Imaging of subcutaneous blood vessels and flow velocity profiles by optical coherence tomography

We have applied a compact low power rapid scanning Doppler Optical Coherence Tomography system to monitor multi-dimensional velocity profiles within the complex vessels and simultaneous real-time non-invasive imaging of skin tissues morphology in vivo, in the wavelength range of 1.3–1.5 nm. Optical clearing of skin tissues has been utilized to achieve depth of OCT images up to 1.7 mm. Current approach enables applying low-power (0.4–0.5 mW) and low-noise broadband near-infrared light sources and obtaining OCT images with down to 12 μm spatial resolution. Two-dimensional time-domain OCT images of complex flow velocity profiles in blood vessel phantom and in vivo subcutaneous human skin tissues are presented. The effect of optical clearing on in vivo images is demonstrated and discussed.     

Experimental study of the multiple scattering effect on the flow velocity profiles measured in Intralipid phantoms by DOCT

Time domain Doppler Optical Coherence Tomography (DOCT) technique was applied to measure flow velocity profiles in highly scattering media. We analyzed the distortions of the measured velocity profiles of the 1% Intralipid solution flow embedded into the scattering medium at different embedding depths. For this purpose a tissue phantom consisting of a plain glass capillary (inner diameter 0.3 mm) embedded into a slab of Intralipid solution mimicking human skin was designed. The measured flow velocity profiles and behavior of distortions caused by multiple scattering are shown.     

In vivo photoacoustic time-of-flight velocity measurement of single cells and nanoparticles

Optical techniques for in vivo measurement of blood flow velocity are not quite applicable for determination of velocity of individual cells or nanoparticles. Here, we describe a photoacoustic time-of-flight method to measure the velocity of individual absorbing objects by using single and multiple laser beams. Its capability was demonstrated in vitro on blood vessel phantom and in vivo on an animal (mouse) model for estimating velocity of gold nanorods, melanin nanoparticles, erythrocytes, leukocytes, and circulating tumor cells in the broad range of flow velocity from 0.1?mm/s to 14?cm/s. Object velocity can be used to identify single cells circulating at different velocities or cell aggregates and to determine a cell's location in a vessel cross-section.     

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.     

Boundary segmentation based on modified random walks for vascular Doppler optical coherence tomography images

Vascular Doppler optical coherence tomography(DOCT) images with weak boundaries are usually difficult for most algorithms to segment. We propose a modified random walk(MRW) algorithm with a novel regularization for the segmentation of DOCT vessel images. Based on MRW, we perform automatic boundary detection of the vascular wall from intensity images and boundary extraction of the blood flowing region from Doppler phase images. Dice, sensitivity, and specificity coefficients were adopted to verify the segmentation performance. The experimental study on DOCT images of the mouse femoral artery showed the effectiveness of our proposed method, yielding three-dimensional visualization and quantitative evaluation of the vessel.     

A method for MR quantification of flow velocities in blood and CSF using interleaved gradient-echo pulse sequences

The aim of this study was to establish a rapid method for in vivo quantification of a large range of flow velocities using phase information. A basic gradient-echo sequence was constructed, in which flow was encoded along the slice selection direction by variation of the amplitude of a bipolar gradient without changes in sequence timings. The influence of field inhomogeneities and eddy currents was studied in a 1.5 T scanner. From the basic sequence, interleaved sequences for calibration and in vivo flow determination were constructed, and flow information was obtained by pairwise subtraction of velocity-encoded from velocity non-encoded phase images. Calibration was performed in a nongated mode using flow phantoms, and the results were compared with theoretically calculated encoding efficiencies. In vivo flow was studied in healthy volunteers in three different areas using cardiac gating; central blood flow in the great thoracic vessels, peripheral blood flow in the popliteal vessels, and flow of cerebrospinal fluid (CSF) in the cerebral aqueduct. The results show good agreement with results obtained with other techniques. The proposed method for flow determination was shown to be rapid and flexible, and we thus conclude that it seems well suited for routine clinical MR examinations.     

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     

光学相干层析成象技术的医学诊断应用

利用超短脉冲飞秒激光建立了OCT实验装置,通过对动物肾脏组织样品的层析成象,OCT图象与传统组织学图谱能找到很好的对应关系;对动物脑梗塞模型组织的扫描成象,得到了脑梗塞侧和正常侧的OCT图象,实验中,大脑病变组织和正常组织能够被正确区分。     

Wide dynamic range detection of bidirectional flow in Doppler optical coherence tomography using a two-dimensional Kasai estimator

We demonstrate extended axial flow velocity detection range in a time-domain Doppler optical coherence tomography (DOCT) system using a modified Kasai velocity estimator with computations in both the axial and transverse directions. For a DOCT system with an 8 kHz rapid-scanning optical delay line, bidirectional flow experiments showed a maximum detectable speed of >56 cm/s using the axial Kasai estimator without the occurrence of aliasing, while the transverse Kasai estimator preserved the approximately 7 microm/s minimum detectable velocity to slow flow. By using a combination of transverse Kasai and axial Kasai estimators, the velocity detection dynamic range was over 100 dB. Through a fiber-optic endoscopic catheter, in vivoM-mode transesophageal imaging of the pulsatile blood flow in rat aorta was demonstrated, for what is for the first time to our knowledge, with measured peak systolic blood flow velocity of >1 m/s, while maintaining good sensitivity to detect aortic wall motion at <2 mm/s, using this 2D Kasai technique.     

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.     

光学相干层析成像系统的实验研究

介绍了作者研究建立的光学相干层析（ＯＣＴ）成像系统,给出了利用该系统得以的实际生物样品光学相干层析图像,并对系统性能和结果作了分析,讨论了影响系统性能的一些因素及改进方法。     

基于光纤光栅传感器的体外血管模型应力测量北大核心CSCD

血管中的血液流动会对血管壁产生周向应力,周向应力与血管的结构及功能变化密切相关,测量体外血管模型的周向应力是生物力学研究中较重要的问题。提出了利用光纤光栅测量血管周向应力的方法,基于微流控技术利用钢针模具建立了集成光纤光栅的三维圆形血管模型,通过仿真研究了不同流动速度与应力的关系。仿真结果得到流速在8 mm/s~75 mm/s范围内,应力随速度的改变呈线性变化。利用光纤光栅传感器测量了流体流动时产生的周向应力,根据实验得到了光栅波长改变量与速度的关系,流速范围在8 mm/s~75 mm/s之间变化时,速度引起波长的变化为0.173 nm。结合仿真实验得到了应力与光栅波长改变量的关系,为血液流动时产生周向应力的体外测量提供了新思路。     

Imaging of subcutaneous microcirculation vascular network by double correlation Optical Coherence Tomography

Spatial distribution of superficial blood vessels in human skin in vivo has been observed by using the double correlation Optical Coherence Tomography (OCT). To remove background noise, reduce the artifacts associated with patient motions and to increase the overall quality of the experimental OCT images an adaptive Wiener filtering technique has been employed. Fourier domain correlation has been subsequently applied to enhance spatial resolution of images of vascular network in human skin in vivo. Image processing has been performed on Graphics Processing Units (GPUs) utilizing Compute Unified Device Architecture (CUDA) framework in the frequency‐domain. This approach allows carrying out image processing in parallel significantly speeding up the computations. The presented results show that the double correlation method permits obtaining 2D/3D OCT images of subcutaneous microcirculation vascular network and its spatial distribution within the human skin with higher spatial resolution compare to the other OCT correlation‐based techniques developed earlier.     

Physical determinants of vascular network remodeling during tumor growth

The process in which a growing tumor transforms a hierarchically organized arterio-venous blood vessel network into a tumor specific vasculature is analyzed with a theoretical model. The physical determinants of this remodeling involve the morphological and hydrodynamic properties of the initial network, generation of new vessels (sprouting angiogenesis), vessel dilation (circumferential growth), vessel regression, tumor cell proliferation and death, and the interdependence of these processes via spatio-temporal changes of blood flow parameters, oxygen/nutrient supply and growth factor concentration fields. The emerging tumor vasculature is non-hierarchical, compartmentalized into well-characterized zones, displays a complex geometry with necrotic zones and “hot spots” of increased vascular density and blood flow of varying size, and transports drug injections efficiently. Implications for current theoretical views on tumor-induced angiogenesis are discussed.     

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。     

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.     

系统中基于快速扫描光学延迟线的色散补偿

分析了光学相干层析成像(Optical Coherence Temography,OCT)系统中色散失配对系统纵向分辨率的影响,详细阐述了快速扫描光学延迟线(Rapid Scanning Optical Delay Line,RSOD)的色散性质,提出并采用基于RSOD的色散补偿方法,实验验证了这种色散补偿方法能够实现OCT系统的纵向分辨率接近于理论值,并因此得到了高质量的OCT图像.     

光学相干层析成像系统中双通快速扫描光学延迟线的数值分析

以matlab为工具,详尽分析双通快速扫描光学延迟线在最佳耦合条件下的光束传输与分布,为双通快速扫描光学延迟线的设计、元件选择和系统调整提供理论依据.得出离焦距离Δf=1μm和Δf=578 μm两个理论上的最佳耦合点.但就实际光路调试来看,离焦距离Δf=1 μm为此系统的最佳耦合点.     

用于眼检的光学相干层析成像技术研究

利用光学相干层析（OCT-Optical Coherent Tomography）技术可以透过低透明介质,特别是生物组织成像,介绍了基于1310nm波长稳定光源的OCT实验装置,实验装置采用SLD超辐射二极管光源,利用该装置对番茄皮进行了实际OCT图样采集,研制成的实验系统具有10μm左右的纵向分辨率,最后对进一步提高眼检OCT系统的性能进行了研究。     

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.