Speckle reduction in optical coherence tomography by path length encoded angular compounding

Abstract
Speckle, a factor reducing image quality in optical coherence tomography (“OCT”), can limit the ability to identify cellular structures that are important for the diagnosis of a variety of diseases. Exemplary embodiments of the present invention can facilitate an implementation of an angular compounding, angular compounding by path length encoding (“ACPE”) for reducing speckle in OCT images. By averaging images obtained at different incident angles, with each image encoded by path length, ACPE maintains high-speed image acquisition and implements minimal modifications to OCT probe optics. ACPE images obtained from tissue phantoms and human skin in vivo demonstrate a qualitative improvement over traditional OCT and an increased signal-to-noise ratio (“SNR”). Accordingly, exemplary embodiments of an apparatus probe catheter and method can be provided for irradiating a sample. In particular, an interferometer may forward forwarding an electromagnetic radiation. In addition, a sample arm may receive the electromagnetic radiation, and can include an arrangement which facilitates a production of at least two radiations from the electromagnetic radiation so as to irradiate the sample. Such exemplary arrangement can be configured to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations.
Description
FIELD OF THE INVENTION

The present invention relates to optical imaging methods and apparatus useful in medical diagnosis and imaging. In particular, the present invention relates to a high speed method for implementing angular compounding, e.g., angular compounding by path length encoding (“ACPE”) for reducing speckle in optical coherence tomography images.


BACKGROUND INFORMATION

Optical coherence tomography (“OCT”) is a technique for obtaining high resolution cross-sectional images of biological tissues. Clinical OCT studies conducted in the gastrointestinal tract and cardiovascular system have shown that OCT is capable of providing images of the architectural (>20 μm) microanatomy of a variety of epithelial tissues, including the layered structure of squamous epithelium and arterial vessels. However, for certain medical applications, such as the early detection of high-grade dysplasia in Barrett's esophagus and the identification of inflammation within atherosclerotic plaques, visualization of structures that are on a size scale of <20 μm may be preferable. OCT systems, with typical axial resolutions ranging from 8-12 μm, have the potential to resolve many of these structures, including nuclei, individual glands, and macrophages. Unfortunately, speckle, which occurs on the same size scale as these features, may prohibit unambiguous including nuclei, individual glands, and macrophages. Unfortunately, speckle, which occurs on the same size scale as these features, may prohibit unambiguous identification of the cellular and subcellular tissue components required for widespread clinical utilization of such technology.


Catheter or endoscope access and high-speed imaging is used in order to perform OCT in the internal organs of patients. In order to minimize diameter, most catheter-based OCT probes employ a single optical fiber to illuminate the sample and detect the signal from the tissue. High frame rates (typically 4-10 frames per second) are preferred for performing OCT imaging while minimizing artifacts caused by patient motion. A way to reduce speckle in OCT images that does not significantly increase the complexity of single optical fiber probe designs while maintaining high frame rates may be beneficial for applying OCT to accurately detect and quantify key microscopic tissue structures in patients.


The reduction of speckle in the OCT images speckle has been previously described. A publication by J. M. Schmitt, “Array Detection for Speckle Reduction in Optical Coherence Microscopy,” Phys. Med. Biol. 42, 1427-1429, 1997, the entire disclosure of which is incorporated herein by reference, describes a procedure for a speckle reduction by averaging multiple images acquired at different angles, known as angular compounding. In this publication, multiple (N) detectors receive images that have been acquired from different angles. The images are averaged incoherently, providing an improvement (√{square root over (N)}) in the signal to noise ratio (“SNR”). While this technique has the advantage that the measurements may be performed in real-time, the experimental apparatus as described therein would not be compatible with a single fiber optic catheter.


Another publication, M. Bashkansky and J. Reintjes, “Statistics and reduction of Speckle in Optical Coherence Tomography,” Opt. Lett. 25, 545-547, 2000, the entire disclosure of which is incorporated herein by reference, describes an alternative technique for angular compounding to reduce speckle. In this method, a retroreflector apparatus is translated in front of the objective lens to change the angle of the incident beam on the tissue. N successive images are acquired and added incoherently to reduce speckle, again improving the SNR by a factor of √{square root over (N)}. While this method may be less complex than the use of multiple detectors, the time needed thereby to acquire the images is increased by N. In addition, the implementation of this method within the confines of a small diameter catheter or endoscope could be difficult.


SUMMARY OF THE INVENTION

According to one exemplary embodiment of the present invention, a method for performing angular compounding to :reduce speckle within OCT images is provided, which may use angular compounding by path length encoding (“ACPE”). With ACPE, a high-speed acquisition can be maintained, and modifications to standard OCT catheter optics are likely to be minimal. In another exemplary embodiment according to the present invention, an apparatus for imaging is provided that uses ACPE.


Accordingly, apparatus probe catheter, and method according to exemplary embodiments of the present invention are provided for irradiating a sample. In particular, an interferometer may forward forwarding an electromagnetic radiation. In addition, a sample arm may receive the electromagnetic radiation, and can include an arrangement which facilitates a production of at least two radiations from the electromagnetic radiation so as to irradiate the sample. Such arrangement can be configured to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations.


According to another exemplary embodiment of the present invention, a reference arm provides a further electromagnetic radiation. In particular, the interferometer receives the first, second and further radiations, and forms a resultant signal based on the first, second and further radiations. A processing arrangement may also be provided for generating a first image based on the first radiation and a second image based on the second radiation, such that the first and second images are different from one another. The further image may be generated based on the first and second images. In addition, the further image may have a noise that is smaller than a noise of the first image and a noise of the second image. Also, the further image may have a signal to noise ratio that is improved according to the equation:








SNR
ACPE

=





S
OCT





var


[

S
OCT

]










i
=
1

N



u
i







i
=
1

N



u
i
2






,




where SNRACPE is the signal to noise ratio, SOCT is an amplitude of a high-pass filtered OCT signal, m is a thickness of the arrangement, ui is an amplitude of a demodulated OCT signal at a spatial location, and N=2m−1. Further, m=2 and N=3 images associated with the at least two radiations may be obtained. The further image may also be generated based on a mathematical combination of the first and second images.


According to yet another exemplary embodiment of the present invention, the sample can be irradiated by the first irradiation at a first angle, and by the second radiation at a second angle, such that the first and second angles different from one another. For example, the first and second angle may be different from one another based on the delay and at least one of a phase and a incident angle of each of the first and second radiations. It is also possible to utilize a detector which detects the first electromagnetic energy, and forwards the detected energy to the processing arrangement.


In still another exemplary embodiment of the present invention, the arrangement can include two sections, each being configured to delay a respective one of the first and second radiations. In particular, a delay of the first radiation is preferably greater than a delay of the second radiation. In addition, the delay of a path of the first radiation compared to a path of the second radiation is at least 500 μm in air. Further, the delay of a path of the first radiation compared to a path of the second radiation is at least 1 mm in air. The arrangement may have a refractive index of at least 1.5 or at least 3.0. The arrangement can include silicon and/or an anti-reflective coating on at least one surface thereof. Such arrangement can be an anti-reflection-coated BK 7 glass. The glass may have a thickness of from about 1.6 mm to about 7.7 mm, and a refractive index of from about 1.51 to about 3.5.


According to yet another exemplary embodiment of the present invention, an apparatus for imaging is provided. The apparatus includes a sample arm that receive an electromagnetic radiation. The sample arm includes an arrangement which facilitates a production of at least two radiations from the electromagnetic radiation so as to irradiate a sample. The arrangement is configured to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations. The apparatus also includes a device for receiving the first and second radiations from the sample arm and at least one third radiation from a reference arm, such that the first and second radiations interfere with the third radiation. Further, the apparatus includes at least one of spectral separating unit which separates spectrum of at least one of the first, second and third radiations into frequency components, and at least one detection arrangement including a plurality of detectors. Each detector is capable of detecting at least a portion of at least one of the frequency components.


In a further exemplary embodiment of the present invention, an apparatus is provided. Such apparatus includes at least one first arrangement that provides at least one first electromagnetic radiation to a sample arm and at least one second electromagnetic radiation to a non-reflective reference arm. A frequency of radiation provided by the first arrangement varies over time. The sample arm receives the first electromagnetic radiation, and includes an arrangement which facilitates a production of at least two radiations from the electromagnetic radiation so as to irradiate a sample. The arrangement is configured to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations. The apparatus also includes at least one second arrangement detecting an interference between the first and second radiations generated at the sample arm and the second electromagnetic radiations generated at the reference.


In still another exemplary embodiment of the present invention, an apparatus is provided. The apparatus includes a at least one first arrangement providing at least one first electromagnetic radiation to a sample arm and at least one second electromagnetic radiation to a reference arm. The first and/or second electro-magnetic radiation have a spectrum which changes over time. The spectrum contains multiple frequencies at a particular time. The sample arm receives the first electromagnetic radiation, and includes an arrangement which facilitates a production of at least two radiations from the electromagnetic radiation so as to irradiate a sample. The arrangement is configured to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations. The apparatus also includes at least one second arrangement detecting an interference between the first and second radiations generated at the sample arm and the second electromagnetic radiations generated at the reference.


Other features and advantages of the present invention will become apparent upon reading the following detailed description of embodiments of the invention, when taken in conjunction with the appended claims.





BRIEF DESCRIPTION OF THE DRAWINGS

The invention is illustrated in the drawings in which like reference characters designate the same or similar parts throughout the figures of which:



FIG. 1A is a schematic diagram of an exemplary embodiment of an ACPE-OCT apparatus according to the present invention.



FIG. 1B is an exemplary illustration of multiple exemplary OCT images of a specimen in or on a sample which can be generated using the exemplary apparatus of FIG. 1A;



FIG. 2A is a schematic diagram of an exemplary embodiment of an Intralipid-Agar phantom according to the present invention.



FIG. 2B is an exemplary OCT image of the phantom of FIG. 2A without the insertion of a BK7 ACPE element.



FIG. 2C is an illustration of exemplary ACPE OCT images obtained by splitting a sample beam in two parts using an exemplary 3.1 mm BK7 glass element.



FIG. 2D is an illustration of an exemplary compounded ACPE image which can be obtained by incoherently averaging the images shown in FIG. 2C;



FIG. 3A is an exemplary OCT image of a ventral forearm obtained in vivo prior to the insertion of the BK7 ACPE element.



FIG. 3B is an exemplary compounded ACPE OCT image of the skin acquired at the same location as that in FIG. 3A.





DETAILED DESCRIPTION

I. Materials And Methods



FIG. 1A shows an exemplary embodiment of an apparatus according to the present invention which uses ACPE. An optical glass 20 is placed in an imaging path 10 of a conventional OCT imaging apparatus 5, splitting the incident field into two beamlets 1 and 2 which are provided on beam paths 30 and 40, respectively. For the purpose of the present discussion, a beamlet can be defined as a portion of a beam. An optical element (e.g., the optical glass 20) causes a portion of the incident beam (beamlet 2) to experience a greater path length delay than beamlet 1. In addition, beamlet 2 illuminates the sample at a different angle than beamlet 1. A lens may be provided to converge the beamlets 1 and 2 onto the sample (e.g., a tissue). As a result, multiple OCT images of a specimen in or on the sample, each acquired at a different angle, can appear simultaneously on the OCT display (see FIG. 1B). In particular, FIG. 1B shows that the top image (i.e., labeled as 1+1) corresponds to the image formed from path 1 (i.e., incident and reflected), the middle image (i.e., labeled as 1+2, 2+1) corresponds to the image formed from path 1 incident, path 2 reflected and path 2 incident, path 1 reflected. Further, the bottom image (i.e., 2+2) of FIG. 1B corresponds to the image formed from path 2 (incident and reflected).


These beamlets 1 and 2, thus encoded by optical path length, also illuminate the sample at different angles. As a result, multiple OCT images, each acquired at different angles, are preferably present in a single OCT frame (as shown in FIG. 1B). For example, when the optical element contains m distinct thicknesses of glass, with each optical thickness a multiple of the others, 2m−1 OCT images can be obtained in one OCT frame. Each image may be separated by a group delay of D(n−1)/2, where D is the thickness and n is the refractive index of the optical material. The distinct OCT images are then averaged to produce a composite OCT image with significantly reduced speckle. Since all of the images are acquired in one OCT frame, single frame acquisition time can be maintained. In addition, the modifications to the OCT probe may involve only the insertion of at least one small optical element in the beam path of the distal optics. These advantages of ACPE allow speckle averaging to be performed within the confines of a small diameter catheter or endoscope, and without compromising the acquisition speed.


Previous attempts of utilizing OCT speckle reduction by image compounding has shown that the addition of N images of the same intensity provides an SNR increase by a factor of √{square root over (N)}. For example, the Bashkansky publication described above describes that the speckle distribution in OCT takes the form of the probability density function:










p


(

S
OCT

)


=


1




2

π








κ




exp


(


-

S
OCT
2



2


κ
2



)







(
1
)








where κ=2ARσ, with AR is the amplitude of the reference field, SOCT is the amplitude of the high-pass filtered OCT signal, and σ is its standard deviation. For this probability density function, it can be demonstrated that the SNR improvement obtained by averaging N images of the same amplitude is also a factor of √{square root over (N)}, a result that has been experimentally described in the Schmitt and Bashkansky publications. For ACPE, the distinct OCT subimages generally may not have equal amplitudes. However, with the assumption of isotropic backscattering, these subimages are related to the original OCT image, S0OCT, by β/m2, where β is the number of path length combinations that contribute to a distinct subimage. As a result, the SNR for ACPE may be defined as











SNR
ACPE

=





S
OCT





var


[

S
OCT

]










i
=
1

N



u
i







i
=
1

N



u
i
2






,




(
2
)








where ui is the amplitude of the demodulated OCT signal at a spatial location, and N=2m−1. In the case of m=2, N=3 images are obtained and the relationships between the amplitudes of the ACPE OCT subimages are S1OCT=S3OCT=¼S0OCT and S2OCT=2S1OCT=½S0OCT. The potential SNR improvement of the compounded m=2 ACPE image can then become SNRACPE/SNR0=1.63, where SNR0 is the signal to noise ratio of S0OCT.


EXAMPLES
II. Example 1

An exemplary polarization-diverse OCT system according to the present invention can be utilized for the examplary apparatus (e.g., as shown in FIG. 1A) that implements ACPE. Using such exemplary system according to the present invention, OCT images may be acquired at 2 frames per second (e.g., 500 axial pixels×500 transverse pixels), which may be displayed with an inverse gray-scale lookup table, and digitally archived. The optical source which can be used in such exemplary OCT system may have a center wavelength of 1310 nm and a bandwidth of 70 nm, and thus providing an axial resolution of approximately 8 μm in the tissue.


A modified hand-held galvanometer probe (e.g., the apparatus of FIG. 1A) can be inserted in the sample arm of the OCT system 5. The objective lens 50 may have a focal length of 25 mm and a numerical aperture (NA) of 0.11, providing a measured 1/e2 focal spot diameter of 23 μm. A square, antireflection-coated D=3.1 mm BK7 glass (n=1.51) (e.g., the optical glass 20, may be inserted between the optical fiber collimator and the objective lens 50 (see FIG. 1A) so that overlaps with half of the illuminating beam. With this exemplary configuration, an OCT image separation of approximately 800 μm can be achieved. When the glass plate is inserted, the spot diameter perpendicular to the glass edge may increase by a factor of two (46 μm). In the plane of the OCT image, however, the transverse resolution is likely preserved.


III. Example 2

A solid phantom consisting of 1% Intralipid solution and Agar can be used to measure a reduction in speckle provided by ACPE. For example, four (4) hairs can be embedded in the Intralipid-Agar gel at different transverse positions and depths. A schematic of the phantom is depicted in FIG. 2A. The corresponding OCT images with and without the BK7 glass plate are shown in FIGS. 2B and 2C, respectively. ROI's labeled 1-5 represent exemplary locations where the SNR improvement by ACPE is preferably measured. The insertion of the BK7 glass plate 20 (with a 3.1 mm BK7 glass element) in the sample arm can produce three copies of the original OCT image (see FIG. 2C), with each image being acquired at a different illumination angles and separated by group delay increments of, e.g., 800 μm. The amplitudes of the signals in the top and bottom images of FIG. 2C can be approximately half of the center image (S1OCT/S2OCT=S3OCT/S2OCT=1:2). The compounded ACPE image shown in FIG. 2D can best obtained by incoherently averaging the three images that are shown in FIG. 2C. A substantial reduction of speckle in the compounded image can be visualized in FIG. 2D. Compared to the original OCT image, the average ACPE SNR improvement for the five regions depicted in FIG. 2B is preferably 1.54±0.12 (mean ± standard deviation).


IV. Example 3

In order to demonstrate SNR improvement in vivo, ACPE OCT imaging can be performed on a ventral forearm of a subject. FIGS. 3A and 3B shows one representative set of images. FIG. 3A shows an exemplary OCT image of the ventral forearm obtained in vivo prior to the insertion of the BK7 ACPE element. Visual assessment of these pictures demonstrates a qualitative improvement in the compounded ACPE image (FIG. 3B). The boundary between the epidermis (E) and dermis (D) is more clearly demarcated with ACPE as shown in FIG. 3B. In addition, horizontal structures consistent with dermal vasculature are more readily identified in the ACPE image of FIG. 3B. The SNR can be measured for the ACPE and original OCT images in FIG. 3B, providing an exemplary SNR improvement of 1.56.


The apparatus and method according to the exemplary embodiments of the present invention are provide to reduce speckle in OCT images that does not decrease the OCT frame rate and requires only minor modifications to the OCT probe. The implementation of ACPE, implements potential compromises between speckle reduction and three other OCT system parameters: a) sample arm transverse resolution, b) total reference arm path length, and c) OCT image sensitivity. In particular, for any given objective lens, ACPE may compromise the transverse resolution in one dimension by underfilling the lens aperture for each individual beamlet. In most cases, increasing the numerical aperture (NA) of the objective can compensate for this resolution loss.


Speckle averaged ACPE-OCT images can be obtained at the same rate as conventional OCT images by scanning an increased reference arm path length delay at substantially the same frequency. In order to acquire each of the individual OCT subimages, the new scan length of the ACPE-OCT system can preferably be L(2m−1), where L is the original scan length of the OCT system. Using phase control RSOD lines, scan ranges up to 10 mm are possible, thus enabling m=3, L=2 mm, and a maximum predicted SNR improvement of ˜2.1.


Increasing the reference arm path length scan range while maintaining the scan rate, may increase the electronic bandwidth and decrease the sensitivity of the OCT system. Also, because ACPE splits the sample arm power into 2m−1 subimages, each subimage contains a fraction of the original sample arm power. When imaging a human tissue, these losses may primarily affect the penetration depth of the OCT image. Since many features of clinical relevance, such as nuclei in patients with Barrett's esophagus or macrophages in atherosclerotic plaques, may bee present at tissue surfaces, for modest m, the improvements in image quality provided by ACPE likely outweigh sensitivity losses. Moreover, ongoing technical developments towards more efficient interferometer designs and higher power, clinically viable OCT sources may render ACPE sensitivity losses a non-issue.


The thickness of the path length encoding optical element described herein in the above-referenced Examples (3.1 mm BK7) may not be sufficient for OCT imaging in some tissues since the provide 800 μm separation between individual subimages. Increasing the thickness of the BK7 glass to 7.7 mm may allow a path length separation of 2 mm. This thickness may be adequate for a free-space, hand-held OCT probes, but can be be problematic in small diameter, flexible catheters, where minimizing the rigid length can be important. In order to increase the optical thickness of the path length encoding element, a higher refractive index material such as silicon (n=3.5) may be used. To create a 2 mm delay with silicon, preferably approximately 1.6 mm of the material can be used. When using high refractive index glass, dispersion imbalances between the reference and sample arms should be considered. For high-resolution OCT imaging (Δλ/λ>10%), appropriate selection of the optical material used for path length encoding will depend on the center wavelength and bandwidth of the source.


Advantages of the exemplary embodiment of the method and apparatus according to the present invention may include the fact that the OCT frame rate is not increased, and the addition of only a single passive element in the OCT probe should be implemented. These features of ACPE make the system and and method of the present invention compatible with OCT imaging in internal organ systems in patients. While implementation of ACPE may facilitate tradeoffs between speckle reduction and system sensitivity, the problems caused by speckle noise are likely more significant for clinical diagnosis than the penetration depth of modem OCT systems, especially at 1300 nm. Since difficulties in interpreting features on the size scale of 20 μm or less is in part a result of speckle noise in OCT images, ACPE would likely significantly improve the capabilities of OCT for the diagnosis of important diseases such as, but not limited to, dysplasia and inflammation in atherosclerosis.


Although only particular exemplary embodiments of the present invention have been described in detail herein above, those skilled in the art will readily appreciate and understand that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of the present invention as defined in the following claims.

Claims
  • 1. An apparatus for irradiating a sample, comprising: a) an interferometer forwarding an electromagnetic radiation;b) a sample arm receiving the electromagnetic radiation, the sample arm including an arrangement which is configured to produce at least two radiations from the electromagnetic radiation so as to irradiate the sample, and to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations;c) a reference arm providing a further electromagnetic radiation, wherein the interferometer receives the first, second and further radiations, and forms a resultant signal based on the first, second and further radiations; andd) a processing arrangement generating a first image based on the first radiation, a second image based on the resultant signal and a further image based on the first and second images,wherein the first and second images are different from one another, andwherein the further image has a signal to noise ratio that is improved according to the equation:
  • 2. The apparatus according to claim 1, wherein the further image has a noise that is smaller than a noise of the first image and a noise of the second image.
  • 3. The apparatus according to claim 1, wherein m=2 and N=3 images associated with the at least two radiations are obtained.
  • 4. The apparatus according claim 1, wherein the further image is generated based on a mathematical combination of the first and second images.
  • 5. The apparatus according to claim 1, wherein the arrangement irradiates the sample by the first irradiation at a first angle, and by the second radiation at a second angle, the first and second angles being different from one another.
  • 6. The apparatus according to claim 5, wherein the first and second angle are different from one another as a function of the delay and at least one of a phase or a incident angle of each of the first and second radiations.
  • 7. The apparatus according to claim 1, further comprising a detector which detects the first electromagnetic radiation, and forwards the detected energy to the processing arrangement.
  • 8. The apparatus according to claim 1, wherein the arrangement includes two sections, each being configured to delay a respective one of the first and second radiations, and wherein a delay of the first radiation is greater than a delay of the second radiation.
  • 9. An apparatus for irradiating a sample, comprising: a) an interferometer forwarding an electromagnetic radiation; andb) a sample arm receiving the electromagnetic radiation, the sample arm including an arrangement which is configured to produce at least two radiations from the electromagnetic radiation so as to irradiate the sample, and to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations, wherein the delay of a path of the first radiation compared to a path of the second radiation is at least 500 μm in air.
  • 10. The apparatus according to claim 9, wherein the delay of the path of the first radiation compared to the path of the second radiation is at least about 1 mm in air.
  • 11. An apparatus for irradiating a sample, comprising: a) an interferometer forwarding an electromagnetic radiation; andb) a sample arm receiving the electromagnetic radiation, the sample arm including an arrangement which is configured to produce at least two radiations from the electromagnetic radiation so as to irradiate the sample, and to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations, wherein the arrangement has at least one of: first optical section with a refractive index of at least 1.5, the first section being structured to propagate the at least two radiations,a second section which has silicon, the second section being structured to propagate the at least two radiations.
  • 12. The apparatus according to claim 11, wherein the refractive index of the optical section is at least 3.0.
  • 13. The apparatus according to claim 11, wherein at least one of the first section or the second section comprises an anti-reflection-coated BK 7 glass.
  • 14. The apparatus according to claim 13, wherein the glass has a thickness of from about 1.6 mm to about 7.7 mm.
  • 15. The apparatus according to claim 11, wherein at least one of the first section or the second section comprises an anti-reflection-coated glass that has a refractive index of from about 1.51 to about 3.5.
  • 16. A method for irradiating a sample, comprising: a. providing an electromagnetic radiation from an interferometer;b. in a sample arm, producing at least two radiations from the electromagnetic radiation so as to irradiate the sample, a first radiation of the at least two radiations being delayed with respect to a second radiation of the at least two radiations;c. providing a further electromagnetic radiation, wherein the interferometer receives the first, second and further radiations and forms a resultant signal based on the first, second and further radiations; andd. generating a first image based on the first radiation, a second image based on the resultant signal and a further image based on the first and second images,wherein the first and second images are different from one another, andwherein the further image has a signal to noise ratio that is improved according to the equation:
  • 17. An apparatus for imaging, comprising: a. a sample arm receiving an electromagnetic radiation, the sample arm including an arrangement which is configured to produce at least two radiations from the electromagnetic radiation so as to irradiate a sample, and to delay a first radiation of the at least two radiations with respect to a second radiation of the at least two radiations;b. a device receiving the first and second radiations from the sample arm and at least one third radiation from a reference arm, wherein the first and second radiations interfere with the third radiation;c. at least one spectral separating arrangement which cooperates with the sample arm, and separates spectrum of at least one of the first, second and third radiations into frequency components; andd. at least one detection arrangement including a plurality of detectors, each detector capable of detecting at least a portion of at least one of the frequency components;e. a reference arm providing a further electromagnetic radiation, wherein the interferometer receives the first, second and further radiations, and forms a resultant signal based on the first, second and further radiations; andf. a processing arrangement generating a first image based on the first radiation, a second image based on the resultant signal and a further image based on the first and second images,wherein the first and second images are different from one another, andwherein the further image has a signal to noise ratio that is improved according to the equation:
  • 18. An apparatus for obtaining information associated with a sample, comprising; a first arrangement configured to separating at least one first electro-magnetic radiation into a first radiation and a second radiation forwarded to a sample, wherein the first and second radiations having different path lengths;a second arrangement configured to received third and fourth radiations from the sample associated with the first and second radiations and a fifth radiation received from a reference, and generate at least one interference signal as a function of the third, fourth and fifth radiations;a third arrangement configured to generate: first data associated with the third radiation which includes a first speckle pattern and second data associated with the fourth radiation which includes a second speckle pattern, andthird data associated with the sample based on the first and second data that has a speckle pattern the amount of which is smaller that the amount of at least one of the first speckle pattern or the first speckle pattern.
  • 19. The apparatus according to claim 18, wherein the first, second and third data are images.
  • 20. The apparatus according to claim 18, wherein the first arrangement includes an optical section with a refractive index of at least 1.5, the optical section being structured to propagate the first and second radiations.
  • 21. The apparatus according to claim 18, wherein the first arrangement includes a section which has silicon that Is structured to propagate the first and second radiations.
  • 22. The apparatus according to claim 18, wherein the first arrangement includes a section which has an anti-reflective coating on at least one surface thereof, the section being structured to propagate the first and second radiations.
  • 23. An apparatus for obtaining information associated with a sample, comprising; a first arrangement configured to separating at least one first electro-magnetic radiation into a first radiation and a second radiation forwarded to a sample, wherein the first and second radiations having different path lengths;a second arrangement configured to received third and fourth radiations from the sample associated with the first and second radiations and a fifth radiation received from a reference, and generate at least one interference information as a function of the third, fourth and fifth radiations; anda third arrangement configured to generate data corresponding to an amount of a ranging depth within the sample associated with the second arrangement, wherein a difference between the path lengths of the first and second radiations is equal or greater than the ranging depth.
  • 24. The apparatus according to claim 23, wherein the first arrangement includes an optical section with a refractive index of at least 1.5, the optical section being structured to propagate the first and second radiations.
  • 25. The apparatus according to claim 23, wherein the first arrangement includes a section which has silicon that Is structured to propagate the first and second radiations.
  • 26. The apparatus according to claim 23, wherein the first arrangement includes a section which has an anti-reflective coating on at least one surface thereof, the section being structured to propagate the first and second radiations.
  • 27. The apparatus according to claim 23, wherein the ranging depth is a penetration depth in the sample, the sample including an anatomical structure.
  • 28. The apparatus according to claim 18, wherein the first, second and the third data are images, the third image data having a noise that is smaller than a noise of the first image data and a noise of the second image data.
  • 29. The apparatus according claim 18, wherein the first, second and the third data are images, and wherein the third arrangement is configured to generate the third image data based on a mathematical combination of the first and second image data.
  • 30. The apparatus according to claim 18, further comprising an arrangement which is configured to irradiate the sample by the first irradiation at a first angle, and by the second radiation at a second angle, the first and second angles being different from one another.
  • 31. The apparatus according to claim 30, wherein the first and second angle are different from one another as a function of a delay between the first and second radiations and at least one of a phase or a incident angle of each of the first and second radiations.
  • 32. The apparatus according to claim 18, further comprising a detector which detects the first radiation, and forwards the detected energy to the third arrangement.
  • 33. The apparatus according to claim 18, further comprising an arrangement which includes two sections, each being configured to delay a respective one of the first and second radiations, and wherein a delay of the first radiation is greater than a delay of the second radiation.
CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority from U.S. patent application Ser. No. 60/459,543 filed on on Mar. 31, 2003, International Patent Application No. PCT/US03/02349 filed on Jan. 24, 2003, and U.S. Patent Applications Ser. Nos. 60/476,600, 60/514,769, filed on Jun. 6, 2003 and Oct. 27, 2003, respectively, the entire disclosures of which are incorporated herein by reference.

PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/US2004/010152 3/31/2004 WO 00 9/29/2005
Publishing Document Publishing Date Country Kind
WO2004/088361 10/14/2004 WO A
US Referenced Citations (280)
Number Name Date Kind
2339754 Brace Jan 1944 A
3090753 Matsuszak et al. May 1963 A
3601480 Sexton Aug 1971 A
3856000 Chikama Dec 1974 A
3872407 Hughes Mar 1975 A
3941121 Olinger Mar 1976 A
3973219 Tang et al. Aug 1976 A
3983507 Tang et al. Sep 1976 A
4030827 Delhaye et al. Jun 1977 A
4140364 Yamashita et al. Feb 1979 A
4141362 Wurster Feb 1979 A
4224929 Furihata Sep 1980 A
4295738 Meltz et al. Oct 1981 A
4300816 Snitzer et al. Nov 1981 A
4303300 Pressiat et al. Dec 1981 A
4428643 Kay Jan 1984 A
4479499 Alfano Oct 1984 A
4533247 Epworth Aug 1985 A
4585349 Gross et al. Apr 1986 A
4601036 Faxvog et al. Jul 1986 A
4607622 Fritch et al. Aug 1986 A
4631498 Cutler Dec 1986 A
4650327 Ogi Mar 1987 A
4744656 Moran et al. May 1988 A
4751706 Rohde et al. Jun 1988 A
4770492 Levin et al. Sep 1988 A
4834111 Khanna et al. May 1989 A
4868834 Fox et al. Sep 1989 A
4890901 Cross, Jr. Jan 1990 A
4892406 Waters Jan 1990 A
4909631 Tan et al. Mar 1990 A
4925302 Cutler May 1990 A
4928005 Lefèvre et al. May 1990 A
4965441 Picard Oct 1990 A
4965599 Roddy et al. Oct 1990 A
4993834 Carlhoff et al. Feb 1991 A
5039193 Snow et al. Aug 1991 A
5040889 Keane Aug 1991 A
5045936 Lobb et al. Sep 1991 A
5046501 Crilly Sep 1991 A
5065331 Vachon et al. Nov 1991 A
5085496 Yoshida et al. Feb 1992 A
5120953 Harris Jun 1992 A
5121983 Lee Jun 1992 A
5127730 Brelje et al. Jul 1992 A
5197470 Helfer et al. Mar 1993 A
5202745 Sorin et al. Apr 1993 A
5212667 Tomlinson et al. May 1993 A
5214538 Lobb May 1993 A
5228001 Birge et al. Jul 1993 A
5248876 Kerstens et al. Sep 1993 A
5262644 Maguire Nov 1993 A
5291885 Taniji et al. Mar 1994 A
5293872 Alfano et al. Mar 1994 A
5293873 Fang Mar 1994 A
5304810 Amos Apr 1994 A
5305759 Kaneko et al. Apr 1994 A
5317389 Hochberg et al. May 1994 A
5318024 Kittrell et al. Jun 1994 A
5321501 Swanson et al. Jun 1994 A
5353790 Jacques et al. Oct 1994 A
5383467 Auer et al. Jan 1995 A
5411016 Kume et al. May 1995 A
5419323 Kittrell et al. May 1995 A
5439000 Gunderson et al. Aug 1995 A
5441053 Lodder et al. Aug 1995 A
5450203 Penkethman Sep 1995 A
5454807 Lennox et al. Oct 1995 A
5459325 Hueton et al. Oct 1995 A
5459570 Swanson et al. Oct 1995 A
5465147 Swanson Nov 1995 A
5486701 Norton et al. Jan 1996 A
5491524 Hellmuth et al. Feb 1996 A
5491552 Knuttel Feb 1996 A
5526338 Hasman et al. Jun 1996 A
5562100 Kittrell et al. Oct 1996 A
5565986 Knüttel Oct 1996 A
5583342 Ichie Dec 1996 A
5590660 MacAulay et al. Jan 1997 A
5600486 Gal et al. Feb 1997 A
5601087 Richards-Kortum et al. Feb 1997 A
5621830 Lucey et al. Apr 1997 A
5623336 Raab et al. Apr 1997 A
5635830 Itoh Jun 1997 A
5649924 Everett et al. Jul 1997 A
5697373 Gunderson et al. Dec 1997 A
5698397 Zarling et al. Dec 1997 A
5710630 Essenpreis et al. Jan 1998 A
5716324 Toida Feb 1998 A
5719399 Alfano et al. Feb 1998 A
5735276 Lemelson Apr 1998 A
5740808 Panescu et al. Apr 1998 A
5748318 Maris et al. May 1998 A
5748598 Swanson et al. May 1998 A
5784352 Swanson et al. Jul 1998 A
5785651 Kuhn et al. Jul 1998 A
5795295 Hellmuth et al. Aug 1998 A
5801826 Williams Sep 1998 A
5803082 Stapleton et al. Sep 1998 A
5807261 Benaron et al. Sep 1998 A
5817144 Gregory Oct 1998 A
5840023 Oraevsky et al. Nov 1998 A
5840075 Mueller et al. Nov 1998 A
5842995 Mahadevan-Jansen et al. Dec 1998 A
5843000 Nishioka et al. Dec 1998 A
5843052 Benja-Athon Dec 1998 A
5847827 Fercher Dec 1998 A
5862273 Pelletier Jan 1999 A
5865754 Sevick-Muraca et al. Feb 1999 A
5867268 Gelikonov et al. Feb 1999 A
5871449 Brown Feb 1999 A
5872879 Hamm Feb 1999 A
5877856 Fercher Mar 1999 A
5887009 Mandella et al. Mar 1999 A
5892583 Li Apr 1999 A
5912764 Togino Jun 1999 A
5920373 Bille Jul 1999 A
5920390 Farahi et al. Jul 1999 A
5921926 Rolland et al. Jul 1999 A
5949929 Hamm Sep 1999 A
5951482 Winston et al. Sep 1999 A
5955737 Hallidy et al. Sep 1999 A
5956355 Swanson et al. Sep 1999 A
5968064 Selmon et al. Oct 1999 A
5983125 Alfano et al. Nov 1999 A
5987346 Benaron et al. Nov 1999 A
5991697 Nelson et al. Nov 1999 A
5994690 Kulkarni et al. Nov 1999 A
6002480 Izatt et al. Dec 1999 A
6004314 Wei et al. Dec 1999 A
6006128 Izatt et al. Dec 1999 A
6010449 Selmon et al. Jan 2000 A
6014214 Li Jan 2000 A
6020963 DiMarzio et al. Feb 2000 A
6033721 Nassuphis Mar 2000 A
6044288 Wake et al. Mar 2000 A
6045511 Ott et al. Apr 2000 A
6048742 Weyburne et al. Apr 2000 A
6053613 Wei et al. Apr 2000 A
6069698 Ozawa et al. May 2000 A
6091496 Hill Jul 2000 A
6091984 Perelman et al. Jul 2000 A
6111645 Tearney et al. Aug 2000 A
6117128 Gregory Sep 2000 A
6120516 Selmon et al. Sep 2000 A
6134003 Tearney et al. Oct 2000 A
6134010 Zavislan Oct 2000 A
6134033 Bergano et al. Oct 2000 A
6141577 Rolland et al. Oct 2000 A
6151522 Alfano et al. Nov 2000 A
6159445 Klaveness et al. Dec 2000 A
6160826 Swanson et al. Dec 2000 A
6161031 Hochman et al. Dec 2000 A
6166373 Mao Dec 2000 A
6174291 McMahon et al. Jan 2001 B1
6175669 Colston et al. Jan 2001 B1
6185271 Kinsinger Feb 2001 B1
6191862 Swanson et al. Feb 2001 B1
6193676 Winston et al. Feb 2001 B1
6198956 Dunne Mar 2001 B1
6201989 Whitehead et al. Mar 2001 B1
6208415 De Boer et al. Mar 2001 B1
6208887 Clarke Mar 2001 B1
6245026 Campbell et al. Jun 2001 B1
6249349 Lauer Jun 2001 B1
6263234 Engelhardt et al. Jul 2001 B1
6264610 Zhu Jul 2001 B1
6272376 Marcu et al. Aug 2001 B1
6274871 Dukor et al. Aug 2001 B1
6282011 Tearney et al. Aug 2001 B1
6297018 French et al. Oct 2001 B1
6308092 Hoyns Oct 2001 B1
6324419 Guzelsu et al. Nov 2001 B1
6341036 Tearney et al. Jan 2002 B1
6353693 Kano et al. Mar 2002 B1
6359692 Groot Mar 2002 B1
6377349 Fercher Apr 2002 B1
6384915 Everett et al. May 2002 B1
6393312 Hoyns May 2002 B1
6394964 Sievert, Jr. et al. May 2002 B1
6421164 Tearney et al. Jul 2002 B2
6445485 Frigo et al. Sep 2002 B1
6445944 Ostrovsky Sep 2002 B1
6459487 Chen et al. Oct 2002 B1
6463313 Winston et al. Oct 2002 B1
6469846 Ebizuka et al. Oct 2002 B2
6475159 Casscells et al. Nov 2002 B1
6475210 Phelps et al. Nov 2002 B1
6485413 Boppart et al. Nov 2002 B1
6485482 Belef Nov 2002 B1
6501551 Tearney et al. Dec 2002 B1
6501878 Hughes et al. Dec 2002 B2
6538817 Farmer et al. Mar 2003 B1
6549801 Chen et al. Apr 2003 B1
6552796 Magnin et al. Apr 2003 B2
6556305 Aziz et al. Apr 2003 B1
6556853 Cabib et al. Apr 2003 B1
6558324 Von Behren et al. May 2003 B1
6564087 Pitris et al. May 2003 B1
6564089 Izatt et al. May 2003 B2
6615071 Casscells, III et al. Sep 2003 B1
6622732 Constantz Sep 2003 B2
6680780 Fee Jan 2004 B1
6685885 Nolte et al. Feb 2004 B2
6687007 Meigs Feb 2004 B1
6687010 Horii et al. Feb 2004 B1
6687036 Riza Feb 2004 B2
6701181 Tang et al. Mar 2004 B2
6738144 Dogariu May 2004 B1
6741355 Drabarek May 2004 B2
6790175 Furusawa et al. Sep 2004 B1
6806963 Wälti et al. Oct 2004 B1
6816743 Moreno et al. Nov 2004 B2
6839496 Mills et al. Jan 2005 B1
6903820 Wang Jun 2005 B2
6949072 Furnish et al. Sep 2005 B2
6980299 de Boer Dec 2005 B1
7006231 Ostrovsky et al. Feb 2006 B2
7061622 Rollins et al. Jun 2006 B2
7190464 Alphonse Mar 2007 B2
7231243 Tearney et al. Jun 2007 B2
7242480 Alphonse Jul 2007 B2
7355716 De Boer et al. Apr 2008 B2
7359062 Chen et al. Apr 2008 B2
7366376 Shishkov et al. Apr 2008 B2
7391520 Zhou et al. Jun 2008 B2
20010047137 Moreno et al. Nov 2001 A1
20020016533 Marchitto et al. Feb 2002 A1
20020064341 Fauver et al. May 2002 A1
20020076152 Hughes et al. Jun 2002 A1
20020085209 Mittleman et al. Jul 2002 A1
20020093662 Chen et al. Jul 2002 A1
20020122246 Tearney et al. Sep 2002 A1
20020140942 Fee et al. Oct 2002 A1
20020158211 Gillispie Oct 2002 A1
20020161357 Rox et al. Oct 2002 A1
20020163622 Magnin et al. Nov 2002 A1
20020172485 Keaton et al. Nov 2002 A1
20020183623 Tang et al. Dec 2002 A1
20020188204 McNamara et al. Dec 2002 A1
20020196446 Roth et al. Dec 2002 A1
20020198457 Tearney et al. Dec 2002 A1
20030023153 Izatt et al. Jan 2003 A1
20030026735 Nolte et al. Feb 2003 A1
20030028114 Casscells, III et al. Feb 2003 A1
20030097048 Ryan et al. May 2003 A1
20030108911 Klimant et al. Jun 2003 A1
20030135101 Webler Jul 2003 A1
20030164952 Deichmann et al. Sep 2003 A1
20030171691 Casscells, III et al. Sep 2003 A1
20030199769 Podoleanu et al. Oct 2003 A1
20030216719 Debenedictis et al. Nov 2003 A1
20030220749 Chen et al. Nov 2003 A1
20030236443 Cespedes et al. Dec 2003 A1
20040054268 Esenaliev et al. Mar 2004 A1
20040072200 Rigler et al. Apr 2004 A1
20040077949 Blofgett et al. Apr 2004 A1
20040086245 Farroni et al. May 2004 A1
20040100631 Bashkansky et al. May 2004 A1
20040100681 Bjarklev et al. May 2004 A1
20040126048 Dave et al. Jul 2004 A1
20040133191 Momiuchi et al. Jul 2004 A1
20040150829 Koch et al. Aug 2004 A1
20040152989 Puttappa et al. Aug 2004 A1
20040166593 Nolte et al. Aug 2004 A1
20040212808 Okawa et al. Oct 2004 A1
20040239938 Izatt Dec 2004 A1
20040263843 Knopp et al. Dec 2004 A1
20050018201 De Boer Jan 2005 A1
20050035295 Bouma et al. Feb 2005 A1
20050046837 Izumi et al. Mar 2005 A1
20050075547 Wang Apr 2005 A1
20050083534 Riza et al. Apr 2005 A1
20050171438 Chen et al. Aug 2005 A1
20060103850 Alphonse et al. May 2006 A1
20060146339 Fujita Jul 2006 A1
20060155193 Leonardi et al. Jul 2006 A1
20060244973 Yun et al. Nov 2006 A1
20070019208 Toida et al. Jan 2007 A1
20070291277 Everett et al. Dec 2007 A1
Foreign Referenced Citations (61)
Number Date Country
4105221 Sep 1991 DE
4309056 Sep 1994 DE
19542955 May 1997 DE
10351319 Jun 2005 DE
0110201 Jun 1984 EP
0251062 Jan 1988 EP
0617286 Feb 1994 EP
0590268 Apr 1994 EP
0728440 Aug 1996 EP
0933096 Aug 1999 EP
1324051 Jul 2003 EP
1426799 Jun 2004 EP
1257778 Dec 1971 GB
2030313 Apr 1980 GB
2209221 May 1989 GB
4135550 May 1992 JP
4135551 May 1992 JP
7900841 Oct 1979 WO
9216865 Oct 1992 WO
9219930 Nov 1992 WO
9303672 Mar 1993 WO
9216865 Oct 1993 WO
9533971 Dec 1995 WO
9628212 Sep 1996 WO
9732182 Sep 1997 WO
9800057 Jan 1998 WO
9801074 Jan 1998 WO
9814132 Apr 1998 WO
9835203 Aug 1998 WO
9838907 Sep 1998 WO
9846123 Oct 1998 WO
9848838 Nov 1998 WO
9848846 Nov 1998 WO
9905487 Feb 1999 WO
9944089 Sep 1999 WO
9957507 Nov 1999 WO
0058766 Oct 2000 WO
0108579 Feb 2001 WO
0138820 May 2001 WO
0142735 Jun 2001 WO
0236015 May 2002 WO
0238040 May 2002 WO
0254027 Jul 2002 WO
03020119 Mar 2003 WO
03052478 Jun 2003 WO
03062802 Jul 2003 WO
2003105678 Dec 2003 WO
2004034869 Apr 2004 WO
20040066824 Aug 2004 WO
2004088361 Oct 2004 WO
2004105598 Dec 2004 WO
20050000115 Jan 2005 WO
2005054780 Jun 2005 WO
2005082225 Sep 2005 WO
2006014390 Feb 2006 WO
2006039091 Apr 2006 WO
2006059109 Jun 2006 WO
2006130797 Dec 2006 WO
2007028531 Mar 2007 WO
2007038787 Apr 2007 WO
2007083138 Jul 2007 WO
Related Publications (1)
Number Date Country
20060227333 A1 Oct 2006 US
Provisional Applications (3)
Number Date Country
60459543 Mar 2003 US
60476600 Jun 2003 US
60514769 Oct 2003 US