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.     

Simultaneous intensity, birefringence, and flow measurements with high-speed fiber-based optical coherence tomography

We demonstrate that tissue structure, birefringence, and blood flow can be imaged simultaneously by use of techniques of polarization-sensitive optical coherence tomography and phase-resolved optical Doppler tomography. An efficient data-acquisition procedure is implemented that optimizes the concurrent processing and display of all three image types. Images of in vivo human skin acquired with a high-speed fiber-based system are presented.     

Real-time phase-resolved functional optical coherence tomography by use of optical Hilbert transformation

We have developed a novel real-time phase-resolved functional optical coherence tomography system that uses optical Hilbert transformation. When we use a resonant scanner in the reference arm of the interferometer, with an axial scanning speed of 4 kHz, the frame rate of both structural and Doppler blood-flow imaging with a size of 100 by 100 pixels is 10 Hz. The system has high sensitivity and a larger dynamic range for measuring the Doppler frequency shift that is due to moving red blood cells. Real-time images of in vivo blood flow in human skin obtained with this interferometer are presented.     

Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity

We have developed a novel phase-resolved optical coherence tomography (OCT) and optical Doppler tomography (ODT) system that uses phase information derived from a Hilbert transformation to image blood flow in human skin with fast scanning speed and high velocity sensitivity. Using the phase change between sequential scans to construct flow-velocity imaging, this technique decouples spatial resolution and velocity sensitivity in flow images and increases imaging speed by more than 2 orders of magnitude without compromising spatial resolution or velocity sensitivity. The minimum flow velocity that can be detected with an axial-line scanning speed of 400 Hz and an average phase change over eight sequential scans is as low as 10 microm/s, while a spatial resolution of 10 microm is maintained. Using this technique, we present what are to our knowledge the first phase-resolved OCT/ODT images of blood flow in human skin.     

光学相干层析多普勒成像功能拓展研究

光学多普勒成像(Optical Doppler tomography,ODT)是一种结合了光学相干层析成像技术(Opticalcoherence tomography,OCT)和多普勒流速仪的非侵入、非接触的成像技术,能够实现对高散介质组织内部的血管分布和血液流速的探测。阐述了基于数字希尔伯特变换的相位分离多普勒光学相干层析成像技术的工作原理,并且通过对玻璃毛细管和生物芯片微通道管中聚苯乙烯溶液流速的实验测量,准确测量管内微粒缓慢移动时的多普勒频移量,获得了玻璃管内和生物芯片微通道管中流速分布曲线,证实了所提方法的可行性。获取的多普勒图像具有较高的空间分辨力和速度分辨力,在未来的临床应用中有潜在的应用价值。     

Real-time flow imaging by removing texture pattern artifacts in spectral-domain optical Doppler tomography

We present a new, simple method to suppress texture pattern artifacts induced by the optical heterogeneity of tissues to improve the performance of flow imaging for real-time phase-resolved optical Doppler tomography. The method performs transverse scanning of the probe beam in the forward and then reverse directions, and it takes average of the spatial phase changes between them to obtain the final velocity image. It relies on the fact that the phase changes between successive axial scans due to the optical heterogeneity of the sample are time independent, while those due to the moving particles are time dependent. We experimentally demonstrate this method by real-time imaging of a flow phantom.     

Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography

We report the development of an optical technique for noninvasive imaging of in vivo blood flow dynamics and tissue structures with high spatial resolution (2-10 microm) in biological systems. The technique is based on optical Doppler tomography (ODT), which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations. The exceptionally high resolution of ODT permits noninvasive in vivo imaging of both blood microcirculation and tissue structures surrounding the vessel, which has significance for biomedical research and clinical applications. Tomographic imaging of in vivo blood flow velocity in the chick chorioallantoic membrane and in rodent skin is demonstrated.     

光学多普勒层析三维矢量测速方法研究

光学多普勒层析术(ODT)是一种高分辨、非侵入的生物医学成像手段,能同时得到组织的结构信息和组织内血管的流速信息.提出了一种新型的基于相位分辨技术的ODT三维矢量测速方法.在ODT系统样品臂的准直镜和聚焦透镜之间加入窄带相位片,形成三个不同的相位延迟,通过计算多普勒频移和不同相位延迟下的多普勒展宽,可得到毛细管内的三维矢量流场分布.对已知浓度的聚苯乙烯溶液进行了一系列不同角度和不同流速的实验,结果证明这种新型的ODT矢量测速方法可以较精确的实现三维矢量流速的测量.     

Speckle variance detection of microvasculature using swept-source optical coherence tomography

We report on imaging of microcirculation by calculating the speckle variance of optical coherence tomography (OCT) structural images acquired using a Fourier domain mode-locked swept-wavelength laser. The algorithm calculates interframe speckle variance in two-dimensional and three-dimensional OCT data sets and shows little dependence to the Doppler angle ranging from 75 degrees to 90 degrees . We demonstrate in vivo detection of blood flow in vessels as small as 25 microm in diameter in a dorsal skinfold window chamber model with direct comparison with intravital fluorescence confocal microscopy. This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.     

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.     

Hemoglobin contrast in magnetomotive optical Doppler tomography

We introduce a novel contrast mechanism for imaging blood flow by use of magnetomotive optical Doppler tomography (MM-ODT), which combines an externally applied temporally oscillating high-strength magnetic field with ODT to detect erythrocytes moving according to the field gradient. Hemoglobin contrast was demonstrated in a capillary tube filled with moving blood by imaging the Doppler frequency shift, which was observed independently of blood flow rate and direction. Results suggest that MM-ODT may be a promising technique with which to image blood flow.     

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.     

Phase-resolved Doppler optical coherence tomography--limitations and improvements

We describe how the simple phase difference averaging causes a systematic bias in the velocity estimation obtained by phase-resolved Fourier domain optical coherence tomography (FdOCT). The magnitude of this bias depends on the signal-to-noise ratio as well as proximity of the measured velocity to the limits of the velocity range. We demonstrate the proper way of data processing, which enables obtaining velocity values free of this error. We validate the improved technique by measurements of flow velocity in glass capillaries, in human retinal vessels, and we compare the results with those obtained by standard phase-resolved FdOCT.     

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.     

Full range complex ultrahigh sensitive optical microangiography

This Letter presents a useful method that combines the full range complex Fourier domain optical coherence tomography (OCT) with the ultrahigh sensitive optical microangiography (OMAG) to achieve full range complex imaging of blood flow within microcirculatory tissue beds in vivo. We propose to use the fast scanning axis to realize the full range complex imaging, while using the slow axis to achieve OMAG imaging of blood flow. We demonstrate the proposed method by using a high speed 1310?nm OCT/OMAG system running at 92?kHz line scan rate to image the flow phantoms in vitro, and the blood flows in tissue beds in vivo.     

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.     

Doppler angle and flow velocity mapping by combined Doppler shift and Doppler bandwidth measurements in optical Doppler tomography

Accurate estimation of flow velocity requires measurement of Doppler angle, which is not available in general clinical applications. We describe a novel method of direct Doppler angle and flow velocity mapping that uses a conventional single-beam optical Doppler tomography system. The Doppler angle is estimated by combination of Doppler shift and Doppler bandwidth measurements, and flow velocity is calculated from the Doppler shift and the estimated Doppler angle. In vivo study of lip microvascularization demonstrates that this method is capable of providing both flow speed and flow direction information.     

Intraluminal fiber-optic Doppler imaging catheter for structural and functional optical coherence tomography

We describe a miniature fiber-optic Doppler imaging catheter for integrated functional and structural optical coherence tomography (OCT) imaging. The Doppler catheter can map blood flow within a vessel as well as image vessel wall structures. A prototype Doppler catheter has been developed and demonstrated for measuring the intraluminal velocity profile in a vessel phantom (conduit). A simple mathematical model is demonstrated to estimate the total flow rate. This estimation technique also enables the spatial range of flow measurements to be extended by approximately two times the normal OCT image-penetration depth. The Doppler OCT catheter could be a powerful device for cardiovascular imaging.     

Doppler-based lateral motion tracking for optical coherence tomography

Nonuniform lateral scanning of the probe beam in optical coherence tomography produces imaging artifacts and leads to a morphologically inaccurate representation of the sample. Here, we demonstrate a solution to this problem, which is based on the Doppler shift carried by the complex-valued depth-resolved scattering amplitude. Furthermore, we demonstrate the feasibility of Doppler flow velocity measurements in underlying flow channels while laterally scanning the imaging probe over large surfaces with arbitrary and varying velocity. Finally, we performed centimeters-long hand-held B-mode imaging of skin in vivo.