The research leading to these results has received funding from the European Research Council under grant agreement ERC-2010-StG-260991.

对于与体积手持光声探测器操作的详细过程描述如下。此过程是根据关于动物和人体试验批准机构法规进行。 1.系统准备<ol><li>为〜15分钟的预热期之前的操作进行切换的激光，用于稳定输出光束。 </li><li>将水包围部分与隔离膜，其是在与皮肤（ 图1）接触。 注:在隔离膜（与皮肤接触），并与换能器（球形探针的中心）的最大灵敏度的区域之间的距离确定了有效的成像深度。 </li><li>填充的绝缘膜，并与去离子水的换能器的表面之间的约100毫升的，由一泵装置的整体体积。 </li><li>确保没有漏水，也没有气泡prese新台币。可替换地，通过提供的水再循环避免气泡。 </li><li>执行该实验在室温和确保耦合介质（水）被维持在该温度下。 </li></ol> 2.影像学准备<ol><li>人体成像的准备。 </li><li>从要被成像的部分具有脱毛洗剂，以避免在图像中的不期望的背景去除毛发（此步骤是可选的）。 </li><li>应用超声凝胶上的区域周围的皮肤，以提供高效的声耦合成像。把光声探测器中的感兴趣区域。确保没有气泡存在于所述超声耦合凝胶。 </li><li>动物成像的准备。 </li><li>确保护理和实验步骤与动物都在与机构和政府规章制度的协议。 </li><li>取下动物的皮毛在该区域的成像与剃须乳液。保护动物的眼睛兽医软膏，以防止干燥，并损害暴露于强脉冲激光辐射。 </li><li>用氯胺酮/甲苯​​噻嗪（100毫克/公斤公斤氯胺酮+ 5mg / kg的甲苯噻嗪KG）在实验前或使用异氟醚麻醉（2-3％（按体积计）的腹膜内注射（IP）的使用0.9升麻醉动物/在实验过程中最小气体流）。通过检查动​​物的后肢的反射确认麻醉。 </li><li>应用超声凝胶上的区域周围的皮肤进行成像，以提供高效的声学耦合，并把光声探测器中的感兴趣区域。确保没有气泡存在于所述超声耦合凝胶。 </li></ol> 3.预视图操作模式<ol><li>建立690纳米和900纳米，10至50赫兹的脉冲重复率之间的成像波长（多个）。选择该参数用于声音数据采集系统 - 1MΩ输入阻抗。获得2030样本对于每个激光脉冲以每秒和12位垂直分辨率40兆次采样的采样率。触发采集与激光Q开关输出。 </li><li>确保操作者和患者使用适于光激发波长（多个）护目镜。设置激光功率，使得光注量在组织表面保持在低于20毫焦/厘米2的实验对近红外波长中，以满足人体实验19安全暴露限制，并防止热应变和皮肤损伤的动物。 </li><li>开始预视图软件具有GPU执行的处理算法，以允许可视化三维图像在对应于激光的脉冲重复速率的帧速率。 </li><li>移动探针和/或以优化的可视化性能和定位感兴趣的结构将被成像的对象。 </li></ol> 4.数据采集<ol><li>数据采集​​扫描（手持）模式。 </li><li>如果需要的话，前采集注射的造影剂来丰富在感兴趣的区域中的对比度。 注:在我们的实验中，我们并没有进行对比度增强人体成像。然而，不同的造影剂可被潜在地用于此目的。吲哚菁绿（ICG）是一种可以在对成人2毫克/千克体重的最大推荐剂量被用于对比增强临床上认可的光造影剂的一个实例。 </li><li>启动数据采集与维护预览软件的执行在3.1中描述的参数的硬件。轻轻移动的成像区域周围的探针来跟踪感兴趣的结构。 注意:当同时采集在多个波长的激光的图像，在手持模式探测运动的速度，必须显著降低（优选低于2毫米/秒为，为了避免在光谱上未混合的图像中的运动有关的伪影的激光脉冲重复为50Hz速率）。 </li><li>数据采集​​的固定模式。 </li><li>所述成像对象（ 例如 ，动物）和手持式探头安装到所述保持器，并开始获取与保持在预视图中软件的执行在3.1中描述的参数。 </li><li>保持的光声探测器，并在实验过程中相同的位置的可视化中的感兴趣区域的动态生物事件的摄像部。 </li><li>注入造影剂，以跟踪其在感兴趣的区域动态分配。 注意:在我们的小鼠实验中，吲哚菁绿（ICG）用于对比度增强。作为一般准则，10纳摩尔或0.4毫克的量/公斤的ICG必须被引入到小鼠循环，以创建具有在体内多光谱optoacoustics可检测的对比度。 注:对比剂必须是批准用于由各个授权人和/或动物使用。 </li></ol> 5.最后确定实验<ol><li>停止激光。 </li><li>从成像区域去除的光声探测器。对动物的研究中，停止麻醉供应。 </li><li>定位红外加热器下的动物保持温暖，并防止与其他动物的接触，直到其从麻醉中完全恢复。从麻醉恢复过程中不要将动物无人值守。 </li></ol> 6.离线数据处理<ol><li>加载包含用于数据处理的软件应用程序所获取的光声信号中的文件（多个）。 </li><li>使用重构算法，以获得对应于所述光吸收对各帧和各波长的体积图像的三维矩阵​​阵列。 注意:对于重建它是优选使用的算法占扭曲因素，如heterogene成象物体在伊蒂埃斯和衰减，最终带宽和检测元件和光注量的变化的几何形状，为了效果，得到的吸收能量的分布更加定量表示。 </li><li>使用一个去混合算法来获得，从每个多波长帧，一组新的三维矩阵​​阵列表示的光吸收为存在于样品中的每个吸收物质。 </li><li>如果需要的话，进一步的处理表示光吸收分布，以便可视化的生物相关的参数和读取的矩阵阵列。 </li></ol>

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The authors have nothing to disclose.

通过光声成像技术在小动物的研究提供了独特的优势创造了强大的动力转换的技术应用到临床实践中，有许多诊断和设想如治疗监测的应用。在乳腺癌和皮肤癌，炎症或外周血管疾病。然而，相对于小鼠或更小的动物，其可通过照射源和检测元件的足够数量的被包围，以创建一个有效的断层图像采集几何结构，对人体和限量光学穿透阻碍实现全身的大尺寸光声断层成像类似于MRI或CT检查。?...

光声（光声）成像每年吸引从生物和医学研究界日益增长的兴趣，这表现在数量不断增加的出版物涵盖各种各样的利用由技术1-5所提供的独特优点的新的应用程序。特别是，能力与在深度远远超出光的扩散极限高时空分辨率的图像进行频谱独特的光吸收剂打开前所未有的功能，用于功能和分子成像6-10。 事实上，光声技术应用到临床实践中译本自带的诊断和许多疾病的治疗监测前景十分广阔。然而，在光散射光子吸收的组织和与光声现象相关联的通常弱响应的有限传播限制了该方法的适用的深度。其结果是，手持optoacoustic探针已试图从本体11,12的外部接近的图像部分，而内窥镜系统所使用的通过自然孔口13插入它们提供从身体内的图像。一些低吸收人体的部位，如女性的乳房，并且也是由断层光声扫描仪14,15进行访问。特别令人感兴趣的是手持式的办法，因为它使大量的通用性，类似于超声。在这里，普通超声线阵探头，光声成像的改编依然充满挑战，主要是由于超声波和optoacoustics之间的断层成像要求根本性的分歧。而在标准超声高帧率被顺序使能发送接收计划采用在kHz范围内的高的脉冲重复频率，实时三维光声成像是通过同时采集的容积断层数据从单个int实现errogating激光脉冲。因此，高品质的光声成像意味着采集的三维数据从成象物体周围尽可能大的立体角。 最近，我们推出了第一台手持式光声探测三维（立体）影像实时16。该系统是基于二维的排列后的球面（蓝点在图1A中）256压电元件覆盖90°的角度阵列上。约为3×3 平方毫米的各个元件的尺寸，以及它们的取向和频率带宽（约2-6兆赫）从围绕球体的中心（黑立方体图一厘米刻度体积保证有效信号采集1A）。摄像区域的光激发设置有通过所述阵列的中央圆柱形腔插入的纤维束，以使任何波长SUSC通过对纤维束被传输的eptible可用于成像。换能器的阵列沿与光纤束的实际图像显示在图1B中 。有效激发并同时检测信号允许深层组织成像单次激励（1激光脉冲），从而在通过激光的脉冲重复频率确定的帧速率实时成像进一步与一个图形 - 启用处理单元（GPU）执行重建程序17。一个圆筒形壳体具有一个透明聚乙烯膜（ 图1C）连接到所述换能器阵列，以围成一个声学传输液体介质（水）。该膜进一步耦合到所述组织通过声凝胶的装置。的光声探测器作为手持操作模式下使用的一个图象被显示在图1D中 。 该证明THRee值维手持式光声成像结​​合实时功能成像能力来与对临床诊断和一些潜在应用的重要优点可以设想的各种迹象，如外周血管病，淋巴系统疾病，乳腺癌，皮肤损害，炎或关节炎18。此外，快速成像能力使与设置在一个固定的位置上的探头动态生物事件的可视化。结合快速波长调谐光学参量振荡器（OPO）激光技术，该方法允许光吸收剂的生物分布的实时成像。因此，新的可能性，可能会同样出现在小动物成像应用， 例如 ，在学习组织的血流动力学， 体内细胞跟踪，药代动力学，器官灌注可视化，有针对性的肿瘤和心血管系统，神经影像学或分子成像。

<table><tbody><tr><td>Optical parametric oscillator (OPO)-based laser</td><td>Innolas Laser GmbH, Krailling (Germany)</td><td>custom-made</td><td>The laser provides laser pulses with a duration around 10 nsec and an energy up to 80 mJ.&lt;br/&gt; The wavelength is tunable between 680-950 nm.</td></tr><tr><td>Spherical array of piezocomposite detectors</td><td>Imasonic SaS, Voray (France)</td><td>custom-made</td><td>The array consists of 256 piezoelectric sensors distributed on a spherical surface.&lt;br/&gt; Each element has dimensions 3 x 3 mm&lt;sup&gt;2&lt;/sup&gt;, a central frequency of 4 MHz and a bandwidth of 100%.&amp;nbsp;</td></tr><tr><td>Data acquisition system (DAQ)</td><td>Falkenstein Mikrosysteme GmbH, Taufkirchen (Germany)</td><td>custom-made</td><td>The DAQ simultaneously acquires 256 signals at 40 megasamples per second and 2,030 samples.&lt;br/&gt; The input impedance is 1 MW.</td></tr><tr><td>Fiber bundle</td><td>CeramOptec GmbH, Bonn (Germany)</td><td>custom-made</td><td>The bundle consists of 480 individual fibers randomly distributed in the input and output.&lt;br/&gt; The numerical aperture of each individual fiber is 0.22.</td></tr><tr><td>Athymic nude mouse</td><td>Harlan Laboratories (The Netherlands)</td><td>Athymic nude - Foxn1&lt;sup&gt;nu&lt;/sup&gt;</td><td>The mouse was 8 weeks old (adult) at the time of the experiment.&lt;br/&gt; The ethical protocol was approved by the Bavarian goverment (number 55.2.1.54-2632-102-11)</td></tr><tr><td>Bepanthen cream</td><td>Bayer AG (Germany)</td><td></td><td>Vet ointment to protect the eyes during anesthesia</td></tr><tr><td>Data processing software</td><td>Matlab (Mathworks, Natick, MA, USA)</td><td>custom-made</td><td>The data processing software was devoped at our institute.&lt;br/&gt; It allows reconstruction at each wavelength and multi-wavelength unmixing, as well as further data processing.</td></tr><tr><td>Water-enclosing part</td><td></td><td>custom-made</td><td>This part contains the water that acts as an acoustic coupling medium between skin and transducer elements</td></tr><tr><td>Indocyanine green (ICG)</td><td>PULSION Medical Systems SE</td><td></td><td>ICG-PULSION (active ingredient: indocyanine green dye) is a drug used in cardiac, circulatory and micro-circulatory diagnostics, liver function diagnostics and ophthalmic angiography diagnostics.</td></tr></tbody></table>

universal hand-held three-dimensional optoacoustic imaging probe for deep tissue human angiography and functional preclinical studies in real time

The exclusive combination of high optical contrast and excellent spatial resolution makes optoacoustics (photoacoustics) ideal for simultaneously attaining anatomical, functional and molecular contrast in deep optically opaque tissues. While enormous potential has been recently demonstrated in the application of optoacoustics for small animal research, vast efforts have also been undertaken in translating this imaging technology into clinical practice. We present here a newly developed optoacoustic tomography approach capable of delivering high resolution and spectrally enriched volumetric images of tissue morphology and function in real time. A detailed description of the experimental protocol for operating with the imaging system in both hand-held and stationary modes is provided and showcased for different potential scenarios involving functional and molecular studies in murine models and humans. The possibility for real time visualization in three dimensions along with the versatile handheld design of the imaging probe make the newly developed approach unique among the pantheon of imaging modalities used in today&#8217;s preclinical research and clinical practice.

代表性的结果，显示了所描述的容积手持式光声探测器的功能，是展示在本节。在所有情况下，光积分通量在皮肤表面上保持在低于20毫焦/厘米2 19中的安全性的暴露极限。 探针在实时跟踪外围人脉管系统的性能被展示在图2中，在此实验的过程中，所述探针缓慢地沿着健康人类志愿者的手，在800纳米的激光器工作在单波长扫描以每秒17 10个脉冲，?...

Watch this Scientific Journal Video about Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time at JoVE.com

Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time

We provide herein a detailed description of the experimental protocol for imaging with a newly developed hand-held optoacoustic (photoacoustic) system for three-dimensional functional and molecular imaging in real time. The demonstrated powerful performance and versatility may define new application areas of the optoacoustic technology in preclinical research and clinical practice.

通用型手持式三维光声成像探测深部组织人力造影和功能的临床前研究中实时

The exclusive combination of high optical contrast and excellent spatial resolution makes optoacoustics (photoacoustics) ideal for simultaneously ...

universal-hand-held-three-dimensional-optoacoustic-imaging-probe-for

Research

JoVE Journal

Bioengineering

10.7K 次观看.  Helmholtz Zentrum München. We provide herein a detailed description of the experimental protocol for imaging with a newly developed hand-held optoacoustic (photoacoustic) system for three-dimensional functional and molecular imaging in real time. The demonstrated powerful performance and versatility may define new application areas of the optoacoustic technology in preclinical research and clinical practice.

视频: Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time

Three-dimensional Optical-resolution Photoacoustic Microscopy

Optical microscopy, providing valuable insights at the cellular and organelle levels, has been widely recognized as an enabling biomedical technology. As the mainstays of in vivo three-dimensional (3-D) optical microscopy, single-/multi-photon fluorescence microscopy and optical coherence tomography (OCT) have demonstrated their extraordinary sensitivities to fluorescence and optical scattering contrasts, respectively. However, the optical absorption contrast of biological tissues, which encodes essential physiological/pathological information, has not yet been assessable. 
The emergence of biomedical photoacoustics has led to a new branch of optical microscopy optical-resolution photoacoustic microscopy (OR-PAM)1, where the optical irradiation is focused to the diffraction limit to achieve cellular1 or even subcellular2 level lateral resolution. As a valuable complement to existing optical microscopy technologies, OR-PAM brings in at least two novelties. First and most importantly, OR-PAM detects optical absorption contrasts with extraordinary sensitivity (i.e., 100%). Combining OR-PAM with fluorescence microscopy3 or with optical-scattering-based OCT4 (or with both) provides comprehensive optical properties of biological tissues. Second, OR-PAM encodes optical absorption into acoustic waves, in contrast to the pure optical processes in fluorescence microscopy and OCT, and provides background-free detection. The acoustic detection in OR-PAM mitigates the impacts of optical scattering on signal degradation and naturally eliminates possible interferences (i.e., crosstalks) between excitation and detection, which is a common problem in fluorescence microscopy due to the overlap between the excitation and fluorescence spectra. 
Unique for optical absorption imaging, OR-PAM has demonstrated broad biomedical applications since its invention, including, but not limited to, neurology5, 6, ophthalmology7, 8, vascular biology9, and dermatology10. In this video, we teach the system configuration and alignment of OR-PAM as well as the experimental procedures for in vivo functional microvascular imaging.

Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging technology capable of imaging optical absorption contrasts in vivo with cellular resolution and sensitivity. Here, we provide a visualized instruction on the experimental protocols of OR-PAM, including system configuration, system alignment, typical in vivo experimental procedures, and functional imaging schemes.

三维光学分辨率的光声显微镜

Optical microscopy, providing valuable insights at the cellular and organelle levels, has been widely recognized as an enabling biomedical technology. As ...

科研

生物工程

Generation and 3-Dimensional Quantitation of Arterial Lesions in Mice Using Optical Projection Tomography

The generation and analysis of vascular lesions in appropriate animal models is a cornerstone of research into cardiovascular disease, generating important information on the pathogenesis of lesion formation and the action of novel therapies. Use of atherosclerosis-prone mice, surgical methods of lesion induction, and dietary modification has dramatically improved understanding of the mechanisms that contribute to disease development and the potential of new treatments.
Classically, analysis of lesions is performed ex vivo using 2-dimensional histological techniques. This article describes application of optical projection tomography (OPT) to 3-dimensional quantitation of arterial lesions. As this technique is non-destructive, it can be used as an adjunct to standard histological and immunohistochemical analyses.
Neointimal lesions were induced by wire-insertion or ligation of the mouse femoral artery whilst atherosclerotic lesions were generated by administration of an atherogenic diet to apoE-deficient mice.
Lesions were examined using OPT imaging of autofluorescent emission followed by complementary histological and immunohistochemical analysis. OPT clearly distinguished lesions from the underlying vascular wall. Lesion size was calculated in 2-dimensional sections using planimetry, enabling calculation of lesion volume and maximal cross-sectional area. Data generated using OPT were consistent with measurements obtained using histology, confirming the accuracy of the technique and its potential as a complement (rather than alternative) to traditional methods of analysis.
This work demonstrates the potential of OPT for imaging atherosclerotic and neointimal lesions. It provides a rapid, much needed ex vivo technique for the routine 3-dimensional quantification of vascular remodelling.

Ex vivo analysis of arterial lesions from animal models of cardiovascular disease classically relies on histological and immunohistochemical techniques. These provide 2-dimensional measurements in 3-dimensional lesions. This manuscript describes the generation of arterial lesions for quantitative analysis in 3-dimensions using optical projection tomography.

生成和动脉病变的小鼠的三维定量使用光学投影层析成像

The generation and analysis of vascular lesions in appropriate animal models is a cornerstone of research into cardiovascular disease, generating ...

医学

Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive performance-competitive means for cortical and internal brain imaging, retaining a significant potential in many neurologic fields.

The present work describes a new protocol to perform non-invasive high-frequency ultrasound and photoacoustic based imaging on rat brain, to efficiently visualize deep subcortical regions and their vascular patterns by directing signals on skull foramina naturally present on animal cranium.

非侵入性的脑实质，血管和代谢高频超声和光声大鼠深脑成像

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central ...

神经科学

A Coregistered Ultrasound and Photoacoustic Imaging Protocol for the Transvaginal Imaging of Ovarian Lesions

Ovarian cancer remains the deadliest of all the gynecological malignancies due to the lack of reliable screening tools for early detection and diagnosis. Photoacoustic imaging or tomography (PAT) is an emerging imaging modality that can provide the total hemoglobin concentration (relative scale, rHbT) and blood oxygen saturation (%sO2) of ovarian/adnexal lesions, which are important parameters for cancer diagnosis. Combined with coregistered ultrasound (US), PAT has demonstrated great potential for detecting ovarian cancers and for accurately diagnosing ovarian lesions for effective risk assessment and the reduction of unnecessary surgeries of benign lesions. However, PAT imaging protocols in clinical applications, to our knowledge, largely vary among different studies. Here, we report a transvaginal ovarian cancer imaging protocol that can be beneficial to other clinical studies, especially those using commercial ultrasound arrays for the detection of photoacoustic signals and standard delay-and-sum beamforming algorithms for imaging.

We report a coregistered ultrasound and photoacoustic imaging protocol for the transvaginal imaging of ovarian/adnexal lesions. The protocol may be valuable to other translational photoacoustic imaging studies, especially those using commercial ultrasound arrays for the detection of photoacoustic signals and standard delay-and-sum beamforming algorithms for imaging.

用于卵巢病变经阴道成像的共注册超声和光声成像方案

Ovarian cancer remains the deadliest of all the gynecological malignancies due to the lack of reliable screening tools for early detection and diagnosis. ...

工程学

An Experimental Protocol for Assessing the Performance of New Ultrasound Probes Based on CMUT Technology in Application to Brain Imaging

The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ultrasound (US) probes. Particularly, a more realistic analysis with application-specific imaging targets can be extremely valuable to assess the expected performance of US probes in their potential clinical field of application.
The experimental protocol presented in this work was purposely designed to provide an application-specific assessment procedure for newly-developed US probe prototypes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology in relation to brain imaging.
The protocol combines the use of a bovine brain fixed in formalin as the imaging target, which ensures both realism and repeatability of the described procedures, and of neuronavigation techniques borrowed from neurosurgery. The US probe is in fact connected to a motion tracking system which acquires position data and enables the superposition of US images to reference Magnetic Resonance (MR) images of the brain. This provides a means for human experts to perform a visual qualitative assessment of the US probe imaging performance and to compare acquisitions made with different probes. Moreover, the protocol relies on the use of a complete and open research and development system for US image acquisition, i.e. the Ultrasound Advanced Open Platform (ULA-OP) scanner.
The manuscript describes in detail the instruments and procedures involved in the protocol, in particular for&#160;the calibration, image acquisition and registration of US and MR images. The obtained results prove the effectiveness of the overall protocol presented, which is entirely open (within the limits of the instrumentation involved), repeatable, and covers the entire set of acquisition and processing activities for US images.

The development of new ultrasound (US) probes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology requires an early realistic assessment of imaging capabilities. We describe a repeatable experimental protocol for US image acquisition and comparison with magnetic resonance images, using an ex vivo bovine brain as an imaging target.

基于 CMUT 技术的新型超声探头在脑成像中的应用研究

The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ...

Switchable Acoustic and Optical Resolution Photoacoustic Microscopy for In Vivo Small-animal Blood Vasculature Imaging

Photoacoustic microscopy (PAM) is a fast-growing invivo imaging modality that combines both optics and ultrasound, providing penetration beyond the optical mean free path (~1 mm in skin) with high resolution. By combining optical absorption contrast with the high spatial resolution of ultrasound in a single modality, this technique can penetrate deep tissues. Photoacoustic microscopy systems can have either a low acoustic resolution and probe deeply or a high optical resolution and probe shallowly. It is challenging to achieve high spatial resolution and large depth penetration with a single system. This work presents an AR-OR-PAM system capable of both high-resolution imaging at shallow depths and low-resolution deep-tissue imaging of the same sample in vivo. A lateral resolution of 4 &#181;m with 1.4 mm imaging depth using optical focusing and a lateral resolution of 45 &#181;m with 7.8 mm imaging depth using acoustic focusing were successfully demonstrated using the combined system. Here,&#160;in vivo&#160;small-animal blood vasculature imaging is performed to demonstrate its biological imaging capability.

Switchable Acoustic and Optical Resolution Photoacoustic Microscopy for In Vivo Small-animal Blood Vasculature Imaging

Here a switchable acoustic resolution (AR) and optical resolution (OR) photoacoustic microscopy (AR-OR-PAM) system capable of both high resolution imaging at shallow depth and low resolution deep tissue imaging on the same sample in vivo is demonstrated.

可切换声光学分辨率光声显微镜<em&gt;体内</em&gt;小动物血液血管成像

Photoacoustic microscopy (PAM) is a fast-growing invivo imaging modality that combines both optics and ultrasound, providing penetration beyond the ...

A High-performance Compact Photoacoustic Tomography System for In Vivo Small-animal Brain Imaging

In vivo small-animal imaging has an important role to play in preclinical studies. Photoacoustic tomography (PAT) is an emerging hybrid imaging modality that shows great potential for both preclinical and clinical applications. Conventional optical parametric oscillator-based PAT (OPO-PAT) systems are bulky and expensive and cannot provide high-speed imaging. Recently, pulsed-laser diodes (PLDs) have been successfully demonstrated as an alternative excitation source for PAT. Pulsed-laser diode PAT (PLD-PAT) has been successfully demonstrated for high-speed imaging on photoacoustic phantoms and biological tissues. This work provides a visualized experimental protocol for in vivo brain imaging using PLD-PAT. The protocol includes the compact PLD-PAT system configuration and its description, animal preparation for brain imaging, and a typical experimental procedure for 2D cross-sectional rat brain imaging. The PLD-PAT system is compact and cost-effective and can provide high-speed, high-quality imaging. Brain images collected in vivo at various scan speeds are presented.

A High-performance Compact Photoacoustic Tomography System for In Vivo Small-animal Brain Imaging

A compact pulsed-laser diode-based photoacoustic tomography (PLD-PAT) system for high-speed in vivo brain imaging in small animals is demonstrated.

高性能紧凑型光声层析成像系统<em&gt;体内</em&gt;小动物脑成像

In vivo small-animal imaging has an important role to play in preclinical studies. Photoacoustic tomography (PAT) is an emerging hybrid imaging modality ...

Hand-held Clinical Photoacoustic Imaging System for Real-time Non-invasive Small Animal Imaging

Translation of photoacoustic imaging into the clinic is a major challenge. Handheld real-time clinical photoacoustic imaging systems are very rare. Here, we report a combined photoacoustic and clinical ultrasound imaging system by integrating an ultrasound probe with light delivery for small animal imaging. We demonstrate this by showing sentinel lymph node imaging in small animals along with minimally invasive real-time needle guidance. A clinical ultrasound platform with access to raw channel data allows the integration of photoacoustic imaging leading to a handheld real-time clinical photoacoustic imaging system. Methylene blue was used for sentinel lymph node imaging at 675 nm wavelength. Additionally, needle guidance with dual modal ultrasound and photoacoustic imaging was shown using the imaging system. Depth imaging of up to 1.5 cm was demonstrated with a 10 Hz laser at a photoacoustic imaging frame rate of 5 frames per second.

A clinical handheld photoacoustic imaging system will be demonstrated for real-time non-invasive small animal imaging.

手持式实时非侵入性小动物成像的临床光声成像系统

Translation of photoacoustic imaging into the clinic is a major challenge. Handheld real-time clinical photoacoustic imaging systems are very rare. Here, ...

<meta charset="utf8"></head><body>使用 EPRI 和超声对肿瘤氧水平进行临床前成像

Tumor Hypoxia Assessment: In Vivo 3D Oxygen Imaging Through Electron Paramagnetic Resonance

The precise and real-time measurement of oxygen partial pressure (pO2) brings valuable information in many pathologies, including cancer. Low tumor pO2 (i.e., hypoxia) is connected to tumor aggressiveness and poor response to therapy. The quantification of tumor pO2 allows the evaluation of treatment effectiveness. Electron Paramagnetic Resonance Imaging (EPRI), particularly Pulse EPRI, has emerged as an advanced three-dimensional (3D) method of assessing tissue oxygenation in vivo. This innovation was enabled by the technological developments in EPR (Electron Paramagnetic Resonance) and the application of the water-soluble oximetric spin probes from the triaryl family, offering fast and sensitive oxygenation data. The relaxation time of the spin probe (T1 and/or T2) provides accurate information about pO2 in selected voxels.
Human glioblastoma LN229 tumors were grown in the interscapular fad pad of BALB/c nude mice. Ultrasound (US) imaging was used as a reference for tumor anatomical information. To image tissue pO2, the animals were placed in a fixed position in the animal bed with fiducials, enabling registration between the imaging modalities. After the OX071 contrast agent was administered, EPRI was performed, followed by US B-mode. Because of the low spin probe toxicity, the procedure can be repeated during tumor growth or treatment. Following imaging, the registration process was carried out using software written in MATLAB. Ultimately, the hypoxic fraction can be calculated for a specific tumor, and the histogram of pO2 tissue distribution can be compared over time. EPRI combined with ultrasound is an excellent tool for oxygen mapping of tumors in the preclinical setting.

<meta charset="utf8"></head><body>肿瘤缺氧评估：通过电子顺磁共振进行体内 3D 氧成像

Quantitative 3D oxygen maps of murine tumors were imaged noninvasively using Pulse Electron Paramagnetic Resonance. Ultrasound B-mode and Power Doppler were used for anatomy and vascular structure. Images from both modalities were superimposed enabling multi-parametric tumor analysis.

肿瘤缺氧评估：通过电子顺磁共振进行体内 3D 氧成像 

The precise and real-time measurement of oxygen partial pressure (pO2) brings valuable information in many pathologies, including cancer. Low tumor pO2 ...

通用型手持式三维光声成像探测深部组织人力造影和功能的临床前研究中实时

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三维光学分辨率的光声显微镜

生成和动脉病变的小鼠的三维定量使用光学投影层析成像

非侵入性的脑实质，血管和代谢高频超声和光声大鼠深脑成像

用于卵巢病变经阴道成像的共注册超声和光声成像方案

基于 CMUT 技术的新型超声探头在脑成像中的应用研究

可切换声光学分辨率光声显微镜

高性能紧凑型光声层析成像系统

手持式实时非侵入性小动物成像的临床光声成像系统

肿瘤缺氧评估：通过电子顺磁共振进行体内 3D 氧成像

肿瘤缺氧评估：通过电子顺磁共振进行体内 3D 氧成像