Real-time, high velocity-resolution color Doppler optical coherence tomography

Color Doppler optical coherence tomography (CDOCT) is a noninvasive optical imaging technique for micrometer-scale physiological flow mapping simultaneously with morphological optical coherence tomography imaging. We have developed a novel CDOCT signal-processing strategy capable of imaging physiological flow rates at 8 frames/s. Our new strategy features hardware-implemented digital autocorrelation across subsequent scans, permitting us to measure 300-Hz-8-kHz Doppler shifts upon signals of 0.6-MHz bandwidth. The performance of the CDOCT system was demonstrated in a flow phantom and in vivo in Xenopus laevis.     

Velocity-estimation accuracy and frame-rate limitations in color Doppler optical coherence tomography

Color Doppler optical coherence tomography (CDOCT) is a recent innovation that allows spatially localized flow-velocity mapping simultaneously with microstructural imaging. We present a theoretical model for velocity-image formation in CDOCT. The proportionality between the heterodyne detector current Doppler power spectrum in CDOCT and the optical source power spectrum is established. We show that stochastic modifications of the Doppler spectrum by fluctuating scatterer distributions in the flow field give rise to unavoidable velocity-estimation inaccuracies as well as to a fundamental trade-off between image-acquisition rate and velocity precision. Novel algorithms that permit high-fidelity depth-resolved measurements of velocities in turbid media are also reported.     

High-flow-velocity and shear-rate imaging by use of color Doppler optical coherence tomography

Color Doppler optical coherence tomography (CDOCT) is capable of precise velocity mapping in turbid media. Previous CDOCT systems based on the short-time Fourier transform have been limited to maximum flow velocities of the order of tens of millimeters per second. We describe a technique, based on interference signal demodulation at multiple frequencies, to extend the physiological relevance of CDOCT by increasing the dynamic range of measurable velocities to hundreds of millimeters per second. The physiologically important parameter of shear rate is also derived from CDOCT measurements. The measured flow-velocity profiles and shear-rate distributions correlate very well with theoretical predictions. The multiple demodulation technique, therefore, may be useful to monitor blood flow in vivo and to identify regions with high and low shear rates.     

Quantification of color alteration in human teeth with optical coherence tomography

It is necessary to develop a laboratory model to evaluate tooth discoloration, because there are several limitations to assessment methods at present stage. Therefore, in this letter, we report the results from a pilot study on using optical coherence tomography imaging method to quantify color alteration in the human teeth treatment with 35% hydrogen peroxide bleaching in vitro. Quantitative comparison of chromogens reduction in dental tissue showed that near infrared attenuation coefficient (μ) increased for enamel with the bleaching passage time and diminution for dentine. Therefore, the precise detection of the change in attenuation coefficient is can accurate quantitative chromogens alteration in tooth. OCT has a potential to become a useful tool for the assessment color alteration in human teeth.     

Interstitial Doppler optical coherence tomography

Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution but has limited imaging depth. We report a novel, linear-scanning, needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system with a 19-guage (diameter of approximately 0.9 mm) echogenic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge, this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.     

相关多普勒光学层析成像

提出了基于互相关的多普勒OCT(correlated Doppler optical coherence tomography, CD-OCT)方法, 能够有效的抑制噪声, 实现低信噪比条件下的流速探测. 对CD-OCT算法进行了详细的推导, 分析了噪声的相关性对该算法结果的影响, 最后基于谱域和时域联合探测方法(joint spectral and time domain optical coherence tomography, STD-OCT)以及CD-OCT算法的对比实验证明了该算法能够进一步实现信噪比的提高, 使测量的结果更为稳定.     

Self-referenced Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) allows simultaneous micrometer-scale resolution cross-sectional imaging of tissue structure and blood flow. We demonstrate a fiber-optic polarization-diversity-based differential phase contrast DOCT system as a method to perform self-referenced velocimetry in highly scattering media. Using this strategy, we reduced common-mode interferometer noise to <1 Hz and improved Doppler estimates in a scattering flow phantom by a factor of 5.     

Higher-order cross-correlation-based Doppler optical coherence tomography

A method based on higher-order cross-correlation is proposed to fetch the Doppler information on flow velocity within areas under low signal-to-noise ratio (SNR) by spectral domain optical coherence tomography. The proposed method is theoretically developed and validated by measurement of a moving mirror with known velocities. Standard deviations of flow velocities of the mirror under different SNRs are determined by the proposed method and compared with those by the modified phase-resolved method. Measurement of flowing particles within a glass capillary is also conducted, and Doppler flow velocity maps of the glass capillary are reconstructed by both methods. All experimental results demonstrate that the proposed method can significantly suppress noise, thus rendering it suitable for flow measurement under low SNR cases.     

Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography

The possibility of measuring a full Doppler flow depth profile in parallel by use of frequency-domain optical coherence tomography is demonstrated. The method is based on a local phase analysis of the backscattered signal and allows for imaging of bidirectional Doppler flow. The Doppler frequency limit is 5 kHz for the presented measurements and is set by half of the frame rate of the CCD detector array. We measured the flow of 0.3-microm microspheres suspended in distilled water at controlled flow rates and in vitro human blood flow through a 200-microm capillary with a real-time color-encoded Doppler tomogram rate of 2-3/s.     

Imaging needle for optical coherence tomography

We describe a miniature optical coherence tomography (OCT) imaging needle that can be inserted into solid tissues and organs to permit interstitial imaging of their internal microstructures with micrometer scale resolution and minimal trauma. A novel rotational coupler with a glass capillary tube is also presented that couples light from a rotating single-mode fiber to a stationary one. A prototype needle with a 27-gauge (~410-mum) outer diameter has been developed and is demonstrated for in vivo imaging. The OCT needle can be integrated with standard excisional biopsy devices and used for OCT-guided biopsy.     

Imaging and quantifying transverse flow velocity with the Doppler bandwidth in a phase-resolved functional optical coherence tomography

The Doppler bandwidth extracted from the standard deviation of the frequency shift in phase-resolved functional optical coherence tomography (F-OCT) was used to image the velocity component that is transverse to the optical probing beam. It was found that above a certain threshold level the Doppler bandwidth is a linear function of flow velocity and that the effective numerical aperture of the optical objective in the sample arm determines the slope of this dependence. The Doppler bandwidth permits accurate measurement of flow velocity without the need for precise determination of flow direction when the Doppler flow angle is within +/-15 degrees perpendicular to the probing beam. Such an approach extends the dynamic range of flow velocity measurements obtained with the phase-resolved F-OCT.     

Doppler optical coherence tomography in cardiovascular applications

The study of flow dynamics in complex geometry vessels is highly important in various biomedical applications where the knowledge of the mechanic interactions between the moving fluid and the housing media plays a key role for the determination of the parameters of interest, including the effect of blood flow on the possible rupture of atherosclerotic plaques. Doppler Optical Coherence Tomography (DOCT), as a functional extension of Optical Coherence Tomography (OCT), is an optic, non-contact, noninvasive technique able to achieve detailed analysis of the flow/vessel interactions. It allows simultaneous high resolution imaging (∼10 μm typical) of the morphology and composition of the vessel and determination of the flow velocity distribution along the measured cross-section. We applied DOCT system to image high-resolution one-dimensional and multi-dimensional velocity distribution profiles of Newtonian and non-Newtonian fluids flowing in vessels with complex geometry, including Y-shaped and T-shaped vessels, vessels with aneurism, bifurcated vessels with deployed stent and scaffolds. The phantoms were built to mimic typical shapes of human blood vessels, enabling preliminary analysis of the interaction between flow dynamics and the (complex) geometry of the vessels and also to map the related velocity profiles at several inlet volume flow rates. Feasibility studies for quantitative observation of the turbulence of flows arising within the complex geometry vessels are discussed. In addition, DOCT technique was also applied for monitoring cerebral mouse blood flow in vivo. Two-dimensional DOCT images of complex flow velocity profiles in blood vessel phantoms and in vivo sub-cranial mouse blood flow velocities distributions are presented.     

Imaging of human breast tissue using polarization sensitive optical coherence tomography

We report a study on the use of polarization sensitive optical coherence tomography (PSOCT) for discriminating malignant (invasive ductal carcinoma), benign (fibroadenoma) and normal (adipocytes) breast tissue sites. The results show that while conventional OCT, that utilizes only the intensity of light back-scattered from tissue microstructures, is able to discriminate breast tissues as normal (adipocytes) and abnormal (malignant and benign) tissues, PS-OCT helps in discriminating between malignant and benign tissue sites also. The estimated values of birefringence obtained from the PSOCT imaging show that benign breast tissue samples have significantly higher birefringence as compared to the malignant tissue samples.     

Imaging magnetically labeled cells with magnetomotive optical coherence tomography

We introduce a novel contrast mechanism for optical coherence tomography (OCT) whereby the optical scattering of magnetically labeled cells is modified by means of an externally applied magnetic field. This modification is made through the addition of a small electromagnet to the imaging arm of a conventional OCT interferometer. We measure the magnetomotive OCT signal by differencing pairs of axial scans (A-scans) acquired with the magnetic field on and off. Magnetomotive contrast is demonstrated in bulk three-dimensional cell scaffolds containing macrophages labeled with microparticles of iron oxide, demonstrating magnetic-specific contrast over a dynamic range of 30 dB.     

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-microm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.     

In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography

An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 microm at ultrahigh speed and with an ocular exposure level of less than 600 microW.     

Real-time detection technique for Doppler optical coherence tomography

We propose and demonstrate a novel detection technique, based on a modified electronic phase-locked loop, for Doppler optical coherence tomography. The technique permits real-time simultaneous reflectivity and continuous, bidirectional velocity mapping in turbid media over a wide velocity range with minimal sensitivity penalty compared with conventional optical coherence tomography, which is a major advance over current postprocessing and discrete parallel detection techniques.     

Phase-referenced Doppler optical coherence tomography in scattering media

We present a fiber-based, low-coherence interferometer that significantly reduces phase noise by incorporating a second, narrowband, continuous-wave light source as a phase reference. By incorporating this interferometer into a Doppler OCT system, we demonstrate significant velocity noise reduction in reflective and scattering samples using processing techniques amenable to real-time implementation. We also demonstrate 90% suppression of velocity noise in a flow phantom.     

光学相干层析术用于鲜红斑痣诊断

光学相干层析术(optical coherence tomography,简称OCT)具有非侵入性,高分辨及高速成像的优点,特别适合于生物医学领域。但由于大部分生物组织具高散射系数,通常仅能对表层组织下数毫米深度内进行成像。穿透深度不足限制了OCT在皮肤科等领域应用。作为常见多发病的鲜红斑痣具有病变组织浅,血管增生明显等特点,所以OCT非常适于鲜红斑痣的检测。通过选择皮肤穿透性好的中心波长为1310nm超辐射二极管,合理优化样品臂和参考臂光强比例及偏振控制,实现了对鲜红斑痣在体成像研究,采集了清晰的OCT图像,得到其关键特征参数,如表皮层厚度,血管直径等,对鲜红斑痣的诊断及制定合理治疗方案具有重要意义。     

Cerebral blood flow imaged with ultrahigh-resolution optical coherence angiography and Doppler tomography

Speckle contrast based optical coherence angiography (OCA) and optical coherence Doppler tomography (ODT) have been applied to image cerebral blood flow previously. However, the contrast mechanisms of these two methods are not fully studied. Here, we present both flow phantom and in vivo animal experiments using ultrahigh-resolution OCA (μOCA) and ODT (μODT) to investigate the flow sensitivity differences between these two methods. Our results show that the high sensitivity of μOCA for visualizing minute vasculature (e.g., slow capillary beds) is due to the enhancement by random Brownian motion of scatterers (e.g., red and white blood cells) within the vessels; whereas, μODT permits detection of directional flow below the Brownian motion regime (e.g., laser-induced microischemia) and is, therefore, more suitable for brain functional imaging.