The subject matter disclosed herein generally relates to optical coherence tomography (OCT). More particularly, the subject matter disclosed herein relates to systems, methods, and computer program products for removing undesired artifacts in Fourier domain optical coherence tomography (FDOCT) systems.
Optical coherence tomography (OCT) is a noninvasive imaging technique that provides microscopic tomographic sectioning of biological samples. By measuring singly backscattered light as a function of depth, OCT fills a valuable niche in imaging of tissue ultrastructure, providing subsurface imaging with high spatial resolution (about 2.0-10.0 μm) in three dimensions and high sensitivity (>110 dB) in vivo with no contact needed between the probe and the tissue.
In biological and biomedical imaging applications, OCT allows for micrometer-scale imaging non invasively in transparent, translucent, and/or highly-scattering biological tissues. The longitudinal ranging capability of OCT is generally based on low-coherence interferometry, in which light from a broadband source is split between illuminating the sample of interest and a reference path. The interference pattern of light reflected or backscattered from the sample and light from the reference delay contains information about the location and scattering amplitude of the scatterers in the sample. In time-domain OCT (TDOCT), this information is typically extracted by scanning the reference path delay and detecting the resulting interferogram pattern as a function of that delay. The envelope of the interferogram pattern thus detected represents a map of the reflectivity of the sample versus depth, generally called an A-scan, with depth resolution given by the coherence length of the source. In OCT systems, multiple A-scans are typically acquired while the sample beam is scanned laterally across the tissue surface, building up a two-dimensional map of reflectivity versus depth and lateral extent typically called a B-scan. The lateral resolution of the B-scan is approximated by the confocal resolving power of the sample arm optical system, which is usually given by the size of the focused optical spot in the tissue.
The time-domain approach used in conventional OCT, including commercial instruments, such as Carl Zeiss Meditec's STRATUSOCT® and VISANTE® products, has been successful in supporting biological and medical applications, and numerous in vivo human clinical trials of OCT reported to date have utilized this approach.
An alternate approach to data collection in OCT has been shown to have significant advantages both in reduced system complexity and in increased signal-to-noise ratio (SNR). This approach involves acquiring the interferometric signal generated by mixing sample light with reference light at a fixed group delay as a function of optical wavenumber. Two distinct techniques have been developed which use this Fourier domain OCT (FDOCT) approach. The first, generally termed Spectral-domain or spectrometer-based OCT (SDOCT), uses a broadband light source and achieves spectral discrimination with a dispersive spectrometer in the detector arm. The second, generally termed swept-source OCT (SSOCT) or optical frequency-domain imaging (OFDI), time-encodes wavenumber by rapidly tuning a narrowband source through a broad optical bandwidth. Both of these techniques may allow for a dramatic improvement in SNR of up to 15.0-20.0 dB over time-domain OCT, because they typically capture the A-scan data in parallel. This is in contrast to previous-generation time-domain OCT, where destructive interference is typically used to isolate the interferometric signal from only one depth at a time as the reference delay is scanned.
In both spectrometer-based and swept-source implementations of FDOCT, light returning from all depths is generally collected simultaneously, and is manifested as modulations in the detected spectrum. Transformation of the detected spectrum from wavelength to wavenumber, correction for dispersion mismatches between the sample and reference arms, and Fast Fourier transformation typically provides the spatial domain signal or “A-scan” representing depth-resolved reflectivity of the sample. The uncorrected A-scan may also include a strong DC component at zero pathlength offset, so-called “autocorrelation” artifacts resulting from mutual interference between internal sample reflections, as well as both positive and negative frequency components of the depth-dependent cosine frequency interference terms. Because of this, FDOCT systems typically exhibit “complex conjugate artifact” due to the fact that the Fourier transform of a real signal, the detected spectral interferogram, is typically Hermitian symmetric, i.e., positive and negative spatial frequencies are not independent. As a consequence, sample reflections at a positive displacement, relative to the reference delay, typically cannot be distinguished from reflections at the same negative displacement, and appear as upside-down, overlapping images on top of genuine sample structure, which generally cannot be removed by image processing. To reduce the likelihood of the occurrence of this symmetry artifact, FDOCT imaging is commonly performed with the entire sample either above or below the reference position, generally limiting the technique to thin samples of 2.0-4.0 mm, and placing the region of maximum SNR, at zero spatial frequency, outside the imaged structure. Resolving this artifact could effectively double the imaging depth, as well as allow the operator to position the most critical region of the sample at the position of maximum SNR.
Developments in FDOCT have shown clinical potential, particularly in retinal imaging, where current generation SDOCT systems allow for high-resolution, motion-artifact-free cross-sectional imaging and rapid volume dataset acquisition. As discussed hereinabove, FDOCT suffers from complex conjugate or mirror image artifacts, in which positive and negative distances relative to the reference pathlength cannot be uniquely resolved. As noted above, current imaging practice avoids this artifact by limiting the sample entirely on one side of the reference pathlength, utilizing only half of the total potential imaging depth. Such imaging practices are sufficient when imaging normal retina and pathologies which fit within about 1-2 mm imaging range of current SDOCT systems, however conjugate artifacts complicate images acquired from patients with poor fixation or head control, and imaging of extended pathologies (such as vitreous strands, deep optic nerve head cups, and choroidal structures) would benefit from full range imaging since sensitivity is limited by the characteristic roll-off associated with the finite spectral resolution of SDOCT systems.
Several approaches for complex conjugate artifact (CCA) removal have been demonstrated, many of which borrow from established techniques of phase shift interferometry for acquiring phase-encoded interferometric signals. These include phase shifting acquired from interferograms by discretely stepping piezoelectric transducer (PZT)-mounted reference reflectors (described, for example, in the article Ultrahigh-Resolution, High-Speed, Fourier Domain Optical Coherence Tomography and Methods for Dispersion Compensation, Wojtkowski et al., Optics Express 12, 2404 (2004), the content of which is incorporated herein by reference in its entirety), electro-optic modulator (described, for example, in the article High Speed Full Range Complex Spectral Domain Optical Coherence Tomography, Gotzinger et al., Optics Express 13, 583 (2005), the content of which is incorporated herein by reference in its entirety), acousto-optic modulator (described, for example, in the article Heterodyne Fourier Domain Optical Coherence Tomography for Full Range Probing with High Axial Resolution, Bachmann et al., Optics Express 14, 1487 (2006), the content of which is incorporated herein by reference in its entirety), instantaneous phase-shifted interferograms acquisition using 3×3 interferometers (described, for example, in the article Real-Time Quadrature Projection Complex Conjugate Resolved Fourier Domain Optical Coherence Tomography, Sarunic et al., Opt Lett 31, 2426 (2006), the content of which is incorporated herein by reference in its entirety) or polarization encoding (described, for example, in the article Elimination of Depth Degeneracy in Optical Frequency-Domain Imaging Through Polarization-Based Optical Demodulation, Vakoc et al., Opt Lett 31, 362 (2006), the content of which is incorporated herein by reference in its entirety), and harmonic lock-in detection of sinusoidal reference phase modulation (described, for example, in the article Resolving the Complex Conjugate Ambiguity in Fourier-Domain OCT by Harmonic Lock-In Detection of the Spectral Interferogram, Vakhtin et al., Opt Lett 31, 1271 (2006), the content of which is incorporated herein by reference in its entirety). Only a few of these techniques may be suitable for high-speed imaging (i.e., about 20 kHz A-scan rate), and of those many require expensive and cumbersome components (electro-optic of acousto-optic modulators, multiple spectrometers). Discretely stepped reference arm phase shifting techniques are limited by the response time of the PZT used.
Accordingly, for the reasons set forth above, it is desirable to provide improved FDOCT systems and methods for removing undesired artifacts. In particular, it is desirable to provide improved SDOCT systems and methods for providing biological sample images such as retinal images.
Methods, systems, and computer program products are disclosed that use integrating buckets techniques for removing undesired artifacts in Fourier domain optical coherence tomography (FDOCT) systems. According to one aspect, a method includes introducing a variable phase delay between a reference arm and a sample arm of an FDOCT interferometer using sinusoidal phase modulation. Further, the method includes acquiring an interferometric intensity signal using an integrating buckets technique. The method also includes resolving the interferometric intensity signal to remove undesired artifacts.
According to another aspect, an FDOCT system includes a reference arm and a sample arm of an FDOCT interferometer. The system also includes a phase controller configured to introduce a variable phase delay between the reference arm and the sample arm using sinusoidal phase modulation. Further, the system includes a signal receiver configured to acquire an interferometric intensity signal using an integrating buckets technique. The system also includes an artifact resolve function configured to resolve the interferometric intensity signal to remove undesired artifacts.
The subject matter described herein may be implemented using a computer program product comprising computer executable instructions embodied in a computer readable medium. Exemplary computer readable media suitable for implementing the subject matter described herein include chip memory devices, disc memory devices, application specific integrated circuits, programmable logic devices, and downloadable electrical signals. In addition, a computer program product that implements a subject matter described herein may reside on a single device or computing platform or maybe distributed across multiple devices or computing platforms.
Preferred embodiments of the subject matter described herein will now be explained with reference to the accompanying drawings of which:
Methods, systems, and computer program products are disclosed that use integrating buckets techniques to provide improvements for removing undesired artifacts in Fourier domain optical coherence tomography (FDOCT) systems. FDOCT images can be corrupted by complex conjugate artifacts such that positive and negative distances cannot be uniquely resolved. Typical FDOCT practice avoids this issue by utilizing half of the available imaging depth. However, imaging of extended pathologies can benefit from full field imaging since sensitivity is limited by the characteristic roll-off associated with the finite spectral resolution of SDOCT systems. Complex conjugate resolved images require acquiring phase and amplitude interferometric data. As described herein, methods, systems, and computer program products are provided for high-speed phase shifted interferogram acquisition using integrating buckets algorithm borrowed from phase-shift interferometry.
In some embodiments of the subject matter disclosed herein, FDOCT interferometers and computer program products for removing undesired artifacts in FDOCT systems use sinusoidal phase modulation. A variable phase delay can be introduced between a reference arm and a sample arm of an FDOCT interferometer using sinusoidal phase modulation. An interferometric intensity signal can be acquired using an integrating buckets technique. The interferometric intensity signal can be resolved to remove undesired artifacts. The FDOCT may include spectral domain optical coherence tomography (SDOCT).
The systems and methods disclosed herein can provide such improvements by sinusoidally driving a reference arm PZT and acquiring phase shifted interferograms by use of an integrating buckets algorithm. The systems and methods disclosed herein can be provided at low cost, can be simple to implement, and can allow for high-speed, in vivo, complex conjugate resolved imaging of a sample.
Referring to the graphs shown in
PZT element 118 can be controlled by a phase delay control function 126 of an FDOCT interferometer control unit 128, which may be a computer configured with suitable functions and input/output devices for operating the interferometer. Phase delay control function 126 can be configured to communicate a sinusoidal PZT driving signal to PZT element 118 for modulating the reference delay. The reference delay can be modulated sinusoidally during N integration buckets per modulation.
In one example, considering a spectrometer-based SDOCT system containing a sinusoidally vibrating mirror in the reference arm, the spectral interferometric SDOCT signal from a summation of m discrete sample reflectors each with reflectivity Am and position Δzm is given by:
In equation (1), ψ and θ are the amplitude and phase, respectively, of the vibrating mirror. The sinusoid frequency for N buckets is ω=2π/(N(τ+Δτ)). Any other suitable sinusoidal signal can be applied to the vibrating mirror. Detector 104 can be used to acquire or measure the spectral interferometric SDOCT signal. Further, detector 104 can be configured to communicate the acquired signal to control unit 128 for further processing to remove undesired artifacts.
In block 202, an interferometric intensity signal is acquired using an integrating buckets technique, which generally operates by integrating a charge acquired by a device such as a CCD over a portion of the cyclical phase modulation. The integrating buckets technique can include determining an integrating bucket over an integration time of detector 104. In particular, a signal receiver 130 of control unit 128 can be configured to receive the spectral interferometric signal measured by detector 104 over an integration time τ. The spectral interferometric SDOCT signal acquired by detector 104 can be phase shifted as a function of the amplitude and phase offset of the sinusoidal PZT driving signal. The amplitude and phase can be optimized for DC and complex conjugate artifact removal and minimal fringe washout.
Given this time-varying modulating signal, the interferometric intensity measured by the CCD (or detector) is the “integrating bucket” signal corresponding to the interferometric signal integrated over the acquisition time of the camera (detector), τ:
In equation (2), Δτ is any time delay of the CCD between sequential A-scans (i.e., camera read-out time), and
for N phase steps.
Rewriting the inteferometric signal sp(k,t) as a sum of Fourier components using Bessel functions of the first kind, the integration in equation (2) can be carried out as (considering a single reflector for simplicity):
I=A
m{cos [2kΔzm]Gp(ψ,θ)−sin [2kΔzm]Hp(ψ,θ)}. (3)
In equation (3), Gp(ψ,θ) and Hp(ψ,θ) are the time-averaged values of the phase modulating signal for the pth integrating bucket and can be represented by the following equations:
By setting the constraints GP (ψ,θ)=cos [φp] and Hp(ψ,θ)=sin [φp], equation (3) reduces to a measured inteferometric signal with a constant phase shift, φp, for each pth step. Values for ψ and θ can then be derived to satisfy these constraints and optimized to reduce fringe washout due to axial motion during each A-scan. Phase shift φp can be converted to axial displacement by zp=φp/(2k0), where k0 is the central wavenumber of the system. Using the sum of angles definition, the recorded interferometric signal becomes discretely stepped cos [α±β]=cos α cos β±sin α sin β (sum of angles), ID=Am{cos [2kΔzm]Gp(ψ,θ)−sin [2kΔzm]Hp(ψ,θ)}=Am cos [2kΔzm+φp] (detected photocurrent of pth phase step of mth reflector).
In another example, Gp(ψ,θ) and Hp(ψ,θ) can be represented by the following equations:
In block 204, an artifact resolve function 132 resolves the interferometric intensity signal to remove undesired artifacts. The measured interferometric signal can then be complex conjugate resolved using a quadrature projection algorithm which is insensitive to chromatic or mis-calibrated phase shifts, which may be directly applied to the integrating bucket-derived phase shifts without modification. Quadrature projection can remove phase noise due to chromaticity of the source and system instability by subtracting the inherent phase offset for each frame. Quadrature components are then calculated for each phase shifted signal by a Fourier decomposition into real and imaginary components. The image can then be complex conjugate resolved by combining the real and imaginary components for each reflector.
The subject matter disclosed herein may be implemented in an FDOCT retinal imaging system.
Reference arm 304 is terminated with a piezo-mirror combination generally designated 314, where a PZT element 316 is driven by a phase control function 126 to sinusoidally oscillate a mirror 318. PZT element 316 as a displacement range of 4.6±1.5 μm at 150 V and internal capacitance of 0.02 μF. Function 126 is synchronized using the output TTL from a CCD generally designated 320.
The spectral interferometric signal can be acquired by detector 104. In this example, detector 104 is a 1024-pixel line-scan CCD. Suitable software contained on control unit 128 can provide real-time acquisition and display functionality. In one experiment, images of the retina were acquired at a 1024 pixels/A-scan at an integration time of 18 μs with a time delay of ˜1 μs per A-scan (corresponding to an A-scan capture rate of 51.9 kHz). An integrating bucket phase stepping algorithm was solved for four integrating buckets and a galvanometer was programmed to acquire four sequential A-scans per lateral location. Densely sampled 3000 line images were captured at 4.33 frames/second. A complex conjugate suppression quadrature projection algorithm was computed during post-processing using MATLAB® 7.1 software available from The MathWorks, Inc., of Natick, Me. Mirror 318 and sample arm galvanometers were aligned to reduce phase noise.
Meshes for Gp(ψ,θ) and Hp(ψ,θ) (shown in
Interferograms acquired for integrating bucket phase steps, 1, 4 and 2, 3 showed decreased fringe amplitude (as shown in
Integrating bucket algorithm performance was quantified using a calibrated reflector in the sample arm. A-scans, acquired at the full scan rate of 51.9 kHz, were complex conjugate resolved. For example,
The experiments include applying the integrating buckets algorithm to in vivo normal retina. In particular, in vivo B-scans of retina with 1024 pts/line, 3000 lines/frame, and 5 mm lateral distance were obtained.
In another experiment with the system shown in
In yet another experiment with the system shown in
In this experiment, acquired integrating bucket spectral interferograms showed decreased fringe amplitude as compared with acquisition with a stationary reference mirror, due to fringe washout. Phase steps 1-2 and 3-4 yielded amplitude decreases of 1.2 dB, while steps 2-3 and 1-4 showed decreases of 6.7 dB. These phase steps corresponded to phase shifts of φ=π/2 and φ=π, respectively, where more significant washout corresponded to larger phase shifts during which the integrating bucket was acquiring over the high-velocity linear portions of the driving sinusoid. Smaller phase steps corresponded to integrating periods over the lower-velocity peak and troughs of the driving signal.
Maximum complex conjugate suppression was measured using a −60 dB calibrated reflector in the sample arm. Complex conjugate corrupted and resolved A-scans are presented in
Complex conjugate unresolved and revolved images of optic nerve head are shown in
Thus, the system used in the experiments acquired discrete phase shifted interferograms using a sinusoidally oscillating reference mirror with integrating buckets algorithm. The technique was demonstrated for four phase steps on a calibrated reflector and in vivo normal retina.
It will be understood that various details of the presently disclosed subject matter may be changed without departing from the scope of the presently disclosed subject matter. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation.
The presently disclosed subject matter claims the benefit of U.S. Provisional Patent Application Ser. No. 60/880,916, filed Jan. 17, 2007, the disclosure of which is incorporated herein by reference in its entirety.
This presently disclosed subject matter was made with U.S. Government support under Grant Nos. R21 RR019769 and R21 EY017393 awarded by National Institutes of Health (NIH). Thus, the U.S. Government has certain rights in the presently disclosed subject matter.
Number | Date | Country | |
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60880916 | Jan 2007 | US |