光声成像技术在生物医学中的研究进展

光声成像是近年来发展较快的无损检测技术,其高分辨率、高对比度的特点使其成为生物医学检测技术的主要发展方向之一。文中从光声成像系统、光声探测器和图像重建算法的角度,对光声成像技术进行了分析。在此基础上,分别结合光声计算层析成像、光声显微成像和光声内窥成像对光声成像系统进行了阐述,探讨了光声探测器在多探头、阵列式、MEMS微型化和光纤F-P腔等方面的研究进展,比较了典型图像重建算法的应用特点,并指出了基于光声技术的生物医学无损成像系统的高分辨率、大探测深度、实时性强、小型化、低成本的研究方向。     

生物声学成像中声速不均匀性解决方法的研究进展

对于以超声波为载体的生物医学声学成像(如超声、光声和磁声成像等)技术,为了简化问题,常在假设待测组织内声速恒定的前提下,重建组织内的声阻抗、光吸收分布、光学特性参数分布或者电导率分布等。但是,实际生物组织内部的声速是存在差异的(最大可达10%),因而在此假设前提下重建出的图像通常是不准确的。在介绍声速不均匀性对声学图像重建影响的基础上,对超声、光声和磁声成像中解决声速不均匀问题的主要方法,特别是光声层析成像中重建组织内声速分布的主要方法进行总结和归纳,讨论各自的优点和不足,并展望未来的可能发展方向。     

光声层析成像技术的研究进展

光声层析成像技术是一种新兴的医学成像技术,具有高分辨率、高对比度、高穿透深度的优点。文章简要介绍光声层析成像技术的原理,并报道基于单聚焦换能器扫描的层析成像技术和基于多探元超声探测方式的层析成像技术,指出该技术在医学检测上具有重要的应用前景。     

中波红外多光谱成像技术研究

多光谱成像技术结合成像和光谱测量技术,同时探测目标的光谱和几何特征,在目标识别和抑制背景杂波方面具有技术优势。研制了一套工作于中波红外波段的四通道多光谱成像系统。利用窄带滤光片和面阵探测器技术,构建了基于时序扫描的凝视成像型红外多光谱成像系统。根据红外探测器性能参数,对各个光谱通道的温度灵敏度进行了估算。在系统设计时通过合理地滤光片布局,尽量延长各个光谱通道的信号积分时间,以提高各个光谱通道温度灵敏度。利用研制的中波多光谱成像系统,对室外进行了成像,并对各个通道的成像结果进行了比较分析。     

基于阵列探测方式的时域光声成像系统

将阵列超声探头和超声相控技术与光声成像相结合的成像系统,与采用水听器的单探头旋转扫描光声成像系统相比,避免了机械旋转机构给光声信号采集所带来的不稳定性,提高了数据采集速度．时域光声信号由64阵元线阵超声探头以电子相控聚焦的方式进行线性扫描采集,然后通过时域后向投影算法进行光声图像的重建．采用波长532nm、重复频率10Hz的脉冲激光,系统可快速重建样品内部光学吸收分部的二维图像,单帧图像数据采集时间小于200s,成像横向分辨率小于2mm．实验结果表明,采用此方法可显著提高系统对光声信号的扫描稳定性和成像效率,该系统是一种有潜在临床应用价值的光声成像系统．     

声成像技术及其在医学超声中的应用

由于声成像技术具有对材料内部力学特性进行成像检测的特点,它已成为医学超声中的重要研究领域。为了提高声成像的空间分辨力,近年来,又发展了光声成像,扫描电子声显微术和扫描探针声显微术等新的近场成像技术。结合同济大学声学研究所部分研究结果,对这些近场成像技术在医学超声中的应用作了简单介绍。     

新型多光谱复眼透镜的研制及应用

传统多光谱成像系统通常借助滤光轮来实现光谱的分离。这种多光谱成像系统一次只能获取一个波段的图像,不仅操作不便,集成度也不高。本文基于微细加工技术将镀膜、光刻及光刻胶热熔等多种工艺相结合,实现了带有光阻挡层的紧凑型多光谱复眼透镜的研制。基于该透镜搭建了一台成像系统。成像结果表明,该透镜可以实现预期的色彩分离和多通道并行成像;由于光阻挡层和信号隔离层的作用,最终获得的图像成像效果清晰且各通道间没有干扰。此外,本文对基于该透镜的多光谱成像系统实际应用方面也做了进一步的探讨。实验结果表明,该系统在发现隐藏信息、生物医学成像等方面都具有较大的应用前景。     

光声显微镜技术的研究进展

光声显微镜技术具有新兴的一种非侵害性的显微成像技术,具有高分辨率、高对比度、穿透深度高的优点。简要介绍光声成像技术机理,总结报道了国内外几种典型的光声显微成像方法和光声显微图像重建算法的发展历程及其最新进展,指出该技术是一种很有应用前景的医学检测方法。     

采用稀疏测量数据的有限角度光声层析成像的研究进展

生物光声层析(Photoacoustic Tomography,PAT)成像可以反映生物组织的光吸收分布,定量测量组织的光吸收系数和散射系数,进而分析组织成分,为疾病的早期诊断和治疗提供可靠的依据。由于成像目标特殊的几何结构以及成像装置的机械结构、空间位置和成像时间等的限制,超声探测器只能在有限的角度范围内扫描,采集到稀疏的光声测量数据,导致重建图像中出现伪影和失真。针对有限角度扫描和稀疏测量数据问题,对目前主流的光声图像重建算法进行综述和分析。     

光声光谱测试技术及在材料分析中的应用

光声光谱作为一种比较新型的材料无损测试技术，具有灵敏度高、能进行微量分析、以及不受样品形状限制等优点。本文对光声光谱测试技术的测试原理及测试系统组成进行了详细说明，并举例说明其在材料分析中的应用。     

Co-registered Frequency-Domain Photoacoustic Radar and Ultrasound System for Subsurface Imaging in Turbid Media

Frequency-domain photoacoustic radar (FD-PAR) imaging of absorbers in turbid media and their comparison and/or validation as well as co-registration with their corresponding ultrasound (US) images are demonstrated in this paper. Also presented are the FD-PAR tomography and the effects of reducing the number of scan lines (or angles) on image quality, resolution, and contrast. The FD-PAR modality uses intensity-modulated (coded) continuous wave laser sources driven by frequency-swept (chirp) waveforms. The spatial cross-correlation function between the PA response and the reference signal used for laser source modulation produces the reconstructed image. Live animal testing is demonstrated, and images of comparable signal-to-noise ratio, contrast, and spatial resolution were obtained. Various image improvement techniques to further reduce absorber spread and artifacts in the images such as normalization, filtering, and amplification were also investigated. The co-registered image produced from the combined US and PA images provides more information than both images independently. The significance of this work lies in the fact that achieving PA imaging functionality on a commercial ultrasound instrument could accelerate its clinical acceptance and use. This work is aimed at functional PA imaging of small animals in vivo.     

Oscillatory Dynamics and In Vivo Photoacoustic Imaging Performance of Plasmonic Nanoparticle‐Coated Microbubbles

Microbubbles bearing plasmonic nanoparticles on their surface provide contrast enhancement for both photoacoustic and ultrasound imaging. In this work, the responses of microbubbles with surface‐bound gold nanorods—termed AuMBs—to nanosecond pulsed laser excitation are studied using high‐speed microscopy, photoacoustic imaging, and numerical modeling. In response to laser fluences below 5 mJ cm^?2, AuMBs produce weak photoacoustic emissions and exhibit negligible microbubble wall motion. However, in reponse to fluences above 5 mJ cm^?2, AuMBs undergo dramatically increased thermal expansion and emit nonlinear photoacoustic waves of over 10‐fold greater amplitude than would be expected from freely dispersed gold nanorods. Numerical modeling suggests that AuMB photoacoustic responses to low laser fluences result from conductive heat transfer from the surface‐bound nanorods to the microbubble gas core, whereas at higher fluences, explosive boiling may occur at the nanorod surface, producing vapor nanobubbles that contribute to rapid AuMB expansion. The results of this study indicate that AuMBs are capable of producing acoustic emissions of significantly higher amplitude than those produced by conventional sources of photoacoustic contrast. In vivo imaging performance of AuMBs in a murine kidney model suggests that AuMBs may be an effective alternative to existing contrast agents for noninvasive photoacoustic and ultrasound imaging applications.     

Multispectral quantitative photoacoustic imaging of osteoarthritis in finger joints

We present in vivo experimental evidence that multispectral quantitative photoacoustic tomography (qPAT) has the potential to detect osteoarthritis (OA) in the finger joints. In this pilot study, two OA patients and three healthy volunteers were enrolled, and their distal interphalangeal (DIP) joints were examined photoacoustically by a multispectral PAT scanner. Images of tissue physiological/functional parameters including oxyhemoglobin, deoxyhemoglobin, oxygen saturation, and water content, along with the tissue acoustic velocity of all the examined joints, were simultaneously recovered using a finite element reconstruction algorithm for multispectral photoacoustic measurements. The recovered multispectral photoacoustic images show that the OA joints have significantly elevated water content, decreased oxygen saturation, and increased acoustic velocity compared to the normal joints.     

Color-coded perfluorocarbon nanodroplets for multiplexed ultrasound and photoacoustic imaging

Laser-activated perfluorocarbon nanodroplets are an emerging class of phase-change, dual-contrast agents that can be utilized in ultrasound and photoacoustic imaging. Through the ability to differentiate subpopulations of nanodroplets via laser activation at different wavelengths of near-infrared light, optically-triggered color-coded perfluorocarbon nanodroplets present themselves as an attractive tool for multiplexed ultrasound and photoacoustic imaging. In particular, laser-activated droplets can be used to provide quantitative spatiotemporal information regarding distinct biological targets, allowing for their potential use in a wide range of diagnostic and therapeutic applications. In the work presented, laser-activated color-coded perfluorocarbon nanodroplets are synthesized to selectively respond to laser irradiation at corresponding wavelengths. The dynamic ultrasound and photoacoustic signals produced by laser-activated perfluorocarbon nanodroplets are evaluated in situ prior to implementation in a murine model. In vivo, these particles are used to distinguish unique particle trafficking mechanisms and are shown to provide ultrasound and photoacoustic contrast for up to 72 hours within lymphatics. Overall, the conducted studies show that laser-activated color-coded perfluorocarbon nanodroplets are a promising agent for multiplexed ultrasound and photoacoustic imaging.

     

Carbon nanotubes as photoacoustic molecular imaging agents in living mice

Photoacoustic imaging of living subjects offers higher spatial resolution and allows deeper tissues to be imaged compared with most optical imaging techniques. As many diseases do not exhibit a natural photoacoustic contrast, especially in their early stages, it is necessary to administer a photoacoustic contrast agent. A number of contrast agents for photoacoustic imaging have been suggested previously, but most were not shown to target a diseased site in living subjects. Here we show that single-walled carbon nanotubes conjugated with cyclic Arg-Gly-Asp (RGD) peptides can be used as a contrast agent for photoacoustic imaging of tumours. Intravenous administration of these targeted nanotubes to mice bearing tumours showed eight times greater photoacoustic signal in the tumour than mice injected with non-targeted nanotubes. These results were verified ex vivo using Raman microscopy. Photoacoustic imaging of targeted single-walled carbon nanotubes may contribute to non-invasive cancer imaging and monitoring of nanotherapeutics in living subjects.     

Ultrasound-modulated optical tomography of biological tissue by use of contrast of laser speckles

Ultrasound-modulated optical tomography based on the measurement of laser-speckle contrast was investigated. An ultrasonic beam was focused into a biological-tissue sample to modulate the laser light passing through the ultrasonic column inside the tissue. The contrast of the speckle pattern formed by the transmitted light was found to depend on the ultrasonic modulation and could be used for imaging. Variation in the speckle contrast reflected optical inhomogeneity in the tissue. With this technique, two-dimensional images of biological-tissue samples of as much as 25 mm thick were successfully obtained with a low-power laser. The technique was experimentally compared with speckle-contrast-based, purely optical imaging and with parallel-detection imaging techniques, and the advantages over each were demonstrated.     

Three-dimensional photoacoustic imaging using a two-dimensional CMUT array

In this paper, we describe using a 2-D array of capacitive micromachined ultrasonic transducers (CMUTs) to perform 3-D photoacoustic and acoustic imaging. A tunable optical parametric oscillator laser system that generates nanosecond laser pulses was used to induce the photoacoustic signals. To demonstrate the feasibility of the system, 2 different phantoms were imaged. The first phantom consisted of alternating black and transparent fishing lines of 180 μm and 150 μm diameter, respectively. The second phantom comprised polyethylene tubes, embedded in chicken breast tissue, filled with liquids such as the dye indocyanine green, pig blood, and a mixture of the 2. The tubes were embedded at a depth of 0.8 cm inside the tissue and were at an overall distance of 1.8 cm from the CMUT array. Two-dimensional cross-sectional slices and 3-D volume rendered images of pulse-echo data as well as photoacoustic data are presented. The profile and beamwidths of the fishing line are analyzed and compared with a numerical simulation carried out using the Field II ultrasound simulation software. We investigated using a large aperture (64 x 64 element array) to perform photoacoustic and acoustic imaging by mechanically scanning a smaller CMUT array (16 x 16 elements). Two-dimensional transducer arrays overcome many of the limitations of a mechanically scanned system and enable volumetric imaging. Advantages of CMUT technology for photoacoustic imaging include the ease of integration with electronics, ability to fabricate large, fully populated 2-D arrays with arbitrary geometries, wide-bandwidth arrays and high-frequency arrays. A CMUT based photoacoustic system is proposed as a viable alternative to a piezoelectric transducer based photoacoustic systems.     

Dual‐Modality Surface‐Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation

Difficulty in visualizing glioma margins intraoperatively remains a major issue in the achievement of gross total tumor resection and, thus, better clinical outcome of glioblastoma (GBM) patients. Here, the potential of a new combined optical + optoacoustic imaging method for intraoperative brain tumor delineation is investigated. A strategy using a newly developed gold nanostar synthesis method, Raman reporter chemistry, and silication method to produce dual‐modality contrast agents for combined surface‐enhanced resonance Raman scattering (SERRS) and multispectral optoacoustic tomography (MSOT) imaging is devised. Following intravenous injection of the SERRS‐MSOT‐nanostars in brain tumor bearing mice, sequential MSOT imaging is performed in vivo and followed by Raman imaging. MSOT is able to accurately depict GBMs three‐dimensionally with high specificity. The MSOT signal is found to correlate well with the SERRS images. Because SERRS enables uniquely sensitive high‐resolution surface detection, it could represent an ideal complementary imaging modality to MSOT, which enables real‐time, deep tissue imaging in 3D. This dual‐modality SERRS‐MSOT‐nanostar contrast agent reported here is shown to enable high precision depiction of the extent of infiltrating GBMs by Raman‐ and MSOT imaging in a clinically relevant murine GBM model and could pave new ways for improved image‐guided resection of brain tumors.     

Validation of temperature imaging by H2O absorption spectroscopy using hyperspectral tomography in controlled experiments

This paper describes a preliminary demonstration and validation of temperature imaging using hyperspectral H2O absorption tomography in controlled experiments. Fifteen wavelengths are monitored on each of 30 laser beams to reconstruct the temperature image in a 381 mm × 381 mm square room-temperature plane that contains a 102 mm × 102 mm square zone of lower or higher temperature. The hyperspectral tomography technique attempts to leverage multispectral information to enhance measurement fidelity. The experimental temperature images exhibit average accuracies of 2.3% or better, with pixel-by-pixel standard deviations of less than 1%. In addition, even when the internal zone is only 4 K cooler than the surroundings, its presence is still detectable; statistical analysis of the associated experimental image reveals a 98% confidence that the internal zone is in fact cooler than the surroundings.     

Radome health management based on synthesized impact detection,laser ultrasonic spectral imaging,and wavelet-transformed ultrasonic propagation imaging methods

A radome must not only withstand various forces during operation, but also provide a window for electromagnetic signals. A radome is generally a composite sandwich structure. Much of the damage to radomes is barely visible to the naked eye on the outer surface, but is severe internally. In this study, a radome health management strategy consisting of in-flight damage event detection and ground damage evaluation processes is proposed. A radome health management system, composed of an on-board subsystem and a ground subsystem, was developed to realize the strategy. An in-flight event detection system was developed based on acoustic emission (AE) technology. A built-in amplifier-integrated PZT sensor was used, and the minimum impact energy that the on-board subsystem can detect was determined. The AE sensor was then switched to an ultrasonic receiver. A scanning laser ultrasonic technology was combined with the ultrasonic receiver to develop a ground nondestructive evaluation subsystem. For in situ damage visualization, laser ultrasonic frequency tomography and wavelet-transformed ultrasonic propagation imaging algorithms were developed in this study. To demonstrate the robustness of the ground subsystem, a damage was generated by 5.42 J impact in a glass/epoxy radome with honeycomb core, and the impact image of 25 mm in diameter invisible outside could be visualized with the combination of ultrasonic spectral imaging (USI) and wavelet-transformed ultrasonic propagation imaging (WUPI), which made the propagation of only the damage-related ultrasonic modes visible.