Ultrasound-guided Ultra-steerable Histotripsy Array System for Non-invasive treatment of Soft Tissue Sarcoma

超声引导超可控组织解剖阵列系统用于软组织肉瘤的无创治疗

• 批准号: 10649994
• 负责人: Zhen Xu
• 金额: $ 54.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649994
• 关键词: 3-Dimensional; Ablation; Acceleration; Acoustics; Adult; Affect; American Cancer Society; Amputation; Anatomy; Animal Model; Animals; Area; Benign; Blood Vessels; Body part; Burn injury; Cancer Center; Canis familiaris; Cartilage; Cells; Cessation of life; Child; Coupling; Data; Development; Ensure; Excision; Fatty acid glycerol esters; Focused Ultrasound Therapy; Follow-Up Studies; Future; Goals; Histologic; Human; Laboratories; Leg; Longterm Follow-up; Malignant - descriptor; Malignant Neoplasms; Mechanics; Mesenchymal; Methods; Michigan; Monitor; Muscle; NCI Center for Cancer Research; Nerve; Operative Surgical Procedures; Patients; Phase; Physiology; Procedures; Property; Radiation; Radiation therapy; Recurrence; Reporting; Resected; Risk; Robotics; Safety; Sampling; Skin; Skin Tissue; Soft Tissue Neoplasms; Soft tissue sarcoma; Speed; Structure; Subcutaneous Tissue; Surface; System; Testing; Thermal Ablation Therapy; Time; Tissues; Toxic effect; Tumor Debulking; Ultrasonic Therapy; Ultrasonography; Universities; Unresectable; Virginia; arm; bone; cancer care; chemotherapy; clinical translation; design; design and construction; fibrosarcoma; image guided; improved; in vivo; in vivo evaluation; individualized medicine; invention; liposarcoma; minimally invasive; neurovascular; non-invasive system; novel; patient subsets; preservation; prototype; safety and feasibility; safety testing; soft tissue; transmission process; treatment strategy; tumor; ultrasound

Ultrasound-guided Ultra-steerable Histotripsy Array System for Non-invasive treatment of Soft Tissue Sarcoma Summary The goal of this project is to develop a novel ultra-steerable histotripsy array system for non-invasive treatment of soft tissue sarcomas (STS). STS are malignant tumors that grow in soft tissues like fat, muscle, cartilage, fibrous tissues, blood vessels, or subcutaneous tissues. The American Cancer Society reports 13,190 new cases and 5,130 deaths of STS annually in the US. Surgery is the first-line treatment for STS. However, when STS encompass or grow near critical structures (e.g., major nerves, blood vessels, and bones), surgical resection is particularly challenging and sometimes these cancers are deemed unresectable. Radiation, chemotherapy, and minimally invasive or non-invasive ablation methods are not effective for STS treatment or have major drawbacks, such that they have very limited use in STS therapy. Histotripsy is a non-invasive ultrasound therapy that mechanically liquefies the target tissue to acellular debris via controlled cavitation. Histotripsy is well-suited for STS treatment because it can debulk and shrink the tumor non-invasively while sparing critical structures, such as major vessels, nerves, and bones. Histotripsy can be used for non-invasive debulking of STS to facilitate or potentially replace surgery. Even though histotripsy has been investigated for the treatment of various tumor types, STS treatment presents unique challenges. 1) STS can grow significantly larger than other types of tumors (>10 cm or >400mL), requiring very fast treatment speed. 2) STS often grow near critical structures and/or close to the skin surface. Treatment strategies need to be developed to avoid damage to critical structures and the skin. 3) Histotripsy treatment is typically guided by 2D B-mode ultrasound imaging, but fast treatment of a large STS requires 3D monitoring capabilities. In this proposal, we will develop a novel ultra-steerable histotripsy phased array system with 3D cavitation monitoring capabilities and special strategies for ultra-fast STS ablation and safe treatment near the skin surface and critical structures. We propose the following three specific aims. Aim 1: To design and construct an integrated histotripsy STS system, consisting of an ultra-steerable histotripsy phased array with transmit-receive capability for 3D cavitation monitoring, ultrasound image guidance, robotic arm assistance, and acoustic coupling. Aim 2: To optimize histotripsy parameters for fast (>10 mL/min) and safe treatment near the skin surface and critical structures and test in ex vivo tissue and excised human and canine STS samples of different histological subtypes. Aim 3: To test the in vivo safety and efficacy of the integrated histotripsy STS system (Aim 1) and optimized parameters for fast and safe treatment near the skin and critical structures (Aim 2) in canine STS patients at the Virginia Tech Animal Cancer Care and Research Center. This project will result in a human prototype histotripsy system with unique treatment and monitoring capabilities as well as parameters optimized for STS therapy. Canine patients are the best large animal model to test the safety and efficacy of histotripsy STS treatment to accelerate the clinical translation, and the veterinary treatment is another application for histotripsy STS therapy before the FDA approval of human use.

超声引导超可控组织摧毁阵列系统用于软组织的无创治疗 肉瘤 总结 本项目的目标是开发一种用于非侵入性治疗的新型超可控组织摧毁阵列系统 软组织肉瘤（STS）STS是一种生长在脂肪、肌肉、软骨等软组织中的恶性肿瘤， 纤维组织、血管或皮下组织。美国癌症协会报告了13，190例新病例 美国每年有5,130人死于STS外科手术是STS的一线治疗方法。然而，当STS 包围或生长在临界结构附近（例如，主要神经，血管和骨骼），手术切除是 特别具有挑战性，有时这些癌症被认为是不可切除的。放疗化疗 最小侵入性或非侵入性消融方法对于STS治疗不是有效的或具有主要缺点， 使得它们在STS治疗中的用途非常有限。组织摧毁术是一种非侵入性超声治疗， 通过受控的空化作用将靶组织机械地降解为无细胞碎片。组织解剖学非常适合 STS治疗，因为它可以非侵入性地缩小肿瘤，同时保留关键结构， 主要血管神经和骨骼组织摧毁术可用于STS的非侵入性减积，以促进或 有可能取代手术。尽管组织摧毁术已被研究用于治疗各种肿瘤 类型，STS治疗提出了独特的挑战。1)STS可以比其他类型的肿瘤生长得更大 （>10 cm或> 400 mL），需要非常快的治疗速度。2)STS通常在关键结构附近生长和/或靠近 皮肤表面。需要制定治疗策略，以避免对关键结构和 皮肤3)组织破坏治疗通常由2D B模式超声成像引导，但是大的组织破坏的快速治疗通常由2D B模式超声成像引导。 STS需要3D监控功能。在这个提议中，我们将开发一种新型的超可操纵组织摧毁术， 相控阵系统具有3D空化监测功能和用于超快STS消融的特殊策略 以及皮肤表面和关键结构附近的安全治疗。我们提出以下三个具体目标。 目的1：设计和构建一种集成的组织碎石STS系统，包括一个超可控的组织碎石器 相控阵具有发射-接收能力，用于3D空化监测、超声图像引导、机器人 手臂辅助和声学耦合。目的2：优化快速（>10 mL/min）和安全的组织破坏参数 皮肤表面和关键结构附近的治疗以及离体组织和离体人类和犬的测试 不同组织学亚型的STS样本。目的3：测试整合的药物组合物的体内安全性和有效性。 组织摧毁术STS系统（目标1）和优化的参数，用于皮肤附近的快速和安全的治疗， 结构（目标2）在犬STS患者在弗吉尼亚理工大学动物癌症护理和研究中心。这 该项目将产生一个具有独特治疗和监测能力的人体原型组织摧毁系统， 以及针对STS治疗优化的参数。犬患者是检验安全性的最佳大型动物模型 组织破坏STS治疗的有效性，以加速临床转化，兽医治疗， 在FDA批准人类使用之前，另一项组织破坏STS疗法的申请。