Percutaneous cardiac HIFU ablation with multimodal image guidance

描述（由申请人提供）：房颤（AF）是最常见的心律失常类型，在一般人群中的估计患病率为0.4%至1%，随年龄增长而增加（80岁以上人群为8%）。除了药物治疗之外，基于电生理学的治疗方式（诸如消融治疗）被广泛用于心律失常。为了治疗AF，消融的最常见解剖目标是肺静脉入口和周围组织。目前，射频（RF）能量通常用于消融心脏中的所述部位。使用RF消融难以控制消融模式，其在产生深损伤方面也具有局限性。如果不能实现心脏组织中的完全电隔离，则复发的可能性很高。高强度聚焦超声（HIFU）方法最近已被尝试用于肺静脉隔离，主要是由于有望产生深度和受控的消融模式。然而，这些尝试缺乏直接的成像引导，因此会对周围组织（如膈神经和食管）造成附带损伤。RF消融方法的众所周知的缺点和早期HIFU结果所呈现的局限性清楚地表明需要将图像引导与有效且良好控制的消融方法集成的系统。我们建议开发设备和系统来解决总结的问题。在我们提出的方案中，常规超声成像用于解剖引导和目标识别，HIFU用于组织消融，光声成像用于监测病变形成。该装置是基于电容式微机械超声换能器（CMUT）技术。CMUT被证明在连续波操作中具有最小的自加热，不像其具有高内部介电损耗的压电对应物。压电换能器的这种自加热是早期心脏HIFU尝试中所经历的附带损伤的部分原因。CMUT也可以在适合于双重成像/治疗操作的大阵列中实现。提出的工作的具体目标如下：1）开发一个大规模的原型（15毫米的足迹）CMUT阵列用于初步的可行性研究和临床适用的，小规模（7毫米的足迹）CMUT阵列集成支持前端电路和后端系统，能够与超声和光声成像相结合的HIFU输送。2)使用系统子组件对离体组织样本和体内开胸和开大腿动物模型进行初步可行性研究，以确定HIFU消融和光声成像的最佳参数。3)利用小型化集成探头（7 mm足迹）在猪模型中进行心脏研究，采用闭合胸部微创模型，通过肋间隙的小切口插入探头。

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, with an estimated prevalence of 0.4% to 1% in the general population, increasing with age (8% for people over 80). In addition to drug treatments, electrophysiology-based treatment modalities such as ablation treatment are wide employed for arrhythmias. To treat the AF the most common anatomical target for ablation is the entrance of pulmonary veins and the surrounding tissue. Currently, radio-frequency (RF) energy is generally used to ablate the described sites in the heart. It is difficult to control the ablation pattern using RF ablation which also has limitations in creating deep lesions. If the total electrical isolation in cardiac tissue cannot be achieved, recurrence becomes highly likely. High-intensity focused ultrasound (HIFU) methods have been attempted lately for pulmonary vein isolation, mainly motivated by the promise of creating deep and controlled ablation patterns. However, these attempts suffered from a lack of direct imaging guidance and consequently collateral damage in surrounding tissues such as the phrenic nerve and the esophagus. The well-known shortcomings of RF ablation methods and the limitations presented by the early HIFU results clearly indicate the need for a system that integrates image guidance with effective and well-controlled ablation methods. We propose to develop devices and systems to address the summarized issues. In our proposed scheme, conventional ultrasound imaging is used for anatomical guidance and target identification, HIFU for tissue ablation, and photoacoustic imaging for monitoring lesion formation. The proposed device is based on the capacitive micromachined ultrasonic transducer (CMUT) technology. CMUTs are proven to have minimal self-heating in continuous wave operation, unlike their piezoelectric counterparts with high internal dielectric losses. This self-heating of piezoelectric transducers was partly responsible for the collateral damage experienced in early cardiac HIFU attempts. CMUTs can also be implemented in large arrays that are suitable for dual imag- ing/therapeutic operation. The specific aims of the proposed work are as follows: 1) Develop a large-scale prototype (15-mm footprint) CMUT array for use in initial feasibility studies and a clinically suitable, small-scale (7-mm footprint) CMUT array integrated with supporting frontend circuits and backend systems, capable of HIFU delivery combined with ultrasound and photoacoustic imaging. 2) Conduct initial feasibility studies on ex-vivo tissue samples and in-vivo open-chest and open-thigh animal models using system subcomponents to determine optimal parameters for both HIFU ablation and photoacoustic imaging. 3) Conduct cardiac studies in the porcine model utilizing the miniaturized integrated probe (7-mm footprint) utilizing a closed chest, minimally invasive model for insertion of the probe through a small incision through the intercostal space.