Name: a coregistered ultrasound and photoacoustic imaging protocol for the transvaginal imaging of ovarian lesions
Uploaded: 2023-03-03T14:15:00
Description: Watch this Scientific Journal Video about A Coregistered Ultrasound and Photoacoustic Imaging Protocol for the Transvaginal Imaging of Ovarian Lesions at JoVE.com

这项工作得到了NCI（R01CA151570，R01CA237664）的支持。作者感谢由Mathew Powell博士领导的整个GYN肿瘤学小组帮助招募患者，放射科医生Cary Siegel，William Middleton和Malak Itnai博士帮助美国研究，以及病理学家Ian Hagemann博士帮助病理学解释数据。作者非常感谢Megan Luther和GYN研究协调员在协调研究时间表，确定研究患者和获得知情同意方面所做的努力。

所有进行的研究都得到了华盛顿大学机构审查委员会的批准。
1. 系统配置：光学照明（图1）
<ol><li>使用 Nd：YAG 激光器泵浦 10 Hz 的脉冲可调谐 （690-890 nm） 钛蓝宝石激光器。</li>
	<li>通过首先用平凹透镜发散光束，然后用平凸透镜准直光束来扩展激光束。使用两个反射镜将光束引导到分束器上（如下所述）。</li>
	<li>通过使用?...

<ol>
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National Cancer Institute Available from: <a target="_blank" href="https://seer.cancer.gov/statfacts/html/ovary.html">https://seer.cancer.gov/statfacts/html/ovary.html</a> (2022)</li><li>Temkin, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Outcomes+from+ovarian+cancer+screening+in+the+PLCO+trial:+Histologic+heterogeneity+impacts+detection,+overdiagnosis+and+survival.">Outcomes from ovarian cancer screening in the PLCO trial: Histologic heterogeneity impacts detection, overdiagnosis and survival.</a> European Journal of Cancer. 87, 182-188 (2017).</li><li>Kobayashi, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+randomized+study+of+screening+for+ovarian+cancer:+A+multicenter+study+in+Japan.">A randomized study of screening for ovarian cancer: A multicenter study in Japan.</a> International Journal of Gynecological Cancer. 18 (3), 414-420 (2008).</li><li>Andreotti, R. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=O-RADS+US+risk+stratification+and+management+system:+A+consensus+guideline+from+the+ACR+ovarian-adnexal+reporting+and+data+system+committee.">O-RADS US risk stratification and management system: A consensus guideline from the ACR ovarian-adnexal reporting and data system committee.</a> Radiology. 294 (1), 168-185 (2020).</li><li>Salehi, H. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+optimal+light+delivery+system+for+coregistered+transvaginal+ultrasound+and+photoacoustic+imaging+of+ovarian+tissue.">Design of optimal light delivery system for coregistered transvaginal ultrasound and photoacoustic imaging of ovarian tissue.</a> Photoacoustics. 3 (3), 114-122 (2015).</li><li>Oppenheim, A. V., Schafer, R. 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光学照明 使用的光纤数量基于两个因素：光照明均匀性和系统复杂性。在皮肤表面具有均匀的光照明图案以避免热点至关重要。同样重要的是，用最少的光纤保持系统的简单和稳健。以前，使用四根独立的光纤已被证明是在几毫米及以上的深度产生均匀照明的最佳选择。此外，与四根光纤的光耦合相对简单和坚固，符合患者研究的需要。我们之前已经证明，使用四根1 mm芯多模光纤...

光声成像或断层扫描 （PAT） 是一种混合成像方式，可测量美国分辨率和深度远超组织光学扩散极限 （~1 mm） 的光吸收分布。在PAT中，纳秒激光脉冲用于激发生物组织，由于光学吸收而导致瞬态温升。这导致初始压力上升，由此产生的光声波由美国换能器测量。多光谱PAT涉及使用可调谐激光器或在不同波长下工作的多个激光器来照亮组织，从而能够重建多个波长的光学吸收图。基于近红外（NIR）窗口内氧合和脱氧血红蛋白的差异吸收，多光谱PAT可以计算出氧合和脱氧血红蛋白浓度、总血红蛋白浓度和血氧饱和度的分布，这些都是与肿瘤血管生成和血液氧合消耗或肿瘤代谢相关的功能生物标志物。PAT在许多肿瘤学应用中都取得了成功，例如卵巢癌1，2，乳腺癌3，4，5，皮肤癌6，甲状腺癌7，8，宫颈癌9，前列腺癌10，11和结直肠癌12。
卵巢癌是所有妇科恶性肿瘤中最致命的。只有38%的卵巢癌在早期（局部或区域）阶段被诊断出来，其中5年生存率为74.2%至93.1%。大多数在晚期诊断，其 5 年生存率为 30.8% 或更低13.目前的临床诊断方法，包括经阴道超声检查（TUS）、多普勒超声、血清癌抗原125（CA 125）和人附睾蛋白4（HE4），被证明对早期卵巢癌诊断缺乏敏感性和特异性14，15，16。此外，大部分良性卵巢病变可能难以用当前的成像技术准确诊断，这导致不必要的手术，增加医疗成本和手术并发症。因此，需要更多准确的非侵入性方法来对附件肿块进行风险分层，以优化管理和结果。显然，需要一种对早期卵巢癌敏感和特异性的技术，并且更准确地从良性病变中识别恶性。
我们小组通过结合临床US系统，用于容纳用于光传递的光纤的定制探针鞘和可调谐激光器1，开发了用于卵巢癌诊断的经阴道US和PAT系统（USPAT）。来自USPAT系统的总血红蛋白浓度（相对量表，rHbT）和血氧饱和度（%sO2）已显示出检测早期卵巢癌和准确诊断卵巢病变以进行有效风险评估和减少不必要的良性病变手术的巨大潜力1，2。目前的系统原理图如图1所示，控制框图如图2所示。该策略有可能整合到现有的TUS卵巢癌诊断方案中，同时提供功能参数（rHbT，%sO2）以提高TUS的敏感性和特异性。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Clinical US imaging system</td>
			<td>Alpinion Medical Systems</td>
			<td>EC-12R</td>
			<td>Fully programmable clinical US system</td>
		</tr>
		<tr>
			<td>Dielectric mirror</td>
			<td>Thorlabs</td>
			<td>BB1-E03</td>
			<td>Used to reflect light along the optical path</td>
		</tr>
		<tr>
			<td>Endocavity US transducer</td>
			<td>Alpinion Medical Systems</td>
			<td>EC3-10</td>
			<td>Transvaginal ultrasound probe</td>
		</tr>
		<tr>
			<td>Laser power meter</td>
			<td>Coherent</td>
			<td>LabMax TOP</td>
			<td>Used to measure laser energy</td>
		</tr>
		<tr>
			<td>Multi-mode optical fiber</td>
			<td>Thorlabs</td>
			<td>FP1000ERT</td>
			<td>Couple laser light to the endocavity ultrasound probe</td>
		</tr>
		<tr>
			<td>Non-polarizing beam splitter plate</td>
			<td>Thorlabs</td>
			<td>BSW11</td>
			<td>For splitting laser beam into sensors to measure energy</td>
		</tr>
		<tr>
			<td>Plano-concave lens</td>
			<td>Thorlabs</td>
			<td>LC1715</td>
			<td>For laser beam expansion</td>
		</tr>
		<tr>
			<td>Plano-convex lens&#160;</td>
			<td>Thorlabs</td>
			<td>LA1484-B</td>
			<td>For laser beam collimation</td>
		</tr>
		<tr>
			<td>Plano-convex lens&#160;</td>
			<td>Thorlabs</td>
			<td>LA1433-B</td>
			<td>Used to focus light into four optical fibers</td>
		</tr>
		<tr>
			<td>Polarizing beam splitter cube</td>
			<td>Thorlabs</td>
			<td>PBS252</td>
			<td>For splitting laser beam into four beams</td>
		</tr>
		<tr>
			<td>Protective probe shealth</td>
			<td>Custom 3D printed</td>
			<td></td>
			<td>Hold and protect the four optical fibers at the tip of the ultrasound probe</td>
		</tr>
		<tr>
			<td>Right angle prism mirror</td>
			<td>Thorlabs</td>
			<td>MRA25-E03</td>
			<td>Used to reflect light along the optical path</td>
		</tr>
		<tr>
			<td>Tunable laser system</td>
			<td>Symphotic TII</td>
			<td>LS-2145-LT50PC</td>
			<td>Light source for multispectral PAT</td>
		</tr>
		<tr>
			<td>USPAT control software</td>
			<td>Custom developed in C++</td>
			<td></td>
			<td>Controls acquisition parameters of the ultrasound machine and the laser wavelength</td>
		</tr>
		<tr>
			<td>USPAT image display software</td>
			<td>Custom developed in C++</td>
			<td></td>
			<td>Displays the US/PAT B-scans and sO2/rHbT maps in real time</td>
		</tr>
	</tbody>
</table>

a coregistered ultrasound and photoacoustic imaging protocol for the transvaginal imaging of ovarian lesions

卵巢癌仍然是所有妇科恶性肿瘤中最致命的，因为缺乏可靠的筛查工具进行早期发现和诊断。光声成像或断层扫描 （PAT） 是一种新兴的成像方式，可以提供卵巢/附件病变的总血红蛋白浓度（相对量表，rHbT）和血氧饱和度 （%sO2），这是癌症诊断的重要参数。结合共同注册超声（美国），PAT在检测卵巢癌和准确诊断卵巢病变方面显示出巨大的潜力，以进行有效的风险评估并减少良性病变的不必要手术。然而，据我们所知，临床应用中的PAT成像方案在不同的研究中有很大差异。在这里，我们报告了一种经阴道卵巢癌成像方案，该方案可能对其他临床研究有益，特别是那些使用商业超声阵列检测光声信号和标准延迟和波束形成算法进行成像的研究。

在这里，我们展示了USPAT成像的恶性和正常卵巢病变的示例。图 3 显示一名 50 岁的绝经前女性，对比增强 CT 显示双侧多囊附件肿块。 图 3A 显示了左侧附件的美国图像，ROI 标记了囊性病变内的可疑实体结节。 图3B 显示了叠加在美国并以红色显示的PAT rHbT图。rHbT在1 cm至5 cm的深度范围内显示出广泛的弥漫性血管分布，水平高达17.1?...

Watch this Scientific Journal Video about A Coregistered Ultrasound and Photoacoustic Imaging Protocol for the Transvaginal Imaging of Ovarian Lesions at JoVE.com

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

我们报告了一种用于卵巢/附件病变经阴道成像的共同注册超声和光声成像方案。该协议可能对其他转化光声成像研究有价值，特别是那些使用商业超声阵列检测光声信号和标准延迟和波束形成算法进行成像的研究。

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. ...

众所周知，卵巢癌是所有妇科恶性肿瘤中最致命的，当卵巢癌在早期和局部阶段被发现时，手术和化疗可以治愈约70%至90%的患者，而在后期诊断时只有20%或更少。众所周知，目前的标准护理方法对早期卵巢癌检测的灵敏度较低。此外，标准护理方法对于卵巢附件病变的准确风险评估的特异性非常低，导致不必要的手术，因此潜在的手术并发症和巨大的医疗成本。因此，需要我们的技术对早期卵巢癌检测敏感，并且具有对卵巢附件病变的准确诊断的特异性。光声断层扫描或PAT用特定波长的近红外光照射，并被氧合和脱氧血红蛋白选择性吸收。光吸收产生的光声波可以映射出血红蛋白对比度，这可以与共配准超声成像的解剖结构共配准。总血红蛋白浓度和氧饱和度提供有关组织血管和耗氧量的功能信息。由于恶性病变通常具有较高的总血红蛋白和较低的氧饱和度，因此这两个自变量可能有助于更早地发现卵巢癌，并准确区分恶性与良性卵巢附件病变，以改善手术治疗建议。我们已经获得了患者数据的试点，结果已经证明，共注册的光声成像结合经阴道超声和卵巢癌血液生物标志物CA 125实际上可以诊断卵巢附件病变。我们的试点数据还显示，有证据表明，共同注册的光声成像可以检测早期卵巢癌和输卵管癌。光声和超声共配准已应用于乳腺癌、皮肤癌、甲状腺癌、宫颈癌、前列腺癌、结直肠癌的检测和诊断。然而，成像探针因不同器官的成像窗口而异。第一台商业共同注册的光声和超声波乳腺成像系统可从Sino Medical Instrument获得。我们预计市场上将有更多商业共同注册的光声超声系统。然而，经阴道光声和超声成像探头需要专门为成像患者设计。首先，首先用平面凹透镜发散光束，然后用平面凸透镜准直光束来扩展激光束。使用两个反射镜将光束引导到分束器上。使用偏振分束器将原始光束分成两束，然后用另外两个第二级分束器将两个光束分开。这样，扩展的激光束将分成四个能量相等的光束。用光纤卡盘安装四根多模光纤，并使用四个平面凸透镜将四束激光束聚焦到四根光纤中。盖住金属盒下的所有光学元件，以确保光路不暴露。将额外的监护仪连接到可编程临床超声或超声系统，以运行PATUS显示软件，以实时可视化相对总血红蛋白，血氧饱和度图和其他功能参数。然后将激光器的内部触发器连接到超声系统的外部触发器，并依次获取五个连续的PAT帧和一个共配准的超声帧。要校准系统，请将激光泵浦能量设置为固定水平。对于每个波长，检查每个光纤尖端的每个脉冲能量输出，以确保每个选定波长处计算的能量密度处于预期值。要准备PATUS成像系统，请打开临床超声系统并启动超声系统软件。按下超声机控制面板上的换能器按钮，打开换能器选择屏幕。然后选择正确的超声换能器。校准激光系统并将每个波长的总脉冲能量输入PATUS显示软件。通过将光纤和探头封闭在探头护套内来组装PATUS探头。对于成像，调整PATUS换能器的位置。低回声目标慢慢出现在B扫描的中心。然后在PATUS控制软件中选择所需的深度，并在控制软件中单击扫描以开始共注册PATUS B模式数据采集。观看 PATUS 图像显示软件，实时查看共配准超声和 PAT B 模式图像。采集时，单波长PA数据显示在超声顶部。重复这些步骤以获取更多图像，如有必要，对第二个病变进行成像。数据采集完成后，PATUS显示软件会收到一个触发器来重建功能图。在这里，左图显示了超声B扫描，而右图显示了与共配准超声重叠的相对总血红蛋白。选择一个感兴趣的区域或ROI，这里是目标卵巢，以计算ROI内的SO2图谱。该图像显示一名 50 岁的绝经前女性，双侧多囊附件肿块通过增强 CT 显示。此处显示左侧附件的超声图像，其感兴趣区域或ROI标记囊性病变内的可疑实性结节。将PAT相对总血红蛋白图叠加到超声上。相对总血红蛋白在1厘米至5厘米的深度范围内显示出广泛的弥漫性血管分布，水平高达17.1。血氧饱和度分布叠加超声，水平低，平均值为46.4%，手术病理显示左右卵巢均分化良好的子宫内膜样腺癌。深度标记在B扫描图像的右侧。该图显示一名患有双侧囊性病变的 46 岁女性。这里显示了右卵巢的超声检查，带有最大直径为4.2厘米的简单囊肿。叠加在共配准超声上的PAT相对总血红蛋白图在病变左侧显示散射信号，平均值低至4.8。血氧饱和度图显示血氧饱和度含量较高，为67.5%，手术病理显示右卵巢正常，伴有滤泡囊肿。对于每个波长，测量四个光纤尖端的总能量输出，并将其与之前的记录进行比较。如果测量值比记录值少一毫焦耳以上，请调整光学元件以最大化能量耦合。使用FDA批准的临床超声系统的体内PAT是PAT临床转化的重要一步。与离体成像相比，体内人体成像在数据采集方面提出了新的挑战。临床PAT数据可以进一步用于计算机辅助诊断研究。我们的技术开发和有希望的试点患者研究结果激励研究人员和公司探索共配准光声和超声在早期卵巢癌检测和手术风险管理方面的全部能力。

Research

JoVE Journal

Engineering

Spatial Separation of Molecular Conformers and Clusters

分子构象器和星团的空间分离

Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold ...

科研

工程学

Fast Imaging Technique to Study Drop Impact Dynamics of Non-Newtonian Fluids

快速成像技术来研究非牛顿流体的跌落冲击动力学

In the field of fluid mechanics, many dynamical processes not only occur over a very short time interval but also require high spatial resolution for ...

Electron Channeling Contrast Imaging for Rapid III-V Heteroepitaxial Characterization

电子通道造影的快速III-V异质特征

Misfit dislocations in heteroepitaxial layers of GaP grown on Si(001) substrates are characterized through use of electron channeling contrast imaging ...

Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents

一个多腔动态单一酶幻影超极化磁共振剂研究的用途

Imaging of hyperpolarized substrates by magnetic resonance shows great clinical promise for assessment of critical biochemical processes in real time. Due ...

Nanostructured Ag-zeolite Composites as Luminescence-based Humidity Sensors

纳米银沸石复合材料作为基于发光的湿度传感器

Small silver clusters confined inside zeolite matrices have recently emerged as a novel type of highly luminescent materials. Their emission has high ...

Demonstration of a Hyperlens-integrated Microscope and Super-resolution Imaging

Hyperlens 综合显微镜和超分辨率成像的演示

The use of super-resolution imaging to overcome the diffraction limit of conventional microscopy has attracted the interest of researchers in biology and ...

Guidelines and Experience Using Imaging Biomarker Explorer (IBEX) for Radiomics

Guidelines and Experience Using Imaging Biomarker Explorer IBEX for Radiomics

使用成像生物标志物探险家 (野山羊) Radiomics 的指南和经验

Imaging Biomarker Explorer (IBEX) is an open-source tool for medical imaging radiomics work. The purpose of this paper is to describe how to use IBEX's ...

Novel Photoacoustic Microscopy and Optical Coherence Tomography Dual-modality Chorioretinal Imaging in Living Rabbit Eyes

新型光声显微镜与光学相干层析成像在活兔眼中的双模脉络成像

Photoacoustic ocular imaging is an emerging ophthalmic imaging technology that can noninvasively visualize ocular tissue by converting light energy into ...

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

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. ...

Femtosecond Laser Filaments for Use in Sub-Diffraction-Limited Imaging and Remote Sensing

飞秒激光丝在亚衍射有限成像和遥感中的应用

Probing remote matter with laser light is a ubiquitous technique used in circumstances as diverse as laser-induced breakdown spectroscopy and barcode ...