Precisely Shaped Acoustic Ablation of Tumors Under 3D Ultrasound Image Guidance

描述（由申请人提供）：最近的许多研究已经证明了间质性消融方法治疗肝脏肿瘤的有效性，包括化学消融、冷冻消融和使用射频、激光、微波或聚焦超声等能量源的热消融。尽管有这些有希望的结果，目前的系统仍然高度依赖于操作人员的技能，并且不能治疗许多肿瘤，因为很少控制坏死区域的大小和形状，也无法控制组织内的消融轨迹。要解决这个问题，需要改进末端执行器的设计，精确地将消融装置导向所需的目标位置，并实时监测坏死区域，以确保完全治疗。术中超声成像可能提供了最佳和最容易获得的靶向方法，但同时手动处理b型超声（US）探头和消融装置是一项具有挑战性的任务，即使是最有经验的医生也容易出现重大错误。组织变形和目标运动使得将烧蚀装置精确地放置到目标中变得极其困难。不规则形状的靶体通常需要多次插入和多个重叠的热损伤，这在不对周围正常组织造成过度损伤的情况下以精确和及时的方式完成更具挑战性。为了解决这些问题，我们建议开发一种创新的方法，在不依赖外部跟踪设备的情况下，对空间注册的未操作的美国体积进行准确的跟踪和工具注册。这种三维超声（3DUS）将与一种灵活的、像蛇一样的轻型、廉价的机器人（称为主动插管（AC））集成在一起，以方便将可操纵的超声热消融器精确放置到肝脏中，并通过实时3D注册超声监测组织消融的进展。最近的植入式或间隙性高功率超声应用器的发展已经证明了非常可控和穿透的加热模式，可以塑造和动态改变，为一致性热手术提供了理想的机制。这种可控性和穿透性是非常理想的，并且将为用于肝肿瘤微创热消融的现有射频和微波（MW）技术提供重大改进。然而，到目前为止，对这种微创技术的广泛评估主要局限于犬体内前列腺和中度灌注组织，并没有包括治疗高度灌注肝组织内肿瘤所需的设计迭代和彻底评估。灌注肝热疗的初步热数据（C部分）令人鼓舞。超声间质热疗法（USITT）技术是有前途的，我们将扩展该技术，以优化其用于肝肿瘤的治疗。这项研究和开发的总体目标是提供一个真正的闭环系统，用于引导、放置、引导、经皮给药适形消融治疗和在线监测治疗。公共卫生相关性：肝细胞癌（HCC）是最常见的原发性肝癌类型，每年在世界范围内诊断的病例超过100万例。特别是在美国，HCC的发病率越来越高，主要是由于已知和临床隐匿的丙型肝炎的发病率。在美国，其他原发性恶性肿瘤也在上升，包括肝内胆管癌。然而，从其他部位转移到肝脏的疾病是美国最常见的肝脏恶性肿瘤，结肠癌和直肠癌占这些原发肿瘤的大多数，这些原发肿瘤发展为孤立的肝脏转移。虽然起源于胃肠道的其他原发肿瘤也常发生肝转移，但发生在其他部位的肿瘤，包括乳腺和肺部的肿瘤，也常发生肝转移。特别是结肠直肠癌，大约20%的患者在初次诊断时就有临床可识别的肝转移。在没有明显转移性疾病的原发结直肠癌切除后，大约50%的患者随后会出现转移性肝病6。根据这些数据，我们可以预计，在美国，每年至少有3万名患者将发展为局限于肝脏的转移性结直肠癌。在选定的患者中，原发性和继发性肝癌的潜在治愈疗法包括手术切除和在某些情况下肝移植。不幸的是，只有一小部分患者适合这些治疗。动脉内入路，如化疗栓塞，虽然在某些情况下治疗有用，但很少能完全摧毁肿瘤。由于这些原因，越来越多的兴趣集中在间质消融方法治疗原发性和转移性肝癌。尽管这些疗法的有效性有所提高，但烧蚀装置的精确靶向和坏死区域的监测仍然是未解决的问题。肝肿瘤的消融治疗的基本原理是显而易见的。首先，这种方法通常可以更好地保存未受损伤的肝实质，从而将治疗特异性地定向到肿瘤位置。这一特征对肝硬化背景的肝细胞癌患者特别有益，因为肝储备通常有限。在转移性疾病的病例中，多发、双侧、中心位置或技术上不可切除的肿瘤可能非常适合这种方法。此外，局部消融治疗可能适用于一些肝切除术后孤立性肝复发的患者，可能比重复肝切除术的发病率低。最近的研究已经证明了多换能器间质超声应用器的显著优势，最显著的是动态调整纵向和角度加热分布的能力，这对于一致性治疗和保存关键的非靶向组织非常重要。最近的研究已经证明了多换能器间质超声应用器的显著优势，最显著的是动态调整纵向和角度加热分布的能力，这对于一致性治疗和保存关键的非靶向组织非常重要。我们的目标是开发一种新的系统，该系统集成了主动插管超声消融器，结合空间注册和3D超声图像引导，广泛负担得起，包括社区医院和卫星诊所。此外，所提出的技术将易于转移到广泛的适应症，并可用于各种烧蚀模式。

DESCRIPTION (provided by applicant): Many recent studies have demonstrated the efficacy of interstitial ablative approaches for the treatment of hepatic tumors, including chemical ablation, cryoablation, and thermal ablation using energy sources like RF, laser, microwave, or focused ultrasound. Despite these promising results, current systems remain highly dependent on operator skill, and cannot treat many tumors because there is little control of the size and shape of the zone of necrosis, and no control over ablator trajectory within tissue. Remedying this problem requires advances in end-effector design, precise steering of the ablator device to the desired target location, and real- time monitoring of the zone of necrosis to ensure complete treatment. Intra-procedure ultrasound imaging provides perhaps the optimal and most readily available method for targeting, but simultaneous manual handling of the B-mode ultrasound (US) probe and the ablator device is a challenging task that is prone to significant errors in the hands of even the most experienced physicians. Tissue deformation and target motion make it extremely difficult to place the ablator device precisely into the target. Irregularly shaped target volumes typically require multiple insertions and several overlapping thermal lesions, which are even more challenging to accomplish in a precise and timely manner without causing excessive damage to surrounding normal tissues. In answer to these problems, we propose to develop an innovative method for accurate tracking and tool registration with respect to spatially-registered intaoperative US volumes without relying on an external tracking device. This three-dimensional ultrasound (3DUS) will be integrated with a flexible, snake-like lightweight and inexpensive robotic, called the Active Cannula (AC), to facilitate precise placement of a steerable ultrasound thermal ablator into the liver and to monitor the progress of tissue ablation with real-time 3D registered ultrasound. Recent developments of implantable or interstitial high-power ultrasound applicators have demonstrated extremely controllable and penetrating heating patterns which can be shaped and dynamically altered, providing an ideal mechanism for conformable thermal surgery. This controllability and penetration is highly desirable and would provide significant improvement over existing RF and microwave (MW) technology used for minimally invasive thermal ablation of liver tumors. However, to date the extensive evaluation of this minimally invasive technology has been limited mostly to in vivo canine prostates and moderately perfused tissues, and have not included the design iterations and thorough evaluations necessary for treating tumors within highly perfused liver tissue. The preliminary thermal data from thermal therapy of perfused liver (Section C) are encouraging. Ultrasound Interstitial Thermal Therapy (USITT) technology is promising and we will extend the technology to optimize its use for the treatment of hepatic tumors. The overall goal of this research and development is to provide a true closed-loop system for steering, placement, guidance, percutaneous delivery of conformal ablative therapy, and on-line monitoring of treatment. PUBLIC HEALTH RELEVANCE: Hepatocellular carcinoma (HCC) is the most common type of common primary liver cancer and is associated with over one million cases diagnosed worldwide each year. In the United States specifically, HCC is being seen with increasing frequency, largely due to the incidence of known and clinically occult hepatitis C. Other primary malignancies are also on the rise in the U.S., including intrahepatic cholangiocarcinoma. Yet, metastatic disease from other sites to the liver is the most common hepatic malignancy overall in the U.S. Cancer of the colon and rectum account for the majority of these primary tumors which develop isolated liver metastases. While other primary tumors originating from gastrointestinal sites often develop hepatic metastases as well, tumors arising in other locations, including those of the breast and lung, also commonly develop hepatic metastases. For colorectal cancer specifically, approximately 20% of patients have clinically recognizable liver metastases at the time of their primary diagnosis. After resection of a primary colorectal cancer in the absence of apparent metastatic disease, approximately 50% of patients will subsequently manifest metastatic liver disease6. Given these figures, one can expect that at least 30,000 patients per year in the United States will develop metastatic colorectal cancer confined to the liver, each year. In selected patients, potentially curative therapies for primary and secondary liver cancer include surgical resection and in some cases liver transplantation. Unfortunately only a small percentage of patients are candidates for these treatments. Intraarterial approaches such as chemoembolization, while therapeutically useful in some cases, rarely achieves complete tumor destruction. For these reasons, an increasing interest has been focused on interstitial ablative approaches for the treatment of primary and metastatic liver cancer. Despite advances in the effectiveness of these therapies, precise targeting of the ablator device and monitoring of the zone of necrosis are still unsolved problems. The rationale for ablation therapy of liver tumors is evident. To begin, this approach often allows for greater preservation of uninvolved hepatic parenchyma, directing the treatment specifically to the tumor location. This feature is particularly beneficial for patients with hepatocellular carcinoma in the background of cirrhosis, where hepatic reserve is often limited. In cases of metastatic disease, tumors which are multiple, bilateral, centrally located, or in areas not technically resectable are potentially well suited for this approach. Additionally, localized ablative therapy may be applicable for some patients with isolated hepatic recurrence following liver resection, perhaps resulting in lower morbidity than repeat hepatic resection. Recent studies have demonstrated significant advantages of multi-transducer interstitial ultrasound applicators, most notably the capability to dynamically tailor the longitudinal and angular heating distribution which are important for conformable treatments and preserving critical non-targeted tissue. Recent studies have demonstrated significant advantages of multi-transducer interstitial ultrasound applicators, most notably the capability to dynamically tailor the longitudinal and angular heating distribution which are important for conformable treatments and preserving critical non-targeted tissue. Our goal is to develop a new system with integrated active cannula ultrasound ablator combination spatially- registered with 3D ultrasound image guidance that is widely affordable, including for community hospitals and satellite clinics. Furthermore, the proposed technology will be readily transferable to wide range of indications and usable with various ablative modalities.