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。     

Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media

An optical Doppler tomography (ODT) system that permits imaging of fluid flow velocity in highly scattering media is described. ODT combines Doppler velocimetry with the high spatial resolution of low-coherence optical interferometry to measure fluid flow velocity at discrete spatial locations. Tomographic imaging of particle flow velocity within a circular conduit submerged 1 mm below the surface in a highly scattering phantom of Intralipid is demonstrated.     

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.     

Doppler standard deviation imaging for clinical monitoring of in vivo human skin blood flow

We used a novel phase-resolved optical Doppler tomographic (ODT) technique with very high flow-velocity sensitivity (10microm/s) and high spatial resolution (10microm) to image blood flow in port-wine stain (PWS) birthmarks in human skin. In addition to the regular ODT velocity and structural images, we use the variance of blood flow velocity to map the PWS vessels. Our device combines ODT and therapeutic systems such that PWS blood flow can be monitored in situ before and after laser treatment. To the authors' knowledge this is the first clinical application of ODT to provide a fast semiquantitative evaluation of the efficacy of PWS laser therapy in situ and in real time.     

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.     

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.     

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.     

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.     

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.     

Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral-domain optical Doppler tomography

We present a moving-scatterer-sensitive optical Doppler tomography (MSS-ODT) technique for in vivo blood flow imaging in real time by using a spectral-domain optical coherence tomography system. In MSS-ODT the influence of stationary scatterers is suppressed by subtracting adjacent complex axial scans before calculating the Doppler frequency shift. We demonstrate that MSS-ODT is a useful technique for accurate determination of blood vessel size by imaging flow in a small capillary tube with a 75 microm inner diameter. The flow profile obtained with MSS-ODT yields a substantially more accurate tube diameter than that obtained with the conventional phase-resolved method, which underestimates the diameter by about 23%. We also demonstrate that MSS-ODT provides improved sensitivity over the conventional phase-resolved method for imaging in vivo blood flow in small vessels in a mouse ear.     

Study on cerebral microcirculation by Optical Doppler Tomography

Optical Doppler Tomography (ODT) provides a novel method to measure the blood flow velocity in vessels with the diameter at micrometer scale. Rats with cranial window are used as a model, and the changes in the blood flow velocity of cerebral arterioles in sensory cortex are measured in real time with an established ODT system, under electrical stimulation and drug administration. The results show significant differences in the blood flow velocity between experimental groups and control groups, demonstrating the feasibility of ODT in the cerebral microcirculation study. Compared with the conventional Doppler ultrasound, ODT provides much higher spatial resolution, and thus holds a promising future in the application of the cerebral microcirculation study, especially in the observation of the blood flow velocity in micrometer scale vessels. Supported by the National Hi-Tech Research and Development Program of China (863 Program)(Grant No. 2006AA02Z4E0), the National Natural Science Foundation of China (Grant Nos. 60378041, 60478040, 60878057 and 30770685), the Program for New Century Excellent Talents in University (Grant No. NCET-04-0528), and the Opening Project of MOE Key Laboratory of Laser Life Science, South China Normal University     

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.     

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.     

高分辨率快速数字化光声CT乳腺肿瘤成像

提出了一种基于聚焦线性阵列探测器的快速光声计算机断层成像技术（光声CT）.在光声二维图像重建中,根据阵列探测器机械扫描和电子扫描相结合的组合扫描模式,提出了改进的有限场滤波反投影重建算法.一方面该算法适合多元探测器旋转扫描模式,另一方面探测器的指向性函数作为反投影的权重因子提高了系统的横向分辨率.同时,该成像系统还利用柱面声透镜实现Z轴方向上的聚焦扫描以实现三维层析成像.实验中,这套成像系统空间分辨率达到0.2mm,Z轴方向分辨率为1.5mm,扫描一幅二维图像仅需150s,得到 关键词： 光声CT 有限场滤波反投影算法 声透镜聚焦 乳腺肿瘤检测     

基于光声成像的生物组织微结构定征研究进展

光声成像是一种新兴的复合型生物医学成像技术,它既具有光学成像丰富的光学对比度,又具有声学成像成像深度深、深层组织空间分辨率高的优点.作为一种非侵入式的成像技术,光声成像逐渐显现出极大的生物医学应用潜力.该文首先介绍了光声成像的物理机制,以及光声显微镜和光声计算机断层成像这两种典型的光声成像技术;然后讨论了从光声射频信号...     

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 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.     

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.     

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.