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Description  |
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an ophthalmological diagnosis apparatus, and more
particularly to an ophthalmological diagnosis apparatus whereby the eye
fundus is illuminated by a beam of laser light and the movement of a
speckle pattern formed by diffused laser light reflected by the tissue of
the fundus at an image plane which is conjugate with the eye fundus is
detected as fluctuation in the speckle light intensity to measure the
blood flow state for ophthalmological diagnosis.
2. Description of the Prior Art
Conventional methods that employ laser light to measure the state of the
blood flow in the eye fundus include those disclosed in Japanese Pat.
Laying-open Nos. 55(1980)-75668 and 56(1981)-49134. Both of these are
methods for determining blood flow velocity based on the laser Doppler
effect, so in each case it is therefore necessary to detect the frequency
shift of the laser light caused by the Doppler effect. This can be done
using either of two arrangements. One comprises splitting the incident
laser beam into two beams forming equal angles with respect to the optical
axis of the incident laser beam and directing the split beams into the eye
to be examined so that they intersect precisely at the position of the eye
fundus blood vessel concerned. The other arrangement is to detect laser
light scattered by the eye fundus blood cells from two different
directions. In both cases the optical system is complex and needs to be
high-precision. In addition, the fact that the angle of beam incidence or
light detection has to be known in advance, the fact that a laser beam
adjusted to a beam diameter that is substantially equal to the diameter of
the blood vessel concerned (which generally measures between several tens
and several hundred micrometers) has to be directed onto the blood vessel
with high precision, and the fact that the person undergoing examination
has to be kept motionless during the period of measurement make these
methods extremely difficult to apply clinically and impair the
repeatability and reliability of the results thereby obtained.
In order to overcome the aforementioned drawbacks the present inventors
have submitted patent applications (Appln. Nos. 61(1986)-38240 and
61(1986)-67339) for a method and apparatus that utilize the laser light
speckle phenomenon. According to this method, a laser beam of a prescribed
diameter that is larger than the diameter of the blood vessels is used to
illuminate the eye fundus so that light scattered and reflected by blood
cells in the eye fundus tissue forms a laser speckle pattern. With the
plane of the eye fundus defined as the object plane, the movement of the
speckle pattern formed at the Fraunhofer diffraction plane with respect to
the object plane or at an image plane that is conjugate with respect to
the eye fundus is then detected as fluctuations in light intensity by
means of finite detecting apertures, and is analyzed to thereby measure
the state of blood flow in the eye fundus.
However, with this method, the speckle pattern formed at the Fraunhofer
diffraction plane consists of superposed fields of light scattered from
all of the scattering points within the region of the fundus illuminated
by the laser beam. As such, light scattered from blood cells in the target
blood vessel is superposed with light scattered from the blood cells of
adjacent blood vessels, making it difficult to evaluate the blood flow in
any one specific blood vessel. In addition, light scattered by the walls
of blood vessels and surrounding tissue is also included, which forms
optical background noise with respect to the light that is scattered by
the blood cells in the target blood vessel. This has made it difficult to
detect signals having a good S/N (signal/noise) ratio at the Fraunhofer
diffraction plane.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide an
ophthalmological diagnosis apparatus that is able to detect speckle
signals with a good S/N ratio and enable accurate measurement of the state
of the blood flow in the eye fundus.
This object of the invention is accomplished by providing an arrangement
having an optical spatial frequency filter at a spatial frequency plane, a
double diffraction optical system whereby an eye fundus image formed at a
first image plane that is conjugate with the eye fundus is reformed at a
second image plane, a magnifying optical system for expanding the eye
fundus image formed on the second image plane, and a detecting aperture
for detecting movement of a laser speckle pattern formed at the image
plane of the magnifying optical system as fluctuations in the intensity of
the speckle light, whereby opthalmological diagnosis is performed by
processing speckle signals obtained by means of the detecting aperture.
In accordance with this arrangement, the image plane is prescribed for
detection of the speckle pattern and fluctuations in the intensity of the
speckle light at the plane are acquired as signals, enabling the desired
blood vessel to be specifically set at the image plane. Thus, in an eye
fundus image obtained by means of an eye fundus camera or other such
conventional optical systems employing laser light there have been
problems such as that unnecessary light reflected or scattered from
surrounding tissue becomes conspicuous, and because of the degradation of
the image contrast and quality caused by the superposition of such light,
the S/N ratio of the output signal becomes insufficient and the image too
small for the specified vessel to be selected. In contrast to this, as in
accordance with the present invention detection of the speckle light is
performed following double diffraction, spatial frequency filtering, and
image formation using a microscope optical system, a specific blood vessel
can be readily selected, unnecessary light can be excluded, and speckle
light can be detected with a good S/N ratio.
Rather than an overall, averaged evaluation of the state of blood flow in a
plurality of blood vessels included within the irradiated region of the
eye, with respect to the measurement of blood flow in the eye fundus
utilizing the speckle phenomenon, this arrangement enables the velocity of
the blood flowing through a single specific blood vessel to be measured.
In addition, as this arrangement involves none of the restrictively high
level of precision that is required of optical systems utilizing the
Doppler method, it has good operability and, therefore, yields data having
good reproducibility.
BRIEF DESCRIPTION OF THE DRAWINGS
The objects and features of the present invention will become more apparent
from the following detailed description in conjunction with the
accompanying drawings in which:
FIG. 1 is a diagram showing the structure of a first embodiment of the
apparatus according to the present invention;
FIG. 2 is a diagram for explaining the structure of a ring slit;
FIG. 3 is a characteristic curve showing the characteristics of a
wavelength separation filter used in the embodiment of FIG. 1;
FIGS. 4 and 5 are block diagrams for explaining the structure of different
signal processors used in the embodiment of FIG. 1;
FIG. 6 is a diagram for explaining an eye fundus image that shows image
plane speckles and a blood vessel image;
FIG. 7 is an explanatory diagram of a detecting aperture according to one
embodiment;
FIG. 8 is a graph for explaining the relationship between frequency and
power spectrum;
FIG. 9 is a graph for explaining the relationship between time delay and
correlation value;
FIG. 10 is an explanatory diagram of a detecting aperture according to
another embodiment;
FIG. 11(A) is a diagram for explaining the rotational adjustment capability
of a slit aperture;
FIG. 11(B) is an explanatory diagram of a reticle;
FIG. 12 is a diagram for explaining an arrangement for a double diffraction
optical system and spatial frequency filtering;
FIGS. 13(A) to 13(C) are explanatory diagrams showing different spatial
frequency filtering embodiments; and
FIG. 14 is a diagram showing the structure of an embodiment that employs an
optical fiber from the detecting aperture to a photomultiplier.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention will now be described in detail with reference to the
embodiments shown in the drawings. The invention is concerned specifically
with the fundus region of the eye, and as such the following description
relates to when an eye fundus camera is used to measure blood flow in the
eye fundus.
FIG. 1 shows an overall schematic view of an apparatus for carrying out the
measurement method according to the present invention. A laser beam such
as from a green-light He-Ne (wavelength: 543.5 nm) type laser beam source
1, for example, passes through a condenser lens 1', and then through a
light intensity adjustment filter 2 for adjusting the intensity of the
beam. Thereafter the beam passes through relay lenses 3 and 4 and is
introduced into the eye fundus illuminating optical system of an eye
fundus camera. A pair of stops 5 and 6 is disposed between the relay
lenses 3 and 4 for selectively adjusting the size and shape of the region
of the eye fundus irradiated by the laser beam. Disposed near the
beam-emitting end of the laser beam source 1 is a shutter 7 which can be
opened or closed as required. As shown in FIG. 2, the laser beam issuing
from the relay lens 4 is reflected by a mirror 9 provided in one portion
of an annular aperture 8a formed in a ring slit 8 disposed in the eye
fundus illuminating optical system, so that the reflected laser beam
travels along the same light path leading to the eye fundus under
examination as that followed by a beam of light directed onto the eye
fundus as illumination for photography and observation. As a result, the
laser beam passes through relay lenses 10 and 11, is reflected by a ring
mirror 12, is converged on the cornea 13a of the eye under examination 13
by an objective lens 13' and then diverges as it moves toward the eye
fundus 13b which it reaches in a diverged state to thereby form an
illuminated region which is larger than the diameter of the blood vessel
referred to earlier.
This illuminated area is also illuminated by the illuminating projector of
the fundus camera, facilitating observation. The system for providing the
illumination for observation is constituted of an observation light source
22, a condenser lens 23, a condenser lens 25, a filter 27 and a mirror 26
disposed on the same light path as a photographic light source 24. As the
path of the laser beam coincides with that of the beam of photographic and
observation light, the laser beam can be made to impinge on the desired
region of the eye fundus 13b by use of the mechanisms for swinging and
tilting the eye fundus camera vertically and horizontally and also by use
of the eye fixation means.
The filter 27 disposed between the condenser lens 25 and the mirror 26 is a
wavelength separation filter which, having the type of characteristics
shown in FIG. 3, filters out green components from the observation and
photographic light.
The speckle light produced when the laser beam is scattered by the blood
cells moving in the blood vessels in the eye fundus enters the objective
lens 13', passes through the ring mirror 12 and then through a
photographic lens 14 to impinge on a wavelength separation mirror 15. Like
the filter 27, the wavelength separation mirror 15 exhibits the type of
spectral characteristics illustrated in FIG. 3, and since it therefore
reflects almost all light components having wavelengths in the green band
and passes other light components, it reflects most of the speckle light
(green) generated by the He-Ne laser beam. A lens 16 images the reflected
light at an image plane 34, and an image is again formed at a plane 35 by
a double diffraction system comprised of lenses 17 and 17'. There is a
spatial frequency plane between the lenses 17 and 17' at which is
disposed a spatial frequency filter 18. The eye fundus image thus filtered
and reformed is then magnified by an objective lens 19a and eyepiece lens
19b of a microscope optical system 19. The magnified image passes through
a detecting aperture 20, is converged once again by a condenser lens 21
and detected by a photomultiplier 40. A shutter 40' is disposed in front
of the photomultiplier 40 and the output signal produced by the
photomultiplier 40 and obtained therefrom when this shutter is open is fed
into a signal processor 50.
As shown in FIG. 4, the signal processor 50 is constituted of an amplifier
51, a filter 52, an A/D (analog/digital) converter 53, a CPU 54, a CRT
display 55, a printer 56, a memory 57 and a keyboard 58. Alternatively,
when photon correlation processing is going to be carried out, a photon
counting unit 51' is provided in front of the amplifier 51, as shown in
FIG. 5.
The light passing through the wavelength separation mirror 15 advances
through a relay lens 28, is reflected by a swingable mirror 29 and a
mirror 30, and is then directed, via a reticle 31, to an eyepiece 33
through which it can be observed or recorded on a photographic film 32.
With the apparatus arranged as described, after the power has been turned
on and the patient positioned, the eye fundus 13b of the eye 13 under
examination is observed by means of the observation light optical system
constituted by the elements 22 to 26 and the laser light beam source 1 is
activated. At this point the filter 2 is used to adjust the light output
to the level used for system set-up and the stops 5 and 6 are used to set
the size and shape of the region illuminated by the laser beam. Next, the
shutter 7 is opened and, after the measurement position has been set, the
speckle pattern is confirmed by means of the observation light optical
system constituted by the elements 28 to 31.
With respect to this embodiment, to facilitate the illumination with the
laser beam, the region of the eye fundus 13b illuminated by the laser beam
at the portions at which measurement is to be carried out is set larger
than the blood vessel, for example to a diameter of 1 mm to 3 mm. Clearly,
then, this can result in the inclusion of a plurality of relatively thick
blood vessels in addition to capillaries. When in this case the detection
is conducted at the Fraunhofer plane the detected light will consist of
superposed rays of light scattered from all the points within the
illuminated region. As such, blood flow information obtained from an
analysis of the speckle signals will be an averaged evaluation of the
state of the blood flow in all the blood vessels falling within the
irradiated region. It is because of this that it has been difficult to
measure the blood flow in a specific single blood vessel. Moreover, light
scattered from the walls of blood vessels and surrounding tissue is also
detected, forming optical background noise which degrades the S/N ratio of
the speckle signals.
For this reason, in accordance with the method of the present embodiment,
detection of the speckle pattern is conducted at a magnified image plane.
That is, a conjugate image of the eye fundus is formed at the image plane
34 shown in FIG. 1. Further, the image is again formed at the plane 35 by
the double diffraction system comprised of lenses 17 and 17'. This image
is then magnified by the objective lens 19a and eyepiece lens 19b of the
microscope optical system 19, and fluctuations in the intensity of the
speckle light are detected by the detecting aperture 20 disposed at the
plane of the magnified image. The light is then converged by a condenser
lens 21 and converted into an electrical signal by the photomultiplier 40,
the shutter 40' being in the open position.
The output produced by the photomultiplier 40 during measurement
constitutes a speckle signal which varies with time in accordance with the
movement of the blood cells. This speckle signal is amplified by an
amplifier 51 provided within a signal processor 50, and if necessary it is
then passed through a band pass filter 52 the band of which is set so as
to remove unnecessary frequency components. As shown in FIG. 4, the signal
is then converted into digital form by an A/D converter 53, after which it
is subjected to frequency analysis by the execution of a frequency
analysis program prepared in advance, and the power spectrum distribution
is thereby obtained.
As thus described in the foregoing, as in accordance with this embodiment
the detecting aperture 20 is disposed at the magnified image plane, the
blood flow in a specific single blood vessel can be measured by selecting
the blood vessel image to be measured in the image area of the region
illuminated by the laser beam and locating the detecting aperture 20
within the blood vessel image, either by adjusting the position of the
detecting aperture 20 or by adjusting the fixation of the eye under
examination 13, Therefore, by employing the detection method and signal
processing described below, it becomes possible to elucidate the blood
flow not as a state but as an absolute velocity value.
Among conventional methods for measuring blood flow velocity as an absolute
value in a single specified blood vessel, there is the laser Doppler
method mentioned in the above. With this method, the blood vessel
concerned is illuminated using laser light tightly focused to form a very
fine beam with a diameter substantially equal to or smaller than the
diameter of the blood vessel upon which the beam impinges at a
predetermined angle, or alternatively, the incident laser beam is split
into two beams that are directed so that they intersect at a position
within the said blood vessel. The operations required for this are
extremely difficult, the optical system complex and the obtained data
inconsistent.
Although the embodiment according to the present invention is based on the
speckle method, it is very practical because, with respect to relatively
large blood vessels, it permits a single specific blood vessel to be
selected and the absolute velocity of the blood flow therein to be
measured. That is, it enables the absolute velocity of the blood flow in a
specific blood vessel to be measured while utilizing the advantages of the
speckle method. Because the laser beam is sufficiently larger than the
diameter of the blood vessel concerned the vessel does not shift out of
the beam, and as the detecting aperture is positioned at a magnified image
plane, adjustment is very simple. Moreover, because measurement can be
carried out regardless of the angle of beam incidence or angle of light
reception and it therefore is not necessary to retrieve the scattered
light from a plurality of directions or detect the light at a determined
angle, obtaining results that have repeatability and reliability is
facilitated. This is a major advantage, compared with the Doppler method.
An embodiment wherein the detecting aperture is located at a magnified
image plane will now be described.
A pinhole, for example, may be utilized as the detecting aperture 20. As an
example, when a magnified image of a desired single blood vessel 60 such
as shown in FIG. 6 is being observed, if a pinhole such as the pinhole 61
shown in FIG. 7 having a smaller diameter than that of the blood vessel,
as observed in the image, is disposed at a portion where the image plane
speckles within the vessel are in motion, speckles passing across the
detecting aperture 20 will give rise to a corresponding fluctuation in the
intensity of the detected light, thereby producing a speckle signal.
As the rate at which image speckles 62 traverse the aperture changes in
proportion to the velocity of the blood flow, an increase in the velocity
of the blood flow produces a corresponding increase in the rate at which
the speckle signal varies with time, which increases the high frequency
component of the signal. After the signal has been subjected to frequency
analysis by the signal processor 50 to obtain the power spectrum
distribution, the configuration of the power spectrum distribution is
evaluated, as shown in FIG. 8, according to mean frequency. Here, there
exists a fixed linear relationship between the blood flow velocity and the
velocity of the image speckles, and between the velocity of the image
speckles and the mean frequency, so that with prior calibration, it is
possible to determine the blood flow velocity. This is the same as the
case where the signal autocorrelation is obtained with the signal
processor 50 and the degree of attenuation evaluated in accordance with
the correlation time. If, as shown in FIG. 9, correlation time .tau. is
taken as the time delay for the correlation value to become 1/2 (or 1/e or
the like), the relationship between the inverse thereof 1/.tau. and image
speckle velocity will be linear. In cases where the light scattered from
the eye fundus is weak, the signal is processed using the photon
correlation method shown in FIG. 5. Comments pertaining to the case
illustrated in FIG. 9 can be regarded as applying in precisely the same
way in the case of the correlation obtained in this case.
Another example of a detecting aperture 20 that can be employed is that of
a slit 63 shown in FIG. 10. With reference to this example, it is
generally preferable that the length 1 of the slit 63 is less than the
diameter of the blood vessel on the magnified image plane and that the
width .omega. thereof is less than the length 1 and as large or larger
than the image plane speckle size. Also, the slit is disposed so that its
long side is perpendicular to the orientation of the blood vessel, that
is, perpendicular to the direction of image plane speckle movement. With
this arrangement, the image plane speckle movement within the blood vessel
can be detected effectively, and even when there is a distribution of flow
velocities within the blood vessel, the velocity can be measured as an
average value. In this regard, therefore, the slit configuration has the
advantage of providing more consistent data than the pinhole type.
However, because the pinhole 61 is non-directional there is no need to
adjust its orientation, but the slit 63 does require to be aligned
perpendicularly with respect to the direction of the blood flow in the
vessel.
One way of doing this is to make the slit aperture a rotatably adjustable
mechanism that is linked to a reticle 64 constituted of x-axis and y-axis
crosshairs, as shown in FIG. 11, and disposed at an image plane 36 formed
in front of the eyepiece 33 of the eye fundus camera shown in FIG. 1. One
method that can be applied is to use the reticle to bring the y-axis into
alignment with the target blood vessel so that the point at which the
crosshairs intersect is at the center of the blood vessel, and then to
position the slit at the magnified image plane so that it is perpendicular
to the direction of the blood flow and, in addition, the center of the
slit coincides with the center of the blood vessel.
The double diffraction system and spatial filtering will now be described
in more detail. With reference to FIG. 1, at the conjugate plane 34 laser
speckle light reflected by the wavelength separation mirror 15 is formed
by the lens 16 into an image of the region of the eye fundus illuminated
by the laser beam. However, there is still the problem of unnecessary
light scattered by the walls of blood vessels and surrounding tissue
superposing on the image and making it difficult to achieve good contrast
for the observation of speckle movement at the image plane. For this, the
type of generally-known double-diffraction and spatial frequency filtering
method shown in FIG. 12 is resorted to. Specifically, the lens 17 is
positioned so it is separated from the image plane 34 by just a focal
distance F which produces a spatial frequency plane at distance F to the
rear of the lens 17.
After the appropriate filtering the image is again formed, via the lens 17'
that is positioned a focal distance F' to the rear of the said plane, at a
plane that is distance F' to the rear of the lens 17'. Therefore, in
contrast to when a single-lens system is used to produce the image, use of
a double-diffraction system allows filtering to be done in spatial
frequency regions. A low-pass filter constituted of a finite aperture 18a
with the optical axis at the center thereof, such as the one illustrated
in FIG. 13(A), is used as the spatial frequency filter 18 when the
reflected light to be filtered out has a pronounced edgewise bend. To
filter out uniform background noise, a high-pass filter with a center
optical axis is used constituted of an optical baffle 18b of a
predetermined diameter, as shown in FIG. 13(B). The said aperture 18a and
baffle 18b can be combined to form the type of band pass filter shown in
FIG. 13(C). Which of these is selected depends on the image conditions.
Also, the diameters of the aperture 18a and the baffle 18b may be made
variable. To detect the moving image speckles with good contrast when the
above-mentioned type of spatial frequency filter 18 is employed, it is
essential that the light source utilized in the apparatus is a laser light
source. The fact that eye fundus cameras were originally intended to be
used with the light from an incandescent lamp source and therefore are not
able to exclude the powerful reflections from the blood vessel walls and
the surrounding tissue produced by laser beam with the high coherency and
relatively high intensity shows that the effect of the double diffraction
and spatial frequency filter is very considerable.
In FIG. 1, optically, the location of the image formation plane 34 is
equivalent to that of the photographic film plane 32. In a conventional
fundus camera, the photographic lens 14 are used to adjust the focus as
required for each fundus concerned. Even if the lenses 14 are moved by
this adjustment, at the film plane 32 the image stays in constant focus.
Therefore, an image that is constantly in focus can also be obtained at
the image plane 34 that is optically equivalent to the film plane 32,
which is effective with respect to the practical utilization of the
embodiment illustrated in FIG. 1.
The speckle light detected by the detecting aperture 20 and converged by
the condenser lens 21, in the embodiment illustrated in FIG. 1, is
directed via an optical fiber 37 and a lens 38 into the photomultiplier
40, as illustrated in FIG. 14, where it can be converted into electrical
signals. This arrangement makes it possible to separate the
photomultiplier 40 from the main unit of the apparatus, which is of
practical benefit. This apparatus according to the invention retains the
original fundus camera functions, so it is possible to make a photographic
record for the purpose of comparison with the results of the blood flow
measurements, and monitoring during measurement is also possible.
In the example of this embodiment a green-light He-Ne laser (wavelength:
543.5 nm) is used as the light source. However the method is precisely the
same with respect to the use of, for example, a blue-light Ar laser
(wavelength: 488.0 nm), or a red-light He-Ne laser (wavelength: 637.8 nm).
If the light source wavelength is changed, all that has to be done is to
use wavelength separation mirrors 27 and 15 (FIG. 1) with wavelength
separation regions that match the wavelength of the light source.
According to the present invention as described in the foregoing, double
diffraction and spatial frequency filtering are carried out, an image is
formed by means of a optical magnifying system, and a specific blood
vessel is then selected for detection and evaluation of speckle signals.
This enables the absolute velocity value of the blood flow in a single
specific blood vessel to be found. The present invention also facilitates
the measurement of the blood flow state with good reproducibility and it
has good operability, and as such is highly effective as an
ophthalmological diagnosis apparatus. In addition, because the optical
system employed does not require the type of precision that is required by
methods such as the Doppler method, the apparatus is easy to be realized.
Moreover, because the image plane has an ample amount of light for
detection purposes, the time required for measurement can be shortened,
easing the strain on the person being examined. The apparatus also
possesses the original functions of an eye fundus camera, so it has a high
clinical utility.
While the invention has been described with reference to a preferred
embodiment, it will be understood by those skilled in the art that various
changes may be made and equivalents may be substituted for elements
thereof without departing from the scope of the invention. In addition,
many modifications may be made to adapt a particular situation or material
to the teachings of the invention without departing from the essential
scope thereof. Therefore, it is intended that the invention should not be
limited to the particular embodiment disclosed as the best mode
contemplated for carrying out the invention, but that the invention will
include all embodiments falling within the scope of the appended claims.
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