1.9. How Can Tumour Blood Flow be Measured?
1.9.5. Laser Doppler Flowmetry
1.9.5.1. Development o f laser Doppler flowmetry X.9.5.1.1. The Doppler principle
Johann Christian Doppler (bom Salzburg Austria, 1803 - died Venice Italy 1853). worked as a mathematical assistant in Salzburg writing on mathematics and electricity before being appointed Professor o f Elementary Mathematics and Practical Geometry at the State Technical Academy in Prague. In May 1842 he presented his paper "On the coloured light o f double stars and some other heavenly bodies" (White 1982) in which he derived the formula for the motion o f source or observer along a line between them. He mentioned the application o f this principle to both light and sound. The first experimental validation was conducted two years later by Buys Ballot. In this experiment he borrowed a locomotive and a flatcar. A trumpeter rode on the flatcar towards a second musician at the station who confirmed that as the train approached the trumpet note fell by one half tone. Initial application o f this finding was confined to astronomy and little use was made for other purposes until the advent o f the laser.
Charles Townes and Arthur Schawlow (1958) developed the idea in which stimulated molecules encounter an electromagnetic wave and give up their energy to the wave thus strengthening it and as this process repeats itself the strength of the wave quickly multiplies. The first laser was developed with the first patent awarded in 1960.
The properties o f laser light which are o f use in laser Doppler flowmetry are the narrow range of wavelengths emitted, their coherence and the fact that the waves all have the same frequency, amplitude and direction.
1.9.5.1.2, Laser Doppler Velocimetry
With the advent of laser light, a technique known as light beating spectroscopy was further developed. The output of two independent lasers simultaneously illuminating a single photomultiplier led to a beat note at the difference in the frequency of the two laser wavelengths. By mixing scattered and unscattered light, Yeh and Cummings (1964) measured the flow velocities in different regions of a fluid undergoing lamellar flow. Laser Doppler Velocimetry then gained widespread use in industrial research
Figure 3 Portrait of Johann Christian Doppler (1803 - 1853)
I.9.5.I.3. Laser Doppler flowmetry
Riva et al. (1972) made the first measurements of blood cell velocity in individual vessels of the retina of rabbits. The first measurements of perfusion were made by Stern from his finger tip (Stern 1975). Having devised an algorithm to quantify the flow from the root
mean square of the bandwidth, he compared flow readings in skin to those made by the xenon washout technique (Stern et al. 1978). Early commercial instruments were produced by Medpacific and Perimed using Helium / Neon laser light.
1.9.5.2. Principles of laser Doppler flowmetry
The tissue is illuminated under laser light which is scattered in both static structures as well as red blood cells in the capillary bed. Photons scattered by moving red blood cells undergo a frequency shift according to the Doppler effect. Conversely light photons scattered by static structures do not undergo a frequency shift. Some of the scattered light reaches a sensitive photodetector and the photocurrent signal contains components from light which has been frequency shifted and that which has not. This signal is processed and the output is proportional to both red blood cell concentration and velocity.
The average depth and subsequent volume of the tissue samples increases with the separation of the laser and photodetector fibres. However because the intensity of the detected light falls off rapidly one is restricted in practice to a separation of not more than l-2mm. p T Z j / / / . / / / , / / / , y7 /7 7 . / / / / / / / / / / 1 \\\\\ \SN\\ \ \ \ \ \ \ \ \ W p h o to d e te c to r cell
Figure 4 Illustration of the principles of laser Doppler flowmetry showing how laser light is scattered and undergoes a frequency shift when it strikes a blood cell
1.9.5.3. Application of laser Doppler flowmetry 1.9.53.1. General
Laser Doppler flowmetry has developed over the past 15 years into a widely used
technique for the monitoring o f tissue perfusion in a wide variety o f applications (Belcaro et al. 1994). Initial studies o f the effects o f pharmacological agents and hyperthermia were mainly carried out in skin although studies in animals have been carried out in muscle, brain, spinal cord, teeth, gut, kidney and many other tissues. Laser Doppler flowmetry has particular clinical applications in the monitoring o f free tissue transfers in plastic surgery, in the assessment of intestinal ischaemia and the effects o f microvascular perfusion in peripheral occlusive vascular disease, Raynauds disease and diabetic
microangiography. A proliferation o f probe types now enables probes to be passed along endoscope working channels and future variations are likely to include remote
monitoring of probes implanted within the body. 19.5.3.2. Liver
Previous studies (Shepherd et al. 1987, Almond and Wheatley 1992) have shown that laser Doppler can be used within the liver substance and produce a linear response to changes in blood flow. However the simultaneous application of the probe to both liver and tumour in a small rodent has not previously been reported. Arvidsson et al. (1988) investigated whether laser Doppler flowmeter readings from the surface o f the liver reflected total hepatic flow in the pig and found that they did although the technique was found to be more sensitive to flow changes arising in the hepatic artery rather than portal vein.
I.9.5.3.3. Tumour
Acker et al. (1990) has measured interstitial tumour blood flow during hyperthermia treatment and has evaluated the amount o f tissue disruption as a result o f interstitial insertion o f the laser Doppler probe. He found that the disrupted tissue was limited to within 0 . 1 2 mm of the probe tip.