基于不同频率成份衰减矫正的光声成像方法

根据超声衰减理论,研究了光声信号不同频率成份随距离的衰减差异,及其对光声图像重建的影响;提出了对光声信号不同频率成份进行衰减矫正的成像方法,此方法增强了光声信号的高频成份,突出了吸收体的边界变化和细微的结构特征,提高了成像系统分辨率,实验结果显示系统分辨率由0.3 mm提高到0.2 mm.实验所用的光源为YAG激光器,波长为1064 nm,重复频率为20 Hz,脉宽为6 ns,探测器为针状的PVDF膜水听器,接收面积的直径为1 mm.     

In vivo dark-field reflection-mode photoacoustic microscopy

Reflection-mode photoacoustic microscopy with dark-field laser pulse illumination and high-numerical-aperture ultrasonic detection is designed and implemented in noninvasively imaged blood vessels in the skin in vivo. Dark-field optical illumination minimizes the interference caused by strong photoacoustic signals from superficial structures. A high-numerical-aperture acoustic lens provides high lateral resolution, 45-120 microm in this system. A broadband ultrasonic detection system provides high axial resolution, estimated to be approximately 15 microm. The optical illumination and ultrasonic detection are in a coaxial confocal configuration for optimal image quality. The system is capable of imaging optical-absorption contrast as deep as 3 mm in biological tissue.     

Intravascular photoacoustic imaging of human coronary atherosclerosis

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. A 1.25?mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30?MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230?nm. Simultaneous imaging with intravascular ultrasound was performed.     

基于代数重建算法的有限角度扫描的光声成像

由于滤波反投影重建算法要求对成像区域进行全方位扫描以获取完全投影数据,它需要较长时间采集大量数据,使其在医学上的应用受到限制。研究了在有限角度下采用代数重建算法进行光声成像的方法,实验用的光源为YAG激光器,波长为1064nm,重复频率20Hz,脉宽为6ns,探测器为针状的磺化聚二氟乙烯(PVDF)膜水听器,接收面积的直径为1mm,从仿真和实验结果表明该方法适用于“非完备投影数据”的光声层析成像。从图像重建效果上与滤波反投影算法相比较,该成像算法提高了重建图像的分辨率和对比度。采用代数重建算法的有限角度的光声成像方法,对临床医学的无损伤检测,具有重要的意义。     

Multifocal optical-resolution photoacoustic microscopy in vivo

Although ultrasound arrays have been exploited in photoacoustic imaging to improve imaging speed, ultrasound-array-based optical-resolution photoacoustic microscopy (OR-PAM) has never been achieved previously to our knowledge. Here we present our development of multifocal OR-PAM using a microlens array for optical illumination and an ultrasound array for photoacoustic detection. Our system is capable of imaging hemoglobin concentration and oxygenation in individual microvessels in vivo at high speed. Compared with a single focus, multiple foci reduce the scanning load and increase the imaging speed significantly. The current multifocal system can acquire 1000 × 500 × 200 voxels at ~10 μm lateral resolution within 4 min.     

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     

In vivo label-free photoacoustic microscopy of cell nuclei by excitation of DNA and RNA

Imaging of cell nuclei plays a critical role in cancer diagnosis and prognosis. To image noninvasively cell nuclei in vivo without staining, we developed UV photoacoustic microscopy (UV-PAM), in which 266 nm wavelength UV light excites unlabeled DNA and RNA in cell nuclei to produce photoacoustic waves. We applied UV-PAM to ex vivo imaging of cell nuclei in a mouse lip and a mouse small intestine and to in vivo imaging of the cell nuclei in the mouse skin. The UV-PAM images of unstained cell nuclei match the optical micrographs of the histologically stained cell nuclei. Given intrinsic optical contrast and high spatial resolution, in vivo label-free UV-PAM has potential for unique biological and clinical application.     

Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries

Capillaries, the smallest blood vessels, are the distal end of the vasculature where oxygen and nutrients are exchanged between blood and tissue. Hence, noninvasive imaging of capillaries and function in vivo has long been desired as a window to studying fundamental physiology, such as neurovascular coupling. Existing imaging modalities cannot provide the required sensitivity and spatial resolution. We present in vivo imaging of the microvasculature including single capillaries in mice using optical-resolution photoacoustic microscopy (OR-PAM) developed in our laboratory. OR-PAM provides a lateral resolution of 5 microm and an imaging depth >0.7 mm.     

Noninvasive photoacoustic angiography of animal brains in vivo with near-infrared light and an optical contrast agent

Optical contrast agents have been widely applied to enhance the sensitivity and specificity of optical imaging with near-infrared (NIR) light. However, because of the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. Here, for the first time to our knowledge, we present noninvasive photoacoustic angiography of animal brains in vivo with NIR light and an optical contrast agent. When indocyanine green polyethylene glycol, a novel absorption dye with prolonged clearance, is injected into the circulatory system of a rat, it obviously enhances the absorption contrast between the blood vessels and the background tissues. Because NIR light can penetrate deep into the brain tissues through the skin and skull, we are able to successfully reconstruct the vascular distribution in the rat brain from the photoacoustic signals. On the basis of differential optical absorption with and without contrast enhancement, a photoacoustic angiograph of a rat brain is acquired that matches the anatomical photograph well and exhibits high spatial resolution and a much-reduced background. This new technology demonstrates the potential for dynamic and molecular biomedical imaging.     

利用维纳滤波改善声透镜光声成像系统的分辨率

为了克服衍射效应对光声成像系统分辨率的限制,需要采用逆卷积方法进行图像反演.从理论上分析了声透镜成像原理,模拟仿真了声透镜的点扩展函数对声透镜成像系统分辨率的影响和维纳滤波解卷积方法复原光声成像的过程,并利用自搭建的声透镜光声成像系统进行了深入的实验研究,得到了物平面上相距4 mm和3 mm的两个黑胶带点的直接成像光声...     

Fast voice-coil scanning optical-resolution photoacoustic microscopy

We developed a photoacoustic imaging system that has real-time imaging capability with optical resolution. The imaging system is capable of scanning at 20 Hz over a 9 mm range and up to 40 Hz over a 1 mm scanning range. A focused laser beam provides a lateral resolution of 3.4 μm as measured in an optically nonscattering medium. Flows of micrometer-sized carbon particles or whole blood in a silicone tube and individual red blood cells (RBCs) in mouse ear capillaries were also imaged in real time, demonstrating the capability to image highly dynamic processes in vivo at a micrometer-scale resolution.     

Lensless high-resolution photoacoustic imaging scanner for in vivo skin imaging

We previously launched a high-resolution photoacoustic (PA) imaging scanner based on a unique lensless design for in vivo skin imaging. The design, imaging algorithm and characteristics of the system are described in this paper. Neither an optical lens nor an acoustic lens is used in the system. In the imaging head, four sensor elements are arranged quadrilaterally, and by checking the phase differences for PA waves detected with these four sensors, a set of PA signals only originating from a chromophore located on the sensor center axis is extracted for constructing an image. A phantom study using a carbon fiber showed a depth-independent horizontal resolution of 84.0 ± 3.5 µm, and the scan direction-dependent variation of PA signals was about ± 20%. We then performed imaging of vasculature phantoms: patterns of red ink lines with widths of 100 or 200 μm formed in an acrylic block co-polymer. The patterns were visualized with high contrast, showing the capability for imaging arterioles and venues in the skin. Vasculatures in rat burn models and healthy human skin were also clearly visualized in vivo.     

多参量光声成像及其在生物医学领域的应用

光声成像兼具声学成像和光学成像两者的优点, 因而成为近十年来发展最迅速的生物医学成像技术之一. 本文介绍了光声成像的特点及其相对于广泛应用的光学成像技术和声学成像技术的优点; 其次, 解释了光声成像的成像原理, 在此基础上介绍了光声断层成像和光声显微镜这两种典型的光声成像方案, 并介绍了它们的技术特点; 然后, 介绍了光声成像对生物组织的生化特性、组织力学特性、血液流速分布、温度分布参数、微结构特性等多信息参量的提取能力, 及其在生物系统的结构成像、功能成像、代谢成像、分子成像、基因成像等多领域的应用; 最后, 展望了光声成像在生物医学领域的应用潜力并讨论了其局限性.     

改进的同步迭代算法在光声血管成像中的应用

光声成像结合了光学成像和声学成像的优点，是一种高分辨率，高对比度的无损伤医学成像技术.一种改进的同步迭代算法应用于光声图像重建.仿真和模拟结果表明，与传统的代数迭代算法相比，在90°，135°，180°的有限场光声成像中，此算法对测量误差的校正和迭代次数的收敛上具有较大的优势，图像重建的速度和成像质量都有了明显的提高.实验中，一种圆形扫描结构的光声成像装置，用于180°的有限场扫描，利用改进的同步迭代算法，重建出了高对比度和高分辨率（60μm）的鸡胚胎光声血管图像.实验证明，这种算法的应用，大幅度减少了数据采集时间，为光声成像技术运用于实时监测血流灌注和肿瘤光动力治疗的血管损伤效应提供了潜在的应用价值. 关键词： 光声成像 有限角度 代数迭代算法 光声血管成像     

基于声学扫描振镜的超声/光声双模态成像技术

超声/光声双模态成像技术因其同时兼具超声的高分辨率结构成像和光声的高对比度功能成像优势,极大地推动了光声成像技术的临床应用推广.传统超声/光声双模态成像技术多基于超声成像所用阵列探头同时收集光声信号,系统结构紧凑且无需图像配准,操作便捷.但该类设备使用阵列探头和多通道数据采集,使得其成本较高;且成像结果易受通道一致性差异影响.本文提出了一种基于声学扫描振镜的超声/光声双模态成像技术,该技术采用单个超声换能器结合一维声学扫描振镜进行快速声束扫描,实现超声/光声双模态成像,是一种小型化、低成本的双模态快速成像技术.本文开展了系列仿体和活体成像研究,实验结果表明:系统有效成像范围为15.6 mm,超声和光声成像B扫描速度分别为1.0 s^–1和0.1 s^–1 (光声成像速度主要受制于脉冲激光器重复频率).基于本文所提技术研究,有助于进一步推动超声/光声双模态成像技术的临床转化和普及;也为基于超声信号检测的多模态成像技术提供了一种低成本、小型化和快速声信号检测的参考方案.     

Multi-color miniature dual-axis confocal microscope for point-of-care pathology

We present a miniature microelectromechanical systems-based dual-axis confocal microscope capable of spatially coregistered fluorescence and reflectance imaging at multiple wavelengths. This device has a 10 mm diameter scan head with a 2 mm diameter tip for convenient use during surgery to guide tumor resection. The microscope has an adjustable focal depth of 20-200 micrometers and is capable of imaging with an axial resolution of 9 micrometers and in-plane resolution of 4 micrometers over a field of view of 450×450 micrometers. Simultaneous two-color imaging of individual optical sections is achieved by using a pair of grating-prism assemblies to compensate for chromatic dispersion in the 2 mm diameter gradient index relay lens at the distal tip of the device. Experimental measurements of the axial response of the microscope, as well as two-color images of a reflective bar target and fresh mouse brain tissues, demonstrate the performance of our device and its potential for multicolor in vivo optical sectioning microscopy.     

滑动焦点光声显微成像方法

在高分辨光声显微成像系统中,只有在有限焦深范围内的吸收体可以获得高分辨率高信噪比的成像,而实际的生物组织往往具有不规则的轮廓,导致成像结果分辨率和信噪比不均匀。提出了一种基于稀疏扫描轮廓的滑动焦点光声显微成像方法,首先在固定的焦点上稀疏扫描轮廓,人工选择轮廓点获取轮廓的稀疏矩阵,然后通过双调和(Biharmonic)插值获取完整的轮廓矩阵,并将轮廓矩阵转化为焦点位置移动矩阵,最后进行二次扫描,根据焦点位置移动矩阵在每次扫描之前调整焦点位置,使得在整个扫描过程中,样品始终处于焦深的范围,从而获得分辨率和信噪比均匀的光声显微图像。通过模型实验和在体皮下血管成像、颅下血管成像,证明了该方法可以有效地提高光声成像的质量。     

超声换能器带宽对光声成像的影响

研究了不同尺寸吸收体产生的光声压的频谱特性：对于厘米量级、毫米量级和几百个微米量级的吸收体,产生光声压频谱的主要范围分别约为20～300kHz、70kHz～2．5MHz和400kHz～20MHz;讨论了不同频率范围的光声信号对重建图像的影响,低频段的光声信号能反映物体的非边界区域,而高频段的光声信号能突出物体的细微结构,尤其是物体的边界特征。提出了不同尺寸的吸收体要选用或设计不同带宽范围的探测器进行检测的方法．当探测器的带宽范围与光声压频谱范围基本吻合时,损失的频率成份较少,重建的光声图像效果较好,这一结论在仿真和实验结果中都得到了证明。实验用的光源为YAG激光器,波长为532nm,重复频率为30Hz,脉宽为7ns,探测器为针状的PVDF膜水听器,接收面积的直径为1mm。     

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中提取组织微结构的尺度、数量密度、弹性等特征参数的研究进展,并展望了其在组织定征和分类上的应用前景。     

光声成像研究进展

本文阐述了光声成像的工作原理,光声信号的产生,传播和探测过程,并总结了光声成像的研究进展,包括时域光声成像和频率域光声成像的研究进展、以及各自的特点,为光声成像领域的研究起到一定的借鉴作用。分析认为光声成像技术有着其他医学成像技术没有的诸多优点,如高分辨率、高对比度、成像深度深等具有广阔的应用前景和较高应用价值,是未来生物医学领域最重要的实时医学成像技术之一,因此得到了国际上的广泛关注。