Novel Nonlinear Ultrasound Methods in Thermometry and Imaging

在过去的几十年里，治疗性超声在医学和生物学中的重要性以及其临床前和临床应用的范围得到了广泛的扩展。根据其与组织的相互作用机制，治疗性超声方法分为两大类：(A)基于热效应的方法，包括物理治疗、热疗和高强度聚焦超声(HIFU)和低强度聚焦超声(LIFU)，以及(B)基于非热效应的方法，包括碎石术、组织碎石术、低强度脉冲超声(LIPUS)和KHz频率功率超声。治疗性超声作为一种非侵入性的临床手段的成功与否，在很大程度上依赖于可靠和实时的成像方法来监测和控制治疗操作。对于那些依赖热效应的治疗性超声模式，除了可靠的成像方法外，另一个具有挑战性的限制是缺乏可靠的、非侵入性的和负担得起的温度测量方法来监测热疗过程中组织温度的变化。目前的研究方案利用我在非线性超声和治疗性超声领域的广泛背景和专业知识来定义一个研究计划，以解决上述限制，并为新的图像引导热疗应用开辟道路。在拟议的研究中将追求两个目标：目标1-开发基于超声的新型非线性测温方法，以使用治疗性超声或间质激光加热方式来监测和控制热疗。开发的方法将在各种体外组织模型中进行测试，以便使用临床超声扫描仪进行实时实施，以进行最终的体内动物研究和人类临床热疗应用。目的2-开发新的基于超声的非线性成像方法，以解决目前超声B型成像在改善信噪比、对比度以及空间和时间分辨率方面的局限性。为此目的，将采用目标1下制定的算法并加以修改。所开发的成像方法可用于监测和控制各种图像引导治疗性超声或组织间激光加热治疗中的治疗过程。拟议的研究计划将通过几个旨在调查基础科学和开发新的治疗和诊断应用的研究项目，提供绝佳的HQP培训机会。此外，学员将有机会通过我的研究实验室目前正在进行的广泛的行业合作计划，在一个跨学科、包容和公平的环境中直接与医疗器械行业互动。

The importance of therapeutic ultrasound in medicine and biology and the span of its pre-clinical and clinical applications have been extensively expanded during past couple of decades. Therapeutic ultrasound modalities based on their mechanisms of interaction with tissue are divided into two main categories: (a) methods based on thermal effects which include physical therapy, hyperthermia, and intensive focused ultrasound that itself is divided into two main modalities: high intensity focused ultrasound (HIFU) and low intensity focused ultrasound (LIFU), and (b) methods based on non-thermal effects which include lithotripsy, histotripsy, low intensity pulsed ultrasound (LIPUS), and kHz-frequency power ultrasound. The success of therapeutic ultrasound as a non-invasive clinical modality greatly depends on reliable and real-time imaging methods to monitor and control the therapy operation. For those therapeutic ultrasound modalities that rely on thermal effects, besides a reliable imaging method another challenging limitation is lack of a reliable, non-invasive and affordable thermometry method to monitor tissue temperature changes during thermal treatments. The current research proposal leverages my extensive background and expertise in the areas of nonlinear ultrasound and therapeutic ultrasound to define a research program toward addressing the above-mentioned limitations and also opening the path toward novel image-guided thermal therapy applications. Two objectives will be pursued in the proposed research: Objective 1 - To develop novel nonlinear ultrasound-based thermometry methods to monitor and control thermal therapies using either therapeutic ultrasound or interstitial laser heating modalities. The developed methods will be tested in various ex vivo tissue models toward real-time implementation using clinical ultrasound scanners for ultimate in vivo animal studies and human clinical thermal therapy applications. Objective 2 - To develop novel nonlinear ultrasound-based imaging methods to address the current limitations of ultrasound B-mode imaging in terms of improvements in SNR, contrast, and spatial and temporal resolutions. The algorithms developed under the Objective 1 will be adopted and modified to this end. The developed imaging methods can be used as the imaging modality for monitoring and controlling therapeutic procedures in various image-guided therapeutic ultrasound or interstitial laser heating treatments. The proposed research program will provide excellent HQP training opportunities through several research projects defined toward investigating the basic science and developing novel therapeutic and diagnostic applications. Moreover, the trainees will have the opportunity to directly interact with medical devices industry through an extensive industry collaboration program that is currently ongoing in my research lab, within an interdisciplinary, inclusive and equitable environment.