WO2003005040A1 - Measuring instrument and method for optical measurement of velocity and direction of particles - Google Patents

Measuring instrument and method for optical measurement of velocity and direction of particles Download PDF

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WO2003005040A1
WO2003005040A1 PCT/NO2002/000239 NO0200239W WO03005040A1 WO 2003005040 A1 WO2003005040 A1 WO 2003005040A1 NO 0200239 W NO0200239 W NO 0200239W WO 03005040 A1 WO03005040 A1 WO 03005040A1
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Dan Östling
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Leiv Eiriksson Nyfotek As
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/12Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
    • A61B3/1225Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes using coherent radiation
    • A61B3/1233Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes using coherent radiation for measuring blood flow, e.g. at the retina
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N15/1456Electro-optical investigation, e.g. flow cytometers without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
    • G01N15/1459Electro-optical investigation, e.g. flow cytometers without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals the analysis being performed on a sample stream
    • G01N2015/1027
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N2015/1486Counting the particles
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N2015/1493Particle size
    • G01N2015/1495Deformation of particles

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  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Length Measuring Devices By Optical Means (AREA)

Abstract

The invention relates to a measuring instrument and a method for the optical measurement of the velocity and direction of particles or other objects, in particular in an eye, comprising a spatially coherent light source, optical devices for focusing light from this towards the particle, optical devices for collecting the light scattered from said particle and directing the collected scattered light on a detector. The optical devices comprise an interferometer arrangement having a reference arm and a measuring arm. The detector is divided in at least three parts for measuring light scattered by the particle in different directions, and the instrument and method is adapted to use the signal from the detectors to obtain the phase or frequency shift of the detected signal in order to estimate the velocity of the particle in more than one dimension.

Description

MEASURING INSTRUMENT AND METHOD FOR OPTICAL MEASUREMENT OF VELOCITY AND DIRECTION OF PARTICLES.
This invention is related to a measuring instrument for optical measurement of the velocity and direction of particles, in particular an eye, comprising a spatially coherent light source and an optical arrangement for focusing light from this (light source) onto the particles, and optical arrangements for focusing the light scattered from the particles towards a detector.
In this context particles are objects in general, for example molecules, blood corpuscles, cells, scattering surface objects and other small objects that scatter the light used. The present invention has its background in optical coherence tomography (OCT) which can measure reflections from scattering particles with a resolution of a few micrometer transversally and in depth [1,4]. By combining OCT with Doppler techniques (DOCT) movements of particles in the measuring volume may be estimated [2,5,6,7] so that a flow profile can be found. In such a DOCT-system only axial movements (along the optical axis of the lens) is measured. Movement normal to the optical axis only yields a spectral broadening of the signal, resulting in limited possibilities of determining flow velocities normal to the optical axis, that is an indication of the velocity is achieved, but not the flow direction. An OCT setup comprising four detectors has been presented for reducing the effect of speckle in the image [3,8] . It is a purpose of the present invention to provide a method for performing vector measurements of particle flows. Such measurements can be made with ordinary Laser Doppler Velocimetry (LDV) , however, with low point resolution, rendering this solution unsuitable in many cases. It is a particular purpose of this invention to enable microscopic measurements of a flow, particularly for measurements of the microcirculation in retinal blood vessels. In this case light is applied and gathered using the pupil of the eye. Commercial equipment based on confocal LDV is available [9], having a number of disadvantages limiting its usefulness. For one thing the depth resolution is poor (300-400μm) . The DOCT technique has good depth resolution and in addition uses a reference beam giving the possibility of using the phase of the signal in order to find the frequency shift.
Another purpose of the invention is to enable measurements of vibrations of particles and small objects. The measuring system gives the possibility of determining the frequency, amplitude and phase of the vibration in addition to the directional vector in space. Configured as a microscope the method can then be used for measuring vibrations and deformation of small particles or cells.
The invention hence relates to a measuring instrument as defined above, and which is characterised as given in the independent claim.
Preferably, the instrument according to the invention comprises a so-called quadrant-detector so that the light beam from the beam splitter is detected in four separate detector elements. By comparing the interference signals from the four detector segments the movements of a scattering particle is measured as a vector, that is, not only in the z direction, but also in the x and y directions. The frequency shift of the signal on the separate segments can then be compared in order to find the size and direction of the velocity components related to the optical axis. By comparing the phases of the interference signals instead of the frequency shift lower velocities can be measured more accurately. The invention is described below with reference to the attached figures, illustrating the invention by way of example.
Figure 1 shows a preferred embodiment of the invention comprising a Michelson interferometer. Figure 2 shows the scattering geometry graphically
Figure 3 is a simplified three-dimensional illustration of the optical beams reaching each part of the detector. Figure 4 illustrates the case of the scattering from the particle in the x-z plane only. Figure 5 shows schematically the different spectra Sι(f) of the detector currents of the four detectors in Figure 1.
Figure 6 illustrates the effect of a fluid of refractive index n around the particle. Figure 7 is a block diagram illustrating the main processing steps for the signals from the detector.
Figure 1 illustrates a version of the invention in the form of a simple Michelson interferometer comprising a reference path 11 and an object path 12. A light source 16 provides the source light for the interferometer. Preferably, the light source is a spatially coherent low coherence length light source 16. An optical light dividing part is provided for splitting the light from the said light source 16 between the reference path 11 and the measuring path 12. The light dividing part is preferably a beam splitter 13. An optical focussing part 18 is provided for focussing some of the light in the said measuring path 12 onto the particles 15 or the like. Preferably, the optical focussing part is single lens or a combination of multiple lenses. The particle 15 or the like typically scatters some of the light incident on it. An optical light collecting part is provided for collecting the light scattered from the particle (s) (15) . This light collecting part could be a second lens arranged anywhere around the particle in order to collect the light scattered from the particle. However, a primary use of this invention is in microscopy applications. In this case the optical light collecting part may be the same lens 18 or lens combination which focuses the light from the source onto the particle. This means that the light collecting lens 18 collects primarily light which is scattered backwards by the particle 15. An optical beam combining part is provided for combining the light having propagated the reference path 11 with the collected 18 scattered light. In the Michelson interferometer configuration shown in Figure 1, the beam combining part is preferably the beam splitter 13.
A detector 14 is arranged for detection of the combined beam resulting from the combination of the scattered light from the object path 12 with the reflected light from the reference path 11 in the beam splitter 13. The detector 14 is provided with at least three detection elements. In Figure 1 a preferred detector 14 having four detection elements 1,2,3,4 in the form of four quadrants. Each detection element can detect the incident light independent of the others, depending on the interference conditions between the two beams.
The signal from the detectors is led in separate conductors 20 to the electronics and signal processing unit 21 for the detection of phase (or frequency shift) and amplitude of the interference signal. The major benefit of the invention is thus obtained using a phase-sensitive detection scheme for the interference signal in combination with a detector with three or more detection elements. The electronics and signal processing unit 21 comprises a particle movement estimation module for calculating the movement of the particle 15 in more than one dimension using the interference signals obtained by the detectors.
The number of detection elements could vary, however in a preferred embodiment of the detector, the detector has four detection elements. The detector could also be of the CCD-type detectors, as known from the field of camera technology.
The detector may have number of different shapes. In a preferred embodiment of the invention the detection elements are substantially equally sized elements arranged at equally spaced angles about the optical axis. The optical length of the reference path 11 is adjustable by providing this path with optical length adjustment means. The optical length adjustment means is a movable reflector, preferably a movable mirror 17 or other movable optical elements 19 in the reference path 12. This can be achieved by an additional function in an oscillator 22. The oscillator 22 is coupled to the movable optical elements 19. Further, the oscillator is coupled to the signal processing unit 21 for providing a reference signal related to the modulation of the reference path 11. In this way a possibility of adjustment of the length of the measuring path 12 is achieved.
Preferably, the mirror 17 in the reference path 16 can be given an oscillating movement by providing a suitable drive signal, for example from an oscillator 22. This results in a varying length of the reference path and a time-varying interference signal on the detector, which hence results in time-varying signals at the output of the detector. Using phase-detecting or tracking methods known to those skilled in the art the phase of the signal being reflected from the object 15 can be found. In the figure the oscillator 22 is in addition connected to the measuring instrument 21 which processes the signals from the detector. Using modulation techniques the phase of the interferometer signals can be determined. By considering the phase of the signal detected, the size as well as the sign of the Doppler induced frequency shift of the reflected signal can be determined. In a further preferred embodiment of the invention the optical focusing part for focusing light in the measuring path 12 onto the particles will be the same lens which is used as an optical light collecting part for collecting the light scattered from the particles, in the form of a single lens. However, if other interferometer configurations are used, these two functions could be performed by two different lenses or a combination of lenses.
In yet another preferred embodiment of the invention the optical arrangement for dividing the light from said light source 16 between a reference path 11 and a measuring path and the optical beam combining part 13 for combining the light having propagated the reference path 11 with the collected 18 scattered light will be a single beamsplitter. In the case of other interferometer configurations, the beam dividing and combining functions will be performed by two or more components.
In the following a more detailed description of the underlying principles of invention will be detailed. Figure 2 illustrates schematically the scattering by an object or particle 15 in a general manner. An incident ray of wave vector ki is incident at an angle θi. The incident ray hits the particle having a velocity vector vp at an angle of θp. The resulting scattered light ray at an angle of θs has a wave vector of ks. By using a low coherence source 16 only light within a limited measuring volume 15 in the focus of the object lens will contribute to the interference signal. Light directed towards the particle and scattered from the particle within a range of angles is such that the resulting signal on each of the segments of the detector can be regarded as a sum of light from all relevant angles of incidence and angles of scattering.
Figure 3 is a three-dimensional diagram illustrating how light arriving at the different segments of the detector may have its origin in incident light from the source 16 being scattered in different directions by the object or particle 15. Beams of light l',2',3',4' give rise to light impinging on the different detector segments 1,2,3,4, respectively.
When the particle moves normally to the optical axis, an ordinary DOCT method will be insensitive because positive and negative frequency shifts will appear symmetrically, giving a broadening of the signal, but no net frequency shift. The DOCT method of processing the signal is considered to be known, for example from the referred publications . However as an aid to understanding the present invention, a short summary of the simplified one-dimensional OCT is repeated. The interference signal from a detector in an ordinary OCT-setup can be written as
A = A0 cos(2π(fs -fR)t + φ0)
where fs and fR are optical frequency from the sample and reference, respectively, and t is time while φ0 is a phase. fs and fR may be Doppler shifted in relation to the source frequency fo
Figure imgf000009_0001
For ordinary OCT we have the situation that
2vr
Δ/=- P
Figure imgf000009_0002
where vp is the velocity component of the particle towards the interferometer. Likewise vr is the velocity of the reference mirror towards the interferometer. λ=nλ0 is the wavelength of the light in the medium of the particle, which has a refractive index of n. vp can be determined from a measurement of fs_fR together with knowledge of vr:
Figure imgf000009_0003
In the more general three-dimensional case, however, light will be divided between the detector segments, effectively breaking the symmetry, so that transversal movements can be detected. With a two part detector movements in two directions can be determined, one along the optical axis and one normal to the optical axis.
The following is an analyses of the three dimensional situation when using a detector consisting of four independent detector segment covering three different spatial angles. Introducing polar coordinates φ and θ the particle velocity vector may be written
Figure imgf000010_0001
Figure imgf000010_0004
Correspondingly, the wave vector of the incident and scattered light can be written
Figure imgf000010_0002
Figure imgf000010_0005
Figure imgf000010_0003
Figure imgf000010_0006
For simplicity, only the angles θ in the xz-plane are illustrated in Figure 2. The resulting Doppler shift in the scattered optical signal in the sample arm is given by
Δ/ = (ks - k: )vP = (ksx - k )vx + (ksy - kiy )vy + (ksz - kb )v2
In ordinary OCT there will only be contributions from the z-component as light enters and is collected along the z-axis. Strictly, this is only valid when using a very small numerical aperture. If the incident and scattered light has a symmetrical distribution around the z-axis there will be a symmetrical broadening of the electrical spectrum due to the contributions from the transversal components of the velocity. This can be used to estimate the velocity, but not the direction, of the transversal component.
Provided the system is arranged in such a manner that ksy-kiy or ksx-kiX is no longer zero, contributions from vy or vx will also be detected. This can for example be achieved by placing four detector elements (a quadrant detector) at four different angles φs (e.g. 0, π/2, π, 3π/2), and a common angle θs. If, in order to simplify the analysis, it is assumed that the incident ray is arranged in such a way that it has cpi<φs and is symmetrical about the z-axis, such that the transversal contributions from k can be neglected we obtain four different Doppler shifts in the light at the four detectors:
Δ/, = (vPx sin θ, + vPz (cosø, + 1)) = Afx + Afz Af2 = k{yPy sin θs + vPz (cos θ, + l))= Afy + Afz Δ 3 = *(- Λ sin θ, + vPz (cos θs + 1)) = -Afx + Afz Δ 4 = k{- Vpy sinø, + vft (cosø, + 1)) = -Afy + Δ/z
where vpx, vpy, and vpz are the velocity components in the x,y and z directions. Δfx, Δfy, and Δfz are the Doppler shifts at the detectors caused by vpx, vpy, and vpz, respectively. This is the Doppler shift experienced by the light scattered from the sample onto the different detector segments. If a measurement provides Δfi, Δf2, Δf3, and Δf4, the velocity components may be found as:
λ 1 vx = (Af -Af)
2 sinø
λ 1 v =(Δ/2-Δ/4) 2 sin6> v2 =(Δ i + Δ/2 + Δ/3 + Δ/4) A l
4 l+cos6>,
As can be seen all detector segments will have a positive contribution Δfz provided vpz is positive. In addition detector segment 1 will have a positive contribution Δfx provided vpx is positive, while detector segment 3 will have a corresponding negative contribution Δfx. By comparing the Doppler shifted signal in quadrant 1 and quadrant 3 one is able to find the velocity component vPχ. Vpx does not contribute to the total Δf in quadrant 2 and 4. Correspondingly it is possible to find vy by comparing quadrant 2 and 4. vz is found by comparing all four quadrants .
The light scattering from the particle 15 is schematically rendered in two dimensions in Figure 4, where the particle moves in the z-x plane (i.e. the special case of vy=0) . Any reference path 11 is omitted for simplicity (i.e. ΔfR=0) . If the object moves the light scattered from the object will have a frequency shift depending on three variables:
The velocity of the particle, v. The angle between the incident light and the velocity vector.
The angle between the velocity vector and the scattered light.
The incident light can be considered as a sum of many plane waves at different angles. In Figure 4 the incident light is drawn along the optical axis (z direction), as an example. The light will be incident from many angles, distributed symmetrically about the optical axis. The angular distribution of the incident light depends on the numerical aperture of the lens and the diameter of the beam at the lens. The angular distribution of the scattered light will in addition depend on the scattering properties of the particles. In this case the velocities vx, vy, and vz are determined from the following equations: vx=Kxy(Af-Af)
vy=Kxy(Af2-Af)
vz=Kz(Afl+Af2+Af2+Af4)
The constants Kxy, Kz can be determined by integration of the (angular distribution of) the three variables mentioned above over the angles θ and φ As an alternative to integration, Kxy, Kz can be found by calibration of the measurement system to known flow conditions.
The frequency shift is given by the components of the beam along the velocity vector. The incident light has frequency fo, while the reflected light has frequency f0+ Δf, where the frequency shift is given by:
Δ/, = k{vPx sinø, + Vpz (costf, + 1)) = Afx + Δ/2 Af2=k(vPz(cosθs+\))=Af2 Δ/3 = *(- ft sin0s + vPz (cos0f + 1)) = -Afx + Δ/z Δ4= (vft(cos^+l))=Δ/z
for the four detector segments 1,2,3,4.
Figure 5 shows schematically the resulting spectra Sι(f) of the detector current from the four quadrants 1,2,3,4 corresponding to the velocity vector given in Figure 4 (i.e the special case of vy=0 and ΔfR=0) . The spectra have a certain width due to the distribution of the angles of light incident on the particle 15 and of the angles of the distributed light. The frequencies corresponding to the peaks of the four spectra Si(f) in Figure 5 can be found using suitable signal processing routines, for example STFT (Short Time Fourier
Transform) .
If the particle 15 moves in a medium of refractive index n behind a surface in the xy-plane, as illustrated in
Figure 6, the following equation given by Snell's law: nsinθs = siaθs ' , gives the relation between the angles θ in the sample and the angles θ' in the instrument. The position of the detectors determine θs' directly, while θs is determined indirectly via the refractive index n. the wavelength λ changes correspondingly through the relation λ=nλ0. Expressing the velocity components in terms of θ's yield:
vx = (Afl - Af) λ° l
2 sin#„
v =(Δ/2-Δ/4)
2 sin#
Figure imgf000014_0001
where λ0 is the wavelength of the light in free space. The frequencies Δfi, Δf2, Δf3, and Δf4, can be determined in many ways. As an alternative to using Fourier domain techniques, as described above, is to use time domain techniques, where a comparison of phase changes in the four detector signals are made. The main steps in a suitable signal processing scheme is illustrated in Figure 7 which will be explained in more detail in the following. Although Figure 7 typically will be interpreted as steps in a method for obtaining the velocity of the particle or object, each block in Figure 7 will typically also correspond to a software module implemented as part of a computer program performing the required signal processing of this invention In one alternative embodiment of the signal processing according to the invention a complex interference signal is formed. This can be done in a measurement 101 using demodulation techniques which results in the I (in phase) and Q (quadrature) components of the interference signal. Such processing can be performed partly in an analogue signal processing circuit or in a digital signal processor, such as a suitable microprocessor utilizing a program for this application, provided that the signals from the detectors are suitably converted or sampled in order to provide data in a digital form using analogue-to-digital converters. It will be understood by those skilled in the art of signal processing that the signal processing steps detailed below also may be performed in a computer, a microprocessor or other similar computing means. The complex interference signal is then
Ac = I + jQ = AeK2π fs-f«)l+M
In an alternative embodiment of the signal processing according to the invention the complex interference, Ac, is estimated 103 using a Hubert transformation on the measured 102 amplitudes. The thus obtained complex interference signal may then be used to find the frequency shift.
For the further processing of the complex interference signal it will normally be necessary to choose 104 a time interval of the signal, i.e. sequence of digitized samples, for processing.
After having chosen a time interval containing a few or many samples, there are several ways of processing the signal in order to obtain the frequency shifts. In one preferred alternative embodiment of the invention the frequency spectra are estimated 107. The weight centre (centroid) of the complex frequency spectrum, fCι, of each detector is thus obtained. Using this result the frequency shifts Δf and the particle velocity vP are estimated 108,109 using the relationships:
Figure imgf000015_0001
Δ/,=/α+Δ/Λ
S(fπ k) is the power spectrum at discrete frequencies fm as calculated from the time interval ΔT at the time tk using the relationship
Figure imgf000016_0001
Another alternative is to estimate the phase changes 106 of the complex interference signal. In this case the velocities may then be found from two consecutive samples at time t and t-T of the phase Φi of the interference signal:
vx = ^-(Φ,(t)- Φ,(t-T)- φ3(t) + φ3(t- T))
Vy = ^-(φ2(t)-φ2(t- T)- φ4(t) + φ4(t - T))
V2 =-^-(φ,(t) - φl(t - T) + φ2(t) - φ2(t - T) + φ3(t) - φ3(t - T) + φ4(t) - φ4(t - T))
As a final step in the processing, the resulting velocities vx, vy, and vz may be displayed 110 using any suitable display means. If the reference mirror is scanned, this movement will in addition contribute to a Doppler shift which is common to all quadrants. If the scanning velocity is known the measured velocity can simply be corrected for this.
An improved resolution of frequency/velocity can be obtained by masking parts of the detector segments in such a way that the angular distribution of the detected light is restricted.
It can therefore also be of interest to replace the quadrant detector by four optical fibres (coupled to each corresponding detector) , arranged symmetrically in the beam of light from the interferometer. An alternative solution is to replace the quadrant detector by four or several smaller detectors.
The invention is described here using an example with a Michelson interferometer, but it will be obvious that other solutions comprising a reference beam can be used as long as an interference signal is obtained which can identify the phase of the reflected signal. In addition, the direction of the wave fronts of the object path has to be maintained. The practical execution of possible changes of the length of the reference arm will vary with the interferometer type.
The range of angles which the measuring instrument is sensitive to will as mentioned depend on the construction of the interferometer, in particular in relation to the numerical aperture and focal length of the lenses in addition to the distance to the measurement objective. These choices will be apparent for one skilled in the art when considering the relevant application. This also applies to the type of light source, including also wavelength range and coherence length applied. For example, the wavelength range can be chosen by considering the expected scattering cross section of the particles, whose movement shall be measured, and the type of sensor chosen on the background of this. Typical wavelength ranges for use in the eye will be 600 to 900 nm, and Si detectors are applied. As light sources superluminescent diodes or femtosecond pulsed lasers can be applied. When the measuring area is in the eye the object lens 18 is replaced by the lens in the eye, and the beam 12 will preferably have a width limited by the pupil. When needed, one or more lenses can be placed in the detector arm in order to adapt the beam diameter to the size of the detector.
References:
[1] D. Huang, E.A. Swanson, C.P. Lin, J.S. Shuman, W.G. Ξtinson, W. Chang, M.R. Hee, T. Flotte, K. Gregory,
C.A. Puliafito, J.G. Fujimoto: Optical Coherence
Tomography. Science, Vol 254, 1178-1181, 1991 [2] Z. Chen, Y. Zhao, S. M. Srinivas, J. S. Nelson, N.
Prakash, R. D. Frosting, "Optical Doppler Tomography", IEEE J. Select. Top. Quant. Elect. , 5, 1134-1142, 1999.
[3] J. M. Schmitt, "Array detection for speckle reduction in optical coherence tomography", Phys . Med. Biol. 42,
1427-1439, 1997. [4] US Pat. 5,459,570, "Method and apparatus for performing optical measurements", Oct. 17, 1995.
[5] US Pat. 5,549,114, "Short coherence length, Doppler velocimetry system", Aug. 27, 1996. [6] US Pat. 5,991,697, "Method and Apparatus for optical
Doppler tomographic imaging of fluid flow velocity in highly scattering media", Nov. 23, 1999.
[7] US Pat. 6,006,128, "Doppler flow imaging using optical coherence tomography", Dec. 21, 1999. [8] US Pat. 6,037,579, "Optical interferometer employing multiple detectors to detect spatially distorted wavefront in imaging of scattering media", Mar. 14,
2000. [9] "Scanning laser Doppler flowmetry: Principle and technique" by Gerhard Zinser, Heidelberg Engineering
GmbH, Heidelberg, Germany, i Pillunat LE, Harris A, Anderson DR, Greve EL (eds) : "Current concepts on ocular blood flow in glaucoma", pp 197-204. Kugler
Publications, The Hague, 1999,
(http : //www. heidelberg-engineering . de/tut/hrf/- hrf-tutorial.html) .

Claims

C l a i m s
1. Measuring instrument for measuring the amplitude and direction of the (velocity of) movement of particles or the like, in particular in an eye, arranged as an interferometer comprising
- a spatially coherent low coherence length light source (16),
- an optical light dividing part (13) for splitting the light from the said light source (16) between a reference path (11) and a measuring path (12),
- an optical focussing part (18) for focussing light in the said measuring path (12) onto the particles (15) or the like, - an optical light collecting part (18) for collecting the light scattered from the particles (15) or the like,
- an optical beam combining part (13) for combining the light having propagated the reference path (11) with the collected (18) scattered light,
- a detector (14) arranged to detect the resulting combined light characterised in that
- the detector (14) is provided with at least three detection elements (1,2,3)
- signal processing means (21) connected to each of said detection elements (1,2,3) for processing, analyzing and presentation of the signals detected by said detection elements (1,2,3) - interference signal processing means (21) for obtaining the phase or frequency shift of the detected signal at each detection element (1,2,3) and
- particle movement estimation means (21) for calculating the movement of the particle (15) in more than one dimension.
2. Instrument according to claim 1, comprising optical length adjustment means (17) arranged in the reference path (11) .
3. Instrument according to claim 1, comprising an oscillator (22) coupled to the optical length adjustment means (17) .
4. Instrument according to claim 1 arranged as a Michelson interferometer where the reference path (11) has a reflector (17) .
5. Instrument according to claim 1, where the reflector (17) is provided with a vibration unit, e.g. a piezoelectric element, in order to provide a vibration movement of the reflector (17) .
6. Instrument according to claim 1, where the detection elements (1,2) are substantially equally sized elements arranged at equally spaced angles about the optical axis.
7. Instrument according to claim 1, comprising four detection elements (1,2,3,4)
8. Instrument according to claim 1, where the optical focussing part (18) for focussing light in the said measuring path (12) onto the particles (15) or the like and the optical light collecting part (18) for collecting the light scattered from the particles (15) is a single lens (18) .
9. Instrument according to claim 1 where the optical arrangement for dividing (13) the light from the said light source (16) between a reference path (11) and a measuring path (12) and the optical beam combining part (13) for combining the light having propagated the reference path (11) with the collected (18) scattered light is a single beamsplitter (13) .
10. Instrument according to claim 1, comprising a demodulation block (101) for providing a complex interference signal from the signal from each detection element (1,2,3,4) .
11. Instrument according to claim 10, comprising a signal phase detection block (106) and a signal frequency detection block (108).
12. Instrument according to claim 10 or 11, comprising a complex frequency spectrum calculation block (105) for calculating a complex frequency spectrum of the signal from each detection element (1,2,3,4).
13. Instrument according to claim 12, comprising a centroid calculation block (107) for obtaining a centroid of the complex frequency spectra.
14. Instrument according to claim 10 or 11, comprising a phase change calculation block (106) for tracking phase changes of the complex interference signals
15. Instrument according to any of the previous claims, comprising a frequency shift calculation block (108) for obtaining frequency shifts of the signals from each detection element (1,2,3,4).
16. Instrument according to claim 15, where the particle movement estimation means (109) for calculating the movement of the particle (15) in more than one dimension is adapted to use the obtained frequency shifts (108) based on the signal from the detection element (1,2,3,4) as inputs data.
17. Instrument according to claim 1, comprising a velocity estimation module (109) for estimating the particle flow in transversal and axial directions.
18. Instrument according to claim 17, comprising a frequency difference calculation module (108) for obtaining a characteristic measure of the particle flow in a transversal direction by a comparison of the frequency shifts of signal from each detection element (1,2,3,4).
19. Instrument according to claim 17, comprising a mean frequency calculation module for obtaining a characteristic measure of the axial flow from the mean frequency shifts of the signals from the detection elements (1,2,3,4) .
20. Instrument according to claim 17, comprising a total flow calculation block for obtaining a characteristic measure of the total flow by adding the flow in the transversal and axial directions.
21. Method for measuring the amplitude and direction of the
(velocity of) movement of particles or the like, in particular in an eye, using an interferometer comprising the steps of providing spatially coherent light using a spatially coherent low coherence length light source (16), dividing the light from the said light source (16) between a reference path (11) and a measuring path (12) using an optical light dividing part (13), focussing light in the said measuring path (12) onto the particles (15) or the like using an optical focussing part
(18), collecting the light scattered from the particles (15) or the like using an optical light collecting part (18) for, combining the light having propagated the reference path
(11) with the collected (18) scattered light using an optical beam combining part (13) for, detecting the resulting combined light using a detector
(14), wherein the method further comprises the steps of
- detecting optical waves scattered by the particle (15) or the like in different directions by a detector (14) provided with at least three detection elements (1,2,3)
- processing and analyzing the signals detected by each said detection elements (1,2) using signal processing means (21) having a separate connection to each of said detection elements (1,2),
- obtaining the phase or frequency shift of the detected signal at each detection element (1,2) using interference signal processing means (101,104,106,108),
- calculating the movement of the particle (15) in more than one dimension using particle movement estimation means (109) .
PCT/NO2002/000239 2001-07-05 2002-06-28 Measuring instrument and method for optical measurement of velocity and direction of particles WO2003005040A1 (en)

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