Imaging and velocimetry of the human retinal circulation with color Doppler optical coherence tomography

Noninvasive monitoring of blood flow in retinal microcirculation may elucidate the progression and treatment of ocular disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Color Doppler optical coherence tomography (CDOCT) is a technique that allows simultaneous micrometer-scale resolution cross-sectional imaging of tissue microstructure and blood flow in living tissues. CDOCT is demonstrated for the first time in living human subjects for bidirectional blood-flow mapping of retinal vasculature.     

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.     

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.     

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.     

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.     

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.     

Simultaneous measurement of flow velocity and Doppler angle by the use of Doppler optical coherence tomography

Monitoring blood flow velocity could have great value for biomedical research and clinical diagnostics. One of current restrictions to determine flow velocity by the use of Doppler optical coherence tomography (Doppler OCT) is that the Doppler angle should be predefined. However, from a practical point of view, it is not easy to predetermine Doppler angle for a flow beneath the tissue surface. In this work, a novel method for measuring both flow velocity and Doppler angle simultaneously by the use of Doppler OCT is proposed and demonstrated. Based on Doppler spectrum analysis, this technique measures both longitudinal and transverse components of flow velocity by detecting its Doppler shift and Doppler bandwidth to determine velocity and Doppler angle simultaneously. Such a technique extends flow velocity measurement into a broadening practical use of Doppler OCT where Doppler angle would not need to be predefined, for example, blood flow beneath the tissue surface. Therefore, with this technique, Doppler OCT could be applied to more practical diagnoses of microcirculation.     

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。     

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.     

Measurement of absolute flow velocity vector using dual-angle, delay-encoded Doppler optical coherence tomography

Single-beam laser Doppler measurements of flow velocity are only sensitive to the velocity component parallel to the optical axis. We describe a simple modification to a standard Doppler optical coherence tomography (OCT) system using a single sample beam that provides velocity information from multiple angles within the beam. By introducing a glass plate midway into the OCT beam path, the sample beam is divided into several components, each with a different group delay and each providing a separate interferogram with its own effective Doppler angle. By combining the Doppler shift measured in each of these component interferograms, the flow velocity vector is fully determined.     

Fiber-optic-bundle-based optical coherence tomography

A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is presented. The experimental results demonstrate this multimode optical fiber-bundle-based OCT system can achieve a lateral resolution of 12 microm and an axial resolution of 10 microm with a superluminescent diode source. This novel OCT imaging approach eliminates any moving parts in the probe and has a primary advantage for use in extremely compact and safe OCT endoscopes for imaging internal organs and great potential to be combined with confocal endoscopic microscopy.     

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.     

Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography

A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.     

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.     

High resolution optical coherence tomography by ?1-optimization

An algebraic optical coherence tomography (OCT) method is presented in this paper for high resolution tomography imaging. The method achieves high resolution by formulating the frequency domain OCT (FD-OCT) into a ?₁-optimization based algebraic reconstruction problem. The performance of the proposed algebraic method is evaluated by simulation and experiment, and compared to the FD-OCT method. It is shown that the proposed method can deliver high resolution beyond the coherence length and imaging depth bigger than the ones of the FD-OCT method. The computational load is greatly reduced compared to the traditional algebraic reconstruction methods.     

High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm

High-speed, high-resolution optical coherence tomography (OCT) imaging of the human retina is demonstrated using a frequency-swept laser at 850 nm. A compact external cavity semiconductor laser design, optimized for swept-source ophthalmic OCT, is described. The laser enables an effective 16 kHz sweep rate with >10 mm coherence length and a tuning range of approximately 35 nm full width at half-maximum, yielding an axial resolution of <7 micro m in tissue.     

利用变迹术和相干门相结合实现光学相干层析成像术轴向超分辨

光学相十层析成像（光学相干层析成像术）的轴向分辨力由光源带宽和探测光束的聚焦条件共同决定。提高光学相干层析成像术轴向分辨力的方法主要基于带宽光源技术。提出了一种将变迹术与光学相十层析成像术相干门有机结合的方法来提高其轴向分辨力。通过适当形式的光瞳滤波器．使光学相干层析成像术系统轴向响应的主瓣宽度缩小到相干门之内,而其旁瓣则处于相干门之外．不对相干成像产生有效贡献。这样．就能在光源带宽不变的条件下,有效提高光学相十层析成像术的轴向分辨力,避免了采用宽带光源所带来的费用昂贵和系统复杂等缺陷。     

Ultra-High Resolution Optical Coherence Tomography (OCT) Using a Halogen Lamp as the Light Source

The axial resolution of optical coherence tomography (OCT) is determined by the coherence length of the light source. We demonstrate for the first time high-resolution OCT of biological tissue using a halogen lamp as the light source for a low coherence interferometer. High-resolution OCT imaging with 3.5 μm resolution was performed successfully for onion and porcine skin, although the coherence light power for illumination of a sample is as small as 100 nW.     

Polarization-resolved second-harmonic-generation optical coherence tomography in collagen

We describe a novel imaging technique, second-harmonic-generation optical coherence tomography (SHOCT). This technique combines the spatial resolution and depth penetration of optical coherence tomography (OCT) with the molecular sensitivity of second-harmonic-generation spectroscopy. As a consequence of the coherent detection required for OCT, polarization-resolved images arise naturally. We demonstrate this new technique on a skin sample from the belly of Icelandic salmon, acquiring polarization-resolved SHOCT and OCT images simultaneously.