Three-dimensional laser-induced photoacoustic tomography of mouse brain with the skin and skull intact

Three-dimensional laser-induced photoacoustic tomography, also referred to as optoacoustic tomography, is developed to image animal brain structures noninvasively with the skin and skull intact. This imaging modality combines the advantages of optical contrast and ultrasonic resolution. The distribution of optical absorption in a mouse brain is imaged successfully. The intrinsic optical contrast reveals not only blood vessels but also other detailed brain structures, such as the cerebellum, hippocampus, and ventriculi lateralis. The spatial resolution is primarily diffraction limited by the received photoacoustic waves. Imaged structures of the brain at different depths match the corresponding histological pictures well.     

利用近红外光激发的光声血管造影成像

利用近红外光结合对应波长的光吸收增强对照剂来实现在体小鼠脑皮层血管的光声成像.近红外光在生物组织上有较深的穿透能力;而作为光吸收增强剂的外源染料吲哚菁绿注射到血液系统后则增加了血管对光的选择性吸收,从而增强了血管光声信号的强度.实验在不破坏脑头皮和头盖骨的前提下,通过静脉注射吲哚菁绿,获得小鼠脑皮层血管的光声造影成像.光声重建的血管网络与小鼠脑部解剖照片相当符合.实验结果证明近红外光结合光吸收增强剂的光声血管造影技术对于开展光声脑功能成像,光声分子成像提供了潜在的可行性. 关键词： 光声成像 光吸收增强剂 血管造影 光声信号     

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     

Near-infrared laser scanning confocal microscopy and its application in bioimaging

Near-infrared (NIR) fluorescence imaging is an important imaging technology in deep-tissue biomedical imaging and related researches, due to the low absorption and scattering of NIR excitation and/or emission in biological tissues. Laser scanning confocal microscopy (LSCM) plays a significant role in the family of fluorescence microscopy. Due to the introduction of pinhole, it can provide images with optical sectioning, high signal-to-noise ratio and better spatial resolution. In this study, in order to combine the advantages of these two techniques, we set up a fluorescence microscopic imaging system, which can be named as NIR-LSCM. The system was based on a commercially available confocal microscope, utilizing a NIR laser for excitation and a NIR sensitive detector for signal collection. In addition, NIR fluorescent nanoparticles (NPs) were prepared, and utilized for fluorescence imaging of the ear and brain of living mice based on the NIR-LSCM system. The structure of blood vessels at certain depth could be visualized clearly, because of the high-resolution and large-depth imaging capability of NIR-LSCM.     

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.     

High-resolution near-infrared tomographic imaging simulations of the rat cranium by use of a priori magnetic resonance imaging structural information

Near-infrared (NIR) optical image reconstruction that incorporates magnetic resonance image (MRI) structural data was tested in a series of simulated reconstructions. NIR diffuse tomography generally suffers from comparatively low spatial resolution. By using the fine structural detail that is available with MRI, combined with the functional information of NIR spectroscopy, it is possible to design a new image-reconstruction methodology that provides high-resolution images that are correlated with hemoglobin concentration and oxygen saturation. To test this concept a MRI spin-echo image of a rat cranium was used to obtain an outline of the bone, brain, and muscle tissues, and this information was incorporated into an iterative-based diffuse tomography reconstruction. These simulations represent what is believed to be the first attempt at evaluating a spatially constrained iterative-reconstruction MRI-NIR imaging modality for brain tissue.     

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...     

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.     

Numerical evaluation of linearized image reconstruction based on finite element method for biomedical photoacoustic imaging

An image reconstruction algorithm for biomedical photoacoustic imaging is discussed. The algorithm solves the inverse problem of the photoacoustic phenomenon in biological media and images the distribution of large optical absorption coefficients, which can indicate diseased tissues such as cancers with angiogenesis and the tissues labeled by exogenous photon absorbers. The linearized forward problem, which relates the absorption coefficients to the detected photoacoustic signals, is formulated by using photon diffusion and photoacoustic wave equations. Both partial differential equations are solved by a finite element method. The inverse problem is solved by truncated singular value decomposition, which reduces the effects of the measurement noise and the errors between forward modeling and actual measurement systems. The spatial resolution and the robustness to various factors affecting the image reconstruction are evaluated by numerical experiments with 2D geometry.     

Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the presence of luminal blood

Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.     

定量光声层析成像的研究进展

光声层析(Photoacoustic tomography,PAT)成像结合了超声成像的高分辨率和光学成像的高对比度的优势,是一种新型的生物医学成像模式。PAT成像算法包含两个逆问题,即根据组织产生的光声信号构建初始声压分布图(即图像重建)以及在此基础上估算成像区域的光学特性参数。后者是一个非线性的不适定问题,通常称为定量光声层析(Quantitative photo-acoustic tomography,q PAT)成像。本文在介绍光声成像原理的基础上,对主要的q PAT算法进行综述,讨论各自的优势和不足,并对未来可能的发展方向进行展望。     

基于柱弥散光源体内辐照的前列腺扫描光声成像仿体实验

光声成像技术是一种非常有前景的前列腺早期检测与成像的新技术. 在现有前列腺光声成像技术中, 通常采用的腺体外光源辐照方式由于受外围组织的影响, 容易减弱深部前列腺组织的光能量吸收, 导致辐照范围减小, 引起光声成像深度不足, 难以实现无损前列腺癌的检测. 本文基于前列腺组织的结构特征, 依据一种以柱状弥散光纤在尿道对前列腺实施光辐照、并利用外置于直肠内的长焦区聚焦式超声换能器检测光声信号的前列腺光声扫描成像技术, 构建了光声成像实验系统, 开展了仿体实验. 测试结果表明, 系统能够实现样品中吸收体的定位和成像, 结合柱弥散光源体内辐照可使成像深度提高, 同时侧向成像范围也较大. 初步结果表明, 借助柱弥散光源进行体内光辐照的光声信号新激发方式结合长焦区超声探头在前列腺癌早期无创诊断上具有潜在的应用前景.     

Feasibility of photoacoustic tomography for ophthalmology

For the eyeball composed of membrane and liquid, the contrast of ultrasound imaging is not high due to its small variance in acoustic impedance. As a new imaging modality, photoacoustic tomography combines the advantages of pure optical and ultrasonic imaging together and can provide high resolution, high contrast images. In this paper, the feasibility of photoacoustic tomography for ophthalmology is studied experimentally. A Q-switched Nd:YAG pulsed laser with 7-ns pulse width is used to generate photoacoustic signal of a porcine eyeball in vitro. The two-dimensional (2D) optical absorption image of the entire eyeball is reconstructed by time-domain spherical back projection algorithm. The imaging results agree well with the histological structure of the eyeball and show a high imaging contrast.     

基于声透镜成像系统的光声层析成像

光声成像是采用“光激发-超声波成像”的新型成像技术，它是检测强散射介质内部光吸收分布的一种有效医学影像技术.用短脉冲激光照射强散射介质(如生物组织)，强散射介质由于光声效应产生超声信号，使用具有成像能力的声透镜把声压分布成像于像面上，然后利用具有空间分辨能力的阵列光声传感器，把同一像面上的光声信号强度记录下来，最后根据光声信号强度的空间分布进行图像重组.根据成像系统物像共轭原理，同一物平面的光声信号到达像面的时延相等，而不同物面的光声信号到达同一个探测器平面的时延各不相同，因此，利用BOXCAR的门控积分 关键词： 光声层析成像 声透镜 光声信号     

光声信号的双谱分析方法研究

基于光声效应的光声光谱技术是光学与声学的有机结合, 可利用不同波长的入射光波, 产生不同的光声信号, 从而为组分识别、组织无损检测等提供高对比度图像, 是一种极具潜力的新型医学诊断技术.但光声光谱检测技术由于受检测方法的制约, 往往扫描时间较长, 而且信号的稳定性和图像识别的准确性也较差. 为了弥补单一光声光谱分析的局限性, 根据光声效应原理和振动理论, 提出了一种光声光谱与光声频谱相结合的双谱分析方法. 该方法通过光声频域信息的定量分析, 可以有效地提高不同组织的光声图像对比度, 从而提高光声成像的组分识别能力, 为光声频谱功能成像奠定理论基础. 实验结果显示, 光声光谱与光声频谱相结合的双谱分析方法可以较好地识别实验组织样品, 可实现高速、高分辨率的组分识别、组织探伤等, 具有广泛的应用前景和重要的临床诊断意义. 关键词： 光声成像 光声光谱分析 光声频谱分析     

Multiple information extracted from photoacoustic radio-frequency signal and the application on tissue classification

Photoacoustic imaging is a hybrid biomedical imaging technique, combining rich optical contrasts and good acoustic resolution in deep tissues. As a noninvasive and nonionized imaging method, photoacoustic imaging has shown great potentials in biomedicine in the past decade. In this review, we give a brief introduction of the physical principle and three major implementations of photoacoustic imaging. Then, we present pictures of some recent progress about the extraction of new imaging parameters from photoacoustic radio-frequency signals. These parameters are highly associated with the tissue microstructure characteristics, including characteristic size, number density, and elasticity. This information could give us insight into various properties of tissue in-depth and be applied to tissue classification for basic research and clinical settings.     

Imaging of small nanoparticle-containing objects by finite-element-based photoacoustic tomography

We present semiquantitative photoacoustic images of small nanoparticle-containing objects having a wide range of contrast levels relative to the background. The images are obtained by a finite-element reconstruction algorithm that is based on the Helmholtz-like photoacoustic wave equation in the frequency domain. Our reconstruction approach is an iterative Newton method coupled with combined Marquardt and Tikhonov regularizations that can extract the spatial distribution of relative optical absorption property in heterogeneous media. We demonstrate experimental images in single- and multiple-object configurations with a circular scanning photoacoustic tomographic system. The results obtained show that millimeter-size nanoparticle-containing objects can be clearly detected in terms of position, size, and relative optical properties.     

Tomographic imaging of absolute optical absorption coefficient in turbid media using combined photoacoustic and diffusing light measurements

We present a new method that can provide high resolution images of absolute optical absorption coefficient in heterogeneous turbid media. In this method, acoustic measurements in conventional photoacoustic tomography are combined with diffusing light measurements to separate the product of absorption coefficient and optical fluence or photon density. We validate this method using a series of tissuelike phantom experiments. The experimental results show that targets as small as 0.5 mm in diameter with optical absorption contrasts as low as 1.5 relative to a 50 mm diameter scattering background medium can be clearly detected.     

Adaptive beamforming for photoacoustic imaging

An adaptive photoacoustic image reconstruction technique that combines coherence factor (CF) weighting and the minimum variance (MV) method is introduced. The backprojection method is widely used to reconstruct photoacoustic tomography images. Owing to the scattering of light, the quality of the photoacoustic imaging can be degraded. CF, an adaptive weighting technique, is known to improve the lateral resolution of photoacoustic images. In addition, an MV adaptive beamforming method can further improve the image quality by suppressing signals from off-axis directions. Experimental studies are performed to quantify the spatial resolution and contrast of the adaptive photoacoustic beamforming methods.     

Multiple passages of light through an absorption inhomogeneity in optical imaging of turbid media

Multiple passages of light through an absorption inhomogeneity of finite size deep within a turbid medium are analyzed for optical imaging by use of the self-energy diagram. The nonlinear correction becomes more important for an inhomogeneity of a larger size and with greater contrast in absorption with respect to the host background. The nonlinear correction factor agrees well with that from Monte Carlo simulations for cw light. The correction is approximately 50%-75% in the near infrared for an absorption inhomogeneity with the typical optical properties found in tissues and five times the size of the transport mean free path.