生物医学光声成像

能够对组织体中的光学吸收体进行量化评估的光声成像(photoacoustic imaging)是一种有发展前景的医学成像模式.文章综述了处于快速发展阶段的光声成像技术.文章首先介绍光声成像的物理基础--光声效应.在此基础上,阐述光声成像技术的优势所在(与光学以及超声成像相比较).然后讨论目前该领域的主要技术路线,包括扫描层析术、计算机层析术以及原位探测成像技术.最后简要总结了光声成像技术在生物医学领域中的主要应用.     

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     

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     

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.     

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.     

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     

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.     

Non-invasive and low-artifact in vivo brain imaging by using a scanning acoustic-photoacoustic dual mode microscopy

Photoacoustic imaging is a potential candidate for in vivo brain imaging, whereas, its imaging performance could be degraded by inhomogeneous multi-layered media, consisted of scalp and skull. In this work, we propose a low-artifact photoacoustic microscopy (LAPAM) scheme, which combines conventional acoustic-resolution photoacoustic microscopy with scanning acoustic microscopy to suppress the reflection artifacts induced by multi-layers. Based on similar propagation characteristics of photoacoustic signals and ultrasonic echoes, the ultrasonic echoes can be employed as the filters to suppress the reflection artifacts to obtain low-artifact photoacoustic images. Phantom experiment is used to validate the effectiveness of this method. Furthermore, LAPAM is applied for in-vivo imaging mouse brain without removing the scalp and the skull. Experimental results show that the proposed method successfully achieves the low-artifact brain image, which demonstrates the practical applicability of LAPAM. This work might improve the photoacoustic imaging quality in many biomedical applications which involve tissues with complex acoustic properties, such as brain imaging through scalp and skull.     

High-contrast imaging based on wavefront shaping to improve low signal-to-noise ratio photoacoustic signals using superpixel method

Photoacoustic(PA) imaging has drawn tremendous research interest for various applications in biomedicine and experienced exponential growth over the past decade. Since the scattering effect of biological tissue on ultrasound is two-to three-orders magnitude weaker than that of light, photoacoustic imaging can effectively improve the imaging depth.However, as the depth of imaging further increases, the incident light is seriously affected by scattering that the generated photoacoustic signal is very weak and the signal-to-noise ratio(SNR) is quite low. Low SNR signals can reduce imaging quality and even cause imaging failure. In this paper, we proposed a new wavefront shaping and imaging method of low SNR photoacoustic signal using digital micromirror device(DMD) based superpixel method. We combined the superpixel method with DMD to modulate the phase and amplitude of the incident light, and the genetic algorithm(GA) was used as the wavefront shaping algorithm. The enhancement of the photoacoustic signal reached 10.46. Then we performed scanning imaging by moving the absorber with the translation stage. A clear image with contrast of 8.57 was obtained while imaging with original photoacoustic signals could not be achieved. The proposed method opens new perspectives for imaging with weak photoacoustic signals.     

Phase-resolved photoacoustic spectroscopy to monitor dental plaque on tooth enamel

Dental plaque is a biofilm on the enamel surface of the teeth, formed by colonizing bacteria. It is essential to monitor the biofilm presence on the surface of the enamel of the teeth, since plaque is a reason for periodontal disease and dental caries. This paper proposes applying photoacoustic spectroscopy to monitor and the phase-resolved photoacoustic method to analyze the biofilm plaque on samples of human dental enamel facets. The biofilm growth occurred in the oral cavity environment at deposition time of 48 and 72?h. Photoacoustic ex vivo monitoring found that: (1) Photoacoustic spectroscopy is a helpful tool to identify the bactericidal effect on dental plaque; (2) the biofilm deposition provides an optical absorption of the Soret band at 410?nm and increase of hydroxyl absorption band; (3) the biofilm thickness by phase-resolved photoacoustic method is in agreement with the literature in situ measurements. These new knowledges may help in development of a greater practicality and safety equipment able to identify and quantify dental biofilm, which may be achieved with low-cost Soret-band light emitting diode as light excitation.     

基于探测超声的新型生物组织光声层析成像

利用一束单频探测超声穿过由脉冲激光照射产生的光声激发区域，使之与光致声场产生相互作用，光声信号将耦合到探测束上，再解调探测超声来重建光吸收区域的图像，可以得到丰富的组织信息.该信息不仅反映了组织中光吸收的特性，也反映了组织的声学特性.实验中，通过旋转超声探测器进行数据采集，并利用滤波反投影算法重建图像，可得到高信噪比的光声层析图像.由于激光的窄光谱线宽，其吸收是特征分子选择性的，所以此方法既是一种无损伤的结构层析成像方法，也可用于组织的功能成像.     

光声内窥镜系统在人体直肠癌离体组织中的实验研究

研制了基于4阵列传感器的光声内窥镜探头,并基于此搭建了光声内窥镜成像系统,开展了仿体实验成像研究,通过内窥镜探头4个阵元位置激光吸收强度的变化情况来分析仿体中吸收体的位置,论证了其定位能力,利用光声内窥镜系统对人体离体的正常组织、直肠癌早期组织进行成像研究;通过对不同阵元位置的光吸收强度分布进行统计分析,证明了光声内窥镜对早期直肠癌组织和正常组织的辨别能力,此项技术有望提高直肠癌早期诊断的准确率,具有潜在的临床应用前景。     

多模态光声分子成像进展*

现代的各种医学影像术,如射线成像、CT、正电子发射(PET)、磁共振(MR)、超声(US)、荧光(FL)等都各具特色,并成功地应用于多种疾病的诊疗。但每种影像术都不能对生物组织做出完整的描述。由若干个成像技术组成的多模态成像技术,是获得组织更多信息的有效途径。光声(PA)成像是能提供组织的成分和功能信息的新成像技术。它不仅灵敏,可以对较深层的组织进行实时、快速、安全的成像,而且可以利用光声光热造影剂实施非侵入的光热靶向治疗。因此,与光声成像相结合的多模态分子成像是实现精准诊疗的重要技术途径。该文以手持US-PA探头的双模态成像系统,直径为1 mm的血管內窥镜US-PA成像系统,可同时用于术前和术中的US-PA-FL三模态成像系统,以及采用外磁场可操控的磁共振-光声光热分子造影剂、进行MR-PA成像引导的光热治疗技术为例,对多模态光声分子成像系统在医学诊断、手术和光热治疗方面的进展做简单介绍。     

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...     

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.     

Nonlinear photoacoustic imaging dedicated to thermal-nonlinearity characterization

We proposed a nonlinear photoacoustic(PA) technique as a new imaging contrast mechanism for tissue thermalnonlinearity characterization. When a sine-modulated Gaussian temperature field is introduced by a laser beam, in view of the temperature dependence of the thermal diffusivity, the nonlinear PA effect occurs, which leads to the production of second-harmonic PA(SHPA) signals. By extracting the fundamental frequency PA and SHPA signal amplitudes of samples through the lock-in technique, a parameter that only reflects nonlinear thermal-diffusivity characteristics of the sample then can be obtained. The feasibility of the technique for thermal-nonlinearity characterization has been studied on phantom samples. In vitro biological tissues have been studied by this method to demonstrate its medical imaging capability,prefiguring great potential of this new method in medical imaging applications.     

Photoacoustic study of thermal properties of biological tissues detected by PVDF film transducer

A PVDF piezoelectric film transducer is used in a photoacoustic piezoelectric technique for studying thermal diffusivities of biological tissues. The experimental precision may be improved by using PVDF films because the acoustic impedance of PVDF films is close to that of biological tissues. Thermal diffusivities of several fresh porcine tissues in vitro are studied and the results are compared with previously obtained ones.     

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.     

Reconstruction of 3D light distribution produced by cylindrical diffuser in deep tissues based on photoacoustic imaging

Measurement of light distribution in biological tissue contributes to selecting strategy and optimizing dose for biomedical application. In this letter, a photoacoustic method combined with Monte Carlo simulation was used to estimate the three-dimensional light distribution in biological tissue. The light distribution was produced by a cylindrical diffuser which interposed into tissues. The light profiles obtained by the method were compared to those detected by photo diodes. The experimental results demonstrate the feasibility of this method. The approach can play a significant role for photo-dosimetry in biomedical phototherapy.     

Real-time flow imaging by removing texture pattern artifacts in spectral-domain optical Doppler tomography

We present a new, simple method to suppress texture pattern artifacts induced by the optical heterogeneity of tissues to improve the performance of flow imaging for real-time phase-resolved optical Doppler tomography. The method performs transverse scanning of the probe beam in the forward and then reverse directions, and it takes average of the spatial phase changes between them to obtain the final velocity image. It relies on the fact that the phase changes between successive axial scans due to the optical heterogeneity of the sample are time independent, while those due to the moving particles are time dependent. We experimentally demonstrate this method by real-time imaging of a flow phantom.