The present invention relates to methods and systems for performing angle-resolved Fourier-domain optical coherence tomography, and more particularly to measuring spatially-resolved angular backscattering distributions from transparent and turbid samples using Fourier-domain optical coherence tomography techniques.
Optical coherence tomography (“OCT”) enables cross-sectional images of biological samples to be obtained with resolution on a scale of several microns to tens of microns, thus allowing for detailed imaging of a tissue microstructure. It has been demonstrated that Fourier-domain OCT (“FD-OCT”) can provide a significantly improved sensitivity over the time-domain OCT, which enables high-speed imaging. For example, FD-OCT has been implemented in two configurations, e.g., spectral-domain OCT (“SD-OCT”) and optical frequency domain imaging (“OFDI”), as described in at least one of International Patent Application PCT/US2004/029148, filed Sep. 8, 2004, U.S. patent application Ser. No. 11/266,779, filed Nov. 2, 2005, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9, 2004. FD-OCT has been shown to have significant potential as a tool for identifying morphological changes in many clinical contexts, including cardiovascular, gastrointestinal, and retinal imaging.
One limitation of conventional OCT systems and methods is that the backscattered light from only one angular range centered at 180 degrees is collected. The same is the case for optical coherence microscopy (“OCM”) systems, in which the array detection can be used to generate en-face two-dimensional images without beam scanning. An example of one such OCM system is shown in
A method and system for acquiring backscattered light at different incident angles in the context of OCT enabling angular compounding employs path length encoding. The example of such system is shown in
Another method and system translates a right angle prism, directing light from the sample arm to different positions on the focusing lens. An example of such system is shown in
In the field of light-scattering spectroscopy, it is known that the angular distributions of backscattered light generally contain information regarding the size distributions of the scattering particles within the tissue. Given the optical resolution limitations of OCT, the ability to derive robust contrast between tissues with subtle differences in reflectance properties may (in certain circumstances) utilize the measurements of the angular distributions of the backscattered light. Depth-resolved angular backscattering measurements using the low-coherence interferometry have been designed for the light-scattering measurements with high angular resolution, as shown in the arrangements of
For example, light from a low-coherence source is divided into two arms of a modified Michelson interferometer, one beam being incident on the sample (or a sample arm) and another being incident on a mirror (or a reference arm). A lens placed in the reference arm can be translated in a direction parallel to the mirror face in order to provide the selectivity for different backscattering angles in the former arm. Measurements of interfered light are generally made in either the time domain (using the arrangement shown in
Accordingly, there is a need to overcome the deficiencies described herein above. Indeed, simultaneously measuring the light that is backscattered from multiple angles in the imaging context of the optical coherence tomography may allow for high levels of speckle reduction and additional forms of image contrast.
Accordingly, there is a need to overcome the deficiencies described herein above.
To address and/or overcome the above-described problems and/or deficiencies, exemplary embodiments of systems, apparatus and methods according to the present invention are provided for measuring spatially-resolved angular backscattering distributions from transparent and turbid samples using Fourier-domain optical coherence tomography principles. In addition, according to further exemplary embodiments of the present invention, systems and methods for utilizing the backscattering distributions are provided for performing speckle reduction and for generating image contrast.
Thus, in accordance with one exemplary embodiment of the present invention, apparatus and method are provided. In particular, at least one first electro-magnetic radiation can be received and at least one second electro-magnetic radiation within a solid angle may be forwarded to a sample. The second electro-magnetic radiation may be associated with the first electro-magnetic radiation. A plurality of third electro-magnetic radiations can be received from the sample which is associated with the second electro-magnetic radiation, and at least one portion of the third electro-magnetic radiation is provided outside a periphery of the solid angle. Signals associated with each of the third electro-magnetic radiations can be simultaneously detected, with the signals being associated with information for the sample at a plurality of depths thereof. The depths can be determined using at least one of the third electro-magnetic radiations without a need to utilize another one of the third electro-magnetic radiations.
In addition, an interference can be detected (e.g., using at least one third arrangement) between the two of the third radiations and at least one fourth radiation associated with the first radiation, and information associated with the sample can be obtained as a function of the depths within the sample based on the interference. Data associated with at least one of birefringence properties, spectroscopic properties, motion, angular back-scattering properties or elastic properties of at least one portion of the sample can be provided as a function of the signals (e.g., using at least one third arrangement). At least one image of at least one portion of the sample can be generated (e.g., using at least one third arrangement) as a function of the signals. The data associated with at least one of birefringence properties, spectroscopic properties, motion, angular back-scattering properties or elastic properties of at least one portion of the sample can also be provided as a function of the signals. The data can be contrast data associated with the image (e.g., using at least one third arrangement). Data associated with scattering characteristics of at least one portion of the sample can also be provided as a function of a combination of the signals. Further, the depths may be determined using a single one of the third electro-magnetic radiations.
According to another exemplary embodiment of the present invention, apparatus and method can provided which facilitate the production of data associated with at least one sample. For example, first information associated with signals for a plurality of electro-magnetic radiations provided from the at least one sample can be received. At least first one of the electro-magnetic radiations may be provided along a first axis, and at least second one of the electro-magnetic radiations can be provided along second axis which is different from the first axis. Data for each of the signals within at least one portion of the first information may include data for a plurality of depths within the sample. Second information associated with contrast data of at least one portion of an image for the at least one sample can be produced as a function of the first information.
In yet another exemplary embodiment of the present invention, further apparatus and method can provided. For example, at least one first electro-magnetic radiation can be received, and at least one second electro-magnetic radiation within a solid angle can be forwarded to a sample. The second electro-magnetic radiation may be associated with the first electro-magnetic radiation. At least two of a plurality of third electro-magnetic radiations may be simultaneously received from the sample which is associated with the second electro-magnetic radiation, and at least one portion of the third electro-magnetic radiations may be provided outside a periphery of the solid angle. An interference between the at least two of the third radiations and at least one fourth radiation associated with the first radiation may be detected. Information associated with the sample can be obtained as a function of at least one depth within the sample based on the interference.
These and other objects, 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.
Further objects, features and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the present invention, in which:
a) and 5(b) are block diagrams of conventional apparatus for performing angle-resolved low-coherence interferometry;
a) and 6(b) are block diagrams of further conventional apparatus for performing the angle-resolved low-coherence interferometry;
a) is a two-dimensional image of a tissue phantom obtained with the exemplary embodiments of the angle-resolved FD-OCT system according to the present invention for averages across one exemplary angular sample;
b) is another two-dimensional image of the tissue phantom obtained with the exemplary embodiments of the angle-resolved FD-OCT system according to the present invention for averages across 400 angular samples;
a) is a graph of an angular distribution obtained from one resolution element within a tissue phantom in accordance with an exemplary embodiment of the present invention;
b) is a graph of an angular distribution obtained from one resolution element using corresponding normalized cross-correlation function in accordance with an exemplary embodiment of the present invention;
Throughout the figures, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the subject invention will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments. It is intended that changes and modifications can be made to the described embodiments without departing from the true scope and spirit of the subject invention as defined by the appended claims.
Exemplary Principle of Angle-Resolved FD-OCT
Angle-resolved FD-OCT is described herein below in a context of Fourier-Domain OCT. For example, in FD-OCT, the interference between reference light and the light backscattered from the imaging sample can be measured in the frequency domain in order to obtain the depth-resolved reflectance of a turbid, semi-turbid, or transparent medium. Electro-magnetic radiation (e.g., light, laser beam, etc.) of the input light source can be split into a reference beam and a sample beam. The sample beam light may be directed to the sample to be imaged, and backscattered light from the sample may be interfered with reference beam light. In the case of angle-resolved FD-OCT, the reference beam can be spatially expanded such that it can be made larger in a cross-sectional area than the cross-sectional area of the sample beam in order to allow for the interference with a range of backscattering angles beyond those subtended by the incident sample beam. The interference between the reference beam and the backscattered light can be measured using, e.g., a detector array, which may consist of (i) detectors integrated onto a single integrated circuit element, and/or (ii) individual detectors provided together in space. The angular dependence of the detected backscattered light with respect to the incident beam may be encoded in the spatial domain, as the distribution of light intensities along at least one dimension of the detector array. The wavelength dependence of the interfered light may be measured, and Fourier analysis axial reflectivity profiles corresponding to different ranges of backscattering angles can be obtained.
For example, the interference signal Si detected by an ith pixel of the detector array as a function of the frequency of laser light vn can be given by the following proportionality expression:
Si(vn)∝P(vn)√{square root over (γr,i(vn)γs,i(vn))}{square root over (γr,i(vn)γs,i(vn))}∫0∞√{square root over (R(z))}cos(4πvnz/c+φ(z))dz (1)
where P(vn) is the total power of the source. R(z) and φ(z) are the amplitude and phase terms of the reflectance profile, respectively. An axial distance z may be expressed as a relative distance, with z=0 corresponding to zero optical path difference between the sample and reference arms. The amount of the sample arm and reference arm electro-magnetic radiation (e.g., light) that reaches pixel i, expressed as fractions of P(vn) can be denoted γs,i and γr,i, respectively. The reflectivity profile R(z) can be obtained as the Discrete Fourier Transform of the sampled interference signal along the dimension i:
√{square root over (R(z))}∝DFT(Si) (2)
Exemplary Principle of Speckle Reduction Using Angle-Resolved FD-OCT
Speckle results from distortions of the backscattered wavefront, which are likely caused by low-angle multiple forward scattering and diffuse multiple backscattering from closely separated refractive index heterogeneities. Angular compounding techniques are generally obtained from an observation that as a result of this interference, fields originating from different backscattering angles are de-correlated. By averaging the signals from different scattering angles incoherently, e.g., averaging of the magnitude of the reconstructed reflectance profiles, a reflectance signal with reduced speckle can be obtained.
The speckle signal-to-noise ratio (“SNR”) can be a measure of the speckle reduction, as the ratio of the mean to the square-root of the variance of pixel intensities within a medium with homogenous scattering properties:
where the angular brackets denote an average over a collection of pixels indexed by k. The speckle SNR can be a normalized measure of the variance of the signal obtained from a homogenous sample. As such, the speckle SNR may differ from the system sensitivity, which can be defined without the presence of speckle as the minimum detectable reflectance. For the exemplary angular compounding method, the SNR may increase proportionally to the square-root of the number of uncorrelated, incoherent averages, N:
SNR(N)=SNR(1)√{square root over (N)}. (4)
An extent to which the SNR can be increased by angular compounding may therefore be dependent on the level of angular decorrelation. In general, higher levels of decorrelation for OCT sample volumes containing large numbers of scatterers can be obtained, as well as those at large optical depths. In comparison, sharp interfaces and scatterers with dimensions that are similar to those of the sample volumes are likely to indicate a small amount of contrast enhancement from angular compounding.
Principle of Extraction of Parameters from Angular Backscattering Distributions for Image Contrast
The angular backscattering patterns of light, which may be measured by the angle-resolved FD-OCT methods and systems, can contain information about the scatterer size and the density of the imaging sample. This information may be relevant in, e.g., a clinical imaging context in order to distinguish between different regions of tissue that have very similar scattering properties that may be used in optical methods that measure the reflectance of light that is backscattered within a single angular range. Image contrast measures can be generated from angular backscattering distributions at each pixel, and such measures can be spatially smoothed, and/or image contrast measures can be generated from spatially smoothed angular backscattering distributions.
Angle-Resolved Fourier-Domain OCT
The FD-OCT techniques of SD-OCT and OFDI systems and method can measure a discrete spectral interference, and may differ in the implementation of this measurement. The OFDI systems and methods can use a wavelength-swept source to record the interference as a function of time, whereas the SD-OCT systems and methods may generally use a spectrometer to image interference spectra onto a detector array or a portion of an array.
Polarization controllers 715, 720 provided before the collimators 725, 730, respectively, can be positioned to maximize the fringe modulation across the frequency range of the wavelength-swept source 705. The imaging optics 770 and 775 consists of a galvanometer mirror 770 with its axis parallel to the plane of the interferometer 707 and perpendicular to the beam which is incident upon it from the beam splitter 750, and a focusing lens 775 that is placed one focal length from the sample 780. The incident beam contacts the horizontal and vertical centers of the galvanometer mirror 770. The light back-reflected from the sample 780 can pass back via the mirror 770 and the focusing lens 775, and may subsequently interfere with the reference beam at the beam splitter 750. The interfered light may be incident on a cylindrical lens 760 which focuses the light onto the line-scan camera 765. The light from a He—Ne laser 700 can be injected into the fiber coupler 710, and may act as a guide beam during the imaging procedure.
The signals from the line-scan camera 765 can be directed toward analog-to-digital (A-D) input ports of a data acquisition (“DAQ”) board 785. For example, in a time period corresponding to one a-line, the DAQ board 785 can obtain m data points from n exposures, where m may be the number of detectors in the line scan camera 765, and n can be the number of frequencies sampled per a-line. The a-line acquisition rate can be determined as the quotient of the line scan camera readout rate and n. The readout from the DAQ board 785 may be synchronized to the frequency-swept laser source 705 using, e.g., TTL trigger signals by the line-scan camera 765 at the beginning of each readout phase.
As shown in the diagram of
2D Detection for Resolution of Azimuthal and Polar Angles
According to a second exemplary embodiment of the present invention, the detection of the interfered light can be performed using a two dimensional array of detectors, with both dimensions corresponding to the angular distribution of backscattered light. The light incident on the sample may be provided by a wavelength-tunable, narrow line-width source. The light backscattered from the imaging sample is interfered with a reference beam that has been expanded along two spatial dimensions. Each detector array element can correspond to a unique range of polar and azimuthal angles of the backscattered light. By sweeping the laser across its tuning range, while acquiring readouts of the detector array, a vector for each discrete azimuth-polar angular pair can be obtained. Fourier-domain optical coherence tomographic reconstruction techniques may be applied the vectors, which can generate depth-resolved reflectance profiles. By scanning the beam across the sample or moving the sample relative to the beam while acquiring readouts of the array, angle-resolved reflectance profiles for different locations on the tissue may be obtained. These profiles can be combined to form two- or three-dimensional cross-sectional reflectance images.
2D Detection for Simultaneous Resolution of Angle and Wavelenth
According to a third exemplary embodiment of the present invention, a detection of the interfered light can be performed using, e.g., a two dimensional array of detectors, with one dimension corresponding to wavelength, and the other to the angle of the backscattered light, as shown in the operational and block diagram of
Fiber-Bundle Optical Probe
A fourth exemplary embodiment suitable for applications using small probe geometries in accordance with the present invention can be used with a fiber bundle, a shown in the operational and block diagram of
Polarization Sensitive Angle-Resolved FD-OCT
Polarimetric measurements in the context of optical coherence tomography may be useful for spatially resolving birefringence in biological tissue. According to a fifth exemplary embodiment according to the present invention, polarimetric measurements can be performed by one or more of the following:
Using the exemplary techniques (a), (b) and/or (c), the birefringence maps of the sample can be obtained by comparing a-lines received at different times, such that the polarization states from which they originated are likely different. Using the exemplary techniques (d), (e) and/or (f), the birefringence maps of the sample can be obtained by comparing a-lines obtained from different backscattering angular ranges such that the polarization states from which they originated are likely different.
Particle Sizing
The angular frequency content obtained from the angle-resolved FD-OCT system and/or method can be analyzed using a computational framework of Mie scattering, provided that the deviations of the beam from planar waves can be accounted for in the analysis. In particular, as the angular scattering distributions which can originate from spherical dielectric scatterers may be determined using the Mie theory, the inverse problem of determining the size distributions of the scatterers from the angular scattering distributions can be performed. The Mie scattering analyses of angular backscattering distributions can enable a measurement of scatterer distributions within epithelial tissues, which may be correlated with dysplastic transitions that precede cancerous lesions.
Angular Decorrelation
Another method of processing angular backscattering distributions acquired from angle-resolved FD-OCT involves analysis of their angular frequency content. Image contrast measures include the angular frequency bin with maximum power and the width of the peak with the highest power. Analysis of the power-spectral density of the angular backscattering distributions is equivalent to analysis of the auto-correlation function by the Wiener-Kinchine theorem. The normalized auto-correlation function C can be provided by:
where j and i can be angular indexes. For example, the width of the central lobe of the autocorrelation function, measured relative to the first minimum, can indicate the extent of the correlation between successive angular samples. This exemplary width can be determined for each pixel of a cross-sectional image obtained using the angle-resolved FD-OCT system and method, thus providing an image with the contrast for the de-correlation level of the angular backscattering distributions.
The exemplary embodiment of the system and method according to the present invention which can be used for reducing speckle was verified by the following experiment. Two-layer tissue phantoms were constructed from aqueous agar gel (0.5% agar by weight) and polymer microspheres of diameter 0.3 mm (Duke Scientific). The phantoms were contained in silicone isolators (Sigma). An initial scattering layer with an approximate depth of 2 mm was formed. A second scattering layer, designed to have a lower scattering coefficient than the first, was formed on top of the first and had an approximate depth of 450 mm. By analyzing the exponential signal attenuation with respect to depth, the total scattering coefficients were estimated to be 24 cm-1 and 12 cm-1 for the first and second layers, respectively.
The two-dimensional image generated from a single angular sample shows significant speckle, as shown in
The effects of angular compounding are striking when applied to esophagus tissue, as shown in the images of
The foregoing merely illustrates the principles of the invention. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present invention can be used with any OCT system, OFDI system, spectral domain OCT (SD-OCT) system or other imaging systems, and for example with those described in International Patent Application PCT/US2004/029148, filed Sep. 8, 2004, U.S. patent application Ser. No. 11/266,779, filed Nov. 2, 2005, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9, 2004, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements and methods which, although not explicitly shown or described herein, embody the principles of the invention and are thus within the spirit and scope of the present invention. In addition, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it is explicitly being incorporated herein in its entirety. All publications referenced herein above are incorporated herein by reference in their entireties.
This application is based upon and claims the benefit of priority from U.S. patent application Ser. No. 60/776,544, filed Feb. 24, 2006, the entire disclosure of which is incorporated herein by reference.
The invention was made with the U.S. Government support under Contract No. R01 CA103769 awarded by the National Institutes of Health. Thus, the U.S. Government has certain rights in the invention.
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