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IEEE PHOTONICS TECHNOLOGY LETTERS, VOL. 22, NO. 20, OCTOBER 15, 2010

Gas-Cell Referenced Swept Source Phase Sensitive Optical Coherence Tomography Roman V. Kuranov, Austin B. McElroy, Nate Kemp, Stepan Baranov, Joe Taber, Marc D. Feldman, and Thomas E. Milner Abstract—Distinct reference and signal interferometers in combination with a gas-cell spectral reference are employed to increase sensitivity and environmental stability of a swept source phase-sensitive optical coherence tomography. A displacement sensitivity (DS) of 65 pm at 280- m depth and DS degradation with depth of 0.0015 rad/mm is achieved. Differential DS of 234 pm in a 127- m-thick scattering phantom is six-fold superior to previously reported values. DS degradation with a depth of 0.026 rad/mm is reported for tissue-like scattering phantoms. Measured depth-dependent DS suggests that digitization time jitter noise contributes to degradation of phase sensitivity with depth. Index Terms—Biomedical optical imaging, optical coherence tomography (OCT), phase measurements.

HASE-SENSITIVE optical coherence tomography (PhS OCT) [1], [2] provides tens of picometers of displacement sensitivity [3], [4]. Unlike detecting amplitude of interference fringes in intensity OCT [5], in PhS OCT phase of the fringes is tracked between successive A-scans. In early studies, PhS-OCT was aimed to detect blood flow in tissues at a fixed depth [1], [2]. Recently, new applications including pico-scale microscopy [3], photothermal [6], [7], or magnetomotive OCT [8], [9] were reported. Time-domain PhS-OCT systems suffered from slow acquisition rates (50–250 A-scans/s [1], [2]) and poor displacement sensitivity: DS pm [2]. Fourier domain (FD) OCT substantially increases both DS (5000 pm) and acquisition rate (10 kA-scans/s) [10]. We distinguish three types of FD OCT systems: 1) spectral domain OCT, or “Spectral OCT” [3], [10]; 2) polygon mirror swept source OCT, or “Polygon-Mirror OCT” [11]; 3) Fourier domain mode-locked swept source OCT, or “FDML OCT” [4]. Broadband-laser-based Spectral OCT has the highest DS of 25 pm (39 kA-scans/s) [3], but due to the lack of balanced detection, its dynamic range, signal-to-noise ratio (SNR), and DS are limited compared with tunable-laser-based OCTs in scattering tis-

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Manuscript received December 16, 2009; revised June 08, 2010; accepted June 19, 2010. Date of publication July 01, 2010; date of current version September 24, 2010. This work was supported in part by the VA Merit grant. R. V. Kuranov was with Volcano Corporation, San Antonio, TX 78247 USA. He is now with the Department of Ophthalmology, University of Texas Health Science Center, San Antonio, TX 78229 USA (e-mail: [email protected]). A. B. McElroy, N. Kemp, and J. Taber are with Volcano Corporation, Billerica, MA 01821S USA (e-mail: [email protected]; [email protected]; [email protected]). S. Baranov is with the Department of Biomedical Engineering, University of Houston, Houston, TX 77204 USA (e-mail: [email protected]). M. D. Feldman is with the Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229 USA (e-mail: [email protected]). T. E. Milner is with the Biomedical Engineering Department, University of Texas, Austin, TX 78712 USA (e-mail: [email protected]). Color versions of one or more of the figures in this letter are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/LPT.2010.2055842

sues. FDML OCT systems (39 pm at 42 kA-scans/s and 102 pm at 370 kA-scans/s [4]) have superior DS and faster acquisition rates over Polygon-Mirror OCT (475 pm at 16 kA-scans/s [11] and 226 pm at 2 kAscans/s [4]), but stability, needed for clinical applications, faces challenges due to polarization-mode dispersion and optical pathlength fluctuations in kilometer-long fiber ring laser cavities [12]. In tunable-laser-based PhS OCTs, the minimal phase values have been reported to be limited [11] by a combination of factors including: 1) SNR of a reference spike; 2) SNR of the signal; 3) the ratio between sampling depth and reference reflector offset mm (1) where is the depth pixel index. In previous reports, either the degradation of phase sensitivity with depth was poor rad/mm (SNR dB, mm [11]) or when DS is less than 100 pm [3], [4], measurements were limited to single surfaces of thin glass slides ( 0.21 mm) [3], [4], or cells ( 0.05 mm). Unfortunately, approaches using a front surface of the sample for a reference to avoid environmental vibration are not suitable for achieving DS less than 1 nm in scattering objects since light power reflecting from a front surface can have low SNR and is unpredictable. Here, we improved sensitivity by an order of magnitude over Polygonal-Mirror PhS OCT systems [11] and suggest (1) to be modified to predict phase degradation with depth . In our single-mode fiber-based PhS-OCT system (Fig. 1), light from a 20-kHz polygon mirror tunable laser (HSL-2000, Santec Corp.) is directed into four optical subsystems (I–IV). Subsystem I is a common path signal interferometer where interference fringes are formed between light reflected from a 96/4 splitter (SP1) and the sample. Subsystem II is a real-time clock based on a Mach–Zehnder interferometer providing the analog-to-digital converter (ADC) with a uniform-frequency optical clock signal. Subsystem III is a gas-cell-based spectral trigger which triggers ADC-card acquisition of each A-scan. Subsystem IV is a common path reference interferometer which removes wavenumber jitter that are identical in signal and reference interferometers. In subsystem I, a 95/5 coupler and a circulator (C1) are used for detection with a balanced photoreceiver and digitization with a 16-bit ADC (ATS660 Alazar Technologies Inc). The sample holder and the 96/4 splitter are fastened to a fixture to minimize pathlength variations between the sample and reference surface. The fixture allowed recording depth-dependent measurements without requiring a reference light from the sample [3], [4], thus preserving optically limited phase sensitivity in scattering objects. The digitized signal is windowed (Hanning) and Fourier transformed to calculate amplitude and phase [4].

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1.2-pm uncertainty. Output of the balanced photoreceiver consists of pulses corresponding to HF absorbance peaks at known optical frequencies (i.e., specific molecular energy levels). We converted centers of the absorbance peaks to zero crossings and produce 0.3-ps digital pulses. We select one pulse corresponding HF absorbance peak nm to to the serve as a spectral trigger. Subsystem IV subtracts phase jumps between successive A-scans starting at different wavenumbers: , where is the wavenumber jump between successive A-scans, originating from: 1) a one-clock period uncertainty due to lack of correlation between sample clock and trigger. 2) A-scan trigger is not associated to a fixed wavenumber. Phase jumps that do not exceed can be removed using a calibration interference signal [11] (2)

Fig. 1. Gas-cell based phase-sensitive OCT system. C1,2—circulators; SP1,2 beam splitters; SCD—single channel detector; DL—delay line

is the phase in the reference interfererence calculated where at , is the phase in the signal interfererence at . In our experiments, phase jump due to a one-clock period unrad, where certainty m/s is the laser sweep rate, nm. The condition that phase jumps do not exceed rad gives a wavelength uncertainty of the A-scan trigger (3)

Fig. 2. OCT point spread function from single reflector at increasing depths using a uniform k-space (blue), linearly interpolated time-domain (red) clock.

Subsystem II allows correct sampling and displaying of signal amplitude and phase in real-time. Because most swept source lasers have a nonlinear sweep rate (i.e., constant), uniformly time-sampled fringes produce a dispersion effect resulting in degradation of the point spread function and reduced SNR with increasing scan depth. Dispersion could be minimized by resampling [13] or a real-time uniform frequency clock approach [14]. Resampling of time-domain data is twice intensive (two digitizing channels are needed) and less efficient compared with a uniform-frequency clock approach (Fig. 2). We report a uniform frequency real-time clock approach for low duty cycle (65% in our case) tunable lasers versus lasers with a duty cycle close to 100% [14]. Here, when amplitude of the uniform-frequency optical clock MHz falls below a threshold value, a pseudoclock is substituted. The pseudoclock provides the ADC a clock signal to maintain uninterrupted operation while no OCT data is acquired in this time interval. Our uniform frequency clock preserves the original point spread function through the entire scan depth ( mm in air) and allows real-time display (39 frames/s of 512 400 pixels) of amplitude and phase M-Mode images. Subsystem III provides a spectral trigger using hydrogen fluoride (HF) gas cell (Wavelength Reference, HF-50) ensuring a temperature/pressure-independent A-scan start wavelength with

where . Center wavelength of fiber Bragg gratings (FBGs), used for A-scan trigger generation [11], depend sharply on temperature and pressure. To satisfy the condition (3) for successful implementation of FBG in the PhS OCT temperature should be stabilized within 2.8 C [15] while the uncertainty in fiber bending curvature should be less than 0.08 m [16]. We separate reference (Subsystem IV) and signal fringes (Subsystem I) into two independent ADC channels to avoid autocorrelation noise between reference spike and signal [11]. This allowed us to achieve SNR dB for the reference spike improving phase sensitivity degradation with depth by an order-of-magnitude compared to previous approaches [11]. Measured phase sensitivity degradation with depth using a mirror in the signal interferometer is shown in Fig. 3. Here, we placed a reflecting mirror in the sample path of the signal interferometer at different distances from splitter SP1. First, we as used in phase microscopy, measured DS is standard deviation (SD) of the phase at a fixed where mirror position through a single M-scan. The DS decreased from 65 3.7 pm at a depth of 280 m to 325 16 pm at a depth of 1900 m. Next, using (1), we calculated SNR-limited DS, DS . DS at 280 m is limited by SNR (1) and the difference between DS and DS at 380 m is statistically insignificant , while for deeper depths, the difference between DS and DS is statistically significant . Our system has measured phase degradation with a depth of rad/mm—1.7 times greater than the rad/mm predicted by (1). Since measured phase degradation is highly linear with depth , the authors explain the difference of 0.00062 rad/mm between predicted and experimental values by a time jitter between signal and reference ADC channel digitizing events (4)

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IEEE PHOTONICS TECHNOLOGY LETTERS, VOL. 22, NO. 20, OCTOBER 15, 2010

temperature and pressure stable and has a DS 7 times better than previously reported values for Polygon Mirror OCT systems [11]. DDS of our PhS-OCT system in scattering media is better than 1 nm up to an 864- m scan depth and is superior to any reported PhS-OCT system. Finally, an algebraic expression including time-jitter noise (5) gives degradation of phase sensitivity with depth consistent with experimental values. REFERENCES Fig. 3. Measured DS—black diamonds, DDS—blue circles, DS —red squares and calculated DS —dashed grey line. Solid lines are linear fits to the data.

where is the time jitter between the trigger and ADC assumes independent jitter in the digitization. The factor of two ADC channels. Minimal phase values that can be detected with tunablelaser-based PhS OCT systems with ADC time-jitter is modified from (1) to (5) Including the time jitter contribution to , our experimental phase degradation with depth (0.0015 rad/mm) is consistent ps per channel. We estimated DS with a time jitter degradation with increasing scan depth due to uncertainty in between ADC channels the start time/wavelength DS by fitting the measured DS and SNR-limited DS (first two points not included) with straight lines and subtracting the acquired DS from DS (gray dashed line in Fig. 3). The measured differential displacement DDS DS relevant to Doppler blood flow measurements [4] is close to the expected value DDS DS for independent successive A-scans. Finally, we examined the system-limited DS and DDS through scattering tissue phantoms using four cylindrical teflon tubes with a 1.6-mm inner diameter and different wall thicknesses. The DS and DDS were measured from the inner surface of the teflon tubes ( , reduced scattering coefficient mm at nm [17]) in the same manner as for DS and DDS. The teflon tubes’ scattering properties are close to those in biological tissues [17] and a cylindrical geometry introduces surface effects similar to those in blood vessels. We observe degradation of the sensitivity of both 179 4.3 pm DS and 234 9.5 pm DDS at a 127 m tube thickness and down to 3670 270 pm DS and 5000 410 pm DDS at 1300- m tube thickness. Sensitivities of 510 12.7 pm DS and 687 18.6 pm DDS at 407 m and 713 12.4 pm DS and 992 18.9 pm DDS at 864 m tube thicknesses were measured. The estimated phase degradation with increasing depth in scattering media was 0.026 rad/mm. To our knowledge, this is the first report of measurement of the OCT DS with increasing depth in scattering media and first reported PhS OCT instrument that can provide a DDS better than 1 nm in scattering media. In conclusion, we have reported a novel PhS OCT system that achieves high phase sensitivity (65 pm). The PhS-OCT system is

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