. by an IBM-AT-type The scanner is controlled computer which is also used for image display and storage. The images are displayed with colours representing a scale of blood flow. Image processing and analysis software is now being developed in conjunction with the clinical evaluation of the instrument. Clinical trials are in progress in various areas of Correspondence
to: T.J.H. Essex
0 1991 Butterworth-Heinemann 0 14 I -.532.5/9 I /O:iO1X9-06
unit
Ia
\ Operator
\,
position :-3
/
/
Figure 1 Typical clinical arrangement of the laser Doppler scanner positioned about 1.6 m above the couch
medicine, including dermatology, vascular disorders and bum assessment, with pro’ected work in breast tumour detection, and study o 1 pressure sore formation. The scanner has been patented by British Technology Group (London, UK)‘.
LASER DOPPLER AND SKIN BLOOD FLOW Conventional laser Doppler blood flowmeters”‘” use optical fibres to carry light from a laser (usually helium-neon) to the skin. The light is scattered in the skin tissue and that which is scattered from moving blood cells experiences a Doppler frequency shift (Figure 2). Optical fibres collect some of this light at the skin surface and return it to the photodetectors. Typical blood cell velocities are of the order of 1 mm s-’ in the capillary loops, giving rise to Doppler frequency shifts of u to 3 kHz, though scattering by faster moving bloo B in deeper vessels extends the spectrum to above 10 kHz. Optical frequency shifts of this magnitude are too small to detect directly, but
for BES J. Biomed. Eng. 1991, Vol. 13, May
189
Laser Doppler blood flow imaging: T.J.H. Fsex and P.O. Byrne Photodiodes
Transmitting
optical fibre
Collecting optical
Laser
fibre
Figure Figure 2 Simplified cross-section of skin. Laser light is scattered the skin tissue and by blood cells in the capillary loops
Lenses k+
mirror
system, and the output is in the form of an image on a computer display rather than a continuous reading. ‘IWE SCANNER Optical and mechanical
considerations
F&we 4 is a representation of the layout of the scanner. The 2mW helium-neon laser is mounted behind the array of four photodiodes and lenses, and the beam passes coaxially through this assembly onto the centre of the 250mm diameter plane-scanning mirror, which directs the beam onto the target. Light scattered from the target is collected by the same mirror and focused by the lenses (50mm diameter, f = 100 mm) onto the four photodiodes (BPW34). The function of the lenses is simply to increase the light collecting area, the spatial resolution being determined by the laser beam diameter, as in the early flying-spot television systems. This has the convenient effect of giving the scanner a great depth of field. The scanning mirror is driven horizontally by a DC motor, gearbox and crank arrangement. This provides smooth continuous motion and the crank is arranged to maintain a constant angular velocity of the mirror during each line of the scan. Between lines the mirror is incremented vertically by a stepper motor. Mirror position information is derived from an optical encoder on the gearbox shaft and by counting pulses sent to the stepper motor. A dedicated microprocessor controls the motors and sends the mirror position signals to the corn uter to enable it to assemble the processed Dopp Per information into an image. The use of a single plane mirror for scanning the laser beam and collecting the scattered light has the advantage that the image of the laser spot on the photodiodes remains stationary as the mirror scans. Ideally the laser beam and collecting lens should be coaxial, but the only disadvantage of using off-axis lenses is that the image of the spot moves over the photodiode depending on the target distance. Using a 5mm square photodiode keeps the image on the active surface for a sufficient range of target distance (0.6-2 m). Studies with different lens configurations showed that the total collecting area is the most important factor for improving the signal-to-noise ratio with no significant disadvantage of using multiple lenses.
Z)oppkr blood flow imaging: T2.H. Fsex and P.O. Byrne
her
The arrangement of four lenses that was finally used makes the best use of the circular mirror area and by summing the photodiodes in two pairs it is possible to use a differential input amplifier. The completed optical assembly is rugged and easy to align.
displayed image 16 colours are assigned to this scale. Some image processing is possible, such as spatial averaging, contrast manipulation and measurement of areas of raised flow. Further processing developments are being made as clinical work progresses.
Scan size and acquisition
SCANNING
speeds
A continuous scanning motion was used to avoid the need for a mirror settling time, which would have been necessary with a stepping scan method before making each pixel measurement. Continuous motion decreases the total scan time but there is then the risk of artefacts due to the movement of the beam (see the Beam movement section). The lowest frequency of interest in the Doppler spectrum is 250Hz, this being a result of filtering to limit artefacts at lower fre uencies. This requires a sample time per pixel of at 8 east 4ms to estimate the power in the spectrum. Using a continuous smooth scanning motion at this rate, the line time is 1 s, and allowing for turnround at the end of lines the total scan time is 6 min, which is quite convenient for clinical use. The outputs of the analogue processor are low-pass filtered at 160 Hz to optimize performance at this pixel rate. Doppler
signal processing
The analogue processing circuit used in the scanner is based on one developed previously for a conventional type of laser Doppler flowmeter and validated against radioisotope-labelled microspheres in cerebral tissue7. (The detailed design of a Doppler signal processor is not the subject of this work.) The analogue processor sends two output signals to the computer’s A/D converter. One is a light intensity signal, formed by summing the outputs of the four photodiodes, the other is the flow-related signal derived from the Doppler spectrum. The Do pler spectrum is the AC component of the photodio dp es’ outputs. The top two photodiodes are summed into one side of an AC-coupled differential amplifier and the bottom two into the other side. This provides rejection of any common mode signals.
Patient
ARTEFACTS
movement
The Doppler spectrum from the photodiodes results from the mixing of the various Doppler-shifted and -unshifted components from the skin, and therefore represents movement of blood cells relative to the static skin tissue. Small movements of the patient, such as those caused by breathing, will therefore not cause additional spectral components affecting the measurement. It is necessary, however, to avoid gross movements of the patient which would distort the image obtained. Beam movement An important source of artefact arises from the laser scanning regions of different reflectivities. This results in a large AC component in the received light intensity. The differential input to the Doppler processor virtually eliminates this. The intensity variations appear as a common mode signal to the photodiodes, i.e. they are highly correlated. The Doppler spectra at each photodiode are not significantly correlated and the differential input allows these signals to pass through to the Doppler processor without the intensity variations. The differential input also rejects other common mode signals, such as laser noise and mains frequency harmonics from room lighting. Spectra were obtained from skin at the normal scanning speed (1 s per line) and a low scanning speed (9s per line), the lower bandwidth limit being 5OHz (Figure 5). Additional spectral components at the higher speed are visible, mainly below 300 Hz, with minimal difference above this frequency. This Range.-51
dBV
B: Stored
Computer
processing
The computer receives the light intensity and blood flux signals from the Doppler processor via an A/D converter, and the mirror position information signals from the motor control microprocessor. Before this information is used to assemble the image, the blood flux signal is compensated for noise effects. Circuit noise and shot noise from the photodiodes appear at the flux output as an offset whose value depends on the received light intensity. This offset increases the effective flux reading. To compensate for this a variable offset is subtracted from the flux value and is obtained from a look-up table of the noise-intensity relationship of the scanner. The intensity output from the Doppler processor is used to index the look-up table. The compensated flux values are represented on a scale of O-255 arbitrary blood flux units. In the
100 mVrs
Status Paused RMS: 250
II
I
I
Ii
ll
I
10 mVrs /DIV
0
vrmsA-stop
Start.
OHz
Frequency (Hz)
spectra from skin, showing addItIona spectral due to scannmg. The lower trace was recorded at a very low scanning speed. the upper a! normal scanning speed Figure 5
Doppler
components
at low
frequencies
J. Biomed. Eng. 1991, Vol. 13, May
191
Lam Doppler bloodjow imaging: TJ,H. Essex and P.O. Byrne
relationship between the spectra obtained is highly repeatable, suggesting that the changes are not due to blood flow variations. The range of frequencies of the additional spectral components suggests that they are the residual effects of the reflectance variations mentioned above not being completely rejected by the differential amplifier. It is therefore necessary to filter the low frequency end of the Doppler spectrum to attenuate these artefact components. A second-order high-pass filter with a cut-off frequency of 250 Hz is used for this purpose. Some residual corn onents remain after filtering, but the nature of the g oppler signal processing is such that lower frequencies carry little weight in the computed flux value. These scanning artefacts and the filtering necessary have an effect on the scanner’s measurements. EVALUATION Flow tests The scanner’s response to changes in flow was evaluated using a suspension of 15pm nylon particles in water, pumped through a test cell. There was no attempt to mimic skin tissue with the set-up, although the reflectance and Doppler spectra were similar to those of skin. The cell consisted of two microscope slides, their faces separated by 0.12 mm, sealed down their long sides, forming a channel of 20 X 0.12 mm. The assembly was sandwiched between two 1 mm thick pieces of silicone rubber acting as diffusers. The stationary laser beam from the scanner was aimed perpendicularly at one of the cell faces. The nylon particle suspensions were pumped through the channel between the slides. Figure 6 shows the scanner outputs obtained for various flow rates. These measurements were made at a fixed particle concentration of 0.2% v/v, and hence represent a velocity relationship. The particle concentration and flow rates chosen were such that the resulting Doppler signals were similar in spectral shape and amplitude to those obtained from normal skin, giving similar output values from the processor. The actual velocities in the cell do not relate directly to those of blood cells in skin, however, because of the transverse cell flow and the different scattering properties of the cell compared with skin.
0
2
4
6
8
Flow through
10
12
14
16
18
20
test rig (p\ s-‘1
Figure 6 Relationship between the scanner processor output and flow through a test rig. Bars show 1 standard deviation from the mean. The processor output is in arbitrary flux units
192
J. Biomed. Eng. 1991, Vol. 13, May
At high flow rates, 14-20 ~1 s-’ and above, the relationship in Figure 6 is a straight line that would intercept the origin, as expected. The dip in the line at lower flows is a result of the filtering at low frequencies to limit scanning artefact. This reduces the sensitivity of the scanner to low blood velocities. Scan speed artefacts Sixty pairs of blood flux values were obtained, each pair being of an identical area of skin scanned at the normal and low scan speeds used to obtain Figure 5. The 250Hz filter was in place for these measurements. Each flux value was the mean of 96 pixel measurements. The difference within each pair was calculated, as well as the mean and standard deviation of all the differences. The same calculations were made for 60 pairs of flux values recorded both at the lower scan speed, representing the variability due to blood flow changes and the measurement technique. The mean change in the flux between low and normal scanning speeds was -0.1 (k8.6) flux units at a mean flux for all points of 82.5 units. In the group of airs at the low speed, the mean change was -2.5 56.6) units and the mean flux for all pints 8 1.8 units. P These results seem to indicate that any error in the flux measurement due to the beam scanning is not significant compared with the variability in the measurement itself. It would be necessary to take a much larger set of readings to extract any systematic error due to the scanning motion.
Clinical
results
Examples of images obtained from the laser Doppler scanner are shown in Figures 7-77. In F&we 7, the dorsal surface of a hand is seen, where the blood flow to one finger was interrupted using an elastic band. There is clearly no flux visible on the scan in this finger. Figure 8 is the chest of a normal subject after he had made a scratch on the skin with his fingernails. No visible changes were apparent on the skin, but the area affected by the scratch is visible as an area of raised blood flux. The increase in area covered by the scan compared with Figure 7 is achieved by placing the subject further from the scanner (1.6 m compared with 600 mm). The subject in Figure 9 had a skin graft performed as a child, about 20 years ago. This area shows a reduced blood flux in the skin. Figure 70 is the result of a series of tests to obtain a dose-response curve for a skin irritant. The patches of raised blood flux are due to various doses of the irritant and the black square is a known reference area. Software is being developed to anal se the dose response in terms of increase in blood Kux and the size of the area affected. The method is quick and convenient compared with methods currentIy in use. Finally, Figure 11 is a scan of a pair of hands, again the dorsal surface. The point of interest on this scan is on the right hand, where there was some inflammation of the tendon of the first finger. This is reflected as an increase in the blood flux in the skin overlying the tendon.
Laser Doppler bloodflow
Relative
perfusion
imaging: i?JH. Fsex and P.O. Byrne
sCOle
Figure 7 her Doppler scan of the dorsal blood flow to one finger interrupted
surface
of a hand
with
2, 2: 5: 7;
100 *
125 h
150 ?I
175 n
Relative perfusion Figure
10
Laser Doppler
scans of responses
ii k
2;
5;
7;
100
A
A
125 Relative
l:O
175
perfusion
200 n
225 A
250 A
to doses of skin irritant
n 200
n 225
A
250
Units
scale
Figure 11 hands;
Units
scale
Laser Doppler scan of the dorsal surface of a pair the tendon of the first finger of the right hand is inflamed.
of
CONCLUSION
;
2:
5;
7;
to”0
125 A
Relative Figure 8 Laser Doppler had scratched his skin
150 A perfusion
175 n
200 A
225 A
250 h
Units
scale
scan of the chest of a normal
subject
who
A scanning laser Doppler instrument has been developed that is able to generate an image of blood flux in the capllaries under the surface of the skin. It has been demonstrated to detect changes in blood flux resulting from injury, disease and temperature. Although it is not possible to calibrate the instrument directly, in most cases a comparison can be made between the area being studied and an adjacent or symmetrically opposite part of the body. Clinical studies are in progress to evaluate the scanner in various areas of medicine.
J. Biomed.
Eng. 1991, Vol. 13, May
193
Laser Doppler blood flow imaging: TJH. Essex and P.O. Byrne
ACKNOWLEDGEMENTS The authors are indebted to the numerous clinicians in the Newcastle hospitals who have contributed advice and effort to this work, and from the Medical Physics Department, Mr E. Horsefield for the mechanical fabrication of the instrument and Professor Boddy for supporting the project. REFERENCES 1. British Technology Group UK Patent Nos GB 2 23 1742 A and WO 90/ 11044. 2. Watkins D, Holloway GA. An instrument to measure cutaneous blood flow using the Doppler shift of laser light. IlL!!X Trans Biomed Eng 1978; BME-25: 28-33.
194 J. Biomed. Eng. 1991, Vol. 13, May
3. Nilsson GE, Tenland T, oberg PA. A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy. IEEE Trans Biomed Eng 1980; BME-27: 12-9. 4. Bonner R, Nossal R. Model for laser Doppler measurements in tissue. A# Opt 1981; 20: 2097-107. 5. Jentink HW, de Mu1 FFM, Hermsen RGAM, Graaff R, Greve J. Monte Carlo simulations of laser Doppler blood flow measurements in tissue. Appl Opt 1990; 29: 2371-81. 6. Nilsson GE. Signal processor for laser Doppler flowmeters. Med Biol Eng Comput 1984; 22: 343-8. 7. Eyre JA, Essex TJH, Flecknell PA, Bartholomew PH, SinclairJI. A comparison of measurement of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres. Clin Phys Physiol Meas 1988; 9: 65-74.
