Transrectal Histotripsy for Focal Ablation of Prostate Cancer

项目总结 局限性前列腺癌的一线根治治疗与显著的发病率和副作用有关 影响尿路、肠道和性生活质量。因此，焦点疗法引起了人们的浓厚兴趣，其中 癌组织被根除，而保留了正常的健康的前列腺和邻近的结构(如尿路 括约肌、直肠和神经血管束)，以便在减少副作用的同时维持肿瘤预后 效果。到目前为止，临床上可用的局部治疗依赖于热消融(加热或冷冻)来诱导 凝固性坏死和细胞死亡。目前，应用最广泛的热疗技术可用于肿瘤的局部治疗。 前列腺癌是经直肠高强度聚焦超声(HIFU)治疗。虽然现有数据表明热能 HIFU的发病率低于根治性治疗，其有效控制癌症的能力仍不确定 报告称，在治疗一年内，多达30%-40%的患者活检呈阳性。热HIFU的局限性 系统，包括热扩散/下沉和最小的实时治疗反馈，可以解释疗效。 担忧。我们的团队开发了一种基于HIFU的方法，称为沸腾组织摩擦(BH)，它使用序列 具有冲击波前沿的毫秒长的HIFU脉冲，用于机械地将目标组织消融为亚细胞碎片 没有热效应，并具有实时超声成像反馈。我们已经开发出第一台原型机 已经证明了经直肠BH用于非热消融的可行性。 犬类模型中的前列腺组织。这项建议的具体目标是建立在先前工作的基础上，以完善 BH技术转变为一种临床可行的前列腺癌局部治疗形式。在目标1中，一种新的经直肠多元素 将开发和建造阵列换能器，以促进使用电子技术进行有效的BH前列腺体积消融 焦点的转向和机械平移。BH传感器将与成像探头相结合 两者都将由Verasonics灵活的超声波平台控制。综合声学 将对BH系统进行表征，并相应地设计BH处理方案 并在组织模体和体外前列腺组织中进行评估。在目标2中，改进了基于超声波的成像 将开发算法，以使用剪切波弹性成像和 利用平面波多普勒成像进行组织液化定量反馈。在目标3中，得到的BH数组 系统、曝光方案和成像算法将在一系列急性和慢性活体实验中进行评估 在犬类模型中进行研究，以证明该装置的安全性和有效性。在项目结束时 在此期间，经直肠BH技术将准备好提交给FDA申请调查设备豁免 为未来的临床试验做准备。

PROJECT SUMMARY First line radical treatments for localized prostate cancer are associated with significant morbidity and side effects impacting urinary, bowel, and sexual quality of life. As a result, there is strong interest in focal therapy in which the cancer tissue is eradicated while sparing normal healthy prostate and adjacent structures (such as urinary sphincter, rectum, and neurovascular bundles) in order to maintain oncologic outcomes while reducing side effects. To date, clinically available focal therapies rely on thermal ablation (heating or freezing) to induce coagulative necrosis and cell death. Presently, the most widely used thermal technique for focal therapy of prostate cancer is transrectal high intensity focused ultrasound (HIFU). While existing data suggest that thermal HIFU has less morbidity than radical treatments, its ability to effectively control cancer is still uncertain with series reporting positive biopsies in up to 30-40% of patients within one year of treatment. Limitations of thermal HIFU systems, including heat diffusion/sinking and minimal real-time treatment feedback, may explain efficacy concerns. Our team has developed a HIFU-based method termed boiling histotripsy (BH) that uses sequences of milliseconds long HIFU pulses with shock fronts to mechanically ablate targeted tissue to subcellular debris without thermal effects and with real-time ultrasound imaging feedback. We have developed the first prototype of a pre-clinical system and have demonstrated the feasibility of transrectal BH for non-thermal ablation of prostate tissue in a canine model. The specific aims of this proposal are built upon the previous work to refine BH technology into a clinically viable format for focal therapy of PCa. In Aim 1, a novel transrectal multi-element array transducer will be developed and built facilitating efficient volumetric BH prostate ablation using electronic steering and mechanical translation of the focus. The BH transducer will be combined with an imaging probe and both will be controlled by a Verasonics Flexible Ultrasound platform. Comprehensive acoustic characterization of the BH system will be performed, and BH treatment protocols will be designed accordingly and evaluated in tissue phantoms and ex vivo prostate tissue. In Aim 2, improved ultrasound-based imaging algorithms will be developed to enable pre-treatment tumor localization using shear wave elastography and quantitative tissue liquefaction feedback using plane wave Doppler imaging. In Aim 3, the resulting BH array system, exposure protocols, and imaging algorithms will be evaluated in a series of acute and chronic in vivo studies in a canine model to demonstrate the safety and efficacy of the device. At the conclusion of the project period, transrectal BH technology will be ready for submission to FDA for an Investigational Device Exemption in preparation for future clinical trials.