Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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OPTICAL COHERENCE TOMOGRAPHY APPARATUS,
OPTICAL FIBER LATERAL SCANNER AND A METHOD FOR STUDYING
BIOLOGICAL TISSUES ZN VIVO
Technical Field
The present invention relates to physical engineering, in particular, to the
study of
internal structure of objects by optical means, and can be applied for medical
diagnostics of
individual organs and systems of human body in vivo, as well as for industrial
diagnostics, for
example, control of technological processes.
1o Background Art
In recent years, there has been much research interest in the optical
coherence
tomography of scattering media, in particular, biological tissues. Optical
coherence tomography
apparatus are fairly well known and comprise a Iow coherent light source and
an optical
interferometer, commonly designed as either a Michelson optical fiber
interferometer or a
15 Mach-Zender optical fiber interferometer.
For instance, an optical coherence tomography apparatus known from the paper
by
X.Clivaz et aL, "High resolution reflectornetry in biological tissues", OPTICS
LETTERS,VoLl7, No.l, January 1, 1992, includes a low coherent light source and
a Michelson
optical fiber interferometer comprising a beam-sputter optically coupled with
optical fiber
2o sampling and reference arms. The sampling arm incorporates an optical fiber
piezoelectric
phase modulator and has an optical probe at its end, whereas the reference arm
is provided with
a reference mirror installed at its end and connected with a mechanical in-
depth scanner which
performs step-by-step alteration of the optical length of this arm within a
fairly wide range (at
least several tens of operating wavelengths of the low coherent light source),
which, in turn,
25 provides information on microstructure of objects at different depths.
Incorporating a
piezoelectric phase modulator in the interferometer arm allows for lock-in
detection of the
information-carrying signal, thus providing a fairly high sensitivity of
measurements.
The apparatus for optical coherence tomography reported in the paper by
J.A.Izatt,
J.G.Fujimoto et al., Micron-resolution biomedical imaging with optical
coherence tomography,
3o Optics & Photonics News, October 1993, Vol. 4, No.lO, p.14-19 comprises a
low coherent light
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source and'an optical fiber interferometer designed as a Michelson
interferometer. The
interferometer includes a beam-splitter, a sampling arm with a measuring probe
at its end, and a
reference arm, whose end is provided with a reference minor, movable at
constant speed and
connected with an in-depth scanner. This device allows for scanning the
difference in the
optical lengths of the sampling and reference arms. The information-carrying
signal is received
in this case using a Doppler frequency shift induced in the reference arm by a
constant speed
movement of the reference mirror.
Another optical coherence tomography apparatus comprising a low coherent light
source
and an optical fiber interferometer having a beam-sputter optically coupled to
a sampling and
reference arms is known from RU Pat: No. 2,100,787, 1997. At least one of the
arms includes
an optical fiber piezoelectric in-depth scanner, allowing changing of the
optical length of said
interferometer arm by at least several tens of operating wavelengths of the
light source, thus
providing ixiformation on microstructure of media at different depths. Since a
piezoelectric in-
depth scanner is a low-inertia element, this device can be used to study media
whose
charachteristic time for changing of optical characteristics or position
relative to the optical
probe is very short (the order of a second).
Major disadvantage inherent in all of the above-described apparatus as well as
in other
known apparatus of this type is that studies of samples in the direction
approximately
perpendicular to the direction of propagation of optical radiation are
performed either by
2o respective moving of the samples under study or by scanning a light beam by
means of bulky
lateral scanners incorporated into galvanometric probes. This does not allow
these devices to be
applied for medical diagnostics of human cavities and internal organs in vivo,
as well as for
industrial diagnostics of hard-to-access cavities. (Further throughout the
text; a device
performing scans in the direction approximately perpendicular to the direction
of propagation of
optical radiation is referred to as a "lateral scanner" in contrast to a
device that allows for
scanning the difference in the optical lengths of interferometer arms referred
to as a "in-depth
scanner").
Apparatus for optical coherence tomography known from U.S. Pat. No. 5,383,467,
1995
comprises a low coherent light source and an optical interferometer designed
as a Michelson
3o interferometer. This interferometer includes a beam-sputter, a sampling arm
with an optical
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fiber sampling probe installed at its end, and a reference arm whose end is
provided with a
reference mirror connected with an in-depth scanner, which ensures movement of
the reference
mirror at a constant speed. The optical fiber sampling probe is a catheter,
which comprises a
single-mode optical fiber placed into a hollow metal tube having a lens system
and an output
window of the probe at its distal end. The optical tomography apparatus
includes also a lateral
scanner, which is placed outside the optical fiber probe and performs angular
and/or linear
scanning of the optical radiation beam in the output window of the optical
fiber probe.
However, although such geometry allows for introducing the probe into various
internal cavities
of human body and industrial objects, the presence of an external relative to
the optical fiber
1o probe lateral scanner and scanning the difference in the optical lengths of
the sampling and
reference arms by means of mechanical movement of the reference mirror
significantly limit the
possibility of using this device for performing diagnostics of surfaces of
human cavities and
internal organs in vivo, as well as for industrial diagnostics of hard-to-
access cavities.
Apparatus for optical coherence tomography known from U.S. Pat. No. 5,582,171,
1996
comprises a low coherent light source and an optical fiber interferometer
designed as a Mach-
Zender interferometer having optical fiber sampling and reference arms and two
beam-splitters.
The reference arm includes a unit for changing the optical length of this arm.
This unit is
designed as a reference mirror with a spiral reflective surface arranged with
a capability of
rotating and is connected with a driving mechanism that sets the reference
minor in motion.
2o The sampling arm is provided with an optical fiber probe having an
elongated metal cylindrical
body with a throughhole extending therethrough, and an optical fiber extending
through the
throughhole. A lateral scanner is placed at the distal end of the probe, which
Iateral scanner
comprises a lens system, a rotatable mirror, and a micromotor for rotating the
mirror, whereas
an output window of the probe is located in the side wall of the cylindrical
body. This device
allows imaging of walls of thin vessels, but is unsuitable as a diagnostic
means to image
surfaces of cavities and internal organs inside a human body, as well as for
industrial
diagnostics of hard-to-access large-space cavities.
Another optical coherence tomography apparatus is known from
U.S. Pat. No. 5,321,501, 1994 and comprises a low coherent light source
optically coupled with
3o an optical fiber Michelson interferometer; which includes a beam-splitter
and optical fiber
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sampling and reference arms. The reference arm has a reference mirror mounted
at its end and
connected with' an in-depth scanner. The latter performs movement of the
reference mirror at a
constant speed, thereby changing the optical length of this arm by at Ieast
several tens of
operating wavelengths of the light source. The interferometer also comprises a
photodetector
whose output is connected vvith a data processing and displaying unit, and a
source of control
voltage connected with the in-depth scanner. The sampling arm incorporates an
optical fiber
probe having an elongated body with a throughhole extending therethrough,
wherein a sheath
with an optical fiber embedded in it extends through the throughhole. The
sheath is attached to
the stationary body through a pivot joint. The probe body contains also a
lateral scanner
to comprising a bearing support, an actuator, and a lens system. The actuator
includes a moving
part and a stationary part, whereas the bearing support, the stationary part
of the actuator and
the lens system are mechanically connected with the probe body. The fiber-
carrying sheath rests
on the moving part of the actuator. The actuator may be a piezoelectric
element, stepper motor,
electromagnetic system or electrostatic system. The distal part of the probe
body includes a lens
system, the end face of the distal part of the optical fiber being optically
coupled with the lens
system, whereas the actuator is connected with a source of control current.
The output of the
data processing and displaying unit of the optical fiber interferometer is the
output of the
apparatus for optical coherence tomography. A disadvantage of this apparatus
is that it is not fit
for diagnostics of surfaces of hard-to-access internal human organs in vivo,
such as, for
example, stomach and larynx, and for industrial diagnostics of surfaces of
hard-to-reach cavities
of technical objects. That is due to the fact that the optical fiber probe in
this apparatus must
have relatively large dimensions since maximum movement of the optical fiber
relative to the
size of the actuator cannot be more than 20%, because of the moving part of
the actuator being
positioned at one side of the fiber-carrying sheath. Besides, the mechanical
movement of the
reference mirror at a constant speed used for scanning the difference in
optical lengths of the
reference and sampling arms restricts the range of objects, which can be
studied i~c vivo by this
apparatus, or by any other apparatus of this kind, to those objects whose
optical characteristics
and position relative to the optical probe do not change practically in the
process of
i
measurements.
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In prior art there are known optical fiber lateral scanners which comprise a
stationary
part, including a bearing support, an electromagnet, and a lens system, and a
moving part
including a permanent magnet attached to an optical fiber (see, e.g.,
U.S. Pat. No. 3,470,320, 1969, U.S. Pat. No. 5,317,148, 1994). In these
devices, the optical
fiber is anchored at one end to a bearing support and serves as a flexible
cantilever, whereas the
free end of the optical fiber is arranged such, that it can move in the
direction perpendicular to
its own axis. The permanent magnet is placed in a gap between the poles of the
electromagnet.
A disadvantage of devices of this type is that the amplitude of optical fiber
deflection is limited
by the allowable mass of the magnet fixedly attached to the optical fiber
(from the point of view
to of sagging), and by difficulties in inducing alternate magnetic field of
sufficient strength when
the device is to have small dimensions.
Another optical fiber lateral scanner according to U.S. Pat. No. 4,236,784,
1979 also
comprises a stationary part, which includes a bearing support, an
electromagnet, and a lens
system, and a moving part, including a permanent magnet. In this device, the
permanent magnet
is made as a thin film of magnetic material coated onto the optical fiber,
whereas the .
electromagnet is arranged as an array of thin-film conductors on a substrate
layer that is placed
orthogonal relative to the end face of the optical fiber. In this device the
small mass of the
magnet limits the strength of the induced field, which, in turn; limits the
amplitude of optical
fiber deflection. An increase in the amplitude of deflection due to an
increase in the field
2o strength is impossible since this would require currents much exceeding
damaging currents for
thin-film conductors. Besides, the array of thin-film conductors, being
positioned across the
direction of propagation of an optical radiation beam, disturbs the continuity
of scanning, thus
resulting in loss of information.
Another optical fiber lateral scanner comprising a stationary part and a
moving part is
known from U.S. Pat. No. 3,941,927, 1976. The stationary part comprises a
bearing support, a
permanent magnet, and a lens system, whereas the moving part includes a
current conductor
arranged as a conductive coating on the optical fiber. The optical fiber is
placed in a gap
between the pole pieces of the permanent magnet and fixedly attached to the
bearing support so
that its free end can move in the direction approximately perpendicular to its
own axis, and
serves as a flexible cantilever: The end face of the distal part of the
optical fiber is optically
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coupled with the lens system, whereas the current conductor is connected with
a source of
control current. In this device the field,strength induced by the current
conductor, when control
current is applied, is limited by a small mass of the conductive coating, thus
limiting the
deflection amplitude of the optical fiber. Due to allocation of the optical
fiber between two pole
pieces of the permanent magnet, the overall dimensions of the device are
relatively large. Thus,
a disadvantage of this lateral scanner, as well as of other known lateral
scanners, is that it is
impossible to provide necessary performance data, in particular, miniature
size, simultaneously
with required deflection amplitude of the optical fiber to incorporate such a
device in an optical
fiber probe of an optical fiber interferometer, which is part of a device for
optical coherence
tomography suited for diagnostics of surfaces of hard-to-access human internal
organs in vivo,
as well as for industrial diagnostics of hard-to-reach cavities.
A particular attention has been given lately to studies of biological tissues
in vivo. For
instance, a method for studying biological tissue in vivo is known from
U.S. Pat. No. 5,321,501, 1994 and U.S. Pat. No. 5,459,570, 1995, in which a
low coherent
optical radiation beam at a given wavelength is directed towards a biological
tissue under study,
specifically ocular biological tissue, and to a reference mirror along the
first and the second
optical paths, respectively. The relative optical lengths of these optical
beam paths are changed
according to a predetermined rule; radiation backscattered from ocular
biological tissue is
combined with radiation reflected from a reference mirror. The signal of
interference
2o modulation of the intensity of the optical radiation, which is a result of
this combining, is used
to acquire an image of the ocular biological tissue. In a particular
embodiment, a low coherent
optical radiation beam directed to biological tissue under study is scanned
across the surface of
said biological tissue.
A method for studying biological tissue in vivo is known from
U.S. Pat. No. 5,570,182, 1996. According to this method, an optical radiation
beam in the
visible or near IR range is directed to dental biological tissue. An image is
acquired by
visualizing the intensity of scattered radiation. The obtained image is then
used for performing
diagnostics of the biological tissue. In a particular embodiment, a low
coherent optical radiation
beam is used, which is directed to dental tissue, said beam being scanned
across the surface of
interest, and to a reference mirror along the first and second optical paths,
respectively. Relative
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optical lengths of these optical paths are changed in compliance with a
predetermined rule;
radiation backscattered from the dental tissue is combined with radiation
reflected by_the
reference mirror. A signal of interference modulation of intensity of the
optical radiation, which
is a result of said combining, is used to visualize the intensity of the
optical radiation
backscattered from said biological tissue. However, this method, as well as
other known
methods, is not intended for performing diagnostics of biological tissue
covered with
epithelium.
Disclosure of invention
The object of the present invention is to provide an apparatus for optical
coherence
l0 tomography and an optical fiber lateral scanner which is part of said
optical coherence
tomography apparatus, with improved performance data, both these devices being
suited for
diagnostics of soft and hard biotissue in vivo, in particular, for performing
diagnostics of human
cavity surfaces and human internal organs, for diagnostics of dental, bony,
and cartilage
biotissue, as well as for industrial diagnostics of hard-to-access cavities of
technical objects.
is Another object of the invention into provide a method for diagnostics of
biotissue in vivo
allowing for diagnostics of biotissue covered with epithelium, in particular,
of biotissue lining
the surface of human internal organs and cavities.
The developed apparatus for optical coherence tomography, similarly to
described above
apparatus known from U.S. Pat. No. 5,321,501 comprises a low coherent light
source and an
20 optical fiber interferometer. The interferometer includes a beam-splitter,
a sampling and
reference optical fiber arms, a photodetector, a data processing and
displaying unit, and a source
of control voltage. The beam-splitter, sampling and reference optical fiber
arms, and the
photodetector are mutually optically coupled, the output of said photodetector
being connected
with said data processing and displaying unit. At least one of the arms
comprises an in-depth
25 scanner having a capability of changing the optical length of said
interferometer arm by at least
several tens of operating wavelengths of the light source. The sampling arm
includes a flexible
part, which is made capable of being introduced into an instrumental channel
of an endoscope
or borescope and is provided with an optical fiber probe having an elongated
body with a
throughhole extending therethrough, an optical fiber extending through the
throughhole, and an
30 optical fiber lateral scanner. The distal part of the optical fiber is
arranged to allow for
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deflection in the direction approximately perpendicular to its own axis. The
optical fiber lateral
scanner comprises a stationary part mechanically connected with the optical
fiber probe body
and a moving part. The stationary part includes a bearing support, a magnetic
system and a lens
system. The end surface of the distal part of the optical fiber is optically
coupled with the lens
system, while the lateral scanner is connected with a source of control
current. The reference
arm has a reference mirror installed at its end, whereas the in-depth scanner
is connected with a
source of control voltage. The output of the data processing and displaying
unit is the output of
the optical coherence tomography apparatus.
Unlike the known apparatus for optical coherence tomography, according to the
1o invention the optical fiber probe is designed miniature, whereas the moving
part of the lateral
scanner comprises a current conductor and said optical fiber, which is rigidly
fastened to the
current conductor. The optical fiber serves as a flexible cantilever, its
proximal part being
fixedly attached to the bearing support. The current conductor is arranged as
at Least one loop,
which envelopes the magnetic system in the area of one of its poles. A part of
the optical fiber is
placed in the area of .said pole of the magnetic system, while the plane of
the loop of the current
conductor is approximately perpendicular to the direction between the poles-of
the magnetic
system. The current conductor is connected with the source of control current.
In one embodiment, the magnetic system includes a first permanent magnet.
In a particular embodiment, the first permanent magnet is provided with a
groove
2o extensive in the direction approximately parallel to the axis of the
optical fiber, said optical
fiber being placed into said groove.
In another particular embodiment, the magnetic system additionally comprises a
second
permanent magnet with one pole facing the analogous pole of the first
permanent magnet,
which is enveloped by the current conductor. Besides, said one pole of the
second permanent
magnet is located near to the optical fiber.
In another embodiment the second permanent magnet has a groove made in the
direction
approximately parallel to the axis of the optical fiber.
In a different embodiment the first and second permanent magnets are aligned
at their
analogous poles, while the optical fiber is placed into a throughhole
extending therethrough in a
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9
direction approximately parallel to the axis of the optical fiber, the
throughhole being formed by
facing grooves made in said analogous poles of the permanent magnets.
In another embodiment the current conductor envelopes the second permanent
magnet.
It is advisable to shape the magnetic system as a parallelepiped.
In one particular embodiment an output window of the optical fiber probe is
arranged
near the image plane of the end face of the distal part of the optical fiber.
It is adrisable to place
the outer surface of the output window at the front boundary of the zone of
sharp imaging.
In another embodiment the output window of tire optical fiber probe is a plane-
parallel
plate. In the longitudinal throughhole of the body of the optical fiber probe
between the lens
to system and the plane-parallel plate there may be additionally installed a
first prism, at least one
operating surface of said first prism being antireflection coated.
In a different embodiment the output window of the optical fiber probe is made
as a
second prism.
It is advisable to make the output window of the optical fiber probe
hermetically closed.
15 In one embodiment the source of control current is placed outside the body
of the optical
fiber probe.
.In another particular embodiment the source of control current is placed
inside the body
of the optical fiber probe and is designed as a photoelectric converter.
In other embodiments of the optical fiber interferometer it is advisable to
make the body
20 of the optical fiber probe as a hollow cylinder, and to use anizotropic
single-mode optical fiber.
It is advisable to make changeable a part of the sampling arm of the
interferometer,
including the part being introduced into an instrumental channel of an
endoscope or borescope,
the chargeable part of said sampling arm being connected by a detachable
connection with the
main part of the sampling arm.
25 It is advisable to make disposable the changeable part of the sampling arm
of
interferometer.
In a particular embodiment the distal end of the optical fiber probe is made
with
changeable tips.
The developed optical fiber lateral scanner, similarly to described above
optical fiber
3o lateral scanner known from U.S. Pat. No. 3,941,927, comprises a stationary
part and a moving
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to
part. The stationary part includes a bearing support, a magnetic system, and a
lens system, said
magnetic system comprising a first permanent magnet: The moving part includes
a movable
current conductor and an optical fiber rigidly fastened to the current
conductor. The optical fiber
serves as a flexible cantilever and is fixedly attached to the bearing support
with a capability for
a distal part of said optical fiber of being deflected in a direction
approximately perpendicular to
its own axis. The end face of the distal part of the optical fiber is
optically coupled with the lens
system, whereas the current conductor is connected with a source of control
current.
Unlike the known optical &ber lateral scanr~e~, according to the invention
tape current
conductor is made as at least one loop, which envelopes the first permanent
magnet in the area
of one of its poles. A part of the optical fiber is located in the area of
said pole of the first
permanent magnet, whereas the plane of the loop of the current conductor is
approximately
perpendicular to the direction between the poles of the first permanent
magnet.
In a particular embodiment the first permanent magnet is provided with a
groove
extensive in a direction approximately parallel to the axis of the optical
fiber, said optical fiber
being placed into said groove.
In another embodiment the magnetic system additionally comprises a second
permanent
magnet, with one pole facing the analogous pole of the first permanent magnet,
which is
envelbped by said current conductor. Besides, said one pole of the second
permanent magnet is
located near to the optical fiber.
2o In a different embodiment the permanent magnets are aligned at their
analogous poles,
whereas the optical fiber is placed into a throughhole extending therethrough
in a direction
approximately parallel to the axis of the optical fiber, the throughhole being
formed by the
facing grooves made in said analogous poles of the permanent magnets.
It is advisable to have the current conductor additionally envelope the second
permanent
magnet.
It is preferable to shape said magnetic system as a parallelepiped.
In one embodiment the optical fiber, bearing support, magnetic system and lens
system
are elements of an optical fiber probe incorporated into an optical fiber
interferometer and are
encased into an elongated body with a throughhole extending therethrough, the
optical fiber
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_-
11
extending through the throughhole. The bearing support, magnetic system and
lens system are
mechanically connected with the body of the optical fiber probe.
In one embodiment the body of the optical fiber probe is made as a hollow
cylinder.
In another particular embodiment an output window of the optical fiber probe
is located
near the image plane of the end face of the distal part of the optical fiber.
It is advisable to place
the outer surface of the output window of the optical fiber probe at the front
boundary of a zone
of sharp imaging.
In a different embodiment the output window of the optical fiber probe is made
as a
plane-parallel plate. The operating surfaces of the plane-parallel plate are
cut at an angle of
to several degrees relative to the direction of propagation of optical
radiation incident on the
output window. The inner surface of the plane-parallel plate may be made
antireflection coated.
In a particular embodiment a first prism is additionally installed in the
longitudinal
throughhole in the body of the optical fiber probe between the lens system and
the plane-
parallel plate. At least one operating surface of this prism is antireflection
coated.
15 In another particular embodiment the output window of the optical fiber
probe is made
as a second prism: The inner surface of the second prism may be antireflection
coated.
It is advisable to make the output window of the optical fiber probe
hermetically closed.
In a particular embodiment the bearing support.is located in the proximal part
of the
longitudinal throughhole in the optical fiber probe body. The proximal part of
the optical fiber
2o is fastened to the bearing support. The current conductor may be connected
with a source of
control current via electrodes attached to the bearing support.
In the developed lateral scanner it is advisable to use anizotropic single-
mode fiber.
In some embodiments the optical fiber probe is made disposable.
In some other embodiments the distal end of the optical fiber probe is made
with
25 changeable tips.
The developed method for studying biological tissue in vivo, similarly to the
described
above method known from U.S. Pat. No: 5,570,182, comprises the steps of
directing a beam of
optical radiation in the visible or near IR range towards a biological tissue
under study and
acquiring subsequently an image of said biological tissue by visualizing the
intensity of optical
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IZ
radiation backscattered by biological tissue under study to use said image for
diagnostic
purpose.
Unlike the known method for studying biological tissue in vivo, according to
the
invention the biological tissue under study is a biological tissue covered
with an epithelium,
whereas in the acquired image the basal membrane of said biological tissue is
identified, which
separates the epithelium from an underlying stroma, and performing diagnostics
of said
biological tissue under study on basis of the state of the basal membrane.
In a particular embodiment said biological tissue is the biological tissue
lining the
surface of human cavities and internal organs. When directing the beam of
optical radiation
to towards said biological tissue, a miniature optical fiber probe is inserted
into the cavity under
study, through which said beam of optical radiation is transmitted from the
proximal end of the
probe to its distal end, whereas said beam of optical radiation is scanned
over said surface under
study in compliance with a predetermined rule.
In a particular embodiment in order to insert the miniature optical fiber
probe into said
human cavity under study, the probe is placed into the instrumental channel of
an endoscope.
In another embodiment a low coherent optical radiation beam is used as said
optical
radiation beam, which is split into two beams. 'The beam directed towards said
biological tissue
is the first beam, whereas the second beam is directed towards a reference
mirror, the difference
in the optical paths for the first and second beams being varied in compliance
with a
2o predetermined rule by at least several tens of wavelengths of said
radiation. Radiation
backscattered from said biological tissue is combined with radiation reflected
from the
reference mirror. The signal of interference modulation of intensity of the
optical radiation,
which is a result of this combining, is used to visualize the intensity of
optical radiation
backscattered from said biological tissue.
In the present invention the moving part of the lateral scanner in the optical
fiber probe
is designed comprising a current conductor, which envelopes the magnetic
system in the area of
one of its poles, and an optical fiber, which is rigidly fastened to the
current conductor, whereas
the optical fiber serves as a flexible cantilever. That allows making smaller
the overall
dimensions of the optical fiber probe in comparison with known arrangements.
The magnetic
3o system includes two permanent magnets aligned at their analogous poles,
whereas the optical
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13
fiber is placed in a throughhole extending therethrough in a direction
approximately parallel to
the axis of the optical fiber, the throughhole being formed by the facing
grooves made in said
analogous poles of the permanent magnets. This configuration ensures
optimization of the
probe design from the point of view of acquisition of maximum amplitude of
deviation of the
beam of optical radiation (~1 mm), whereas having limited dimensions of the
optical fiber
probe, namely, its length is no more than 27 mm, and diameter is no more than
2.7 mm. This
allows fox making the optical fiber probe as a miniature optical fiber probe,
which can be
installed in the distal end of the instrumental channel of an endoscope or
borescope, the optical
fiber probe being incorporated into the sampling arm of the optical fiber
interferometer which is
to part of apparatus for optical coherence tomography. One part of the
sampling arm of the optical
fiber interferometer is made flexible, thus allowing for inserting it into
said channels. Miniature
dimensions of the optical fiber probe as well as the flexible arrangement of
the sample arm
allow to bring up the optical radiation to the hard-to access parts of
biological tissue of internal
human organs and cavities, including soft biological tissue (for example,
human mucosa in
gastrointestinal tracts) and hard biological tissue (for example, dental,
cartilage and bony
tissue). That makes it possible to use the developed apparatus for optical
coherence tomography
together with devices for visual studying of biological tissue surfaces, for
example, with devices
for endoscopic studying of human gastrointestinal and urinary tracts,
laparoscopic testing of
abdominal cavity, observing the process of treatment of dental tissue. Using
an output window
2o allows to arrange the optical fiber probe hermetically closed, which, in
turn, allows for
positioning the optical fiber probe directly on the surface of object under
study, in particular,
biological tissue. Having the outer surface of the output window at the front
boundary of a zone
of sharp imaging ensures high spatial resolution (I S-20 p,m) during scanning
of a focused
optical beam along the surface of object under study. Arranging the source of
control current as
2s a photoelectric transducer and locating it inside the body of the optical
fiber probe allows to
avoid introducing electrical cords into the instrumental channel. Having
antireflection coated
inner surface of the output window designed either as a plane-parallel plate
or as a prism, allows
for a decrease in losses of optical radiation, whereas having beveled
operating sides of the
plane-parallel plate eliminates reflection from the object-output window
boundary. Using
30 anizotropic optical fiber excludes the necessity of polarization control in
process of making
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I4
measurements, whereas using a single-mode optical fiber allows for more simple
and lower-cost
realization of the device.
In vivo diagnostics of biological tissue covered with epithelium on basis of
the state of
basal membrane, according to the developed method, allows for early non-
invasive diagnostics
of biological tissue. The use of the optical fiber probe of the invention, of
which the lateral
scanner of the invention is a part, allows for diagnostics of the state of
biological tissue lining
the surface of hard-to-access cavities and internal organs of a patient, for
example, by placing
the optical fiber probe into an instrumental channel of an endoscope. Using
low coherent optical
radiation for implementing the developed method ensures high spatial in-depth
resolution. -
Brief Description of Drawings
The features and advantages of the invention will be apparent from the
following detail
descriptiowof preferred embodiments with reference to the accompanying
drawings, in which:
Fig. 1 is a schematic diagram of one particular embodiment of the developed
apparatus
for optical coherence tomography suitable for implementing the developed
method for studying
1 s biological tissue in vivo.
Fig. 2 is a cross-sectional view of one particular embodiment of the developed
miniature
optical fiber probe.
Fig. 3, 4 are general views of particular embodiments of the developed optical
fiber
lateral scanner.
2o Fig. SA, SB, and SC are cross-sectional views of particular embodiments of
a distal part
of the developed optical fiber probe.
Fig. 6A and 6B are schematic diagrams of particular embodiments of the
interferometer
arm comprising an in-depth scanner.
Fig. 7A, 7B, 7C, 7D, and 7E are images of a uterine cervix obtained by using
the
25 developed method.
Fig. 8A shows a tomographic image of a front abdominal wall, Fig. 8B shows the
structure of a tooth with a compomer filling.
Modes for Carrying out the Invention
CA 02535715 1999-02-09
1.5
The operation of the developed apparatus for optical coherence tomography and
the
developed optical fiber probe will be best understood from the following
description of carrying
out the method for diagnostics of biological tissue in vivo.
The method for diagnostics of biological tissue in vivo is carried out. the
following way.
An optical beam in the visible or IR range is directed, for instance, with the
aid of a
laser, toward a biological tissue under study, the later being a biological
tissue covered with
epithelium. An image of the biological tissue covered with epithelium is
obtained by visualizing
the intensity of back-scattered optical radiation beam with, for example, a
confocal microscope.
In the acquired image, the basal membrane is identified, which separates the
epithelium from
to underlying stroma. Diagnostics is made on basis of the state of said basal
membrane.
In a specific embodiment, said biological tissue covered with epithelium is a
biological
tissue lining the surface of cavities and internal organs of a patient. In
this case, when directing
an optical beam to said biological tissue, a miniature optical fiber probe 8
is inserted into
patient's cavity under study (one embodiment of the probe is shown in Fig. 2).
It is advisable to
15 place probe 8 at the distal end of the instrumental channel of an
endoscope. Said optical
radiation beam is transmitted through probe 8 from its proximal end to its
distal end. Scanning
of said optical radiation beam is performed along the surface under study in
accordance with a
predetermined rule.
In a preferred embodiment of the method an optical low coherent radiation beam
is used
2o as the optical radiation beam. This embodiment of the developed method may
be realized with
the aid of the device, a schematic diagram of which is shown in Fig. f, and
with the aid of an
optical fiber probe shown in Fig. 2, as follows.
Optical fiber probe 8 is installed at the distal end of the instrumental
channel of an
endoscope (not shown in the drawing), the outer surface of an output window 31
of optical fiber
25 probe 8 is brought into contact with the biological tissue lining the
surface of cavities and
internal organs of a patient under study. It must be noted that for some
embodiments for better
serviceability a part of sampling optical fiber arm 4 of an interferometer 2
may be made
changeable, specifically, disposable, and in this case it is connected with
the main part of
sampling arm 4 by a detachable connection (not shown in the drawing). An
optical low coherent
30 radiation beam is formed using a source 1, which can be arranged, for
example, as a
CA 02535715 1999-02-09
16
superluminiscent diode. This optical radiation beam passes to optical fiber
interferometer 2,
which is a Michelson interferometer, and is then split into two beams by means
of a beam-
splitter 3 of optical fiber interferometer 2. The first beam is directed
toward biological tissue
under study using optical fiber sampling arm 4 and optical fiber probe 8. Said
beam is scanned
over the surface under study in compliance with a predetermined rule using
optical fiber probe 8
as follows.
An optical fiber 13, which may be a PANDA-type optical fiber, extends
through.a
throughhole 12 of an elongated body 11 of optical probe 8 and provides for
propagation of the
first low coherence optical radiation beam from a proximal part 20 of optical
fiber 13 to its
distal part 14. Body 11 of optical fiber probe 8 may be made of stainless
steel. Tn a particular
embodiment the length of body 11 is no more than 27 mm, whereas its diameter
is no more than
2.7 mm.
Body 11 comprises also a lateral scanner 15 (see also Fig. 3 and Fig. 4) which
is
connected with a source of control current (not shown in the drawing). Said
source of control
current may be located inside body 11 of optical fiber probe 8 and may be
arranged as a
photoelectric converter (not shown in the drawing). Lateral scanner 15 has a
stationary part,
which is mechanically connected with body 11 and includes a bearing support
16, magnetic
system 17, and lens system 18, and a moving part, which includes a current
conductor 19 and
optical fiber 13, which serves as a flexible cantilever and is rigidly
fastened to current conductor
2o I9 which may be made of insulated copper wire. Referring to Fig.l, bearing
support 16 is
placed in the proximal part of a throughhole 12 of body 11, proximal part 20
of optical fiber 13
being fixedly attached to bearing support 16. By the way, bearing support I6
may be located
between magnetic system 17 and lens system 18, magnetic system 17 being placed
in the
proximal part of throughhole 12 of body I 1, whereas a middle part of optical
fiber 13 is
connected with bearing support 16 (this embodiment is not shown in a drawing).
A distal
part 14 of optical fiber 13 is placed so that it can be deflected in the
direction A-A,
approximately perpendicular to its own axis. The end face 21 of distal part 14
of optical fiber 13
is optically coupled with lens system 18.
Magnetic system 17 of lateral scanner 15 shown in Fig. 3 comprises a first
permanent
3o magnet 22, which has a groove 23 extensive in a direction approximately
parallel to the axis of
CA 02535715 1999-02-09
17
optical fiber 13, whereas optical fiber 13 is placed in said groove 23.
Current conductor 19 is
arranged as at least one loop 24 of wire which envelopes magnetic system 17,
i.e., first
permanent magnet 22, in the area of one of its poles 25. A part 26 of optical
fiber I3 is placed in
the area of pole 25. The plane of loop 24 of current conductor 19 is
approximately
perpendicular to the direction between poles of permanent magnet 22. Current
conductor I9 via
electrodes 27, which are fixed on bearing support 16, is connected with a
source of control
current (not shown in the drawing) which is placed outside body 11.
In a particular embodiment of lateral scanner 15 indicated in fig. 4 magnetic
system T7
additionally includes a second permanent magnet 28. First and second magnets,
22 and 28,
1o respectively, are aligned at their analogous poles 25 and 29, whereas
magnets 22 and 28 are
used to form a stationary magnetic field and may be made from NiFeB material.
Optical
fiber 13 is placed into a throughhole 30 extending therethrough approximately
parallel to the
axis of optical fiber 13. The throughhole 30 is formed by facing grooves made
in aligned poles
25, 29 of permanent magnets 22 and 28. Diameter of throughhole 30 is
determined by
predetermined amplitude of deflection of optical fiber 13 with maximum
magnetic field
intensity in the area of current conductor 19. Current conductor 19 envelopes
permanent
magnets 22, 28 in the area of their aligned poles 25, 29.
An output window 31 of optical fiber probe 8 is placed near to the image plane
of end
face 21 of distal part 14 of optical fiber 13. In one embodiment shown in Fig.
4 and SA, an
output window 31 is arranged as a plane-parallel plate 32. Plane-parallel
plate 32 is optically
transparent in the range of operating frequencies, being made of material
allowed for use in
medical purposes. Bevel angle of the operating sides of plane-parallel plate
32 relative to the
direction of propagation of optical radiation beam incident on~ output window
31 is determined
by a given level of reflections of the optical radiation beam from the front
side of plane-parallel
plate 32 to the viewing angle of the optical system and must not be more than
an angle of
divergence of the optical radiation beam. In embodiment shown in Fig. 5A,
operating sides of
plane-parallel plate 32 are cut at an angle of several degrees relative to the
direction of
propagation of the optical radiation incident on output window 31. A first
prism (not shown in
the drawing) may be additionally installed between lens system 18 and plane-
parallel plate 32.
Referring to.Fig. 5B and SC output window 31 is made as a second prism 33,
which may have
CA 02535715 1999-02-09
I8
various configurations. First prism and second prism 33 are used to provide
lateral view on
surface under study with the aid of optical fiber probe 8. Specific
configurations of said prisms
are defined by a predetermined angle of lateral view. The values of refractive
index of plate 32
and prism 33 are chosen such as to provide a minimum level of reflections from
the boundary
"output window 31 - surface under study" and must be maximally close to the
refractive index
value of the object under study. The inner surfaces of plane-parallel plate 32
and prism 33 are
made antireflection coated in order to decrease losses: The distal part of
optical fiber probe 8,
which includes output window 31, may be made with changeable tips.
Magnetic system 17 of lateral scanner 15 ensures establishing of a stationary
magnetic
to field. The field lines of the magnetic field induced by magnetic system 17
are situated in the
plane of loop 24 of current conductor 19 and cross the loop 24 in the
direction approximately
orthogonal to the direction of the current in the loop 24 of current conductor
19. So, when
control current is applied in current conductor 19, there occurs a force that
affects current
conductor 19 in the direction approximately orthogonal to the plane of loop 24
of current
IS conductor 19. This force being proportional to the current strength in
current conductor 19 and
to the intensity of stationary magnetic field induced by magnetic system 17,
causes respective
movement of current conductor 19. Since the proximal part 20 of optical fiber
13 is fastened in
bearing support 16 as a free cantilever, and current conductor I 9 is rigidly
fixed to optical fiber
13, then when control current is applied in current conductor 19, there occurs
a deflection of
2o distal part 14 of optical fiber 13 in the direction approximately
perpendicular to its own axis. In
a particular embodiment an amplitude of this deflection of distal part I4 of
optical fiber 13 is
~0.5 mm. Lens system 18 ensures focusing of the optical radiation beam that
has passed
through optical fiber l3 onto the surface of biological tissue under study.
The second optical radiation beam by means of reference arm 5 is directed to a
reference
25 mirror 9. Reference arm 5 contains an in-depth scanner 10 connected with a
source of control
voltage (not shown in the drawing). With the aid of in-depth scanner 10 the
difference in the
optical lengths of arms 4,5 of interferometer 2 is changed at a constant
velocity V by at least
several tens of operating wavelengths of light source 1.
Referring to Fig. 1, reference minor 9 is stationary, whereas in-depth scanner
10 is made
3o as an optical fiber piezoelectric transducer known from RU Pat. No.
2,100,787
CA 02535715 1999-02-09
19
(US Pat. No. 5,867,268). In this embodiment in-depth scanner 10 comprises at
least one body
which has piezoelectric properties, exhibits a high perpendicular inverse
piezoeffect, and has an
electric field vector when an electric field is applied to electrodes, which
are mechanically
connected with said body, whereas an optical fiber is mechanically connected
with said
electrodes. A dimension of said piezoelectric body in a direction
substantially perpendicular
with said electric field vector is essentially larger than a dimension of said
body in a direction
substantially aligned with said electric field vector. The length of the
optical fiber exceeds
substantially the diameter of said piezoelectric body.
In-depth scanner 10 may be made analogous with in-depth scanners described in
1o U.S. Pat. No 5,321,501. In this case, reference mirror 9 is made movable at
a constant speed,
and in-depth scanner 10 being connected with reference minor 9, may be made as
mechanisms
of different types providing for necessary moving of reference mirror 9 (Fig.
6A).
In-depth scanner 10 may be designed according to the paper by K.F.Kwong,
D.Yankelevich et al, "400-Hz mechanical scanning optical delay line", Optics
Letters, Vo1.18,
No.7, April 1, 1993, as a disperse grating delay line (Fig. 6B) comprising a
first lens 34,
diffraction grating 35 and second lens 36, all these elements being arranged
in series along the
optical axis. Second lens 36 is optically coupled with reference mirror 9
placed so that it can
swing relative to the direction of propagation of incident optical radiation.
Using beam-splitter 3 the radiation backscattered from said biological tissue
is
combined with the radiation reflected from reference mirror 9. Changing the
difference in the
optical lengths of arms 4,5 with in-depth scanner 10 leads to interference
modulation of
intensity of combined optical radiation at the output of beam-sputter 3 at a
Doppler frequency f
2V/~,, where ~, is the operating wavelength of source 1. Besides, the rule of
interference
modulation corresponds to the change in the intensity of optical radiation
backscattered from
biological tissue under study at different depths. Then an image of biological
tissue under study
is acquired by visualizing intensity of optical radiation backscattered from
biological tissue
under study by using the signal of interference modulation of intensity of the
optical radiation,
which is the result of said combining, as follows.
A photodetector 6 provides for conversion of the combined optical radiation
from the
3o output of beam-splitter 3 into an electrical signal which arrives at a
processing and displaying
CA 02535715 1999-02-09
unit 7. Unit 7 is used to form images of an object under study by visualizing
the intensity of
back-scattered coherent radiation and may be made, for example, similarly to
the data
processing and displaying unit discussed in the paper by V.M.Gelikonov et al.,
"Coherent
optical tomography of microinhomogeneities in biological tissues" JETP Lett.,
v. 61, No 2, pp.
5 149-153. This data processing and displaying unit comprises a band-pass
filter, a log amplifier,
an amplitude detector, an analog-to-digital converter, and a computer, all
these elements being
connected in series. Band-pass filter of unit 7 sorts the signal at a Doppler
frequency, thereby
improving the signal-to-noise ratio. Once the signal is amplified; it arrives
at a detector that
sorts a signal proportional to the waveform envelope of this signal: The
signal sorted by the
1 o amplitude detector of unit 7 is proportional to the signal of interference
modulation of intensity
of the combined optical radiation. Analog-to-digital converter of unit 7
converts the signal from
the output of the amplitude detector into a digital format. Computer of unit 7
provides for
acquisition of images by displaying on a video monitor the intensity of the
digital signal (said
displaying may be performed as described, for instance, in the paper by
H.E.Burdick "Digital
15 imaging: Theory and Applications", 304 pp., Me Graw Hill, 1997). Since the
digital signal
corresponds to the change in intensity of optical radiation backscattered from
biological tissue
at different depths, the image displayed on the monitor corresponds to an
image of biological
tissue under study. The biological tissue basal membrane, which separates the
epithelium from
underlying stroma, is identified in the acquired image. Diagnostics is made on
basis of the state
2o of the basal membrane.
Diagnostics of biological tissue with the aid of the method of the invention
is illustrated
with several clinical cases, whereas the examination of patients took place in
hospitals of
Nizhny Novgorod (Russia).
Namely, an examination of women, which had no pathology in the uterine cervix,
with
the aid of the developed method allowed obtaining images of healthy epithelium
of the uterine
cervix (Fig: 7A and 7B). It can be seen from these images that biological
tissue covered with
healthy epithelium 45 has a smooth basal membrane 46, which separates
stratified squamous
epithelium 45 from underlying connective tissue 47.
CA 02535715 1999-02-09
21
It can be seen from images shown in Fig. 7C and 7D that pathological regions
of
biological tissue are characterized by a change in the shape of the basal
membrane 46, or
violation of its integrity, or its absolute destruction.
Fig. 7C shows an image of a pathological region of the uterine cervix,
obtained with the
aid of the developed method, of a female patient L, 31 years old, in which
there can be seen
appendages of the basal membrane 46 in an arc form, i.e. an alteration of the
shape of the basal
membrane 46 not affecting its integrity. The clinical diagnostics of female
patient I. was
precancer of uterine cervix. Standard colposcopy technique revealed a
phenomenon known as
so-called mosaic. Information obtained with target biopsy and subsequent
morphological study
to of biopsy material provided grounds for diagnosing.cervical intraepithelial
neoplasia of the a
degree.
Fig.7D shows an image of a pathological region of.the uterine cervix, obtained
with the
aid of the developed method; of a female patient G., 25 years old, in which
there can be
distinctly indicated structural changes in stratified squamous epithelium 45
and different extents
of changes in the basal membrane 46. Female patient G. was admitted to the
clinic for a
suspicion for uterine cervix cancer Tla. During the further course of
treatment the patient
underwent Ionization (i.e., conical removal of pathological region) in the
uterine cervix. Based
on the results of morphological study of the removed material the diagnostics
was made as
follows: cervical intraepithelial neoplasia of the III degree with transition
into cancer in situ and
2o microcarcinoma. It is well known from morphological research that exactly
this stage in the
development of malignant process originating in the basal and parabasal layers
of cells is
accompanied by alterations in shape and an occurrence of microruptures of the
basal membrane.
Fig. 7E presents a tomographic image of a tumor region where the basal
membrane is
not seen. This image was obtained with an examination of a female patient M.,
66 years old that
was admitted to the clinic for uterine cervix cancer Tlb. This diagnostics was
made clinically
and confirmed morphologically based on the results of biopsy.
Thus, the above examples demonstrate a possibility for using the developed
method for
studying biological tissue in vivo in diagnostics of different stages of
uterine cervix cancer.
Fig. 8 A and Fig. B illustrate opportunities to obtain images of other human
biological
3o tissues with the aid of the apparatus and lateral scanner of the present
invention. In particular,
CA 02535715 1999-02-09
22
Fig. 8 A demonstrates a tomographic image of a front abdominal wall obtained
during a
laporoscopic examination of a female patient E., 22 years old. On this
tomo.graphic image one
can see the serous membrane 37 with a layer of connective tissue,
characterized by high
reflectivity of optical radiation, the subserous Iayer 38 including loose
connective tissue and
blood vessels 39, characterized by low reflectivity of optical radiation, and
underlying muscle
layers 40.
Fig. 8b shows a tomographic image of a tooth of a patient K., 56 years old; on
which
one can distinctly see the enamel 41, dentine 42, the boundary enamel-dentine
43 and a
compomer filling 44.
to
Industrial Applicability
The invention can be applied for medical diagnostics. of individual organs and
systems
of human body in vivo, for example, of hard-to-access cavities and internal
organs, as well as
for industrial diagnostics, for instance, for control of technological
processes. It should be noted
that the invention can be implemented with using standard means.
