Absolute depth resolution in circular ranging optical coherence tomography

Abstract

an apparatus comprising: an electromagnetic radiation source that generates radiation for irradiating a sample located at an optical path depth, the electromagnetic radiation source configured to provide radiation to the sample to facilitate determining the optical path depth within the sample; an interferometer; and a data collection and processing system, wherein the interferometer comprises a reference arm to which a first portion of the radiation is sent; a sample arm to which a second portion of the radiation is sent; a first optical subsystem coupled to the sample arm to interrogate the sample using the radiation sent to the sample arm and to collect backscattered radiation from the sample; and a second optical subsystem coupled to the reference arm and the first optical subsystem to generate interference patterns between the collected backscattered radiation and the radiation sent to the reference arm, the data collection and processing system being in communication with the interferometer and configured to calculate the optical path depth of the sample from the received interference patterns.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is based on and claims priority to U.S. Provisional Patent Application No. 62 / 929,390, filed November 1, 2019, the entire disclosure of which is incorporated herein by reference.

[0002] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT: This invention was made with Government support under Grant No. P41EB015903 awarded by the National Institutes of Health. The United States Government has certain rights in this invention. [Background technology]

[0003] Subsampling OCT is an imaging technique that can operate at high speeds and long distances. Subsampling OCT achieves this by performing optical domain compression of the generated interference signal through the use of optical subsampling. Typically, this is achieved by using a single frequency comb source, i.e. a light source with individual spectral lines that are equally spaced in optical frequency. However, these techniques cannot determine absolute depth, which can be a limitation in certain applications. Summary of the Invention

[0004] Therefore, new systems, methods and media for resolving absolute depth in circular ranging optical coherence tomography are desired.

[0005] In one embodiment, an apparatus of the present invention provides an interferometer comprising: an electromagnetic radiation source that generates radiation for irradiating a sample located at an optical path depth, the electromagnetic radiation source configured to provide radiation to the sample to facilitate determining the optical path depth within the sample; a reference arm to which a first portion of the radiation is sent; a sample arm to which a second portion of the radiation is sent; a first optical subsystem coupled to the sample arm to interrogate the sample with the radiation sent to the sample arm and collect backscattered radiation from the sample; and a second optical subsystem coupled to the reference arm and the first optical subsystem to generate interference fringes between the collected backscattered radiation and the radiation sent to the reference arm; and a data collection and processing system configured to calculate the optical path depth of the sample from the received interference fringes.

[0006] In some embodiments of the apparatus, the electromagnetic radiation source may include a frequency comb source. In various embodiments of the apparatus, the frequency comb source may generate a first frequency comb having a first free spectral range (FSR) and a second frequency comb having a second FSR different from the first FSR. In some embodiments of the apparatus, the data acquisition and processing system may be configured to acquire a first interferometric data set using the first frequency comb, acquire a second interferometric data set using the second frequency comb, determine a phase shift between the first interferometric data set and the second interferometric data set, and determine an optical path depth of the sample based on the phase shift.

[0007] In certain embodiments of the apparatus, the frequency comb source may comprise a degenerate frequency comb source. In some embodiments of the apparatus, the degenerate frequency comb source may comprise a chirped frequency comb source. In various embodiments of the apparatus, the data acquisition and processing system may be configured to analyze the interference fringes to generate a first point spread function (PSF) and a second PSF, calculate a shift between the first PSF and the second PSF, and determine an optical path depth within the sample based on the shift. In some embodiments of the apparatus, the frequency comb source may comprise a stepped frequency comb having a free spectral range, the frequency comb may comprise a plurality of frequency comb lines, and the frequency comb lines may be modulated by a particular amount to vary the frequency. In some embodiments of the apparatus, the data acquisition and processing system may be configured to obtain a first interferometric data set without modulating the frequency comb lines, obtain a second interferometric data set by modulating the frequency comb lines, determine a phase shift between the first interferometric data set and the second interferometric data set resulting from modulating the frequency comb lines, and determine an optical path depth of the sample based on the phase shift.

[0008] In some embodiments of the above apparatus, the electromagnetic radiation source may further include a continuously swept source, and the data acquisition and processing system may be configured to acquire a first interferometric data set using the frequency comb source, acquire a second interferometric data set using the continuously swept source, determine a swept source optical path depth within the sample based on the second interferometric data set, and determine an optical path depth of the sample based on matching the swept source optical path depth to the first interferometric data set.

[0009] In some embodiments of the apparatus, the electromagnetic radiation source may include a stretched pulse active mode-locked laser. In various embodiments of the apparatus, the electromagnetic radiation source may include a distributed Fabry-Perot etalon filter. In some embodiments of the apparatus, the Fabry-Perot etalon filter may include a silicon wafer (Si-wafer). In some embodiments of the apparatus, the first optical subsystem may include an optical circulator circuit for sending radiation to the sample and sending backscattered radiation from the sample to the optical waveguide. In various embodiments of the apparatus, the reference arm may include an active phase modulator for complex demodulation of the interference pattern. In certain embodiments of the apparatus, the data acquisition and processing system may be further configured to calculate a plurality of optical path delays of the sample corresponding to a plurality of optical path depths within the sample when calculating the optical path depth of the sample.

[0010] In some embodiments of the method, the electromagnetic radiation source may include a frequency comb source. Various embodiments of the method may further include generating, by the frequency comb source, a first frequency comb having a first free spectral range (FSR) and a second frequency comb having a second FSR different from the first FSR. Certain embodiments of the method may further include acquiring, by the data acquisition and processing system, a first interferometric data set using the first frequency comb, acquiring, by the data acquisition and processing system, a second interferometric data set using the second frequency comb, determining, by the data acquisition and processing system, a phase shift between the first interferometric data set and the second interferometric data set, and determining, by the data acquisition and processing system, an optical path depth of the sample based on the phase shift.

[0011] In some embodiments of the method, the frequency comb source may include a degenerate frequency comb source. In various embodiments of the method, the degenerate frequency comb source may include a chirped frequency comb source. Certain embodiments of the method may include analyzing the interference pattern with a data acquisition and processing system to generate a first point spread function (PSF) and a second PSF, calculating with the data acquisition and processing system a shift between the first PSF and the second PSF, and determining with the data acquisition and processing system an optical path depth within the sample based on the shift.

[0012] In some embodiments of the method, the frequency comb source may include a stepped frequency comb having a free spectral range, the frequency comb may include a plurality of frequency comb lines, and the method may further include modulating the frequency comb lines by a particular amount to vary the frequency. Certain embodiments of the method may further include acquiring, by the data acquisition and processing system, a first interferometric data set without modulating the frequency comb lines, acquiring, by the data acquisition and processing system, a second interferometric data set by modulating the frequency comb lines, determining, by the data acquisition and processing system, a phase shift between the first interferometric data set and the second interferometric data set resulting from modulating the frequency comb lines, and determining, by the data acquisition and processing system, an optical path depth of the sample based on the phase shift.

[0013] In certain embodiments of the above method, the electromagnetic radiation source may further comprise a continuously swept source, and the method may further include acquiring, by the data collection and processing system, a first interference data set using a frequency comb source; acquiring, by the data collection and processing system, a second interference data set using the continuously swept source; determining, by the data collection and processing system, a swept source optical path depth within the sample based on the second interference data set; and determining, by the data collection and processing system, an optical path depth of the sample based on comparing the swept source optical path depth to the first interference data set.

[0014] In various embodiments of the method, the electromagnetic radiation source may include a stretched pulse active mode-locked laser. In some embodiments of the method, the electromagnetic radiation source may include a distributed Fabry-Perot etalon filter. In some embodiments of the method, the Fabry-Perot etalon filter may include a silicon wafer. In certain embodiments of the method, the first optical subsystem may include an optical circulator circuit for sending radiation to the sample and sending backscattered radiation from the sample to the optical waveguide. In some embodiments of the method, the reference arm may include an active phase modulator for complex demodulation of the interference pattern. In various embodiments of the method, calculating the optical path depth of the sample may further include calculating a plurality of optical path delays of the sample corresponding to a plurality of optical path depths in the sample.

[0015] In another embodiment, a method of the present invention includes generating radiation for irradiating a sample located at the optical path depth by an electromagnetic radiation source that provides radiation to the sample to facilitate determining an optical path depth within the sample; transmitting a first portion of the radiation by the electromagnetic radiation source to a reference arm of an interferometer; transmitting a second portion of the radiation by the electromagnetic radiation source to a sample arm of the interferometer; interrogating the sample with the radiation transmitted to the sample arm by a first optical subsystem coupled to the sample arm to generate backscattered radiation; collecting the backscattered radiation from the sample by the first optical subsystem; generating an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm by a second optical subsystem coupled to the reference arm and the first optical subsystem; and calculating the optical path depth of the sample from the received interference pattern by a data acquisition and processing system in communication with the interferometer.

[0016] Various objects, features and advantages of the disclosed subject matter will become more fully apparent from the following detailed description of the disclosed subject matter when considered in conjunction with the following drawings, in which like reference characters refer to like elements and in which: [Brief description of the drawings]

[0017] [Figure 1] Figures 1A and 1B compare the physically measured CR-OCT mapping using a non-degenerate frequency comb source (Figure 1A) and a degenerate (chirped) frequency comb source (Figure 1B) (ZPL = zero path length). [Figure 2A] Experimental CR-OCT setup showing an SPML laser with a degenerate frequency comb output. Fresnel reflection of the silicon etalons results in a finesse of 2.1 per etalon, resulting in a total finesse of 5.1 after four etalons. LD is the laser module driver, DDG is the digital delay generator, PG is the pattern generator, A is the amplifier, EOM is the electro-optic modulator, PC is the polarization controller, CFBG is the continuous fiber Bragg grating, SOA is the semiconductor optical amplifier, FP is the Fabry-Perot etalon spectral filter, OSA is the optical spectrum analyzer, ISO is the optical isolator, and PG is the signal generator. Silicon wafer photograph included with permission from WaferPro. [Figure 2B] FIG. 1 shows the measured etalon transmission at 232.5 THz for silicon wafers 1 (green line), 2 (red line) and 4 (blue line) in series. [Figure 2C] The etalon FSR across the spectrum is shown. The red dots show the experimental data, and the blue line shows the theoretical curve. [Figure 2D] 1 shows the degenerate frequency comb spectrum at the SPML output. [Figure 2E] A zoomed-in plot of the three comb lines at the SPML output is shown. [Diagram 3](A)-(D) show numerical simulations of CR depth signals using a degenerate frequency comb and a distributed silicon etalon. (A) shows the simulated mirror signals for various set orders for a degenerate frequency comb spectrum centered at 1290 nm with a bandwidth of 100 nm. (B) shows the superimposed mirror signals from the blue (Sb, centered at 1265 nm) and red (centered at 1315 nm, Sr) as a function of set order. (C) shows the blue and red band point spread functions (PSFs) at the 9th set order and the CR A-line showing the walk-off. (D) shows the recovered order parameters and the extracted PSF widths before and after correcting for the degenerate frequency comb chirp using D=0.54×10-3ps2. [Figure 4A] 4A-4D show an experimental implementation of absolute delay ranging using a degenerate frequency comb. Figure 4A shows the PSF calculated from the full spectrum. [Figure 4B] The overlaid PSFs from the blue and red subbands are shown. [Figure 4C] 4B shows the PSF as in FIG. 4A, but after dechirping with calculated order parameters and D=0.54×10−3 ps2. [Figure 4D] Measured PSF widths before (red, squares) and after (black, circles) dechirping are shown as a function of set order. [Figure 5A] 5A-C show absolute height topographical imaging of a stack of US one-cent coins using the proposed CR-OCT system. Figure 5A shows a photograph (top of Figure 5A) and an intensity depth projection (bottom of Figure 5A). [Figure 5B] The corresponding circular depth map is shown at the bottom of FIG. 5A. [Figure 5C] The reconstructed absolute depth corresponding to the lower part of FIG. 5A is shown. [Figure 6]Images depicting the resolution of the absolute position of a surgical tool using the proposed CR-OCT system. Surgical forceps are placed on a tissue (chicken skin) sample. The images depict the en-face intensity projection (top row), the circular depth map (middle row) and the retrieved absolute depth map (bottom row), where the color / shade scale depicts the depth (see scales on the right side of the middle and bottom rows). [Figure 7] 1 shows interference fringes and frequency comb traces for a source where the frequency comb has been modulated, tuned and / or shifted. [Figure 8] 1 illustrates depth determination using a light source with a step laser and a sweeping laser. [Figure 9] FIG. 1 is a diagram of an interferometer system that may be used with various embodiments disclosed herein. [Figure 10] 1 shows an example of a system for resolving absolute depth in CR-OCT according to some embodiments of the disclosed subject matter. [Figure 11] 1 illustrates example hardware that can be used to implement computing devices and servers according to some embodiments of the disclosed subject matter. [Figure 12] 1 shows an example of a process for resolving absolute depth in CR-OCT according to some embodiments of the disclosed subject matter. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] In accordance with some embodiments of the disclosed subject matter, mechanisms (which may include systems, methods, and media) are provided for resolving absolute depth in circular ranging optical coherence tomography.

[0019] Subsampling OCT is an imaging technique that offers high speed and can operate over long distances. Subsampling OCT achieves this by performing optical domain compression of the generated interference signal through the use of optical subsampling. Typically, this is achieved by using a frequency comb source, i.e. a light source with individual spectral lines that are equally spaced in optical frequency.

[0020] One possible drawback of subsampling OCT is that the absolute delay (and therefore position) of the sample is not measured. Instead, the relative positions of the features of the sample are measured. In the present invention, a method and device are presented that provides both compressive and absolute delay / position sensing. In a particular embodiment, this can be based on using an imperfect (or degenerate) frequency comb, i.e. one with spectral lines that are not intentionally placed on an equally spaced grid in optical frequencies. This approach can be used in many different applications, including any application of subsampling OCT where knowing the absolute position of the sample is of additional value. This can be used, for example, to measure the distance between a surgical tool and a tissue sample or to measure the topography of the sample. The latter can be used in diverse fields, such as performing dynamic autofocusing.

[0021] In Fourier domain optical coherence tomography, an interference signal is generated that spans an RF bandwidth proportional to the product of three parameters: imaging range, imaging speed, and the inverse of the axial resolution. The circular ranging (CR) OCT architecture was introduced to facilitate long-range imaging by decoupling the imaging range from the signal RF bandwidth. As a result, current CR-OCT systems resolve the relative depth location of the scattering, rather than the absolute depth. Introduced herein is an improved implementation of CR-OCT, which in certain embodiments uses a degenerate frequency comb source that allows for the retrieval of absolute depth information with minimal impact on the previously described advantages of CR in terms of RF bandwidth compression. It is shown that this degenerate frequency comb can be created with relatively simple modifications to the excitation frequency comb source design, and absolute ranging capabilities are demonstrated through imaging studies and simulations.

[0022] In Fourier-domain optical coherence tomography, the generated optical signals are captured using an acquisition system with a finite electronic bandwidth. For applications requiring a long depth range compared to the 1-2 mm imaging depth of OCT for most samples, most of the acquired signal bandwidth is dedicated to measuring signal-void regions located in front of the sample surface or past the deepest imageable depth. CR-OCT captures these signals with higher data efficiency by superimposing equally spaced depth points onto a single measurement depth. This is done in the optical domain, which allows the electronic acquisition to operate with reduced bandwidth and less noise. As such, CR-OCT decouples imaging range and acquisition bandwidth, making simultaneous high-speed and long-range imaging more practical.

[0023] The CR-OCT technique is illustrated in FIG. 1A, showing the circular mapping of the physical delay coordinate (z-axis) to the measured circular delay coordinate (xy-plane). It should be noted that each measured delay is a superposition of a set of equally spaced physical delays. This interval is referred to as the circular delay range. Importantly, it can be seen from this figure that a distribution of reflected signals that spans only a delay range smaller than the circular delay range can be resolved in the measured / circular delay space without overlapping artifacts. A frequency comb source combined with complex (in-phase and quadrature) detection of interference fringes provides circular ranging, where the circular delay range is proportional to the inverse of the free spectral range (FSR) of the frequency comb source, i.e., Δτ=1 / (2fsr). For convenience, one can define a corresponding circular depth range that is the product of the circular delay range and the speed of light in the material being imaged. Note that the term delay is always defined in this specification in relation to the reference arm delay.

[0024] One consequence of the circular mapping shown in FIG. 1A is that the absolute delay of the sample is not measured. Herein, we present a method to resolve the absolute delay in CR-OCT. Absolute ranging is achieved by employing a degenerate frequency comb, i.e., a frequency comb with unequally spaced optical frequency lines. We demonstrate that a chirped frequency-degenerate comb source allows the measurement of absolute position while maintaining a high compression factor (the core motivation behind CR-OCT). Furthermore, we show that it is straightforward to modify existing CR-OCT sources to generate a degenerate comb output.

[0025] As a starting point, it is instructive to consider a simple approach to resolving absolute delays in a CR-OCT system using a "dual FSR" approach. Now consider a first measurement using a first frequency comb source with a given FSR, i.e., fsr1. A given signal can then be localized to a delay imposed by an unknown integer fraction (called the order) of cycles of the corresponding circular delay range [Δτ=1 / (2fsr1)]. If a second measurement of the same sample is acquired with another FSR, i.e., fsr2, the signal may appear at a different circular delay depending on its absolute position. Thus, by measuring the relationship between the circular delays measured using each of fsr1 and fsr2, the integer order parameters in each measurement can be extracted, and thereby the absolute delays. This can be analogized to measuring the elapsed time of an event using a stopwatch with a second hand but no minute hand. A single stopwatch cannot distinguish between an elapsed time of 17 seconds and 1 minute and 17 seconds, for example. By adding a second stopwatch that runs a known amount faster than the original, it becomes possible to calculate minutes (i.e., orders of magnitude) using the difference in the measurements of the seconds hands of the two stopwatches.

[0026] Although simple to understand, the dual FSR method may have drawbacks, at least for certain applications. First, although it is possible to generate two frequency combs with different FSRs, the overall light source may be complex; for example, this can be done by illuminating the sample simultaneously or sequentially with two frequency comb sources, or by using a single frequency comb source whose free spectral range can be adjusted (changed) between images or A-lines. Second, the acquisition of two A-lines is required to add the absolute depth measurement, which doubles the number of measurements and reduces the efficiency / compression advantage of the CR approach. Nevertheless, certain applications may be tolerant of this trade-off of absolute depth information for a more complex light source and a slightly slower acquisition speed.

[0027] This work presents an implementation based on a similar principle, but where the source implementation is simpler and the compression penalty is minimized. Rather than using two separate FSRs, a frequency comb with a continuously chirped FSR is used, i.e. a degenerate frequency comb (DFC). The principle of this approach is similar to that of the dual FSR described above, i.e. the change in FSR over optical frequency provides a clock with a changing rate that can be used to decode the absolute delay. However, the information is contained within one depth measurement (A-line) in this case. Furthermore, a chirped FSR can be created simply by using a distributed Fabry-Perot etalon in a laser source, fsr(ω)=c / (2n g (ω)l), where ω is the angular optical frequency, n g is the group index of the etalon, l is the etalon thickness, and c is the speed of light. Figures 1A and 1B compare the absolute-to-measured delay mapping of the proposed approach (Figure 1B) to the conventional single FSR CR-OCT approach (Figure 1A). By using a degenerate frequency comb, the spiral mapping of the physical delay to the measured delay becomes optical frequency dependent, thus resulting in the chirp for three discrete optical frequencies and three delays shown in Figure 1B. The absolute delay is calculated using the variance in the spectrally resolved circular delay (which in this case depends on the optical frequency). Knowing the absolute delay of the scattered signal then allows the measured interference fringes to be dechirped to produce an image with transform-limited axial resolution resolved over the absolute delay.

[0028] In various embodiments, the CR-OCT system may be implemented using a degenerate frequency comb by placing a distributed Fabry-Perot etalon at 1.29 μm in a stretched-pulse active mode-locked (SPML) laser architecture (FIG. 2A). The DFC-SPML had a sweep speed of 194 THz / μs and a repetition rate of 7.6 MHz with a 76% duty cycle. 2A silicon (Si) wafer providing a group velocity dispersion of 100 nm / km was used as the etalon. The 280 μm thick wafer provided an FSR of 146.7 GHz at the center optical frequency and a circular depth range of about 1 mm in air. The single-pass transmission and frequency-dependent FSR are shown in Figures 2B and 2C. The spectrum at the DFC-SPML output and a zoomed-in plot of the three comb lines are shown in Figures 2D and 2E. The coherence length of the source was measured to be about 2 cm (double-sided FWHM around the zero-path length). This source combined with a simple interferometer and acquisition system provided the measured fringe signal. Complex demodulation of the fringe signal was performed using an active (LiNbO3) phase modulator in the reference arm.

[0029] A numerical forward model of the CR-OCT fringe signal was generated from the system described above, i.e., using the same source characteristics and interferometer design. Using this model, a processing pipeline was built and verified to extract absolute depth information from the mirror fringe signal. As a starting point, Fig. 3(A) presents the simulated point spread function (PSF) for the mirror signal generated by processing the degenerate frequency comb signal using a conventional CR-OCT approach. The mirror was placed at the same circular depth (0 mm), but the circular depth range was of a different order (the circular depth range is defined by the average FSR of the DFC). Here, one can see the expected chirp (blurring) of the PSF due to the use of a degenerate frequency comb. Next, a dual-band processing approach was used to separately analyze the detected fringes in separate bands, referred to herein as the "blue" and "red" spectral bands, centered at 1265 nm (237.2 THz) and 1315 nm (228.1 THz), respectively. The difference in the average FSR within each band is approximately Δ=1.3 GHz, with fsr r >fsr b (Δτ r <Δτ b). The simulated PSFs for the same mirror positions are plotted in Fig. 3(B). Here, the overall chirp in Fig. 3(A) can be decomposed into two PSFs that walk off each other. Using the measured depth shift ΔL between the blue and red band PSFs (Fig. 3(C)), the order parameter k is calculated as follows:

[0030]

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[0031] In the formula, fsr b,r are the average FSRs in the blue and red bands, respectively.

[0032] Next, we developed a technique to remove the chirp (axial blur) caused by the use of a degenerate frequency comb (see Fig. 3(A)). i ) is the measured complex interference fringe s(ω i ) and exp[iDk(ω-ω0) 2 ], where k is an integer depth order parameter (Figure 3(D)). The parameter D is given by the properties of the degenerate frequency comb as:

[0033]

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[0034] We then applied this processing pipeline to experimental data. Figures 4A-4D show PSF measurements at a circular depth of about 250 μm using a degenerate frequency comb for order parameters in the range of ±10, acquired analogously to the simulated data of Figures 3(A)-3(D). Figures 4A and 4B show the PSFs using the full band and the red / blue spectral bands, respectively. The PSF walk-off was extracted by A-line cross-correlation. Note that in practice, PSF wrapping at the edges of the circular depth range must be taken into account. At these boundaries, the true PSF shift is given by the measured shift ΔL′ and the blue band circular depth range (because fsr r >fsr b Since, ΔL=ΔL'±cΔτ b It was confirmed that the orders calculated from the measured PSF shifts in Figure 4B matched the set orders of each measurement (set orders from -10 to 10). Using this solved order parameter, the chirp (broadening) of the full spectrum data was corrected as described in equation (1) to generate the dechirp PSF (Figure 4C). The recovered PSF widths before and after correction are shown in Figure 4D. Due to the PSF asymmetry, the root mean square

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[0035] To test the reconstruction of absolute depth information from a sample, a stack of nine US one-cent coins was imaged (Figure 5A). The circular wrap image and absolute topographic image are shown in Figure 5B and Figure 5C, respectively. It should be noted that the absolute image spans a much larger depth range but retains the same height resolution (given by the axial resolution) as the conventional circular wrap image depth range. Errors in the measured height are likely derived from low measurement SNR; research into SNR requirements and noise mitigation strategies in absolute delay-resolution CR-OCT is ongoing and beyond the scope of this work.

[0036] In a second experiment, the technique was used to provide feedback on the absolute positioning of a surgical tool relative to the tissue surface (Figure 6). Figure 6 shows images depicting the resolution of the absolute position of a surgical tool using the proposed CR-OCT system. Surgical forceps were placed on a tissue (chicken skin) sample. The images depict the EN-FACE intensity projection (top row), the circular depth map (middle row), and the retrieved absolute depth map (bottom row), where the color / shade scale depicts the depth (see scale on the right side of the middle and bottom rows). The absolute topographic image (bottom row), but not the circular wrapped conventional CR topographic image (middle row), allows the measurement of the proximity of the tool to the tissue. This absolute depth mapping technique enables applications such as surgical guidance with high depth perception, which would benefit from real-time stereoscopic vision for visualizing complex organs within the surgical field during the procedure.

[0037] Finally, a brief comment is made on the amount of etalon dispersion required to perform absolute ranging. Returning again to the dual FSR technique as a simplified example, by setting ΔL=δZ for k=1 in equation (1), where δZ is the Fourier transform limited axial resolution of each measurement, the minimum FSR difference, Δ min can be estimated and obtained as follows:

[0038]

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[0039] During the ceremony,

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[0040]

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[0041] In the formula, k max =l c / (2ΔL k=l ), and l c is the coherence length, and ΔL k=l is ΔL for k = 1, i.e., the difference in circular depth range. Note that in the degenerate frequency comb technique, this limitation can be overcome by shifting the spectral window closer to the center frequency, thereby reducing the difference FSR between measurements.

[0042] In this work, we numerically and experimentally demonstrate and verify that a degenerate frequency comb constructed from dispersive Fabry-Perot etalons can be used to retrieve absolute delay positions without significantly affecting the measurement compression. The current work focuses on the principles and first order implementation, which has several limitations. First, uncoated Si etalons (Si wafers) are used, and multiple etalons are cascaded due to the resulting low finesse. Custom-designed coated silicon (or other dispersive material) etalons offering higher finesse values ​​would improve the system performance, including the coherence length and the measured signal-to-noise ratio. The processing approach uses a simple red / blue subband analysis based on cross-correlation and PSF shift measurements. This can likely be augmented to better exploit the continuous chirping that occurs through the spectral bands. In this context, the construction of absolute delay-resolving algorithms that impose minimal processing penalties compared to conventional CR-OCT is crucial and is the subject of ongoing research.

[0043] In various embodiments, the above procedures can be performed using a number of different types of electromagnetic radiation sources, and in some instances the procedures can be modified depending on the type of source used.

[0044] <Dual FSR> In some embodiments, the source may be modified to generate a frequency comb with two different FSRs, as in the "dual FSR" approach disclosed above, where two A-lines are collected for each data point, one A-line for each of two different FSRs, and the A-line data corresponding to the two FSRs are combined to determine absolute depth.

[0045] <Degenerate frequency comb> In embodiments as disclosed herein, a source that generates a degenerate frequency comb can be used to determine absolute depth. In addition to the above embodiment that uses a dispersive etalon to create a degenerate (chirped) source, in other embodiments, a prism or a programmable laser can be used to create the degenerate frequency comb. In various embodiments, the above technique of using an SPML laser to generate a degenerate frequency comb can also be achieved using other types of laser sources, such as PCML, FDML, or typical external cavity lasers. Furthermore, the degenerate frequency comb created by any of the specific techniques need not be continuous.

[0046] <Modulating / tuning / shifting frequency comb lines> In some embodiments, a source generating a stepped frequency comb with known FSR can be used, where the frequency comb lines are shifted, tuned and / or modulated in the spectral domain by a known amount (Δf) using a frequency shifter, phase modulator, etalon angle adjustment means or other suitable means. For example, in some embodiments, a frequency shifter or phase modulator can be placed at the laser output before the interferometer. In other embodiments, the etalon angle adjustment can be performed inside the laser cavity by angle adjusting (or changing the refractive index or other means) the spectral filter itself that generates the frequency comb. Similar to the dual FSR approach described above, two A-lines (depth signals) are detected, which are obtained with and without comb line shifting / tuning / modulation.

[0047] The comb line shift in the spectral domain results in an optical delay (τ) dependent phase shift Δφ between the measured fringe signals (depth signals). Figure 7 shows an example of a continuously swept fringe with two different delays τ1 and τ2 in the time and optical frequency domain, where the frequency domain trace shows the shift of the frequency comb between the two delays. The measured phase shift Δφ can be seen in the stepped fringe in Figure 7 and is used to solve for the absolute depth. The phase difference at the baseband edge is given by

[0048]

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[0049] The absolute depth is determined as follows.

[0050]

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[0051] In general, the frequency shift Δf must be small enough to avoid π phase ambiguity in the measured phase shift at the maximum target depth,

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[0052] In the formula, N k is the number of orders in the coherence length.

[0053] <Step laser, plus sweep laser> In some embodiments, a combination of stepped and swept laser sources can be used to obtain absolute depth information from a sample. A stepped laser (Laser 1, FIG. 8) with known FSR may be used to detect A-lines (depth signals) from the sample. As mentioned above, this creates a depth ambiguity for the circular range (Δτ=1 / FSR, LB=c / FSR / 2) in the A-lines collected with Laser 1. To complement this data, a narrow linewidth (long coherence length) continuously swept laser (Laser 2, FIG. 8) can be used to obtain a second A-line (depth signal) of the same sample (e.g., the cornea and / or crystalline lens as shown in FIG. 8, top right). The relative depth (order) of the obtained depth signal can be compared to the absolute depth obtained with the stepped laser (Laser 1) versus the swept laser (Laser 2) to determine the absolute depth of the data obtained with the frequency comb of Laser 1.

[0054] In general, the axial resolution of Laser 2 should be half the circular range (LB) of Laser 1 or better. Also, to maximize the sweep speed of Laser 2, the optical bandwidth of Laser 2 should be kept to a minimum, and ideally the A-line rates of Laser 1 and Laser 2 should be the same or very similar. Finally, the coherence length of Laser 2 should be equal to or greater than the coherence length of Laser 1.

[0055] FIG. 9 illustrates an interferometer system that can be used with various embodiments of the present invention. FIG. 9 illustrates a Mach-Zehnder interferometer that can be implemented using free-space optics (FIG. 9, panel A) or a fiber configuration (FIG. 9, panel B). Other types of interferometers (e.g., Michelson interferometers) are also applicable. The light source LS in either FIG. 9, panel A or panel B can be an SPML laser with a degenerate frequency comb as in FIG. 2 or other types of lasers (e.g., PCML, FDML or conventional external cavity lasers), a light source where the lines of a stepped frequency comb are shifted, tuned or modulated, a dual FSR light source, or a light source combining a stepped frequency comb with a swept laser.

[0056] Beam B9 emitted from LS is directed to the interferometer input, where it is split into two paths of approximately equal length using a beam splitter (BS3). B10 is directed to the sample S. Backscattered light from the object of interest is then directed to the interferometer output (B11). In the reference arm, beam B12 is directed to a phase modulator (PM). The beam after PM (i.e., beam B13) is directed to the interferometer output and interferes with beam B11 after being combined with it by BS4. The output beam B14 is then detected by a detector D (e.g., a photodiode). Alternatively, a fiber-based interferometer as shown in FIG. 2B readily allows for balanced detection due to the π phase shift between the output beams B14 and B15. The detected signals are digitized at a sampling rate fs using a data acquisition and processing system, which may comprise a data acquisition board or a real-time oscilloscope (DAQ). Multiple wavelength sweeps (A1, A2, . . . , An) may be acquired to form a two- or three-dimensional image.

[0057] Referring to FIG. 10, an example system (e.g., data collection and processing system) 1000 for resolving absolute depth in CR-OCT is shown in accordance with some embodiments of the disclosed subject matter. As shown in FIG. 10, a computing device 1010 can receive interference data from an optical interferometer system 1000. In some embodiments, the computing device 1010 can execute at least a portion of a system for resolving absolute depth 1004 to determine absolute depth based on the interference data received from the optical interferometer system 1000. Additionally or alternatively, in some embodiments, the computing device 1010 can communicate information regarding the interference data received from the optical interferometer system 1000 to a server 1020 via a communication network 1006, which can execute at least a portion of a system for resolving absolute depth 1004 to determine absolute depth based on the interference data. In some such embodiments, the server 1020 may return information to the computing device 1010 (and / or any other suitable computing device) indicative of the output of the system for resolving absolute depth 1004, such as absolute depth information. This information may be transmitted and / or presented to a user (e.g., a researcher, an operator, a clinician, etc.) and / or stored (e.g., as part of a research database or medical record associated with the subject).

[0058] In some embodiments, the computing device 1010 and / or the server 1020 may be any suitable computing device or combination of devices, such as a desktop computer, a laptop computer, a smartphone, a tablet computer, a wearable computer, a server computer, a virtual machine executed by a physical computing device, etc. As described herein, the system for resolving absolute depth 1004 may present information about the interference data and / or the absolute depth information to a user (e.g., a researcher and / or a physician).

[0059] In some embodiments, the optical interferometer system 1000 may include an electromagnetic radiation source 1002, which may be any source suitable for optical interferometry, such as CR-OCT. In other embodiments, the electromagnetic radiation source 1002 may be located near the computing device 1010. For example, the electromagnetic radiation source 1002 may be combined with the computing device 1010 (e.g., the computing device 1010 may be configured as part of an apparatus for capturing and / or storing optical interferometry information). In other embodiments, the electromagnetic radiation source 1002 may be connected to the computing device 1010 by a cable, a direct wireless link, or the like. Additionally or alternatively, in some embodiments, the electromagnetic radiation source 1002 may be located near and / or remote from the computing device 1010 and may communicate information to the computing device 1010 (and / or the server 1020) via a communications network (e.g., communications network 1006).

[0060] In some embodiments, the communication network 1006 may be any suitable communication network or combination of communication networks. For example, the communication network 1006 may include a Wi-Fi network (which may include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, etc., conforming to any suitable standard, such as CDMA, GSM, LTE, LTE ADVANCED, WiMAX, etc.), a wired network, etc. In some embodiments, the communication network 1006 may be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a corporate or university intranet), any other suitable type of network, or any combination of suitable networks. Each of the communication links illustrated in FIG. 10 may be any suitable communication link or combination of communication links, such as a wired link, an optical fiber link, a Wi-Fi link, a Bluetooth link, a cellular link, etc.

[0061] FIG. 11 illustrates example hardware 1100 that may be used to implement a computing device 1010 and a server 1020, according to some embodiments of the disclosed subject matter. As illustrated in FIG. 11, in some embodiments, the computing device 1010 may comprise a processor 1102, a display 1104, one or more inputs 1106, one or more communication systems 1108, and / or memory 1110. In some embodiments, the processor 1102 may be any suitable hardware processor or combination of processors, such as, for example, a central processing unit, a graphics processing unit, etc. In some embodiments, the display 1104 may comprise any suitable display device, such as, for example, a computer monitor, a touch screen, a television, etc. In some embodiments, the input 1106 may comprise any suitable input device and / or sensor that may be used to receive user input, such as, for example, a keyboard, a mouse, a touch screen, a microphone, etc.

[0062] In some embodiments, communications system 1108 may comprise any suitable hardware, firmware, and / or software for communicating information over communications network 1006 and / or any other suitable communications network. For example, communications system 1108 may comprise one or more transceivers, one or more communications chips and / or chipsets, etc. In more particular examples, communications system 1108 may comprise hardware, firmware, and / or software that can be used to establish a Wi-Fi® connection, a Bluetooth® connection, a cellular connection, an Ethernet® connection, etc.

[0063] In some embodiments, the memory 1110 may comprise one or more of any suitable storage devices that may be used to store instructions, values, etc. that the processor 1102 may use, for example, to present content via the display 1104, to communicate with the server 1020, etc., via the communication system(s) 1108, etc. The memory 1110 may include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, the memory 1110 may include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, etc. In some embodiments, the memory 1110 may be encoded with a computer program for controlling the operation of the computing device 1010. In such embodiments, the processor 1102 may execute at least a portion of the computer program to present content (e.g., images, user interfaces, graphics, tables, etc.), receive content from the server 1020, transmit information to the server 1020, etc.

[0064] In some embodiments, the server 1020 may comprise a processor 1112, a display 1114, one or more inputs 1116, one or more communication systems 1118, and / or memory 1120. In some embodiments, the processor 1112 may be any suitable hardware processor or combination of processors, such as, for example, a central processing unit, a graphics processing unit, etc. In some embodiments, the display 1114 may comprise any suitable display device, such as, for example, a computer monitor, a touch screen, a television, etc. In some embodiments, the input 1116 may comprise any suitable input device and / or sensor that can be used to receive user input, such as, for example, a keyboard, a mouse, a touch screen, a microphone, etc.

[0065] In some embodiments, communications system 1118 may comprise any suitable hardware, firmware, and / or software for communicating information over communications network 1006 and / or any other suitable communications network. For example, communications system 1118 may comprise one or more transceivers, one or more communications chips and / or chipsets, etc. In more particular examples, communications system 1118 may comprise hardware, firmware, and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, etc.

[0066] In some embodiments, the memory 1120 may comprise one or more suitable storage devices that may be used to store instructions, values, etc. that the processor 1112 may use, for example, to present content via the display 1114, to communicate with one or more computing devices 1010, etc. The memory 1120 may include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, the memory 1120 may include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, etc. In some embodiments, the memory 1120 may be encoded with a server program for controlling the operation of the server 1020. In such embodiments, the processor 1112 may execute at least a portion of the server program to transmit information and / or content (e.g., organization identification and / or classification results, user interfaces, etc.) to one or more computing devices 1010, receive information and / or content from one or more computing devices 1010, receive instructions from one or more devices (e.g., personal computers, laptops, tablet computers, smartphones, etc.), etc.

[0067] In some embodiments, any suitable computer-readable medium may be used to store instructions for performing the functions and / or processes described herein. For example, in some embodiments, the computer-readable medium may be transitory or non-transitory. For example, a non-transitory computer-readable medium may include media such as magnetic media (hard disks, floppy disks, etc.), optical media (compact disks, digital video disks, Blu-ray disks, etc.), semiconductor media (RAM, flash storage, Electrically Programmable Read-Only Memory (EPROM), Electrically Addressable Programmable Read-Only Memory (EEPROM), etc.), any suitable medium that is not transitory or lacks any semblance of permanence during transmission, and / or any suitable tangible medium. As another example, a transitory computer-readable medium may include signals on a network, in wires, in conductors, in optical fibers, in circuits, or in any suitable medium that is transitory and lacks any semblance of permanence during transmission, and / or may include any suitable intangible medium.

[0068] In some embodiments, the optical signal is detected by a photodiode. It should be appreciated that any optional electronic conversion device can be used to perform this detection function, including, but not limited to, photodetectors, photodiodes, line scan and two-dimensional cameras, and photodiode arrays.

[0069] It should be noted that the term "mechanism" as used herein can encompass hardware, software, firmware, or any suitable combination thereof.

[0070] FIG. 12 illustrates an example process 1200 for resolving absolute depth in CR-OCT according to some embodiments of the disclosed subject matter. As illustrated in FIG. 12, at 1202, the process 1200 can generate radiation for illuminating a sample located at an optical path depth, and an electromagnetic radiation source can provide radiation to the sample to facilitate determining the optical path depth within the sample. At 1204, the process 1200 can send a first portion of the radiation to a reference arm of an interferometer. At 1206, the process 1200 can send a second portion of the radiation to a sample arm of an interferometer. At 1208, the process 1200 can interrogate the sample with the radiation sent to the sample arm to generate backscattered radiation. At 1210, the process 1200 can collect the backscattered radiation from the sample. At 1212, the process 1200 can generate an interference fringe between the collected backscattered radiation and the radiation sent to the reference arm. Finally, at 1214, the process 1200 can calculate the optical path depth of the sample from the received interference fringes.

[0071] The above steps of the process of Figure 12 may be performed or carried out in any order or sequence, including but not limited to the order and sequence shown, and some of the above steps of the process of Figure 12 may be performed or carried out substantially simultaneously or in parallel, if desired, to reduce latency and processing times.

[0072] Thus, although the present invention has been described with reference to particular embodiments and examples, the present invention is not necessarily limited thereto, and many other embodiments, examples, uses, modifications, and evolutions of modifications from the embodiments, examples, uses are intended to be encompassed within the scope of the appended claims.

Claims

1. an electromagnetic radiation source that generates radiation for illuminating a sample located at an optical path depth, the electromagnetic radiation source configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; An apparatus comprising an interferometer and a data acquisition and processing system, the electromagnetic radiation source comprises a frequency comb source; the frequency comb source generates a first frequency comb having a first free spectral range and a second frequency comb having a second free spectral range different from the first free spectral range; The interferometer comprises: a reference arm through which the first portion of radiation is delivered; a sample arm through which the second portion of the radiation is delivered; a first optical subsystem coupled to the sample arm for interrogating the sample with the radiation transmitted to the sample arm and for collecting backscattered radiation from the sample; a second optical subsystem coupled to the reference arm and to the first optical subsystem for generating an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; The data acquisition and processing system includes: communicating with the interferometer and calculating the optical path depth of the sample from the received interference fringes; acquiring a first interference data set using the first frequency comb; acquiring a second interferometric data set using the second frequency comb; an apparatus configured to determine a phase shift between the first and second interferometric data sets; and determine the optical path depth of the sample based on the phase shift.

2. An electromagnetic radiation source that generates radiation for irradiating a sample located at an optical path depth, the electromagnetic radiation source configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; An apparatus comprising an interferometer and a data acquisition and processing system, the electromagnetic radiation source comprises a degenerate frequency comb source; the degenerate frequency comb source comprises a chirped frequency comb source; The interferometer comprises: a reference arm through which the first portion of radiation is delivered; a sample arm through which the second portion of the radiation is delivered; a first optical subsystem coupled to the sample arm for interrogating the sample with the radiation transmitted to the sample arm and for collecting backscattered radiation from the sample; a second optical subsystem coupled to the reference arm and to the first optical subsystem for generating an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; The data acquisition and processing system includes: communicating with the interferometer and calculating the optical path depth of the sample from the received interference fringes; the data acquisition and processing system analyzes the interference pattern to generate a first point spread function and a second point spread function; Calculating a shift between the first point spread function and the second point spread function; an apparatus configured to determine the optical path depth within the sample based on the shift.

3. An electromagnetic radiation source generating radiation for irradiating a sample located at an optical path depth, the electromagnetic radiation source configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; An apparatus comprising an interferometer and a data acquisition and processing system, the electromagnetic radiation source comprises a frequency comb source; the frequency comb source comprises a stepped frequency comb having a free spectral range; the stepped frequency comb comprises a plurality of frequency comb lines; the frequency comb lines are modulated by a particular amount to vary their frequency; The interferometer comprises: a reference arm through which the first portion of radiation is delivered; a sample arm through which the second portion of the radiation is delivered; a first optical subsystem coupled to the sample arm for interrogating the sample with the radiation transmitted to the sample arm and for collecting backscattered radiation from the sample; a second optical subsystem coupled to the reference arm and to the first optical subsystem for generating an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; The data acquisition and processing system includes: communicating with the interferometer and calculating the optical path depth of the sample from the received interference fringes; the data acquisition and processing system acquires a first interferometric data set without modulating the frequency comb lines; modulating the frequency comb lines to obtain a second interferometric data set; determining a phase shift between the first interference data set and the second interference data set resulting from modulating the frequency comb lines; an apparatus configured to determine the optical path depth of the sample based on the phase shift.

4. An electromagnetic radiation source generating radiation for irradiating a sample located at an optical path depth, the electromagnetic radiation source configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; An apparatus comprising an interferometer and a data acquisition and processing system, the electromagnetic radiation source comprises a frequency comb source; The interferometer comprises: a reference arm through which the first portion of radiation is delivered; a sample arm through which the second portion of the radiation is delivered; a first optical subsystem coupled to the sample arm for interrogating the sample with the radiation transmitted to the sample arm and for collecting backscattered radiation from the sample; a second optical subsystem coupled to the reference arm and to the first optical subsystem for generating an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; The data acquisition and processing system includes: communicating with the interferometer and calculating the optical path depth of the sample from the received interference fringes; the electromagnetic radiation source further comprises a continuously swept source, the data acquisition and processing system acquiring a first interferometric data set using the frequency comb source; acquiring a second interferometric data set using the continuously swept source; determining a swept source optical path depth within the sample based on the second interferometric data set; an apparatus configured to determine the optical path depth of the sample based on comparing the swept source optical path depth to the first interference data set.

5. 5. Apparatus according to any one of claims 1 to 4, wherein the electromagnetic radiation source comprises a stretched pulse actively mode-locked laser.

6. The apparatus of any one of claims 1 to 4, wherein the electromagnetic radiation source comprises a distributed Fabry-Perot etalon filter.

7. 7. The apparatus of claim 6, wherein the distributed Fabry-Perot etalon filter comprises a silicon wafer.

8. The apparatus of claim 1 , wherein the first optical subsystem comprises an optical circulator circuit that delivers the radiation to the sample and delivers the backscattered radiation from the sample to an optical waveguide.

9. Apparatus according to any one of claims 1 to 4, wherein the reference arm comprises an active phase modulator for performing complex demodulation of the interference fringes.

10. The apparatus of any one of claims 1 to 4, wherein the data collection and processing system is further configured to, when calculating the optical path depth of the sample, calculate multiple optical path delays of the sample corresponding to multiple optical path depths within the sample.

11. generating, by an electromagnetic radiation source, radiation for illuminating a sample located at an optical path depth; wherein the electromagnetic radiation source is configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; using the electromagnetic radiation source to send a first portion of the radiation into a reference arm of an interferometer; sending a second portion of the radiation into a sample arm of the interferometer using the electromagnetic radiation source; interrogating the sample with radiation transmitted to the sample arm by a first optical subsystem coupled to the sample arm to generate backscattered radiation; collecting the backscattered radiation from the sample by the first optical subsystem and generating, by a second optical subsystem coupled to the reference arm and the first optical subsystem, an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; calculating, by a data acquisition and processing system in communication with the interferometer, the optical path depth of the sample from the received interference fringes, the electromagnetic radiation source comprises a frequency comb source; The method comprises: generating, by the frequency comb source, a first frequency comb having a first free spectral range and a second frequency comb having a second free spectral range different from the first free spectral range; acquiring, by the data acquisition and processing system, a first interferometric data set using the first frequency comb; acquiring, by the data acquisition and processing system, a second interferometric data set using the second frequency comb; determining, by the data acquisition and processing system, a phase shift between the first interferometric data set and the second interferometric data set; determining, by the data acquisition and processing system, an optical path depth of the sample based on the phase shift.

12. A method for detecting a sample position at an optical path depth, comprising: generating radiation by an electromagnetic radiation source for irradiating a sample located at an optical path depth; wherein the electromagnetic radiation source is configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; using the electromagnetic radiation source to send a first portion of the radiation into a reference arm of an interferometer; sending a second portion of the radiation into a sample arm of the interferometer using the electromagnetic radiation source; interrogating the sample with radiation transmitted to the sample arm by a first optical subsystem coupled to the sample arm to generate backscattered radiation; collecting the backscattered radiation from the sample by the first optical subsystem and generating, by a second optical subsystem coupled to the reference arm and the first optical subsystem, an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; calculating, by a data acquisition and processing system in communication with the interferometer, the optical path depth of the sample from the received interference fringes, the electromagnetic radiation source comprises a frequency comb source; the frequency comb source comprises a degenerate frequency comb source; the degenerate frequency comb source comprises a chirped frequency comb source; The method comprises: analyzing the interference pattern with the data acquisition and processing system to generate a first point spread function and a second point spread function; calculating, by the data acquisition and processing system, a shift between the first point spread function and the second point spread function; determining, by the data acquisition and processing system, the optical path depth within the sample based on the shift.

13. A method for detecting a sample position at an optical path depth, comprising: generating radiation by an electromagnetic radiation source for irradiating a sample located at an optical path depth; wherein the electromagnetic radiation source is configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; using the electromagnetic radiation source to send a first portion of the radiation into a reference arm of an interferometer; sending a second portion of the radiation into a sample arm of the interferometer using the electromagnetic radiation source; interrogating the sample with radiation transmitted to the sample arm by a first optical subsystem coupled to the sample arm to generate backscattered radiation; collecting the backscattered radiation from the sample by the first optical subsystem and generating, by a second optical subsystem coupled to the reference arm and the first optical subsystem, an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; calculating, by a data acquisition and processing system in communication with the interferometer, the optical path depth of the sample from the received interference fringes, the electromagnetic radiation source comprises a frequency comb source; the frequency comb source comprises a stepped frequency comb having a free spectral range; the stepped frequency comb comprises a plurality of frequency comb lines; The method comprises: modulating the frequency comb lines by a specific amount to change their frequency; acquiring, with the data acquisition and processing system, a first interferometric data set without modulating the frequency comb lines; modulating the frequency comb lines to obtain a second interferometric data set with the data acquisition and processing system; determining, by the data acquisition and processing system, a phase shift between the first interferometric data set and the second interferometric data set resulting from modulating the frequency comb lines; determining, by the data acquisition and processing system, the optical path depth of the sample based on the phase shift.

14. A method for detecting a sample position at an optical path depth, comprising: generating radiation by an electromagnetic radiation source for irradiating a sample located at an optical path depth; wherein the electromagnetic radiation source is configured to provide the radiation to the sample to facilitate determining the optical path depth within the sample; using the electromagnetic radiation source to send a first portion of the radiation into a reference arm of an interferometer; sending a second portion of the radiation into a sample arm of the interferometer using the electromagnetic radiation source; interrogating the sample with radiation transmitted to the sample arm by a first optical subsystem coupled to the sample arm to generate backscattered radiation; collecting the backscattered radiation from the sample by the first optical subsystem and generating, by a second optical subsystem coupled to the reference arm and the first optical subsystem, an interference pattern between the collected backscattered radiation and the radiation transmitted to the reference arm; calculating, by a data acquisition and processing system in communication with the interferometer, the optical path depth of the sample from the received interference fringes, the electromagnetic radiation source comprises a frequency comb source; the electromagnetic radiation source further comprising a continuously swept source; The method further comprising: acquiring, by the data acquisition and processing system, a first interferometric data set using the frequency comb source; acquiring, by the data acquisition and processing system, a second interferometric data set using the continuously swept source; determining, by the data acquisition and processing system, a swept source optical path depth within the sample based on the second interferometric data set; The method further comprising determining, by the data acquisition and processing system, the optical path depth of the sample based on matching the swept source optical path depth to the first interferometric data set.

15. The method of any one of claims 11 to 14, wherein the electromagnetic radiation source comprises a stretched pulse actively mode-locked laser.

16. The method of any one of claims 11 to 14, wherein the electromagnetic radiation source comprises a distributed Fabry-Perot etalon filter.

17. The method of claim 16 , wherein the distributed Fabry-Perot etalon filter comprises a silicon wafer.

18. The method of any one of claims 11 to 14, wherein the first optical subsystem comprises an optical circulator circuit that delivers the radiation to the sample and delivers the backscattered radiation from the sample to an optical waveguide.

19. The method according to any one of claims 11 to 14, wherein the reference arm comprises an active phase modulator for performing a complex demodulation of the interference pattern.

20. The method of any one of claims 11 to 14, wherein calculating the optical path depth of the sample further comprises calculating a plurality of optical path delays of the sample corresponding to a plurality of optical path depths within the sample.

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