Real-time spectroscopic photoacoustic/ultrasound (PAUS) scanner withsimultaneous fluence and motion compensation to guide and validateinterventions: system development and preclinical testing.

摘要 本计画的目标是发展一套临床上即时光谱光声/超音波（PAUS）系统 通过UW和GE Research之间的合作，为介入手术提供分子指导。 最近，我们提出了一种新的，快速扫描的概念PA成像。为了将这一概念付诸实践，我们首先 开发了一种独特的，紧凑的，二极管泵浦的，可调谐的（700 - 900 nm）激光器，工作在非常高的（高达1000 Hz）重复频率和相对较低（~1 mJ）的脉冲能量，以及光纤传输系统， 将激光脉冲耦合到成像探头中。除了US B模式和所有其他US模式外， 同时产生实时（50 Hz）光谱PA图像，这是第一次合并 进行实时PAUS成像。一个独特的功能是自动在线激光通量补偿和运动 校正，使得能够在每个图像像素处进行定量光学吸收光谱。光谱可以 根据分子成分（药物/造影剂）识别对US不透明的物质，并进行量化 组织功能变化（例如，血氧及其浓度）;此外， 使用PA可以更好地可视化针操作。 UW将与GE Research合作，将光谱PAUS集成到高端US扫描仪中， 临床级PAUS系统，并测试其是否可以在总体上改善介入手术指导， 特别是在复发性甲状腺肿瘤的乙醇（EA）消融治疗中。 大多数甲状腺癌患者经过初步治疗后的预后非常好，但复发率 或者持久性可以高达30%。如果确认癌症复发，则可采用图像引导的非手术治疗， 因为EA或射频消融（RFA）通常是更有创手术的替代方法。 尽管超声有助于定位EA和RFA针，但消融区域的在线成像和 消融术对US来说仍然很困难。当复发结节（尤其是其中的毛细血管网）不完全 如果不进行治疗，癌症会复发并可能转移。我们假设实时光谱 PAUS将提高消融手术的有效性，并显著减少手术重复。如果 在这个初始阶段取得成功后，该项目将进入临床试验，以指导和验证消融治疗 并探索实时光谱PAUS用于其他介入手术。 SA1将我们独特的激光和扫描光纤传输系统与临床GE US扫描仪集成， 实时光谱PAUS。然后，SA2将开发用于运动校正的实时信号处理工具 以及用于光谱PAUS的注量补偿和成像协议。SA3将专注于优化 使用体模和离体研究的PAUS系统。最后，在SA4中，开发的PAUS系统将用于 用三种体内模型测试PAUS指南的临床适用性，包括 甲状腺癌、接近人体解剖结构的动物模型以及对人类受试者的试点测量。

Abstract The goal of this project is to develop a clinical real-time spectroscopic photoacoustic/ultrasound (PAUS) system for molecular guidance of interventional procedures through a partnership between UW and GE Research. Recently, we proposed a new, fast-sweep concept for PA imaging. To put this concept into practice, we first developed a unique, compact, diode-pumped, tunable (700 -900 nm) laser operating at very high (up to 1000 Hz) repetition rates and relatively low (~ 1 mJ) pulse energies, and a fiber-optic delivery system to sequentially couple laser pulses into the imaging probe. In addition to US B-mode, and all other US modes, the system simultaneously produces real-time (50 Hz) spectroscopic PA images, which were combined for the first time for real-time PAUS imaging. A unique feature is automatic on-line laser-fluence compensation and motion correction, enabling quantitative optical absorption spectroscopy at every image pixel. Spectroscopy can identify substances opaque to US based on their molecular constituents (drugs/contrast agents), and quantify tissue functional changes (e.g., blood oxygenation and its concentration) within the image; in addition, manipulation with a needle is better visualized with PA. UW will work with GE Research to integrate spectroscopic PAUS into a high-end US scanner to create a clinical-grade PAUS system, and test whether it can improve interventional procedure guidance in general and, particularly, in ethanol (EA) ablation therapies of recurrent thyroid tumors. The prognosis for most people with thyroid cancer after primary treatment is very good, but the recurrence rate or persistence can be up to 30%. If recurrent cancer is confirmed, image-guided nonsurgical procedures such as EA or radio frequency ablation (RFA) are commonly used alternatives to more invasive procedures. Although US helps position EA and RFA needles, on-line imaging of the ablative area and confirmation of ablation remain difficult for US. When the recurrent nodule (especially the capillary network in it) is not entirely treated, the cancer will return with possible metastasis. We hypothesize here that real-time spectroscopic PAUS will improve the efficacy of ablation procedures and dramatically reduce procedure repetitions. If successful in this initial stage, the project will move to a clinical trial to both guide and validate ablative therapies and explore real-time spectroscopic PAUS for other interventional procedures. SA1 will integrate our unique laser and scanning fiber-optic delivery system with a clinical GE US scanner for real-time spectroscopic PAUS. Then, SA2 will develop real-time signal processing tools for motion correction and fluence compensation and imaging protocols for spectroscopic PAUS. SA3 will focus on optimizing the PAUS system using phantom and ex vivo studies. Finally, in SA4 the developed PAUS system will be used to test the clinical applicability of PAUS guidance with three in vivo models, including small animal studies of thyroid cancer, an animal model approximating human anatomy, and pilot measurements on human subjects.