# Patent

## Title
Process, system and software arrangement for determining at least one location in a sample using an optical coherence tomography

## Abstract

A system, process and software arrangement are provided to determine at least one position of at least one portion of a sample. In particular, information associated with the portion of the sample is obtained. Such portion may be associated with an interference signal that includes a first electro-magnetic radiation received from the sample and a second electro-magnetic radiation received from a reference. In addition, depth information and/or lateral information of the portion of the sample, may be obtained. At least one weight function can be applied to the depth information and/or the lateral information so as to generate resulting information. Further, a surface position, a lateral position and/or a depth position of the portion of the sample may be ascertained based on the resulting information.

## Background
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation application of U.S. patent application Ser. No. 11/200,228 filed Aug. 8, 2005, now U.S. Pat. No. 8,081,316 issued on Dec. 20, 2011 and claims priority from U.S. Patent Application Ser. No. 60/599,809 filed Aug. 6, 2004, the entire disclosures of which is are incorporated herein by reference. This application also relates to U.S. Publication No. 2002/0198457, the entire disclosure of which is incorporated herein by reference.


FIELD OF THE INVENTION
The present invention relates generally to imaging using optical coherence tomography (“OCT”), and more particularly to processes, systems and software arrangements which are capable of determining at least one location in a sample using OCT technique(s).
BACKGROUND OF THE INVENTION
Optical coherence tomography (“OCT”) is an imaging technique that can measure an interference between a reference beam of light and a detected beam reflected back from a sample. A detailed system description of convention time-domain OCT has been provided in Huang et al. “Optical coherence tomography,” Science 254 (5035), 1178-81 (1991). The spectral-domain variant of optical coherence tomography (“OCT”), called spectral-domain optical coherence tomography (“SD-OCT”), is a technique is a technology that is suitable for ultrahigh-resolution ophthalmic imaging. This technique has been described in Cense, B. et al., “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography”, Optics Express, 2004 and in International Patent Publication No. WO 03/06280 In addition, U.S. patent application Ser. No. 10/272,171 filed on Oct. 16, 2002, Wojtkowski et al., “In Vivo Human Retinal imaging by Fourier Domain Optical Coherence Tomography”, Journal of Biomedical Optics, 2002, 7(3), pp. 457-463, Nassif, N. et al., “In Vivo Human Retinal Imaging by Ultrahigh-Speed Spectral Domain Optical Coherence Tomography,” Optics Letters, 2004, 29(5), pp. 480-482, also relates to this subject matter. In addition, optical frequency domain interferometry (“OFDI”) setup (as described in Yun, S. H. et al., “High-Speed Optical Frequency-Domain Imaging, Optics Express, 2003, 11(22), pp. 2953-2963, International Publication No. WO 03/062802 and U.S. Patent Application Ser. No. 60/514,769 filed on Oct. 27, 2004 further relate to the subject matter of the present invention.
The imaging range (e.g., a depth of the image), in SD-OCT and OFDI are generally fixed by parameters of a spectrometer. The imaging range in conventional time-domain OCT systems can be determined by the magnitude of the sweep in a reference arm length. In such systems, the overall reference arm length generally determines the position of the imaging region of a sample. By increasing the reference arm length or by moving a reference arm sweep to deeper lengths, the imaging region may be made deeper, while reducing the reference arm length can moves the imaging region to a more shallow area of the sample.
These technologies have been successfully applied to imaging biological sample. However, such biological samples may often contain irregular surfaces and structures that can make imaging problematic. For example, a curved topology of a retina generally indicates that retinal surface may appear at one depth for a particular scan, while appearing at a different depth for a scan at a different lateral location. In addition, a motion of the sample may further compounds this problem. One of the advantages of the above-referenced imaging techniques and systems employing such techniques is that they do not contact the sample and that they are non-invasive. However, this means that it is often impossible to eliminate or significantly reduce the motion of the sample relative to the imaging device. Referring to the example of retinal imaging, any slight motion on the part of the subject whose retina is being imaged would likely result in undesirable variations in position of the entire eye, in addition to the topological variations inherent in the eye itself. It should be understood that techniques to stabilize and account for motion and topological variations may significantly facilitate the application of these imaging technologies by addressing the motion problem described above.
One possible approach to address for these variations may be to increase the imaging range so as to accommodate these variations due to motion or topology. Again, using the retinal sample as an example, if the range in position of the retinal surface is 10 mm, it is possible to use a system which provides an overall imaging depth of 12 mm. With such system, the consideration for the movement of the surface from image to image are not essential since the retina would likely always be within the proper range. However, using this approach may have the effect of degrading the signal-to-noise ratio and sensitivity of the image.
Accordingly, a method to track the location of features within the sample for the purpose of determining the most appropriate imaging position and range is likely desirable. Previous techniques typically used the position of the surface of the sample as determined from a structural (intensity) image (e.g., using a cross-correlation technique or a peak signal), and provided to adapt a ranging location. (See U.S. Pat. Nos. 6,191,862 and 6,552,796). However, the detection of such prior techniques was not robust.
SUMMARY OF THE INVENTION  
In contrast to the conventional techniques, an exemplary embodiment of a system, process and software arrangement according to the present invention is capable of using real time dynamic feedback to detect an axial location of features within a sample, and adjust the scan position and range accordingly. For example, an approximate location of a surface in a depth profile of an Optical Coherence Tomography scan may be located. The determination of the approximate location of the surface can be used to generate a feedback signal to, e.g., a ranging device in the reference arm. In addition, a dynamically-adjustable parameter can be used to determine the responsiveness of the feedback loop.
For example, the exemplary embodiments of the present invention, in contrast with the previously implemented systems, provide techniques for locating different types of features in the sample. These include, but are not limited to, structural (or intensity) features traditionally used in tracking techniques, as well as features of flow, birefringence, or spectroscopic data, and combinations thereof. For example, flow is described in Z. Chen et al., “Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography,” Opt. Lett. 22, 1119-21 (1997), and Y. Zhao et al., “Phase-Resolved Optical Coherence Tomography and Optical Doppler Tomography for Imaging blood flow in human skin with fast scanning speed and high velocity sensitivity,” Opt. Lett. 25, 114-6 (2000). The birefringence is described in J. F. de Boer et al., “Two dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22, 934-6 (1997). J. F. de Boer et al., “Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography,” Opt. Lett. 24, 300-2 (1999), C. E. Saxer et al., “High-speed fiber-based polarization-sensitive optical coherence tomography of in vivo human skin,” Opt. Lett, 25, 1355-7 (2000), and B. H. Park et al., “Real-time multi-functional optical coherence tomography.” Optics Express 11, 782 (2003). Further, the spectroscopic data is described in U. Morger et al., “Spectroscopic optical coherence tomography,” Opt. Lett. 25(2), 111-3 (2000), and B. Hermann et al., “Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography,” Opt. Express 12(8), 1677-88 (2004). In addition, a reactivity parameter that affects how the evolution of these features can be used to alter system acquisition parameters e.g., (imaging location, window, range) during the acquisition.
According to one exemplary embodiment of the present invention, a system, process and software arrangement are provided to determine at least one position of at least one portion of a sample. In particular, information associated with the portion of the sample is obtained. Such portion may be associated with an interference signal that includes a first electro-magnetic radiation received from the sample and a second electro-magnetic radiation received from a reference. In addition, depth information and/or lateral information of the portion of the sample, may be obtained. At least one weight function can be applied to the depth information and/or the lateral information so as to generate resulting information. Further, a surface position, a lateral position and/or a depth position of the portion of the sample may be ascertained based on the resulting information.
In another exemplary embodiment of the present invention, the depth information can include (i) flow information within the at least one portion of the sample, (ii) birefringence information and polarization information associated with the at least one portion of the sample, (iii) spectroscopic information of the at least one portion of the sample, and/or (iv) intensity information of the portion of the sample. In addition, a length of the reference can be modified based on the surface position and/or the depth position. After the length is modified, the depth information and/or the lateral information may be obtained based on a new position of the reference. In addition, the length of the reference can be modified using a controllable parameter. The controllable parameter may be a responsiveness parameter which is used to dynamically control a level of modification of the length of the reference.
According to a further exemplary embodiment of the present invention, after ascertaining the particular information, at least further one of the surface position, the lateral position and/or the depth position is estimated and/or predicted as a function of the particular information. Further, the procedure can be performed a number of times to obtain a set of data associated with the particular information; and the estimation and/or prediction can be based on (or using) the set of data.
In another exemplary embodiment of the present invention, a delay arrangement can be provided which is associated with the sample and/or the reference, and facilitates variable transmissive optical paths therein. Further, at least a section of a particular path of the sample and/or the reference may be non-reciprocal. The reference can receive radiation via a path that is different from a path along which the radiation is transmitted from the reference.
According to still another exemplary embodiment of the present invention, the portion can include a feature of the sample, and the lateral position of the feature may be determined. The lateral information can include (i) flow information within the at least one portion of the sample, (ii) birefringence information and polarization information associated with the at least one portion of the sample, (iii) spectroscopic information of the at least one portion of the sample, and/or (iv) intensity information of the portion of the sample. A lateral scan range of the sample can be modified based on the lateral position. After modifying the lateral scan range, the depth information and/or the lateral information may be obtained based on a new lateral scan range. The lateral scan range may be modified using a controllable parameter (e.g., a responsiveness parameter which is used to dynamically control a level of modification of the lateral scan range).
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.



BRIEF DESCRIPTION OF THE DRAWINGS
Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures shoeing illustrative embodiments of the invention, in which:
FIG. 1 is a block diagram of an exemplary embodiment of a spectral domain optical coherence tomography (“SD-OCT”) arrangement according to the present invention which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 2 is a block diagram of an exemplary embodiment of an optical frequency domain interferometry (“OFDI”) arrangement according to the present invention which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 3 is a high level diagram of another exemplary SD-OCT system that includes a transmissive delay line and a broadband source coupled into a splitter, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 4 is a high level diagram of another exemplary OFDI system that includes a transmissive delay line and a swept source coupled into a splitter, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 5 is a high level diagram of yet another exemplary SD-OCT system that excludes a Mirror in the transmissive reference arm, which is coupled to one of two splitter, and which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 6 is a high level diagram of yet another exemplary OFDI system that excludes a mirror in the transmissive reference arm, which is coupled to one of two splitter, and which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 7 is a high level diagram of yet another exemplary SD-OCT system similar to that of FIG. 5, except that a circulator is provided between the source and the first splitter, and which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 8 is a high level diagram of yet another exemplary OFDI system similar to that of FIG. 6, except that a circulator is provided between the source and the first splitter, and which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 9 is a flow diagram of an exemplary embodiment of a real-time polarization-sensitive data acquisition and processing software according to the present invention, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 10 is a system diagram of an exemplary embodiment of a polarization-sensitive OCT (“PS-OCT”) system (and waveforms used for the signals generated by the source), which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention;
FIG. 11 is a flow chart of an exemplary embodiment of a method according to the present invention which implements a tracking technique that uses a dynamic responsivity parameter;
FIG. 12 is an exemplary illustration of a software interface which operates with the system, process and software arrangement according to the present invention which includes adaptive ranging activation/locking checkmark control and responsivity slide bar control;
FIG. 13 is an exemplary image of a portion of a retina acquired using a technique without tracking; and
FIG. 14 is an exemplary image of a portion of a retina acquired using motion tracking according to an exemplary embodiment of the present invention.



DETAILED DESCRIPTION
FIG. 1 shows an exemplary embodiment of a sample configuration of a spectral domain optical coherence tomography (“SD-OCT”) arrangement which can be used for implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. A detailed description of operation of this arrangement is described in detail in International Patent Publication No. WO 03/062802. In particular, as shown in FIG. 1, a high-powered superluminescent diode source (“HP-SLD”) 10 generates an electro-magnetic radiation or light signal which is transmitted through a first polarization controller (“PC”) 20′ and an optical isolator 30 so as to facilitate a one way propagation of an electro-magnetic energy to reach a signal splitter 40. The signal splitter forwards one portion of the split signal to a reference arm (which includes a second PC 20′′, a reference, certain optics and a neutral density filter (“NDF”) 50) and another portion of the split signal to a sample arm (which includes a third PC 20′′′, certain optics and a sample 60 such as the eye). Thereafter, an electromagnetic signal is reflected from the sample 60 and is combined with the light from the reference arm to form an interference signal. This interference signal is forwarded to a fourth PC 20′′, and forwarded to a collimator (“Col”) 70, a transmission grating (“TG”) 80, an air-spaced focusing lens (“ASL”) 90, and a linescan camera (“LSC”) 100 to be detected by a detecting arrangement (e.g., provided in the linescan camera), and then analyzed by a processing arrangement, e.g., a computer (not shown). Such processing arrangement is capable of implementing the various exemplary embodiments of the system, process and software arrangement according to the present invention.
FIG. 2 shows an exemplary embodiment of an optical imaging frequency domain intereferometry (“OFDI”) arrangement according to the present invention which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. A detailed description of various embodiments of the OFDI arrangement is provided in U.S. Patent Application Ser. No. 60/514,769. For example, the light source may be a wavelength-swept source 110. In order to generate a synchronization signal, a portion of the laser output (for example—20%) is obtained, and detected using a fast InGaAs photo-detector through a narrowband fixed-wavelength filter. The detector generates a pulse when the output spectrum of the laser sweeps through the narrow passband of the filter. The detector pulse is fed to a digital circuit 120, e.g., a synchronous TTL pulse generator, for converting the resultant signal to a TTL pulse train. The TTL pulses are used to generate gating pulses for signal sampling. 90% of the remaining light is directed to the sample arm and 10% to the reference mirror 130. This exemplary arrangement can utilize an optical probe based on a galvanometer mirror (e.g., scanner) 140 and an imaging lens. The galvanometer-mounted mirror 140 is controlled by a glava-driver 145 so as to scan the probe light transversely on the sample 60. The total optical power illuminated on the sample 60 may be approximately 3.5 mW. The light reflected from the reference mirror 130 and the sample 60 is received through magneto-optic circulators 150′, 150′′, and combined by a 50/50 coupler 160. A fiber-optic polarization controller may be used in the reference arm to align polarization states of the reference and sample arms.
In general, a relative intensity noise (“RIN”) of the received light signal may be proportional to a reciprocal of the linewidth, and the relatively high RIN can be reduced by dual balanced detection (e.g., using a dual balanced receiver 170). The differential current of two InGaAs detectors D1 and D2 in the receiver 170 may be amplified using trans-impedance amplifiers (“TIA”) having a total gain of 56 dB, and passed through a low pass filter (“LPF”) with a 3-dB cutoff frequency at approximately half the sampling rate. The common-noise rejection efficiency of the receiver 170 may be typically greater than 20 dB. In addition to the RIN reduction, the balanced detection may provide other significant benefits—a suppression of a self-interference noise originating from multiple reflections within the sample and optical components; an improvement in the dynamic range; and a reduction of a fixed-pattern noise by greatly reducing the strong background signal from the reference light. Thereafter, a detecting arrangement 180 receives such signals, and forward them to a processing arrangement 190 (e.g., a computer) which implements the exemplary embodiments of the system, process and software arrangement according to the present invention to reduce dispersion, and assist in displaying a resultant image that is based on the original image and the reduction of the dispersion.
Both of these exemplary arrangements, e.g., the SD-OCT arrangement described above with reference to FIG. 1 and the OFDI arrangement described above with reference to FIG. 2, are capable of using real time dynamic feedback to detect an axial location of features within a sample, and adjust the scan position and range accordingly. For example, an approximate location of a surface in a depth profile of the OCT scan may be located. The determination of the approximate location of the surface can be used to generate a feedback signal to, e.g., a ranging device in the reference arm of these systems. In addition, a dynamically-adjustable parameter can be used by these exemplary systems to determine the responsiveness of the feedback loop.
FIG. 3 shows a high level diagram of another exemplary SD-OCT system 200 that includes a transmissive delay line and a broadband source coupled into a splitter, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. In particular, the exemplary system of FIG. 3 illustrates a broadband source 210 (e.g., a high-powered superluminescent diode) is coupled to a fiber splitter 220, which may have the particular splitting ratios (e.g., 50/50, 80/20, 90/10 or 99/1). One portion of the split signal is transmitted from the splitter 220 to a sample 230, and the other portion of the split signal is transmitted from the splitter 220 to a reference arm. The exemplary reference arm can include a stationary mirror 240 and a variable length transmissive delay arrangement 250. Such configuration of the reference arm in this exemplary embodiment can be differentiated from a delay line in which the overall reference optical path length is generally controlled by moving the mirror itself. The light signal returning from both the sample arm 230 and the reference arm (240, 250) interfere upon their return path through the splitter 220, and are detected with a spectrometer 260 as described above.
FIG. 4 shows a high level diagram of another exemplary OFDI system 300 that includes a transmissive delay line and a swept source coupled into a splitter, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. In particular, the exemplary system of FIG. 4 illustrates a swept source 310 is coupled to a fiber splitter 320, which is similar to the splitter 220 may have the particular splitting ratios (e.g., 50/50, 80/20, 90/10 or 99/1). Similarly to the description of the system shown in FIG. 3, one portion of the split signal is transmitted from the splitter 320 to a sample 330, and the other portion of the split signal is transmitted from the splitter 320 to a reference arm. Again, the exemplary reference arm can include a stationary mirror 340 and a variable length transmissive delay arrangement 350. The light signal returning from both the sample arm 330 and the reference arm (340, 350) interfere upon their return path through the splitter 320. However, in contrast with the system shown in FIG. 3, the system of FIG. 4 includes a photodiode 360 which is used for the detection of the interfered signal.
FIG. 5 shows a high level diagram of yet another exemplary SD-OCT system 200′, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. In the this exemplary embodiment, the transmissive reference arm excludes the mirror. However, the splitter 220 as shown in FIG. 5 is coupled to another splitter 255, as well as to the transmissive delay arrangement 250. In addition, the light is reflected back from the sample 230 and the reference arm and light the second splitter 255 which splits the signal and forward the split portions of the reflected signal to two separate spectrometers 260′, 260′′, respectively.
FIG. 6 shows a high level diagram of yet another exemplary OFDI system 300′ that has similar changes as illustrated in FIG. 5. Indeed, the transmissive reference arm excludes the mirror, and other splitter 355 to receive the reflected signal from the first splitter 320 and from the transmissive delay arrangement 350. In addition, two separate diodes 360′, 360′′ are provided to detect the split signals from the second splitter 355.
FIGS. 7 and 8 show high level diagrams of still further another exemplary systems 200′′, 300′′, i.e. SD-OCT and OFDI, respectively, that are similar to those of FIGS. 5 and 6. The main difference between the exemplary embodiments shown in FIGS. 7 and 8 and those illustrated in FIGS. 5 and 6 is the presence of a circulator 215, 315 in the systems of FIGS. 7 and 8 coupled between the source 210, 310 and the first splitter 220, 320, respectively. This will affect the choice of splitting ratios used in the respective first splitters 220, 320 depending on the application. For example, when using such systems to image the biological tissue, where sample reflectivity is typically very low, the use of the configuration of the systems shown in FIGS. 7 and 8 (with the splitters 220, 230 with the ratios of 90/10 or 99/1) may be preferable so as to detect more of the light returning from the sample 230, 330. The use of such splitting ratios for the configurations of the systems shown in FIGS. 5 and 6 would likely result in a detection of a significantly smaller proportion of the light returning from the sample 23, 330. In addition, the systems of FIGS. 7 and 8 have one detection arrangement (i.e., the spectrometer 260 and the diode 360).
FIG. 9 shows a flow diagram of an exemplary embodiment of a real-time polarization-sensitive data acquisition and processing software 400 according to the present invention, which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. For example, the exemplary software begins a main thread by acquiring a chunk of data 405, which is them processed 410 as soon as it is acquired. This procedure may include an activation of even and odd A-line processing threads 460, 430, respectively to convert the detected interference patterns into Stokes parameters and phase information, as well as updating the intensity image. When the initial processing of the data has been completed, the birefringence and flow threads 450, 440, respectively can perform their respective analysis and image updates. The save thread 420 can writes raw data to a disk once the image is completely acquired.
FIG. 10 is a system diagram of an exemplary embodiment of a polarization-sensitive OCT (“PS-OCT”) system 500 (and waveforms used for the signals generated by the source), which is capable of implementing the exemplary embodiments of the system, process and software arrangement according to the present invention. For example, a low-coherence source 502 (e.g., AFC BBS1310) with a center wavelength of 1310 nm, a FWHM bandwidth of 70 nm, and total output power of 9 mW was linearly polarized may be used in this system such that equal-magnitude wave components are aligned parallel and perpendicular to the optic axis of an electro-optic polarization modulator 505. Light is coupled through a standard single-mode fiber to a polarization-independent optical circulator 510, and then divided by a fiber optic splitter 515 in a 90/10 ratio into sample and reference arms.
For example, 2.5 mW of source light may be incident onto the surface of the sample in a focused spot of, e.g., 30-mm diameter. A grating-based rapid scanning optical delay line 520 (“RSOD”) can be used with the source spectrum offset on the scanning mirror to provide both group and phase delay scanning so as to generating a carrier frequency at about 800 kHz. A two-step voltage function may be used to drive the polarization modulator 505 such that it is synchronized with the 1-kHz triangular scanning waveform of the RSOD 520, such that the polarization states that are incident upon the sample during inward and outward A-line scans can be orthogonal in the Poincaré sphere representation. A polarizing cube can be inserted into the reference arm to ensure that light in the RSOD 520 is provided in substantially the same linear state, regardless of the polarization state at the sample. Static polarization controllers in the detection and reference arms may be aligned for an equal distribution of the reference arm light over both the horizontal and vertical detection channels for both input polarization states. Electronic signals from each detector can be amplified, filtered and digitized with a 12-bit 5-Msample_s analog-to-digital board (e.g., National Instruments NI 6110).
The exemplary techniques that are described herein below (e.g., adaptive ranging techniques) according to the present invention can be implemented using the exemplary systems described above with reference to FIGS. 1-9, as well as other systems which are within the scope of the present invention, and with those systems that are known and understood to those having ordinary skill in the art. For example, a processing arrangement (e.g., the computer 190, 550 of FIGS. 2 and 9, respectively) may be used to a control waveform output to various components of the system as well as acquiring data from the detector arm of the interferometer. This technique is described in B. H. Park et al., “Real-Time Multi-Functional Optical Coherence Tomography,” Opt. Exp. 11(7), 782 (2003). The rapid scanning optical delay line (RSOD) as described above and discussed in G. J. Tearney et al., “High-Speed Phase- and Group-Delay Scanning with a Grating-Based Phase Control Delay Line,” Opt. Lett. 22(23), 1811 (1997) in the reference arm can be controlled by the sum of, e.g., two functions: (i) a triangular wave with an amplitude and frequency related to the depth range and scan rate, and (ii) an offset voltage that shifts the depth range. A single image can be divided into data chunks, each consisting of a small number, D, of consecutive depth scans of length N points.
A position function, e.g., a weighted first moment, may be calculated according to the following:




  
    
      
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where d and n is a depth scan and point within the depth scan, respectively, and thus Wd,n represents a weight for a particular position in the image. For example, this weight may be equal to the reflected light intensity on either a linear or logarithmic scale, depending on user preference during software initialization. In most cases, using the logarithm of the intensity gives more intuitive results, as the intensity image itself is shown on a logarithmic scale as well.

An exemplary graphic user interface 700 according to the present invention with can be used with this technique during acquisition has two controls related to adaptive ranging, as shown in FIG. 12. For example, the RSOD offset voltage, Voffset, can be initially set to zero. When the activation/locking checkmark control is activated, the software may store the most current first moment as a separate variable, PL. The slide bar control determines a responsivity parameter, R. For each subsequent data chunk, a change in offset voltage, ΔVoffset, may be determined by the product of the responsivity, R, and the difference between the calculated first moment for the current data chunk, P, and the locking value, PL, as provided by:

ΔVoffset−=R·(P−PL).  (2)

This value can be added to the offset voltage, and the updated value may be transmitted to the RSOD between the acquisition of the data chunks. Equation (2) is similar to Hooke's law governing a spring, where R can be equated to a spring constant. The fact that R can be dynamically controlled during acquisition then allows for a determination of the appropriate parameters for optimal damping of patient movement. The ranging procedure continues for each data chunk until the check mark control is deactivated, and the software relocks on to a new position when it is activated again.
It should be understood that the above description is merely an exemplary implementation of an exemplary embodiment of the technique according to the present invention. On having ordinary skill in the are can easily modify and customize it according to the concepts described herein. For example, depending on the application, it is possible to constantly (e.g., periodically) update the scanning range within an image. Alternatively or in addition, it may be beneficial to only update the position between images or between sets of images. These exemplary variations can be easily accomplished by altering the size of the data chunk to be anywhere from a single depth profile, to a particular fraction of an image, to several images.
As described above, the weight function can be based on the reflected intensity on either a linear or logarithmic scale, depending on the type of tissue being scanned. A wide array of other functions based on intensity can also be used, such as, e.g., an exponential, a (fractional) power of the intensity or a higher order polynomial could be used to enhance weakly reflecting features that use tracking. Indeed, it may be beneficial for certain situations to base the weight function on something entirely different. Various extensions of OCT, such as polarization-sensitive OCT (“PS-OCT”) and optical Doppler tomography (“ODT”), can enhance contrast by providing images of phase retardation and flow, respectively.
Multi-functional techniques that are capable of measuring intensity, flow, the full gamut of polarization properties, and even spectroscopy of a sample have also been demonstrated. It is also possible to base the above-described weighting function on any of such features. For example, it is possible to base the weight function on a flow if it is particularly important to track the location of blood vessels. The flexibility in the type of weighting function can even allow us to combine the various types of data at our disposal. A weight that is a combination of some function involving flow and some other function involving phase retardation may allow for the tracking of vessels surrounded by a muscular sheath. The fact that different mathematical functions can be used further enables for an emphasis or de-emphasis of certain information as. For example, it is possible to use a combination of spectroscopic data and flow, with an emphasis on the latter, so as to distinguish and lock on blood containing certain features, and would preferentially focus on those with a flow component.
The position function, P, can also be configured to the type of tissue being analyzed. For example, it is possible to focus the tracking on the position of superficial or deeper structures by changing to what power the depth, n, of a point is raised, e.g.,




  
    
      
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        3
        )
      
    
  




increasing x can put more emphasis on deeper structures of interest whereas decreasing x would emphasize more superficial layers. Alternatively, it is possible to utilize linear combinations of higher order moments, e.g., using the second moment of position combined with a weight based on flow could track the location of a changing flow profile. Another potentially useful application is with tracking locations where features might have phase wrapping. Some examples of this are with flow determined by phase shifts or birefringence as determined by cumulative phase retardation. In both these cases, the mere presence of the source of contrast can potentially be misleading and only by observing their spatial distribution can we ascertain a more accurate description of the tissue. It can easily be seen that the combination of position and weight functions can be adapted to track the location of a wide variety of features, both in terms of their inherent properties (intensity, phase retardation, flow, etc.) and in terms of their spatial properties.
Further, the nature of the feedback loop can be configured to a particular application as well. One way of visualizing the feedback loop can be as a potential well. Equation (2) described above can be equated to Hooke's law governing the motion of a spring, which acts a quadratic potential well. Altering the responsivity parameter generally alters the width of the well, and enable a quick correction for under- or over-damping of motion artifact. It is also possible to modify the nature of the potential well itself, e.g., creating a square well or using another function based on the difference between the current position as the locked position. Indeed, it is possible to use higher order polynomials of not only the difference in position, but also the derivatives of the position as well to design the feedback loop to respond to velocity or acceleration of the tissue in question. Further, instead of using such functions to modify the change in offset voltage, the functions can modify other statistic of the offset voltage such as acceleration. In addition, a locking scheme can be used where the exemplary technique according to the present invention may lock on to a tissue displacement in response to acoustic, photothermal or other external stimuli to the tissue. FIG. 13 shows an exemplary image 800 of a portion of a retina acquired using a technique without tracking. The benefits of the present invention can be ascertained by reviewing an image 900 illustrated in FIG. 14 which corresponds to the of the retina displayed in the image 800 of FIG. 13. However, the image 900 of FIG. 14 was acquired using motion tracking according to an exemplary embodiment of the present invention.
Another manner of visualizing the effect of the dynamic responsivity parameter is that the user can use such parameter to control how the system reacts to and anticipates any changes in the position of features being imaged. The example of the usefulness of such exemplary feature is as follows: assume a feature is moving at a constant velocity. An autoranging procedure that merely takes the position from time point to time point will likely be at least slightly behind the true position of an object. This is due to the time the procedure has reacted to a specific position, and thus the object will likely have already moved to a new one. Using the exemplary reactivity parameter in accordance with the present invention, the system can overcompensate for the difference between the current and locked positions, and thus predict where the feature of interest would likely appear. Due to the fact that this is a dynamically controllable parameter, the user may use it to quickly tailor the response to fit the imaging subject.
The exemplary tracking technique according to the present invention described above is not limited to axial degrees of freedom. By providing a feedback loop to the lateral motion controllers, an x-y galvo set, the exemplary tracking technique can also provide a transversal lock on blood vessels or other structures that can be distinguished through their structure, polarization properties or velocity through, e.g., a Doppler shift. Similar feedback loops can be applied for controlling the range of the image by tracking the boundaries of the region of interest.
FIG. 11 is a flow chart of an exemplary embodiment of a method according to the present invention which implements a tracking technique that uses a dynamic responsivity parameter. This exemplary technique can be implemented using the exemplary systems shown in FIGS. 1-8, and described herein. In particular, the RSOD offset voltage is initially set to 0 in step 610, and a continuous data acquisition loop is started in step 620. A position function, P, can then be evaluated for each newly acquired data chunk. For example, the data chunk may be obtained from the loop in step 630. For example, the data chunk acquisition provided in step 630 can be obtained from blocks 410-460 as shown in FIG. 9.
Then, the position function, P, can be evaluated in step 640. If tracking is not active, then the program updates the value of a locking position PL in step 660. Otherwise, the procedure is continued to step 670 in which a reactivity/reaction parameter, R, is obtained from the interface. One of the goals of the tracking procedure, when activated, is to maintain the position of the most recently acquired data chunk as close to this locking value as possible. This is done by determining the change in the RSOD offset voltage most appropriate for the given value of the responsivity in step 680, and offset voltage, Voffset, is updated in step 690. Finally, the new voltage is transmitted in step 695, and the process returns to step 630. Thus, this exemplary technique facilitates the most current evaluation of the position function.
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. For example, the invention described herein is usable with the exemplary methods, systems and apparatus described in U.S. Patent Application No. 60/514,769. 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, all publications, patents and patent applications referenced above are incorporated herein by reference in their entireties.

## Claims

1. A system to determine at least one position of at least one portion of a sample, comprising:
a computer input arrangement which obtains information associated with an interference signal that includes a first electro-magnetic radiation received from the sample and a second electro-magnetic radiation received from a reference; and
a computer processing arrangement which:
I. obtains at least one of depth information of the at least one portion of the sample based on multiple points within a single A-line of the first electro-magnetic radiation,
II. applies at least one weight function to the depth information so as to generate resulting information,
III. ascertains a particular information which is at least one of a surface position or a depth position of the at least one portion of the sample based on the resulting information,
IIIA. modifies a range of the reference based on the particular information, and
IV. generates an image of the at least one portion of the sample based on the obtained depth information of the at least one portion of the sample, and wherein the modification of the range of the reference is performed during the generation of the image.

2. The system according to claim 1, wherein the computer processing arrangement generates the image based on the depth information that includes flow information within the at least one portion of the sample.

3. The system according to claim 1, wherein the computer processing arrangement generates the image based on the depth information that includes at least one of birefringence information and polarization information associated with the at least one portion of the sample.

4. The system according to claim 1, wherein the computer processing arrangement generates the image based on the depth information that includes spectroscopic information of the at least one portion of the sample.

5. The system according to claim 1, wherein, after ascertaining the particular information, the processing arrangement:
V. at least one of estimates or predicts at least one of the surface position or the depth position of yet to be acquired another portion of the at least one sample as a function of the particular information.

6. The system according to claim 5, wherein the processing arrangement:
VI. performs at least one of procedures (I)-(IV) to obtain a set of data associated with the particular information; and
VII. performs procedure (V) based on the set of data.

7. The system according to claim 1, wherein the computer processing arrangement generates the image based on the depth information that includes intensity information of the at least one portion of the sample.

8. The system according to claim 1, further comprising a delay arrangement associated with at least one of the sample and the reference, and which facilitates variable transmissive optical paths therein.

9. The system according to claim 1, wherein the computer processing arrangement obtains the information for at least a section of a particular path of the at least one of the sample and the reference that is non-reciprocal.

10. The system according to claim 1, wherein the computer processing arrangement the second radiation received from the reference is via a path that is different from a path along which the radiation is transmitted to the reference.

11. The system according to claim 9, wherein the computer processing arrangement receives the information associated with the second radiation received from the reference that is a transmissive reference.

12. The system according to claim 1, wherein, after modifying the range, the computer processing arrangement performs at least one of procedures (I)-(IV) based on a new position of the reference.

13. The system according to claim 1, wherein the computer processing arrangement modifies the range of the reference using a controllable parameter.

14. The system according to claim 13, wherein the controllable parameter is a responsiveness parameter which is used to dynamically control a level of modification of the range of the reference.

15. The system according to claim 1, wherein the at least one portion includes a feature of the sample, and wherein the computer processing arrangement determines the lateral position of the feature.

16. The system according to claim 1, wherein the computer processing arrangement generates the image based on lateral information of the at least one portion of the sample that includes flow information within the at least one portion of the sample.

17. The system according to claim 1, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes at least one of birefringence information and polarization information associated with the at least one portion of the sample.

18. The system according to claim 1, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes spectroscopic information of the at least one portion of the sample.

19. The system according to claim 1, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes intensity information of the at least one portion of the sample.

20. The system according to claim 1, wherein the computer processing arrangement modifies a lateral scan range of the sample automatically based on a lateral position which is part of a particular information during the generation of the image.

21. The system according to claim 20, wherein, after modifying the lateral scan range, the computer processing arrangement performs at least one of procedures (I)-(III) based on a further lateral scan range.

22. The system according to claim 14, wherein the computer processing arrangement modifies a lateral scan range using a controllable parameter.

23. The system according to claim 22, wherein the controllable parameter is a responsiveness parameter which is used to dynamically control a level of modification of the lateral scan range.

24. A process to determine at least one position of at least one portion of a sample, comprising:
obtaining information associated with with an interference signal that includes a first electro-magnetic radiation received from the sample and a second electro-magnetic radiation received from a reference;
obtaining depth information of the at least one portion of the sample based on multiple points within a single A-line of the first electro-magnetic radiation;
applying at least one weight function to the at least one of the depth information so as to generate resulting information;
with a computer arrangement, ascertaining a particular information which is at least one of a surface position or a depth position of the at least one portion of the sample based on the resulting information;
modifying a range of the reference based on the particular information; and
generating an image of the at least one portion of the sample based on the obtained depth information of the at least one portion of the sample, wherein the modification of the range of the reference is performed during the generation of the image.

25. A non-transitory computer-accessible hardware medium which includes thereon software, wherein, when executed by a computer processing arrangement, the software configures the computer processing arrangement to execute procedures to determine at least one position of at least one portion of a sample, the software comprising:
a first set of instructions which, when executed by the computer processing arrangement, obtains information associated with an interference signal that includes a first electro-magnetic radiation received from the sample and a second electro-magnetic radiation received from a reference;
a second set of instructions which, when executed by the computer processing arrangement, obtains depth information of the at least one portion of the sample based on multiple points within a single A-line of the first electro-magnetic radiation;
a third set of instructions which, when executed by the computer processing arrangement, applies at least one weight function to the depth information so as to generate resulting information;
a fourth set of instructions which, when executed by the computer processing arrangement, ascertains a particular information which is at least one of a surface position or a depth position of the at least one portion of the sample based on the resulting information;
a further set of instructions which, when executed by the computer processing arrangement, modifies a range of the reference based on the particular information; and
a fourth set of instructions which, when executed by the computer processing arrangement, generates an image of the at least one portion of the sample based on the obtained depth information of the at least one portion of the sample, and wherein the modification of the range of the reference is performed during the generation of the image.

26. The computer-accessible medium according to claim 25, wherein the depth information includes flow information within the at least one portion of the sample.

27. The computer-accessible medium according to claim 25, wherein the depth information includes at least one of birefringence information and polarization information associated with the at least one portion of the sample.

28. The computer-accessible medium according to claim 25, wherein the depth information includes spectroscopic information of the at least one portion of the sample.

29. The computer-accessible medium according to claim 25, wherein the depth information includes intensity information of the at least one portion of the sample.

30. The computer-accessible medium according to claim 25, further comprising a fifth set of instructions which, when executed by the computer processing arrangement, after the particular information is ascertained, at least one of estimates or predicts at least one of the surface position, the lateral position and the depth position of yet to be acquired another portion of the at least one sample as a function of the particular information.

31. The computer-accessible medium according to claim 30, wherein at least one of second through fourth sets of instructions are executed to obtain a set of data associated with the particular information, and wherein the fourth set is executed based on the set of data.

32. The computer-accessible medium according to claim 25, wherein the depth information includes intensity information of the at least one portion of the sample.

33. The computer-accessible medium according to claim 25, wherein the computer processing arrangement obtains data associated with signals received from a delay arrangement, which is associated with at least one the sample and the reference, and facilitates variable transmissive optical paths therein.

34. The computer-accessible medium according to claim 25, wherein the computer processing arrangement obtains data associated with signals received from at least a section of a particular path of the at least one of the sample and the reference that is non-reciprocal.

35. The computer-accessible medium according to claim 25, wherein the computer processing arrangement obtains data associated with signals received from the reference that receives radiation via a path that is different from a path along which the radiation is transmitted from the reference.

36. The computer-accessible medium according to claim 34, wherein the reference is a transmissive reference.

37. The computer-accessible medium according to claim 25, wherein, after modifying the range, at least one of second through fourth sets are executed based on a new position of the reference.

38. The computer-accessible medium according to claim 25, further comprising an eighth set of instructions which, when executed by the computer processing arrangement, modifies the range of the reference using a controllable parameter.

39. The computer-accessible medium according to claim 38, wherein the controllable parameter is a responsiveness parameter which is used to dynamically control a level of modification of the range of the reference.

40. The computer-accessible medium according to claim 25, wherein the computer processing arrangement obtains data associated with signals received from the at least one portion that includes a feature of the sample, and wherein the computer processing arrangement is configured to determine a lateral position of the feature.

41. The computer-accessible medium according to claim 25, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes flow information within the at least one portion of the sample.

42. The computer-accessible medium according to claim 25, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes at least one of birefringence information and polarization information associated with the at least one portion of the sample.

43. The computer-accessible medium according to claim 25, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes spectroscopic information of the at least one portion of the sample.

44. The computer-accessible medium according to claim 25, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and wherein the lateral information includes intensity information of the at least one portion of the sample.

45. The computer-accessible medium according to claim 25, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and further comprising an eighth set of instructions which, when executed by the computer processing arrangement, modifies a lateral scan range of the sample automatically based on the lateral position during the generation of the image.

46. The computer-accessible medium according to claim 45, wherein, after modifying the lateral scan range, the second through fourth sets are executed based on a new lateral scan range.

47. The computer-accessible medium according to claim 25, wherein the computer processing arrangement further obtains lateral information of the at least one portion of the sample based on the multiple points within the single A-line of the first electro-magnetic radiation, and further comprising a ninth set of instructions which, when executed by the computer processing arrangement, modifies the lateral scan range using a controllable parameter.

48. The computer-accessible medium according to claim 47, wherein the controllable parameter is a responsiveness parameter which is used to dynamically control a level of modification of a lateral scan range.