Methods and systems for performing angle-resolved fourier-domain optical coherence tomography

The present invention relates to a method and system for performing an angle-resolved Fourier domain optical coherence tomography, and more specifically, a transparent sample and a transparent sample performed using the method of Fourier domain optical coherence tomography. It relates to the measurement of spatially resolved backscatter distribution by angle from opaque samples.

(Cross-reference to related applications) This application is based on US Patent Application No. 60 / 776,544, filed February 24, 2006. Furthermore, this application claims the priority benefit of this U.S. patent application, and the disclosure of this U.S. patent application is incorporated herein by reference in its entirety. Has been done. (Federal-funded R & D description) The present invention has been realized with the support of the United States Government under Contract No. R01 CA103769 granted by the National Institutes of Health. Therefore, the US Government has certain rights in the present invention.

According to Optical Coherence Tomography (OCT), it is possible to obtain cross-sectional images of biological samples at resolutions on the order of microns (μm) to tens of microns, and therefore tissue. It is possible to image the microstructure in detail. It has been demonstrated that Fourier-Domain OCT (FD-OCT) can provide significantly improved sensitivity over time-domain OCT, which enables high-speed imaging. More specifically, FD-OCT is, for example, International Patent Application No. PCT / US2004 / 029148 filed on September 8, 2004, and US Patent Application No. 1 filed on November 2, 2005. Spectral-Domain OCT (SD), as described in at least one of US Patent Application Nos. 10 / 501,276 filed on 11 / 266,779 and 9 July 2004. -OCT and Optical Frequency Domain Imaging: OFDI) is implemented in two configurations. FD-OCT has shown great potential as a tool for identifying morphological changes in many clinical environments, including cardiovascular, gastrointestinal, and retinal imaging.

One limitation of conventional OCT systems and methods is that only backscattered light from one angular range centered at 180 degrees is collected. Such limitations also apply to Optical Coherence Microscopy (OCM) systems. In this case, by using array detection, it is possible to generate a front two-dimensional image without scanning the beam. E. View Repair (E. OCM as described above in "Full-Field Optical Coherence Microscopy" (Optics Letters, 23 (4): 244-246, 1998) by Beaurepaire et al. An example of the system is shown in Figure 1. Acquiring backscattered light from different angles using an Angular Compounding technique that can reduce Speckle. Speckles generally appear as checkered patterns within the scattered regions of the image, which makes it even more difficult to discern subtle differences in tissue reflectance. ..

Methods and systems for acquiring backscattered light at different angles of incidence in an OCT environment that achieves angle synthesis utilize path length encoding. N. Iftimia (N. Iftimia et al., "Speckle Reduction in Optical Coherence Tomography by'Path Length Encoded' Angular Compounding" (Journal of Biomedical) An example of such a system described in Optics), 8 (2): 260-263, 2003) is shown in Figure 2. For example, by arranging the optical glass in the path of the imaging beam, the incident field can be divided into a plurality of beamlets. Due to this optical glass, a part of the incident beam (beamlet 2) causes a delay of a path length larger than that of the beamlet 1. Furthermore, the beamlet 2 irradiates the sample at a different angle than the beamlet 1. As a result, multiple OCT images of the sample (each acquired at different angles) will appear simultaneously on the OCT display. Although the above methods and systems are suitable for high-speed imaging, they generally do not scale properly for many angles and may require a trade-off between spatial resolution and the number of acquisition angles. is there.

Another method and system directs the light from the sample arm to different positions on the Focusing Lens by translating the right angle prism. M. Bashikanski (M. Bashkansky et al., "Statistics and Reduction of Speckle in Optical Coherence Tomography" (Optics) An example of the above system described in Letters), 25 (8): 545-547, 2000) is shown in Figure 3. In the above methods and systems, backscattered light is generally collected in a narrow angle range centered at 180 degrees, but the angle of incidence of the incident beam with respect to the normal of the sample changes with the position of the prism. Such methods and systems are likely not to provide (or, in some cases, tolerate) measurements of angled backscatter distribution. The speed at which the image can be acquired will be limited by the speed at which the translational motion of the prism is possible in the vibration scheme. In yet another method and system, it is possible to simultaneously detect OCT signals by four detectors, which realizes angle synthesis for speckle reduction. JM Schmidt (JM) Schmitt) "Array Detection for Speckle Reduction in Optical Coherence Microscopy" (Physics in Medicine and Biology, 42 (7)) An example of the above system described in (1427 to 1439, 1997) is shown in FIG. Specifically, the reference beam in this system is generally no larger than the incident beam. Therefore, the above system would not be useful for measuring backscatter distribution by angle. Furthermore, each detector element receives backscattered light at different angles, but the solid angle whose range is determined by the light collected by a predetermined detector element is defined by the incident beam. It is completely contained in. Detection in the above system is performed in the time domain.

In the field of light scattering spectroscopy, it is known that the angular distribution of backscattered light generally contains information about the size distribution of scattered particles in the tissue. When the optical resolution of OCT is limited, the ability to derive stable contrast between tissues with slight differences in reflectance characteristics is (in certain situations) measurement of the angular distribution of backscattered light. It is possible to use. "Measurement of Angular Distributions by Use of Low-Coherence Interferometry for Light-Scattering Spectroscopy" by A. Wax et al. (Optical Letter (Optical Letter) Optics Letters), 26 (6): pp. 322-324, 2001), as well as the composition of Figures 5 (a) and 5 (b), as well as JW. Pyhtila et al., "Determining Nuclear Morphology Using an Improved Angle-Resolved Low Coherence Interferometry System" (Optics Express) ), 15 (25): pp. 3474-3484, 2003), as shown in the configurations of FIGS. 6 (a) and 6 (b), for light scattering measurements with high angular resolution. To this end, Depth-Resolved Angular Backscattering Measurements have been designed using low coherence interferometry.

For example, the light from a low coherence source is split into two arms of an improved Michelson interferometer, one beam incident on the sample (or sample arm) and the other beam mirrored (or). It is incident on the reference arm). In order to provide the selectivity of various backscatter angles in the former sample arm, it is possible to translate the lens placed in the reference arm parallel to the mirror surface. Interferometric light measurements are generally taken in the time domain (using the configurations shown in FIGS. 5 (a) and 5 (b)) or (shown in FIGS. 6 (a) and 6 (b)). Performed in the frequency domain (using the configuration being done). With these techniques, it is generally not possible to measure backscatter distributions by angle at the same time, and the measurement speed will also be limited by the speed at which the lens can be accurately translated. .. Although optimized for angle, point sampling, and in-situ measurements, the currently implemented angle-resolved LCIs described above are probably not suitable for in vivo clinical imaging.

<p> Therefore, there is a need to overcome the above-mentioned drawbacks. In fact, by simultaneously measuring backscattered light from a plurality of angles in the imaging environment of the optical interference tomography method, it is possible to realize a high degree of speckle reduction and an additional form of image contrast.</p><p> Therefore, there is a need to overcome the above-mentioned drawbacks.</p>

<p> From transparent and turbid samples using the principles of Fourier domain optical coherence tomography to address the aforementioned problems and / or drawbacks and / or to overcome the aforementioned problems and / or drawbacks. Representative examples of systems, devices, and methods according to the present invention, such as measuring the spatially resolved backscatter distribution by angle, are provided. Furthermore, according to a further representative embodiment of the present invention, there are also systems and methods that utilize backscatter distribution to achieve speckle reduction and generate image contrast.</p><p> Therefore, according to a typical embodiment of the present invention, devices and methods are provided. Specifically, it is possible to receive at least one first electromagnetic wave, and it is possible to transfer at least one second electromagnetic wave within the solid angle to the sample. The second electromagnetic wave can be associated with the first electromagnetic wave. It is possible to receive multiple third electromagnetic waves from a sample associated with the second electromagnetic wave, and at least one portion of the third electromagnetic wave is provided outside the outer edge of the solid angle. It is possible to simultaneously detect the signals associated with each of the third electromagnetic waves, and these signals are associated with the sample information at multiple depths within the sample. By using at least one of the third electromagnetic waves, it is possible to determine multiple depths within a sample without the need to utilize another of the third electromagnetic waves.</p><p> Furthermore, it is possible to detect interference between two of the third electromagnetic waves and at least one fourth electromagnetic wave associated with the first electromagnetic wave, interfering with the information associated with the sample. Can be obtained as a function of depth in the sample based on. It is possible to provide data associated with at least one of the birefringence, spectroscopic, motion, angled backscattering, or elastic properties of at least one portion of the sample as a function of the signal. It is possible to generate at least one image of at least one part of the sample as a function of the signal. It is also possible to provide data associated with at least one of the birefringence, spectroscopic, motion, angle backscattering, or elastic properties of at least one portion of the sample as a function of the signal. The data may be contrast data associated with the image. It is also possible to provide the data associated with the scattering properties of at least one portion of the sample as a function of the signal combination. Furthermore, it is possible to determine the signal depth using a single third electromagnetic wave.</p><p> According to another representative embodiment of the present invention, it is possible to provide an apparatus and a method for smoothly performing the generation of data associated with at least one sample. For example, it is possible to receive first information associated with multiple electromagnetic signal signals provided by at least one sample. It is possible to provide at least the first of the electromagnetic waves along the first axis, and provide at least the second of the electromagnetic waves along a second axis that is different from the first axis. Is possible. Each data of the signal in at least one portion of the first information can include data of multiple depths in the sample. It is possible to generate a second piece of information associated with the contrast data of at least one portion of the image of at least one sample as a function of the first piece of information.</p><p> In yet another representative embodiment of the present invention, it is possible to provide additional devices and methods. For example, it is possible to receive at least one first electromagnetic wave and transfer at least one second electromagnetic wave within the solid angle to the sample. It is possible to associate the second electromagnetic wave with the first electromagnetic wave. It is possible to simultaneously receive at least two of the third electromagnetic waves from the sample associated with the second electromagnetic wave, providing at least one portion of the third electromagnetic wave outside the outer edge of the solid angle. It is possible to do. It is possible to detect interference between at least two of the third electromagnetic waves and at least one fourth electromagnetic wave associated with the first electromagnetic wave. The information associated with the sample can be obtained as a function of at least one depth within the sample based on interference.</p><p> The purpose and other purposes, features, and advantages of the invention as described above will be apparent by reference to the following detailed description of the embodiments of the invention in the context of the appended claims. Will be.</p>

Further objectives, features, and advantages of the present invention will become apparent with reference to the following detailed description presented in the context of the accompanying drawings showing exemplary embodiments of the invention. Let's go.

Throughout these drawings, the same reference numerals and letters are used to represent similar features, elements, components, or parts of the illustrated embodiments, unless otherwise noted. Further, in the following, the present invention will be described in detail with reference to the accompanying drawings, but this description is presented in the context of exemplary embodiments. It should be construed that it is possible to make changes and modifications to the illustrated examples without departing from the true scope and spirit of the invention as set forth in the appended claims. ..

(Typical principle of angle-resolved FD-OCT) Hereinafter, the angle-resolved FD-OCT will be described in the environment of the Fourier domain OCT. For example, in FD-OCT, the frequency of interference between the reference light and the light backscattered from the imaging sample is frequencyed in order to obtain the depth-resolved reflectance of the opaque medium, semi-turbid medium, or transparent medium. It is possible to measure in the domain. It is possible to split the electromagnetic waves of the input light source (eg, light, laser beam, etc.) into a reference beam and a sample beam. It is possible to guide the sample beam light to the sample to be imaged, and the backscattered light from the sample can interfere with the reference beam light. In the case of the angle-resolved FD-OCT, the cross-sectional area can be made larger than the cross-sectional area of the sample beam in order to realize interference with the backscattering angular range beyond what is defined by the incident sample beam. As such, it is possible to extend the reference beam spatially. The interference between the reference beam and the backscattered light can be measured, for example, using a detector array. This detector array can consist of (i) detectors integrated on a single integrated circuit element and / or (ii) individual detectors provided together in space. .. The angular dependence of detected backscattered light on an incident beam can be encoded in the spatial domain as a distribution of light intensity along at least one dimension of the detector array. It is possible to measure the wavelength dependence of the interfering light, and it is possible to obtain a Fourier analysis axial reflectance profile corresponding to a range of different backscatter angles.

For example, the frequency of laser light ν_nInterference signal S detected by the i-th pixel of the detector array as a function of_iCan be given by the proportional equation of the following equation (1).

<maths num="1"><img file="JP2009527770A_D0001.tif" /></maths>

Here, P (ν_n) Is the total power of the source. R (z) and φ (z) are the amplitude and phase terms of the reflectance profile, respectively. The axial distance z can be expressed as a relative distance, and z = 0 corresponds to a zero optical path difference between the sample arm and the reference arm. P (ν_n), The amount of electromagnetic waves (eg, light, etc.) of the sample arm and reference arm reaching pixel i, respectively, is γ._{s, i}And γ_{r, i}It is possible to write as. The reflectance profile R (z) can be obtained as a discrete Fourier transform of the interference signal sampled along the dimension i as in Eq. (2) below.

<maths num="2"><img file="JP2009527770A_D0002.tif" /></maths>

(Typical principle of speckle reduction using angle-resolved FD-OCT) Speckles result from backscattered wave front distortions, which are probably caused by a variety of low-angle forward scatterings and due to multiple indices of refraction with values close to each other. Diffuse the various backscatters that occur. The angle synthesis method is generally obtained from the observation that a plurality of fields generated as a result of the above-mentioned interference and derived from different backscatter angles have no correlation. Reflectance with reduced speckle by averaging signals from different scattering angles in an incoherent state, for example by averaging the magnitude of the reconstructed reflectance profile. You can get a signal.

The signal-to-noise ratio (SNR) of the speckle is the average of the pixel intensities with respect to the square root of the dispersion of the pixel intensities in the medium having the scattering characteristics of homogeneity, as shown in the following equation (3). As a value of the ratio of values, it can be used as a measure of speckle reduction.

<maths num="3"><img file="JP2009527770A_D0003.tif" /></maths>

Here, the angle brackets (&lt;&gt;) represent the average value of the collection results of the pixels indexed by k. The speckle SNR can be a normalized measure of the variance of the signal obtained from a sample of homogeneity. Therefore, the speckle SNR is different from the system sensitivity and can be defined without the presence of speckle as the minimum detectable reflectance. In a typical angle synthesis method, the SNR can be increased in proportion to the square root of the number N of the uncorrelated incoherent mean, as in Eq. (4) below.

<maths num="4"><img file="JP2009527770A_D0004.tif" /></maths>

Therefore, the extent to which SNR can be increased by angle synthesis can depend on the level of Angular Decorrelation. In general, it is possible to obtain relatively high levels of decorrelation in the volume of OCT samples containing a large number of scatterers, as well as those located at large optical depths. In contrast, sharp interfaces and scatterers with dimensions similar to those of the sample volume are likely to show a slight amount of contrast improvement due to angular synthesis.

(Principle of extracting image contrast parameters from backscatter distribution by angle) The angle-resolved backscatter pattern of light that can be measured by angle-resolved FD-OCT methods and systems can include information about the scatterer size and density of the imaging sample. This information discriminates between different regions of tissue that can be used in optical methods to measure the reflectance of backscattered light within a single angular range and that have very similar scattering properties. Therefore, for example, it may be suitable in a clinical imaging environment. Image contrast measures can be generated from the angled backscatter distribution at each pixel, such measures can be spatially smoothed and / or a measure of image contrast. Can be generated from the spatially smoothed backscatter distribution by angle.

(Angle-resolved Fourier domain OCT) The FD-OCT method in the SD-OCT and OFDI systems and the SD-OCT and OFDI methods can measure discrete spectral interference and may differ in performing this measurement. OFDI systems and methods can record interference as a function of time by using a wavelength sweeping source, and SD-OCT systems and methods generally interfere by using a spectrometer. It is possible to image the spectrum on a detector array or part of a detector array.

FIG. 7 shows a schematic view of a typical example of the angle-resolved FD-OCT imaging system according to the present invention. This typical system is an image capture camera (line scanning camera) with a wavelength sweep source (wavelength sweep laser source) 705, an interferometer 707, and a corresponding electronic circuit (computer and data acquisition (DAQ) card) 785. It is possible to have multiple modules such as) 765. For example, the laser output can be directed to an optical coupler 710, which can split the light into two arms of the interferometer 707. The collimated light supplied by the reference arm collimator 725 can enter a cylindrical lens telescope with elements 735, 740 and 745. This cylindrical lens telescope is capable of extending the beam to the dimensions of the line scanning camera 765. By arranging the free space coupler 712 having a variable distance in front of the collimator 725 in the reference arm, it is possible to smoothly adjust the length of the reference arm. The collimated light from the sample arm collimator 730 can be directed to the sample through a linear polarizer 755 and a beam splitter 750, in which case the above light is an imaging optic that focuses the light on the sample 780. It can be incident on 770 and 775.

By arranging the polarization controllers 715 and 720 provided in front of the collimators 725 and 730, respectively, Fringe modulation over the frequency range of the wavelength sweep source 705. Modulation) can be maximized. The imaging optics 770, 775 are arranged at one focal length from the sample 780 and the galvanometer mirror 770 whose axes are parallel to the plane of the interferometer 707 and perpendicular to the beam incident from the beam splitter 750. It is composed of a focusing lens 775. The incident beam is in contact with the horizontal and vertical centers of the galvanometer mirror 770. The light reflected and returned from the sample 780 can be returned through the mirror 770 and the focusing lens 775 and then can interfere with the reference beam in the beam splitter 750. This interference light can enter the cylindrical lens 760 that focuses on the line scanning camera 765. The light from the helium-neon (He-Ne) laser 700 can be injected into the fiber coupler (optical coupler) 710, and this light can function as a guide beam in the imaging process procedure.

The signal from the line scanning camera 765 can be sent to the analog / digital (A / D) input port of the data acquisition (DAQ) board 785. For example, within a period corresponding to one a-line, the DAQ board 785 can acquire m data points from n exposures, where m is a line scanning camera. It may be the number of detectors in 765, where n may be the number of frequencies sampled per aline. The aline acquisition speed can be determined as a quotient of the reading speed of the line scanning camera and n. Reads from the DAQ board 785 can be synchronized, for example, to a frequency sweep laser source (wavelength sweep laser source) 705 using a TTL trigger signal from the line scanning camera 765 at the beginning of each read period. Is.

As shown in FIG. 8, a typical example of a wavelength sweeping source is a semiconductor optical as a gain element. It can be constructed as a ring cavity laser with an Amplifier: SOA) 845 and a galvanometer mirror filter 800, which is a galvanometer mirror 802, a telescope 805, 810, a grating 815, and a fiber collimator. It is possible to have an 820. By providing two polarization controllers 825, 840, it is possible to optimize the polarization of the laser, which causes the output coupler 835 to provide the laser output. The output coupler 835 is capable of splitting light approximately equally between the output port 836 and the laser port 837, in principle. The optical circulator 830 can guide the light from the laser port 837 to the galvanometer mirror filter 800 via the polarization controller 840, and the light returned from the galvanometer mirror filter 800 is transferred to the polarization controller 825. It is possible to lead to SOA845 via. The wavelength reflected from the galvanometer mirror filter 800 generally changes as the galvanometer mirror 802 rotates. By using the optical isolator 850, it is possible to separate the laser from the rest of the typical system.

(Two-dimensional (2D) detection for azimuth and polar decomposition) According to a second representative embodiment of the present invention, interference light detection can be performed using a two-dimensional array of detectors in which both dimensions correspond to the angular distribution of backscattered light. It is possible. The light incident on the sample can be supplied by a narrow line width source with adjustable wavelength. The light backscattered from the imaging sample interferes with the reference beam extended along two spatial dimensions. Each detector array element can accommodate a unique range of backscattered polar and azimuth angles. By sweeping the laser over its adjusted range while taking the readings of the detector array, it is possible to get the paired vectors of each discrete azimuth and polar angle. It is possible to apply the Fourier domain optical coherence tomography reconstruction method to the vector, which makes it possible to generate a depth-resolved reflectance profile. It is possible to obtain angle-resolved reflectance profiles at different locations on the tissue by scanning the beam across the sample or by moving the sample relative to the beam while obtaining array readings. Is. By synthesizing these profiles, it is possible to form a two-dimensional or three-dimensional cross-sectional reflectance image.

(Two-dimensional (2D) detection for simultaneous angle and wavelength resolution) According to a typical third embodiment of the present invention, for example, as shown in the operation diagram and the block diagram of FIG. 9, one dimension corresponds to a wavelength and the other dimension is backscattered. Interference light can be detected by using a two-dimensional array of detectors that correspond to the angle of light. The light incident on the sample can be supplied by a broadband source. The light backscattered from the sample can interfere with the reference beam extended along one spatial dimension, which can correspond to the angle of the backscattered light. The interfering light 900 can enter the diffraction grating 905, thereby separating the light along another dimension corresponding to the wavelength. The separated light 910 can then be incident on the two-dimensional detector array 915. Depth-resolved reflections by applying Fourier domain optical coherence tomography reconstruction to the coherence spectrum along each one-dimensional portion of the detector array reads corresponding to a particular backscatter angle range. It is possible to provide a rate profile. It is possible to obtain angle-resolved reflectance profiles at different points on the tissue by scanning the beam across the sample or by moving the sample relative to the beam while obtaining array readings. Is. By synthesizing these profiles, it is possible to form a two-dimensional or three-dimensional cross-sectional reflectance image.

(Fiber bundle optical probe) A fourth representative embodiment suitable for applications using the small probe shape according to the present invention can be used with a fiber bundle as shown in the operation diagram and the block diagram of FIG. According to this representative embodiment, it is possible to transmit and receive light to and from the imaging sample 1000 by using the optical fiber array 1025. One or more fibers in the array 1025 are called "delivery fibers" and through these fibers it is possible to send and receive light 1010 to and from sample 1000. Each fiber in the array 1025 can accommodate the inherent narrow angular range of angular backscatter. A lens 1020 placed in front of the fibers can function to increase the amount of light collected by each fiber. The lens 1015, which is placed in front of the lens 1020, functions to focus the light on the sample 1000 and to collimate the light backscattered from the sample 1000 before collection by the lens 1020.

(Polarization sensing type angle-resolved FD-OCT) Polarization measurements in the environment of optical coherence tomography will be useful for the spatial decomposition of birefringence in biological tissues. According to a fifth representative embodiment according to the present invention, it is possible to carry out polarization measurement by performing one or more steps in each of the following steps.

a) The step of changing the polarization of light before reception in the interferometer and the step of fixing the polarization state of the reference arm and / or the sample arm. b) The step of changing the polarization of the sample beam only as a function of time c) The step of changing the polarization of only the reference beam as a function of time d) The step of changing the polarization state of one or more parts of the reference beam as a function of space so that at least two characteristic parts of the reference beam with different polarization states can exist. e) Polarize one or more parts of the backscattered light as a function of space prior to interference with the reference beam so that at least two distinctive parts of the sample beam with different polarization states can exist. Stage to change f) The step of changing the polarization state of one or more parts of the interfering light as a function of space so that at least two distinctive parts with different polarization states can exist.

By using the typical methods (a), (b), and / or (c) described above and comparing the received alines at different time points so that the polarization states from which these methods are derived are probably different. , It is possible to obtain a birefringence map of a sample. Using the typical methods (d), (e), and / or (f) described above, compare the alines obtained from different backscatter angle ranges so that the polarization states from which these methods are derived are probably different. By doing so, it is possible to obtain a birefringence map of the sample.

(Particle sizing) Angular frequency content obtained from angle-resolved FD-OCT systems and / or methods using the Mie scattering arithmetic framework where analysis can compensate for beam deviations from plane waves. Can be analyzed. Specifically, since it is possible to determine the angle-based scattering distribution that can occur from a spherical dielectric scatterer using the Mie theory, the size distribution of the scatterer is determined from the angle-based scattering distribution. It is possible to carry out the opposite problem. By Mie scattering analysis of the backscatter distribution by angle, it is possible to realize the measurement of the scatterer distribution in the epithelial tissue, and the scatterer distribution in the epithelial tissue is intermuted with the hypoplastic transition preceding the cancer lesion. It can be related.

(Decorrelation by angle) Another method of processing angle-resolved backscatter distributions obtained from angle-resolved FD-OCTs involves analysis of their angular frequency content. The image contrast measure includes the Angular Frequency Bin with the maximum power and the width of the peak with the maximum power. The analysis of the power-spectral density of the backscatter distribution by angle is equivalent to the analysis of the autocorrelation function by the Wiener-Khinchin theorem. The normalized automatic correlation function C can be provided by Eq. (5):

<maths num="5"><img file="JP2009527770A_D0005.tif" /></maths>

Here, j and i may be an index of angles. For example, the width of the Central Lobe of the automatic correlation function measured in relation to the first minimum value can indicate the degree of correlation between consecutive angular samples. By determining the above typical width for each pixel of the cross-sectional image obtained using the angle-resolved FD-OCT system and method, it has a level of contrast at the level of decorrelation of the angle-resolved backscatter distribution. It is possible to provide an image.

(Example) Representative examples of the systems and methods according to the invention that can be used to reduce speckle were verified by the following experiments. A two-layer tissue phantom with a water-soluble agar gel (0.5% by weight (percent) agar) and a 0.3 mm diameter Polymer Microsphere (obtained from Duke Scientific) Formed. This tissue phantom was housed in a silicone isolator (obtained from Sigma). The first scattering layer (first scattering layer) with a suitable depth of 2 mm was formed. A second scattering layer designed to have a smaller scattering factor than the first scattering layer was formed on top of the first scattering layer. This second scattering layer had a depth of about 450 mm. By analyzing the exponential signal attenuation in relation to depth, the total scattering factor was 24 cm for each of the first and second layers.^-1And 12 cm^-1Was estimated.

The two-dimensional image generated from a single angled sample shows a large speckle, as shown in Figure 11 (a), in which case the boundaries between the two layers are clear. Not in a visible state. In the angle-combined image, the speckle is significantly reduced, and the boundary between the two layers is clearly visible, as shown in FIG. 11 (b). It is not likely that the in-image resolution of FIG. 11 (b) will be significantly lower than the in-image resolution of image 11 (a) by qualitative inspection. A typical graph of the distribution by angle obtained from a point 500 mm below the surface of the phantom and the corresponding automatic correlation function are shown in FIGS. 12 (a) and 12 (b).

The effect of angle synthesis is prominent when applied to esophageal tissue, as shown in the images of FIGS. 13A-13D. These images were obtained from pigs in vitro, and the sample to be imaged was lightly compressed by coverslip to improve the visibility of the layers underlying the epithelium. Specifically, as shown in FIG. 13A, images generated from a single angled sample are state-of-the-art in terms of, for example, the features to be decomposed and the graininess resulting from the speckle. It is qualitatively similar to that obtained by the conventional OFDI system of. In this typical image, the scattering layer within the epithelium is only faintly visible (see arrow). In the case of the composition of the three angles shown in the image of FIG. 13B, the speckle reduction level is such that this layer can be decomposed only in a specific part of the image. In the case of the average of 30 or more angles shown in the images of FIGS. 13C and 13D, the scattering layer is clearly decomposed over the length of the image. Similar improvements in detail achieved by angular synthesis are also observed within the area of submucosal tissue that underlies the lamina propria and epithelium.

The above contents merely exemplify the principle of the present invention. Various changes and modifications to the embodiments to be described will be apparent to those skilled in the art in light of the disclosure of the specification of the present application. In fact, the devices, systems, and methods according to typical embodiments of the present invention, along with any OCT system, OFDI system, spectral domain OCT (SD-OCT) system, or other imaging system, and, for example, International Patent Application No. PCT / US2004 / 029148 filed on September 8, 2004, US Patent Application No. 11 / 266,779 filed on November 2, 2005, and July 9, 2004. It can be used with those described in U.S. Patent Application No. 10 / 501,276 filed in, and the contents of these patent applications are incorporated herein by reference in their entirety. It is included. Therefore, a person skilled in the art, although not explicitly illustrated and described herein, implements the principles of the invention and has numerous systems, devices, and devices that belong to the spirit and scope of the invention. It should be understood that it is possible to come up with a method. Furthermore, in the above, the knowledge of the prior art is explicitly included in the present specification even if it is not explicitly included by quoting in the above description. All the documents referred to above are included in the present specification by reference in the present specification.

<figref num="1">FIG. 6 is a block diagram of a conventional device for performing optical coherence microscopy (OCM).</figref><figref num="2">It is a block diagram of a conventional apparatus for performing a path length encoding type angle synthesis that reduces the speckle of optical coherence tomography (OCT).</figref><figref num="3">It is a block diagram of the conventional OCT apparatus for carrying out the reduction of speckle.</figref><figref num="4">It is a block diagram of the conventional OCT apparatus which performs array detection for speckle reduction.</figref><figref num="5(a)">FIG. 6 is a block diagram of a conventional device for performing an angle-resolved low coherence interferometry.</figref><figref num="5(b)">FIG. 6 is a block diagram of a conventional device for performing an angle-resolved low coherence interferometry.</figref><figref num="6(a)">FIG. 3 is a block diagram of a further conventional device for performing angle-resolved low coherence interferometry.</figref><figref num="6(b)">FIG. 3 is a block diagram of a further conventional device for performing angle-resolved low coherence interferometry.</figref><figref num="7">It is a schematic diagram of a typical example of the angle-resolved FD-OCT system according to the present invention using a single-dimensional detector array, and is a rectangular shape oriented perpendicular to the surface of the interferometer. It is the schematic which has the gray dashed line area.</figref><figref num="8">It is the schematic of the typical example of the wavelength sweep type laser source used in the system shown in FIG. 7.</figref><figref num="9">It is a schematic operation diagram of the interference detection in another typical embodiment of the angle-resolved FD-OCT system according to the present invention that utilizes a two-dimensional detector array for simultaneous detection of wavelength and angle. ..</figref><figref num="10">It is a schematic operation diagram of the imaging optics provided in a further representative embodiment of the angle-resolved FD-OCT system according to the present invention that is compatible with an endoscopic probe.</figref><figref num="11(a)">It is a two-dimensional image of a tissue phantom obtained by a representative example of an angle-resolved FD-OCT system according to the present invention for averaging over one typical angled sample.</figref><figref num="11(b)">Another two-dimensional image of the tissue phantom obtained by a representative example of the angle-resolved FD-OCT system according to the invention for averaging over 400 angled samples.</figref><figref num="12(a)">It is a graph of the distribution by angle obtained from one decomposition element in the tissue phantom according to the typical embodiment of the present invention.</figref><figref num="12(b)">It is a graph of the distribution by angle obtained from one decomposition element using the corresponding normalized cross-correlation function according to a typical embodiment of the present invention.</figref><figref num="13A">An image of typical esophageal tissue obtained from the synthesis of one angled sample, with arrows pointing to a thin scattering layer within the epithelium.</figref><figref num="13B">An image of typical esophageal tissue obtained from the synthesis of three angled samples, with arrows pointing to a thin scattering layer within the epithelium.</figref><figref num="13C">An image of typical esophageal tissue obtained from the synthesis of 30 angular samples, with arrows pointing to a thin scattering layer within the epithelium.</figref><figref num="13D">An image of typical esophageal tissue obtained from the synthesis of 400 angular samples, with arrows pointing to a thin scattering layer within the epithelium.</figref>