Dual-mode Ultrasound Arrays for Image-Guided Surgery

描述（由申请人提供）：本研究的长期目标是开发双模超声阵列（DMUA）系统，用于使用高强度聚焦超声（HIFU）对癌症肿瘤进行无创治疗。这些DMUA系统将能够产生治疗性脉冲HIFU光束，用于局部破坏目标组织，并使用相同的阵列元素对目标区域及其周围环境进行实时间歇成像。使用1-MHz的压电复合材料64元件DMUA原型，我们已经证明了使用相同换能器进行成像和治疗的可行性。使用适当的现场模拟工具，我们建议开发设计程序，允许同时优化成像和治疗的dmua。此外，我们建议设计和构建实时波束形成和信号处理能力，以允许在实际的实时测试中使用DMUA系统。这将是计划进行体内动物试验之前的必要步骤。我们将集中精力开发基于图像的反馈，这将有助于在存在组织异质性和强散射物体的情况下重新聚焦HIFU光束。这将允许使用DMUA系统对腹部器官（如肝脏和肾脏）的肿瘤进行无创治疗（通过在肋骨处重新聚焦）。此外，我们将开发参数成像方法，以评估治疗性HIFU剂量应用之前，期间和之后的治疗组织。特别是，我们将研究在亚治疗暴露于目标的HIFU光束时成像局部吸收、灌注和粘弹性特性（剪切模量和剪切粘度）的可行性。这些参数化成像方法将用于基于dmua的成像和用于图像引导的商用超声扫描仪。这对于更好地理解由（可能）有限的带宽和dmua的波束形成能力所施加的限制是必要的。此外，如果超声作为一种图像引导方式仍然可行，则仍然需要定量超声成像。我们设想，在拟议研究的资助期内，将开发一个具有基于图像反馈的完全可操作的实时DMUA系统，并在体外进行全面测试。一旦该系统到位，我们计划与临床同事建立合作，在体内测试该系统，为靶向临床应用做准备。如果我们成功了，我们的DMUA系统将至少为其他图像引导模式（如MRI， CT或诊断超声）增加重要价值。然而，如果基于DMUA的图像质量可以提高到定量空间精确成像的水平，那么DMUA系统将为图像引导手术提供一种独特的方法。具体地说，我们将有能够在病变形成之前、期间和之后评估目标区域的自我引导治疗阵列。基于图像的反馈将有助于最大化目标的治疗剂量，同时最大限度地减少可能与治疗性HIFU光束相互作用的干预关键组织结构的附带损伤。这对于非侵入性应用HIFU治疗肝脏和肾脏肿瘤至关重要。公共卫生相关性：将开发用于癌症和其他组织异常的无创治疗的新一代超声阵列系统。该系统的显著特点是它能够向目标组织提供高强度聚焦超声（HIFU），并使用相同的阵列元素提供来自治疗体积的图像反馈。治疗和成像坐标系之间的内在匹配将导致图像引导手术的新范式。空间精确的基于图像的反馈将通过在存在组织异质性和其他强散射障碍物的情况下重新聚焦HIFU光束来提高治疗效果。此外，在应用HIFU之前、期间和之后，在治疗性HIFU光束的确切位置对组织反应的参数成像提供了一个独特的机会来监测治疗的进展并可能评估其结果。

DESCRIPTION (provided by applicant): The long-term objective of this research is the development of dual-mode ultrasound array (DMUA) systems for the noninvasive treatment of cancer tumors using high intensity focused ultrasound (HIFU). These DMUA systems will be capable of generating therapeutic pulsed HIFU beams for localized destruction of targeted tissue and intermittently imaging the targeted region and it's surroundings in real- time using the same array elements. Using a piezocomposite 1-MHz 64-element DMUA prototype, we have demonstrated the feasibility of using the same transducer for imaging and therapy. Using appropriate field simulation tools, we propose to develop design procedures that will allow the simultaneous optimization of DMUAs for both imaging and therapy. Furthermore, we propose to design and build the real-time beamforming and signal processing capabilities to allow the use of DMUA systems in realistic real-time testing. This will be a necessary step before planning to perform in vivo animal testing. We will focus our efforts on the development of image-based feedback that will help refocus the HIFU beam in the presence of tissue heterogeneity and strongly scattering objects. This will allow the use of DMUA systems for the noninvasive treatment of tumors in abdominal organs such as liver and kidney (by refocusing in the presence of the ribs). In addition, we will develop parametric imaging methods to assess the treated tissue before, during, and after the application of therapeutic HIFU dose. In particular, we will investigate the feasibility of imaging local absorption, perfusion, and viscoelastic properties (shear modulus and shear viscosity) during sub-therapeutic exposure to HIFU beams at the target. These parametric imaging methods will be developed for both DMUA-based imaging and commercial ultrasound scanners for image guidance. This is necessary to provide better understanding of the limitations imposed by the (possibly) limited bandwidth and beamforming capabilities of DMUAs. In addition, quantitative ultrasonic imaging is still needed if ultrasound is to remain viable as an image-guidance modality. We envision a fully operational real-time DMUA system with image-based feedback will be developed and fully tested in vitro during the funding period of the proposed research. Once this system is in place, we plan to establish collaborations with clinical colleagues to test this system in vivo in preparation for targeted clinical applications. If we are successful, our DMUA system will add, at a minimum, significant value to other image-guidance modalities, e.g. MRI, CT, or diagnostic ultrasound. However, if the quality of DMUA- based images can be brought to levels where quantitative spatially accurate imaging can be assured, then DMUA systems will provide a unique approach to image-guided surgery. Specifically, we will have self- guided therapeutic arrays capable of assessing the target region before, during, and after lesion formation. The image-based feedback will help maximize the therapeutic dose at the target while minimizing collateral damage to intervening critical tissue structures that may interact with the therapeutic HIFU beam. This will be essential for the noninvasive application of therapeutic HIFU to liver and kidney tumors. PUBLIC HEALTH RELEVANCE: A new generation of ultrasound array systems for the noninvasive treatment of cancer and other tissue abnormalities will be developed. The distinguishing characteristic of the system is its capability to deliver high intensity focused ultrasound (HIFU) to the target tissue and provide image feedback from the treatment volume using the same array elements. The inherent registration between the therapeutic and imaging coordinate systems will lead to a new paradigm in image-guided surgery. Spatially accurate image- based feedback will improve the treatment efficacy by refocusing the HIFU beam in the presence of tissue heterogeneities and other strongly scattering obstacles. Furthermore, parametric imaging of the tissue response at the exact location of the therapeutic HIFU beam before, during, and after the application of HIFU provides a unique opportunity to monitor the progression of the treatment and potentially assess its outcome.