Passive Cavitation Imaging for Guidance and Control of Ultrasound Ablation

项目描述（申请人提供）：本项目的总体目标是开发用于热烧蚀制导和控制的被动空化成像新技术。这项研究是基于这样的假设，即由治疗性超声光束引起的空化或微泡活动可以通过超声阵列被动成像，提供有关空间依赖性超声强度、温度和体内组织活力的具体信息。在被动空化成像中，超声诱导的组织内微泡活动是由空化和沸腾引起的局部声发射无创地绘制的。这些声发射通过超声成像阵列被动检测，过滤和综合聚焦形成图像，描绘整个成像区域稳定空化，惯性空化和组织沸腾的位置和强度。初步数据表明，这些被动空化图像可以准确地描述原位治疗超声束的空间分布，解析空化引起的声发射的单个来源，并用于预测局部组织温度升高导致热凝性坏死。这种空化成像技术将为超声消融提供以前无法获得的指导和控制，极大地增强了这种无创和微创癌症治疗方式。该研究将从优化被动空化成像方法开始，包括声发射信号的滤波和波束形成，以最大限度地提高图像分辨率、灵敏度和定量精度。优化的被动空化成像方法将用于绘制生理盐水溶液和离体肝组织中的局部稳定空化和惯性空化，测量空化阈值作为温度和超声振幅的函数。被动空化图像将获得在治疗性超声暴露牛肝体外和猪肝在体内。测量超声消融过程中被动空化图像、组织温度和组织组织学变化之间的相关性，并辅以物理建模和统计分析，将指导超声消融控制策略的发展。基于实验数据的多元统计模型将根据所考虑的三个波段的成像声发射预测局部组织温度和凝血，从而允许规范超声消融的治疗进展指标和终点。基于这些预测局部组织消融的新模型的测量精度，将评估这种方法用于闭环超声消融控制的可行性。该项目的成功完成将为未来临床系统的发展提供可行性，该系统通过被动空化成像来指导和控制超声消融。这些指导和控制方法将大大提高肝癌和软组织肿瘤超声消融及其他临床应用的疗效和安全性。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop the novel technology of passive cavitation imaging for guidance and control of thermal ablation. This investigation is based on the hypothesis that cavitation, or microbubble activity caused by therapeutic ultrasound beams, can be passively imaged by ultrasound arrays, providing specific information about spatially-dependent sonication intensity, temperature, and tissue viability in vivo. In passive cavitation imaging, ultrasound-induced microbubble activity within tissue is mapped noninvasively from locally occurring acoustic emissions caused by cavitation and boiling. These acoustic emissions are detected passively by an ultrasound imaging array, filtered, and synthetically focused to form images depicting locations and strengths of stable cavitation, inertial cavitation, and tissue boiling throughout the imaged region. Preliminary data indicates that these passive cavitation images can accurately depict spatial profiles of therapeutic ultrasound beams in situ, resolve individual sources of cavitation-induced acoustic emissions, and be used to predict local tissue temperature elevations causing thermal coagulation necrosis. This cavitation imaging technology will provide previously unavailable guidance and control for ultrasound ablation, greatly enhancing this modality for noninvasive and minimally invasive cancer treatment. The proposed research will begin with optimization of methods for passive cavitation imaging, including filtering and beamforming of acoustic emission signals to maximize image resolution, sensitivity, and quantitative accuracy. Optimized passive cavitation imaging methods will be used to map localized stable and inertial cavitation in saline solution and ex vivo liver tissue, measuring cavitation thresholds as functions of temperature and sonication amplitude. Passive cavitation images will be acquired during therapeutic ultrasound exposures both on bovine liver in vitro and porcine liver in vivo. Measured correlations between passive cavitation images, tissue temperature, and tissue histologic changes during ultrasound ablation, with complementary physical modeling and statistical analysis, will guide development of control strategies for ultrasound ablation. Multivariate statistical models based on experimental data will predict local tissue temperature and coagulation based on imaged acoustic emissions in the three bands considered, allowing specification of treatment progress indicators and end points for ultrasound ablation. Feasibility of this approach for closed-loop ultrasound ablation control will be assessed, based on measured accuracy of these new models for prediction of local tissue ablation. Successful completion of this project will show feasibility for future development of a clinical system providing guidance and control of ultrasound ablation by passive cavitation imaging. These guidance and control methods will provide greatly improved efficacy and safety for ultrasound ablation of liver cancer and soft tissue tumors as well as other clinical applications. PUBLIC HEALTH RELEVANCE: Liver cancer, both primary and metastatic, is a major public health problem, accounting for the largest cancer- related mortality in the world, with only a small fraction of patients eligible for curative resection or transplantation. Minimally invasive and noninvasive ablation methods provide an important alternative but have significant problems with incomplete treatment, tumor recurrence, and complications caused by imprecise treatment. Ultrasound ablation is a particularly promising approach, potentially offering more precise and reliable treatment, but will not realize its full potential without effective feedback, control and image guidance. Our passive cavitation imaging technology has the potential to greatly improve guidance and control of minimally-invasive and noninvasive ultrasound tumor ablation, providing more precise, selective, predictable, and consistent ablation of liver cancer as well as soft tissue tumors and other clinically important targets, and thus fewer complications, reduced tumor recurrence, and improved patient outcomes.