Pulsed Focused Ultrasound (pFUS) exposures and devices for tissue permeabilization without contrast agents

项目总结 根据最近来自世界各地的报告，需要持续评估危重病患者的肺水肿 新冠肺炎对患者来说是必不可少的。胸部X光检查在疾病早期降低了敏感性；传染性 这种病毒和运送不稳定的低氧血症患者的风险使胸部CT成为有限的选择 疑似或确诊为新冠肺炎的患者。肺部超声(Lus)是非电离和安全的，并有 最近出现了一种有用的分诊和监测工具，用于量化新冠肺炎患者的肺水肿。在……里面 LUS，称为A线的成像伪影(与肺表面平行的周期性水平线，表示正常 充气模式)和B线(彗星状高回声区域，表示肺泡或间质异常) 都进行了评估。B线起源于肺泡水肿区的声学混响，它们的数量和 众所周知，厚度与水肿的严重程度相关。然而，B线的可视化和量化 需要大量的培训，即使这样，也高度依赖操作员和机器。这部分归因于 对B线形成的确切物理机制的理解仍然不完整。在这种紧急情况下 我们建议对目前关于超声空化辅助实体肿瘤药物输送的奖项进行竞争性修订 以我们在剖析美国成像伪影和超声仪器起源方面的专业知识为基础 1)识别逻辑单元中B线伪影的来源和特定的相关RF信号特征的能力；以及2) 在已有认识的基础上，开发出单元素、可穿戴、自动化、非成像的肺 超声传感器(LUSS)，用于持续监测肺部病理，同时最大限度地减少提供者的时间、风险 病毒暴露和辐射。个别粘接剂Luss元素将在特定的患者身上附着 解剖位置类似于心电导联，超声信号将被收集和处理 自动算法提供可用于临床决策的肺水肿评分。我们有 设计了一项原则研究的证明，以尽可能短的时间将该设备迅速投入临床， 具体目标如下。在SA1中，我们将对患有以下疾病的非COVID患者进行标准LU检查 收集原始射频信号数据以了解心源性肺水肿的B-line表现 原始射频信号和开发自动信号处理算法。在SA2中，我们将设计和制造单个- Element Luss原型并验证针对肺部LUS成像的自动信号处理算法- 模仿基于海绵的幻影。在为期9个月的项目结束时，原型装置将准备好投入使用 不仅是COVID19患者，还有其他ED患者，对他们来说，持续的肺部状况评估是必不可少的 (细菌性肺炎、心源性水肿、透析)。我们在这里的商业化方法是广泛授权 这项简单的技术使拥有广泛销售和分销能力的大型超声制造商可以 将技术带给用户。

PROJECT SUMMARY According to recent reports from across the world, the need to continuously evaluate lung edema in critically ill COVID-19 patients is essential. Chest x-ray has reduced sensitivity early in the disease; the contagiousness of the virus and the risk of transporting unstable patients with hypoxemia make chest CT a limited option for the patient with suspected or established COVID-19. Lung ultrasound (LUS) is non-ionizing and safe, and has recently emerged as a useful triage and monitoring tool for lung edema quantification in COVID-19 patients. In LUS, imaging artifacts termed A-lines (periodic horizontal lines parallel to the lung surface indicating a normal aeration pattern) and B-lines (comet-like hyperechoic regions indicating an alveolar or interstitial abnormality) are evaluated. B-lines stem from acoustic reverberations within regions of alveolar edema, and their number and thickness are known to be correlated with edema severity. However, visualization and quantification of B-lines requires substantial training, and even then, are highly operator and machine dependent. This is in part due to a still incomplete understanding of the exact physical mechanism of B-line formation. In this emergency competitive revision to the current award on ultrasound cavitation-aided drug delivery to solid tumors we propose to build on our expertise in dissecting the origins of US imaging artifacts and ultrasound instrumentation capabilities to 1) identify the origins of B-line artifact in LUS and specific associated RF signal features, and 2) based on the attained understanding, develop a single-element, wearable, automated, non-imaging lung ultrasound sensor (LUSS) for continuous monitoring of lung pathology while minimizing provider time, risk of virus exposure, and radiation. Individual adhesive LUSS elements will be attached to patients in specific anatomic locations similarly to ECG leads, and ultrasound signals will be collected and processed with automated algorithms to provide lung edema score that can be used in clinical decision making. We have designed a proof of principle study scaled to the shortest timeline possible to get the device into the clinic quickly, with the following specific aims. In SA1 we will perform standard LUS exams in non-COVID patients with cardiogenic pulmonary edema while collecting raw RF signal data to understand the manifestation of B-lines in raw RF signals and develop automated signal processing algorithm. In SA2 we will design and fabricate single- element LUSS prototype and validate the automated signal processing algorithm against LUS imaging in lung- mimicking sponge-based phantom. By the end of the 9-month project the prototype device will be ready for use in not only COVID19 patients, but other ED patients for whom continuous evaluation of lung condition is essential (bacterial pneumonia, cardiogenic edema, dialysis). Our commercialization approach here is to broadly license this simple technology so that large ultrasound manufacturers with broad sales and distribution capabilities can get the technology to the users.