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。所呈现的手持式光声成像探头是理想的人体成像，因为它同许多的超声检查的优点，如便携使用，分辨率高，非电离激发和实时能力。然而，最优的硬件设计和RECOnstruction程序用于光声成像显著从那些在超声扫描仪通常使用的不同。这是由于两种模式的最佳操作特性的根本差异，如脉冲重复频率，检测到的超声响应，强调信号的激励机制，以及由此产生的图像重建方法的振幅。特别是，optoacoustics固有作为原则上可以用一个单一的询问激光脉冲来产生从所述成像的对象的完整体积的断层的数据集，因为还证明在此工作的三维成像模态。此外，探针可同时提供超声图像的自适应可实现和保持为在我们的研究日程1日后步骤。 与其他公认的临床成像模态，例如磁共振成像（MRI）或X射线计算机断层扫描（CT），optoa相比coustic断层是不是全身成像方式，但基于组织的光审讯可以提供显著更丰富，更具体的对比。实际上，内源性光吸收对比度不仅能提供高解析度的组织形态，但也呈现高重要性为临床决策功能性和潜在的目标分子的信息。相比提供者为其他成像方式20,21的分子成像的容量进一步强烈对比剂的显著较大可用性支持接近的光学成像方法。此外，光声方法的高时间分辨率这里演示， 即 ，高帧频（实时）的三维成像，通常不提供与目前任何其它模式中的临床或实验室使用。最后，同时采集多波长数据带来了一个额外的第五维度为实时volumetRIC可视化，允许执行组织的发色和特殊的生物标记物的生物分布的真三维光谱观测。 三维光声手持式探针的潜在应用不限于临床影像，但它也可表示在生物研究用动物模型中一个非常重要的工具。实际上，动物比小鼠大通常不适合于断层光声系统和手持式的方法来进行成像可能是更方便的。此外，体积某些区域进行实时光学对比度和超分辨率（三维）影像代表给药，血液动力学改变或药代动力学的研究具有得天独厚的优势。 总之，我们希望为手持式光声成像的方法引入将促使该技术的临床转化和显著推进临床前和b在许多前沿iological的研究也是如此。

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，所以血管的所有扫描位置是实时可视化的实现。重建图像中的所有三个方向上的代表最大强度投影（MIP）被显示在图2中，在测量过程中实时可视化允许具有GPU实现Then中的滤波反投影算法17。 实时多光谱成像能力被展示在图3中，具体地，测量是通过扫描探针沿着具有血管具有不同尺寸和氧饱和度水平，以及一个黑色素富含皮肤色素沉着10名健康人的手腕进行。将50赫兹的脉冲重复率与波长调谐能力在每个脉冲的基础激光被用在这种情况下。激光被调谐到730和850纳米用30纳米的步骤（5个波长）之间的多个波长，对应于在黑色素，单调增加的氧合血红蛋白的吸收和在脱氧的吸收特征峰的吸收一个单调减少血红蛋白。采集一个完整的多光谱数据集的需要，由于激光的快速调谐容量只有100毫秒。 MIP的图像沿深度方向为3种不同波长的光，对应于该探针的相同位置上，显示在图3A中 。 图3B示出氧合血红蛋白的未混合的分布（HBO 2），脱氧血红蛋白（HBR）和黑色素在红色，蓝色和黄色，分别的，而它是进一步假定的吸收是仅归因于这三种发色成分。由此，红色和蓝色的结构在图3中最有可能代表动脉和静脉，分别，而黄色的斑对应于皮肤的色素沉着。强烈的光吸收黑色素可以减少穿透这种方法在人与黝黑的皮肤适用的深度，虽然进一步的测试显然是必要的，以得出量化的结论。 图4示出在体内成像的动态过程的能力。这里，在中指的循环使用邻通过一个橡胶带的装置bstructed和数据采集18中释放出来。被获取的单个波长的图像的一个序列，在每秒10帧通过激光的脉冲重复率来确定。四MIP图像沿1秒间隔的横向和深度方向进行展示，其中，所述第二图像对应于所述时刻的循环恢复后。的波长为900毫微米，所以光声信号的振幅是与血液体积和血液氧合增加两者。 最后， 图5展示了介绍系统的使用ICG作为造影剂9来跟踪在一个三维的鼠标区域灌注动力学的能力。八周龄雌性裸鼠CD-1小鼠被用于活体实验。实验过程符合机构和巴伐利亚州政府的规章制度一致。脑血管是通过将鼠标在纯氧仰卧位置和2％异氟醚成像用于麻醉。兽医软膏用于保护小鼠的眼中。 10，ICG稀释在50ml的生理盐水中纳摩尔注入开始的光声数据采集后5秒。激光的波长以每秒50次的速率调整到730，760，800，850和900nm的针对每个脉冲的基础。对于每个组波长，ICG的分布未混合通过假定光吸收仅是由于此代理以及血红蛋白的氧合和脱氧的形式。 MIP的图像沿着相应于未混合的ICG分布为5个不同时刻的深度方向示于图5A（时间后喷射，也表示）。 ICG在血浆中的吸收光谱显示在图5B中 。这个特定的实验表明，所建议的方法能够simultane的<html> ously渲染真正五维（ 即 ，频谱富集时间分辨三维）断层数据，其随后被用来重建和光谱UNMIX各种特性的发色团，并在实时的外源剂的分布。 <img alt="图1" fo:content-width="7in" src="/files/ftp_upload/51864/51864fig1highres.jpg" width="700" /> 图1:手持式三维光声探头的布局压电元件（蓝点）相对于利息（黑色立方体）的区域（A）分布（B）换能器阵列的实际画面（TA。 ）和纤维束（FB），（C）的水包围的部分。（D）的光声探测器如在手持操作模式下所用的实际图片。<html> .JPG"TARGET ="_空白"&gt;请点击这里查看该图的放大版本。 <img alt="图2" fo:content-width="7in" src="/files/ftp_upload/51864/51864fig2highres.jpg" width="700" /> 图2:人末梢脉管系统追踪光吸收沿着连续四象三个笛卡尔方向上的最大强度投影图像。这里，激光的混合物在10脉冲每秒的操作用波长始终设定在800纳米。灰度配色方案代表了在任意单位的对象的光吸收ħ强度。 <a href="https://www.jove.com/files/ftp_upload/51864/51864fig2highres.jpg" target="_blank">请点击这里查看该图的放大版本。</a> s.jpg"宽度="700"/&gt; 图3:特定的内源性的生色团的手持式成像（A）中沿深度方向为对应于三个连续脉冲三种不同波长的光吸收的最大强度投影图像。在这种情况下，激光在每秒50个脉冲（探头未动）操作。显示氧化及脱氧血红蛋白和黑色素的分布（二）未混合光谱图像。 <a href="https://www.jove.com/files/ftp_upload/51864/51864fig3highres.jpg" target="_blank">请点击这里查看该图的放大版本。</a> <img alt="图4" fo:content-width="7in" src="/files/ftp_upload/51864/51864fig4highres.jpg" width="700" /> 图4:血流量的实时成像光学吸收的沿深度最大强度投影图像和对应于四个不同时刻的横向方向。在中指的循环实验前被拦截，并在实验过程中释放（0秒）。 <a href="https://www.jove.com/files/ftp_upload/51864/51864fig4highres.jpg" target="_blank">请点击这里查看该图的放大版本。</a> <img alt="图5" fo:content-width="7in" src="/files/ftp_upload/51864/51864fig5highres.jpg" width="700" /> 图5:在小鼠中的光学造影剂的分布的实时成像 ICG的造影剂（A）的分布（最大强度投影沿深度方向）上为四个不同时刻注射剂之后（在0秒）。 （B）ICG血浆消光光谱。 <a href="https://www.jove.com/files/ftp_upload/51864/51864fig5highres.jpg" target="_blank">请点击这里查看吨的放大版本。</a>他的身影。

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

Nanyang Technological University

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

Three-Dimensional Ultrasonic Needle Tip Tracking with a Fiber-Optic Ultrasound Receiver

Ultrasound is frequently used for guiding minimally invasive procedures, but visualizing medical devices is often challenging with this imaging modality. When visualization is lost, the medical device can cause trauma to critical tissue structures. Here, a method to track the needle tip during ultrasound image-guided procedures is presented. This method involves the use of a fiber-optic ultrasound receiver that is affixed within the cannula of a medical needle to communicate ultrasonically with the external ultrasound probe. This custom probe comprises a central transducer element array and side element arrays. In addition to conventional two-dimensional (2D) B-mode ultrasound imaging provided by the central array, three-dimensional (3D) needle tip tracking is provided by the side arrays. For B-mode ultrasound imaging, a standard transmit-receive sequence with electronic beamforming is performed. For ultrasonic tracking, Golay-coded ultrasound transmissions from the 4 side arrays are received by the hydrophone sensor, and subsequently the received signals are decoded to identify the needle tip&#39;s spatial location with respect to the ultrasound imaging probe. As a preliminary validation of this method, insertions of the needle/hydrophone pair were performed in clinically realistic contexts. This novel ultrasound imaging/tracking method is compatible with current clinical workflow, and it provides reliable device tracking during in-plane and out-of-plane needle insertions.

Accurate and efficient visualization of invasive medical devices is extremely important in many ultrasound-guided minimally invasive procedures. Here, a method for localizing the spatial position of a needle tip relative to the ultrasound imaging probe is presented.

基于光纤超声接收机的三维超声针尖跟踪

Ultrasound is frequently used for guiding minimally invasive procedures, but visualizing medical devices is often challenging with this imaging modality. ...

工程学

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

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, ...

Dual Raster-Scanning Photoacoustic Small-Animal Imager for Vascular Visualization

Imaging of vascular networks on small animals has played an important role in basic biomedical research. Photoacoustic imaging technology has great potential for application in the imageology of small animals. The wide-field photoacoustic imaging of small animals can provide images with high spatiotemporal resolution, deep penetration, and multiple contrasts. Also, the real-time photoacoustic imaging system is desirable to observe the hemodynamic activities of small-animal vasculature, which can be used to research the dynamic monitoring of small-animal physiological features. Here, a dual-raster-scanning photoacoustic imager is presented, featuring a switchable double-mode imaging function. The wide-field imaging is driven by a two-dimensional motorized translation stage, while the real-time imaging is realized with galvanometers. By setting different parameters and imaging modes, in vivo visualization of small-animal vascular network can be performed. The real-time imaging can be used to observe pulse change and blood flow change of drug-induced, etc. The wide-field imaging can be used to track the growth change of tumor vasculature. These are easy to be adopted in various areas of basic biomedicine research.

A dual raster-scanning photoacoustic imager was designed, which integrated wide-field imaging and real-time imaging.

用于血管可视化的双栅格扫描光声小动物成像仪

Imaging of vascular networks on small animals has played an important role in basic biomedical research. Photoacoustic imaging technology has great ...

Multispectral Optoacoustic Tomography for Functional Imaging in Vascular Research

Microcirculatory impairment has been recognized in various disease processes, underlying this growing theme within vascular research. In recent years, the development of live imaging systems has set the (analytical) pace in both basic and clinical research, with the objective of creating new instruments capable of providing real-time, quantifiable endpoints with clinical interest and application. Near-infrared spectroscopy (NIRS), positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) are available, among other techniques, but cost, image resolution, and reduced contrast are recognized as common challenges. Optoacoustic tomography (OT) offers a new perspective on vascular functional imaging, combining state-of-the-art optical absorption and spatial resolution capacities (from micrometer optical to millimeter acoustic resolution) with tissue depth. In this study, we tested the applicability of multispectral optoacoustic tomography (MSOT) for functional imaging. The system uses a tunable optical parametric oscillator (OPO) pumped by an Nd: YAG laser, providing excitation pulses sensed by a 3D probe at wavelengths from 680 nm to 980 nm. Images obtained from the human forearm were reconstructed through a specific algorithm (supplied within the manufacturer&#39;s software) based on the response of specific chromophores. Maximal Oxygenated Hemoglobin (Max HbO2) and Deoxygenated Hemoglobin (Max Hb), Total Hemoglobin (HbT), and mean Oxygen Saturation (mSO2) to vascular density (&#181;Vu), inter-unit average distances (&#950;Ad), and capillary blood volume (mm3) may be measured using this system. The applicability potential found with this OT system is relevant. Ongoing software developments will surely improve the utility of this imaging system.

The present protocol describes the acquisition of multispectral optoacoustic images of in vivo human skin vasculature. These include the quantification of hemoglobin and melanin, regarded as chromophores of interest for functional analysis.

用于血管研究功能成像的多光谱光声断层扫描

Microcirculatory impairment has been recognized in various disease processes, underlying this growing theme within vascular research. In recent years, the ...

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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