利用连续光声成像监测动物脑部血液动力学变化

基于B型扫描超声诊断仪和线性阵列探测器的快速光声成像系统被搭建,并用于脑部血液动力学的监测研究。实验中,小鼠脑部皮层的全景血管网络分布图像通过光声探测器双扫描采集接收的方式被重建出来。然后,针对小鼠的脑中动脉,利用阵列电子扫描采集方式,光声成像实现了局部连续地监测由静脉注射生理盐水和吲哚菁绿引起的脑部血液动力学反应,成功地利用光声图像记录其光吸收的改变。实验展示了光声快速成像获取脑部功能信号的应用潜力。     

基于频域反卷积滤波器的光声成像

采用探测器的脉冲响应在频域反卷积滤波光声信号以进一步提高光声成像的分辨率.由仿真和实验结果表明,频域反卷积滤波重建相对于时域反投影重建和滤波反投影重建具有更好的成像效果,明显地提高重建图像的分辨率,经仿真结果的计算,其重建图像的分辨率由2.58 mm提高到了0.16 mm.实验所用的光源为YAG激光器,波长为1064 ...     

热声、光声双模态早期乳腺肿瘤成像系统

本文提出一种热声、光声双模态乳腺肿瘤检测成像系统。本装置中,脉冲微波和脉冲激光分别为热声、光声激发源,产生的热声、光声信号被同一个超声探测器、同一套数据采集装置接收,用同一种成像算法重建出图像。该系统可同时获取多种互补的诊断参数,提高检测早期乳腺肿瘤的准确率。     

基于非线性热扩散效应的亚衍射极限光声二次谐波显微成像技术

本文提出了一种基于非线性热扩散效应的光声二次谐波显微SH-PAM成像技术,用于实现亚衍射极限光声成像。生物组织受到强度调制的高斯激光束辐射时,组织吸收光子形成高斯分布的温度场,由于热扩散系数非线性热效应引起的非线性光声PA效应,从而产生光声二次谐波信号。模拟和试验结果均表明,重建后的光声二次谐波成像的横向分辨率超过了传统光学成像分辨率。本文通过仿体样品验证了该方法的可行性,并且对人表层皮肤细胞进行了成像,以证明其对生物样品的成像能力。该方法扩展了传统光声成像的范围,为超分辨成像开辟了新的可能性,为生物医学成像和材料检测提供了新的方法。     

基于压缩感知理论的光声成像方法研究现状

光声成像是一种新兴的无损生物医学成像方法,因其兼具高灵敏的光学对比度和超声能够对深层组织进行高分辨成像的优点,已经成为当前生物医学成像领域发展最快的技术之一。光声成像的光吸收对比度能够反映生物组织微小的组织病变,与血氧饱和度等多种功能和生理信息紧密相关,目前已被证明在肿瘤血管新生研究、早期癌症检测和心血管疾病诊断等方面有很大的应用潜力。基于超声阵列探测的常规光声计算层析成像系统,数据采集量大,由此导致的较低数据采集和成像速度成为制约该技术临床应用和转化的重要因素。压缩感知理论可以在远低于Nyquist采样定理的欠采样方式下,高质量重建信号,已被广泛用于信号处理和传统的医学图像重建领域。自2009年压缩感知理论被应用于光声成像以来,已有的研究结果表明,该方法为解决目前大区域光声成像的数据采集和成像速度问题提供了一条有效的途径。本文将重点介绍压缩感知理论用于光声成像的基本原理、研究现状、面临的问题和应用前景。     

光声结构与功能成像技术研究进展

光声成像技术利用短脉冲激光激发产生光声信号,可重建出组织的光吸收分布图像,它结合了纯光学成像的高对比度和纯声学成像的高分辨率特性.光声成像技术不仅能够有效的刻画生物组织结构,还能够精确实现无损功能成像,为研究生物组织的形态结构,生理、病理特征,代谢功能等提供了全新手段.本文简要分析了光声信号产生的机理,总结报道了目前实验室几套典型的成像系统及其最新应用进展,指出光声成像作为一种新型的生物医学成像方法,可望引发生物医学影像领域的一次革新.     

提高光声成像质量的Renyi熵方法

针对光声成像数据采集系统中获得的超声数据存在杂波问题,提出一种先基于Renyi熵分离超声信号和杂波,再利用分离后的超声数据进行光声成像的方法。光声成像平台实验表明,通过Renyi熵的直方图来选择超声信号和杂波分离的阈值,可以有效地滤除超声信号中的大部分杂波。成像重构的评估结果也验证了该结论。可见,该文提出的方法能有效滤除超声采集数据中的杂波,从而提高光声成像的质量。     

生物组织光声粘弹显微成像

提出一种反演生物组织粘弹信息的新型无损光声粘弹显微成像方法,它是以强度调制激光作为激发源,通过检测光声（Photoacoustic,PA）信号的相位重建组织粘弹特性分布的成像方法.实验利用不同浓度的琼脂样品来验证光声粘弹显微测量中相位随浓度变化的依赖关系.利用埋有头发丝的琼脂样品来测试这种显微方法的成像分辨率.利用具有不同粘弹性的离体生物组织来验证系统的成像能力.实验结果表明,这种新方法能够高分辨率和高对比度地重建出具有不同粘弹性的生物组织的光声粘弹显微图像,有望实现组织结晶类病变水平的显微在体检测.     

基于直线电机的大视场快速光声显微成像系统

光声成像技术是近年来发展的一种新型的无损医学成像技术,它是以脉冲激光作为激发源,以检测的声信号为信息载体,通过相应的图像重建算法重建组织内部结构和功能信息的成像方法。该方法结合了光学成像和声学成像的特点,可提供深层组织高分辨率和高对比度的组织层析图像,在生物医学临床诊断以及在体成像领域具有广泛的应用前景。目前光声成像的扫描方式主要有基于步进电机扫描方式和基于振镜的扫描方式,本文针对目前步进电机扫描速度慢(10 mm×10 mm;0.001帧/s),振镜扫描范围小(1 mm2)的不足,发展了基于直线电机扫描的大视场快速光声显微成像系统。同一条扫描线过程中直线电机速度最高可达200 mm/s。该技术采用逐线采集光声信号的方式,比逐点采集光声信号的步进电机快800倍。该系统对10 mm×10 mm全场扫描的扫描速度为0.8帧/s。最大可扫描视场范围可以达到50 mm×50 mm。大视场快速光声显微成像系统的发展将为生物医学提供新的成像工具。     

基于光谱编码的血管内光声组分成像

光声成像突破了传统的光学成像和超声成像在生物组织成像领域的困境,该技术基于光声(Photoacoustic,PA)效应,脉冲激光激励下的生物组织产生超声信号,超声信号被接收后,通过反投影算法将其携带的时间信息和强度信息转化为能够反映生物组织吸收结构和分布的可视化图像。基于不同生物组织的光吸收差异,当激发光强度均匀且稳定时,光声成像反映的就是该物质对于该波长光的吸收特性。本文中,我们基于导管式的血管内光声断层扫描平台结合多波长激发的光声成像算法开发了基于光谱编码的血管内光声组分成像系统,实现了在离体血管斑块中脂质组分的定量成像,高分辨获得了脂质核心的大小形态和边界信息,表征了斑块内的脂质相对含量。     

Integrating photoacoustic microscopy with other imaging technologies for multimodal imaging

As a hybrid optical microscopic imaging technology, photoacoustic microscopy images the optical absorption contrasts and takes advantage of low acoustic scattering of biological tissues to achieve high-resolution anatomical and functional imaging. When combined with other imaging modalities, photoacoustic microscopy-based multimodal technologies can provide complementary contrast mechanisms to reveal complementary information of biological tissues. To achieve intrinsically and precisely registered images in a multimodal photoacoustic microscopy imaging system, either the ultrasonic transducer or the light source can be shared among the different imaging modalities. These technologies are the major focus of this minireview. It also covered the progress of the recently developed penta-modal photoacoustic microscopy imaging system featuring a novel dynamic focusing technique enabled by OCT contour scan.     

In vivo imaging of subcutaneous structures using functional photoacoustic microscopy

Functional photoacoustic microscopy (fPAM) is a hybrid technology that permits noninvasive imaging of the optical absorption contrast in subcutaneous biological tissues. fPAM uses a focused ultrasonic transducer to detect high-frequency photoacoustic (PA) signals. Volumetric images of biological tissues can be formed by two-dimensional raster scanning, and functional parameters can be further extracted from spectral measurements. fPAM is safe and applicable to animals as well as humans. This protocol provides guidelines for parameter selection, system alignment, imaging operation, laser safety and data processing for in vivo fPAM. It currently takes approximately 100 min to carry out this protocol, including approximately 50 min for data acquisition using a 10-Hz pulse-repetition-rate laser system. The data acquisition time, however, can be significantly reduced by using a laser system with a higher pulse repetition rate.     

Integrated Photoacoustic Ophthalmoscopy and Spectral-domain Optical Coherence Tomography

Both the clinical diagnosis and fundamental investigation of major ocular diseases greatly benefit from various non-invasive ophthalmic imaging technologies. Existing retinal imaging modalities, such as fundus photography¹, confocal scanning laser ophthalmoscopy (cSLO)², and optical coherence tomography (OCT)³, have significant contributions in monitoring disease onsets and progressions, and developing new therapeutic strategies. However, they predominantly rely on the back-reflected photons from the retina. As a consequence, the optical absorption properties of the retina, which are usually strongly associated with retinal pathophysiology status, are inaccessible by the traditional imaging technologies.Photoacoustic ophthalmoscopy (PAOM) is an emerging retinal imaging modality that permits the detection of the optical absorption contrasts in the eye with a high sensitivity^4-7 . In PAOM nanosecond laser pulses are delivered through the pupil and scanned across the posterior eye to induce photoacoustic (PA) signals, which are detected by an unfocused ultrasonic transducer attached to the eyelid. Because of the strong optical absorption of hemoglobin and melanin, PAOM is capable of non-invasively imaging the retinal and choroidal vasculatures, and the retinal pigment epithelium (RPE) melanin at high contrasts ^6,7. More importantly, based on the well-developed spectroscopic photoacoustic imaging^5,8 , PAOM has the potential to map the hemoglobin oxygen saturation in retinal vessels, which can be critical in studying the physiology and pathology of several blinding diseases ⁹ such as diabetic retinopathy and neovascular age-related macular degeneration.Moreover, being the only existing optical-absorption-based ophthalmic imaging modality, PAOM can be integrated with well-established clinical ophthalmic imaging techniques to achieve more comprehensive anatomic and functional evaluations of the eye based on multiple optical contrasts^6,10 . In this work, we integrate PAOM and spectral-domain OCT (SD-OCT) for simultaneously in vivo retinal imaging of rat, where both optical absorption and scattering properties of the retina are revealed. The system configuration, system alignment and imaging acquisition are presented.     

窄等离子体吸收谱线宽度的纳米金锥用于光声成像

无损光声成像技术结合了纯光学成像高选择特性和纯超声成像中深穿透特性的优点,克服了光散射限制,实现了对活体深层组织的高分辨、高对比度成像。该成像技术对内源物质例如脱氧血红蛋白、含氧血红蛋白、黑色素、脂质等进行成像,提供了活体生物组织结构和功能信息,已经在生物医学领域表现出巨大的应用前景。然而,很多与病理过程相关的特征分子的光吸收能力较弱,在活体环境中难以被光声成像系统所识别,从而限制了光声成像技术的应用范围。基于功能纳米探针的光声成像-光声分子成像极大拓展光声成像的应用范围,可以在活体层面对病理过程进行分子水平的定性和定量研究,将为实现目标疾病的早期诊断提供强大的技术支持。本文发展在近红外具有窄吸收线宽(半高宽仅为60 nm)的纳米金锥作为新型的光声探针。通过选择不同径长比的纳米金锥,可以任意调节纳米金锥的吸收峰。通过调谐激光器的波长,可实现对不同吸收峰纳米金锥的选择性激发。纳米金锥将有可能用于多光谱光声成像,实现对不同靶标的目标分子探测。     

Comparison of Deconvolution Filters for Photoacoustic Tomography

In this work, we compare the merits of three temporal data deconvolution methods for use in the filtered backprojection algorithm for photoacoustic tomography (PAT). We evaluate the standard Fourier division technique, the Wiener deconvolution filter, and a Tikhonov L-2 norm regularized matrix inversion method. Our experiments were carried out on subjects of various appearances, namely a pencil lead, two man-made phantoms, an in vivo subcutaneous mouse tumor model, and a perfused and excised mouse brain. All subjects were scanned using an imaging system with a rotatable hemispherical bowl, into which 128 ultrasound transducer elements were embedded in a spiral pattern. We characterized the frequency response of each deconvolution method, compared the final image quality achieved by each deconvolution technique, and evaluated each method’s robustness to noise. The frequency response was quantified by measuring the accuracy with which each filter recovered the ideal flat frequency spectrum of an experimentally measured impulse response. Image quality under the various scenarios was quantified by computing noise versus resolution curves for a point source phantom, as well as the full width at half maximum (FWHM) and contrast-to-noise ratio (CNR) of selected image features such as dots and linear structures in additional imaging subjects. It was found that the Tikhonov filter yielded the most accurate balance of lower and higher frequency content (as measured by comparing the spectra of deconvolved impulse response signals to the ideal flat frequency spectrum), achieved a competitive image resolution and contrast-to-noise ratio, and yielded the greatest robustness to noise. While the Wiener filter achieved a similar image resolution, it tended to underrepresent the lower frequency content of the deconvolved signals, and hence of the reconstructed images after backprojection. In addition, its robustness to noise was poorer than that of the Tikhonov filter. The performance of the Fourier filter was found to be the poorest of all three methods, based on the reconstructed images’ lowest resolution (blurriest appearance), generally lowest contrast-to-noise ratio, and lowest robustness to noise. Overall, the Tikhonov filter was deemed to produce the most desirable image reconstructions.     

基于动态聚焦的声聚焦光声内窥成像算法研究

目的 声聚焦光声内窥成像具有成像深度大的优点,是一种非常有前景的功能成像技术,该技术被广泛应用于直肠、食道等内窥成像中。声聚焦光声内窥成像通常采用基于单个聚焦超声传感器的侧向扫描方式,同时采用传统的B扫描方法进行重建,会大大降低图像质量。为了获得高质量的图像,本文提出了几种动态聚焦的声聚焦光声内窥成像算法。方法 本文使用几种动态聚焦算法进行了数值仿真,并搭建系统进行了仿体实验验证,从横向分辨率和信噪比等多方面比较了各算法在动态聚焦中的成像效果。结果 相比B扫描方法,动态聚焦后的图像在离焦区域的横向分辨率与信噪比方面都有提升,仿真模拟中最高可将离焦区域的成像目标分辨率提升约26倍,其信噪比经动态聚焦后最高可提高2.3倍左右,实验中的远距离点目标经动态聚焦重建后分辨率提升3～6倍。结论 整体而言,基于时空响应的算法和合成孔径聚焦重建算法是在实验条件下更为适用的算法。本工作对后续的声聚焦光声内窥成像的设计具有指导意义。     

光声成像及其在生物医学中的应用

光声成像是一种新近迅速发展起来、基于生物组织内部光学吸收差异、以超声作媒介的无损生物光子成像方法,它结合了纯光学成像的高对比度特性和纯超声成像的高穿透深度特性的优点,以超声探测器探测光声波代替光学成像中的光子检测,从原理上避开了光学散射的影响,可以提供高对比度和高分辨率的组织影像,为研究生物组织的结构形态、生理特征、代谢功能、病理特征等提供了重要手段,在生物医学临床诊断以及在体组织结构和功能成像领域具有广泛的应用前景.对光声成像技术的机理、光声成像技术和方法、光声图像重建算法以及光声成像在生物医学上的应用情况作一个简单介绍,希望有助于推动我国在该领域的科研和开发应用工作的迅速发展.     

一体化的光声-荧光显微镜用于活体肿瘤成像

报道了一种利用单一波长激发的同时产生光声和荧光信号的显微成像系统,本成像系统具有超高的成像分辨率(<6μm)。借助外源的造影剂在近红外的吸收特性,利用光声-荧光显微成像系统对活体肿瘤进行光声/荧光成像。实验结果表明,光声-荧光显微镜在早期肿瘤的成像和检测等方面具有潜在的应用价值。因此,通过研究和选择适当的双模态造影剂,该系统在不同病理模型中可以提供更准确的组织信息及生理参数。     

Optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation

Fast functional and molecular photoacoustic microscopy requires pulsed laser excitations at multiple wavelengths with enough pulse energy and short wavelength‐switching time. Recent development of stimulated Raman scattering in optical fiber offers a low‐cost laser source for multiwavelength photoacoustic imaging. In this approach, long fibers temporally separate different wavelengths via optical delay. The time delay between adjacent wavelengths may eventually limits the highest A‐line rate. In addition, a long‐time delay in fiber may limit the highest pulse energy, leading to poor image quality. In order to achieve high pulse energy and ultrafast dual‐wavelength excitation, we present optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation and a signal separation method. The signal separation method is validated in numerical simulation and phantom experiments. We show that when two photoacoustic signals are partially overlapped with a 50‐ns delay, they can be recovered with 98% accuracy. We apply this ultrafast dual‐wavelength excitation technique to in vivo OR‐PAM. Results demonstrate that A‐lines at two wavelengths can be successfully separated, and sO₂ values can be reliably computed from the separated data. The ultrafast dual‐wavelength excitation enables fast functional photoacoustic microscopy with negligible misalignment among different wavelengths and high pulse energy, which is important for in vivo imaging of microvascular dynamics.