iPPSIS: implanted Passive Pressure Sensor Interrogated with (ultra)-Sound

项目摘要/摘要 脑脊液动力学的改变可能发生在创伤性脑损伤、蛛网膜下腔 和/或脑室出血、脑肿瘤或中枢神经系统感染，均可导致 颅内压升高。神经外科医生通过放置脑室分流术来治疗颅内压升高，这是 让多余的脑脊液排出，从而减轻大脑的压力。超过50%的分流装置在第一次分流失败 一年了，所有的分流最终都失败了。分流失败最常发生在1岁以下儿童和 占住院费用的10多亿美元。不幸的是，验证患者是否有分流 功能障碍在年轻患者中尤其困难，因为症状是非特异性的(头痛、恶心或 疲劳)和现有的非侵入性测试(MRI和CT)都很昂贵，而且不直接测量压力。仅限 出现这些症状的分流患者中有46%存在功能障碍，而其余患者 不必要的费用，暴露在辐射中，或可能导致脑损伤的侵入性调查。至 为了解决这个问题，我们建议创建IPPSIS(植入式被动压力传感器审问(ULTRA)) 声音)，它由被动的、微型制造的压力传感器“目标”组成，该传感器偏转以响应 压力增加，并可用超声波定量测量。我们假设，重新思考 目前无线压力传感器的方法和消除对射频遥测的依赖将导致 无线传感器是无源的(不需要电池)，与MRI兼容，并且稳定，可用于长期临床监测 (年)。按照《外国投资协定》的要求，不包括未公布的初步数据。然而，我们的分析 微制造靶设计和超声分辨率的计算，这是植根于 经过几十年的研究，证明了可行性和成功的高概率。我们将首先设计iPPSIS 对于儿科人群，由于头骨缩小，需求显著，技术障碍较低 厚度。在分流放置期间，传感器将通过标准的毛刺孔植入硬膜下。 手术，并将继续运作，因为病人的头骨愈合和改造。目标1侧重于 一种新型的、极其稳定的金属微压传感器的构建和表征 对生理“恶劣环境”的高度抵抗力。目标2专注于测试一种新的操作员- 独立的超声测量和一种新的可穿戴式超声波换能器，将使长期 持续监测。AIM 3寻求在体外严格测试iPPSIS，并在体内收集可行性数据 猪肿瘤模型(n=2)，经历几个月的快速颅内压变化。证明……的严酷 通过我们的方法，我们组建了一支具有微型机电专业知识的团队 系统设计、超声波、神经外科和活体猪模型。完成后，iPPSIS将完全 功能正常，并准备好进行进一步的翻译测试。更广泛地说，这项工作为一种新的范式铺平了道路 超声生物传感器的问世，这将首次实现连续的深层组织测量。

PROJECT SUMMARY/ABSTRACT Changes to cerebral spinal fluid flow (CSF) dynamics may occur with traumatic brain injury, subarachnoid and/or intraventricular hemorrhage, brain neoplasms, or central nervous system infection, and can all lead to increased intracranial pressure (ICP). Neurosurgeons treat elevated ICP by placing a ventricular shunt, which allows excess CSF to drain, thereby relieving the pressure on the brain. Over 50% of shunts fail in the first year, and all shunts fail eventually. Shunt failure most commonly occurs in children under the age of 1 year and accounts for over $1 billion in hospital admission costs. Unfortunately, verifying that a patient has a shunt dysfunction is particularly difficult in young patients, as symptoms are non-specific (headache, nausea, or fatigue) and existing non-invasive tests (MRI and CT) are costly and do not directly measure pressure. Only 46% of shunt patients presenting with these symptoms have a dysfunction, while the remaining patients incur unnecessary expense, exposure to radiation, or invasive investigations that may result in brain injury. To address this issue, we propose to create iPPSIS (implanted Passive Pressure Sensors Interrogated with (ultra) Sound), which is composed of a passive, microfabricated pressure sensor “target” that deflects in response to increased pressure and can be quantitatively measured with ultrasound. We hypothesized that rethinking the current approach to wireless pressure sensors and removing the dependence on RF telemetry would lead to a wireless sensor that is passive (no batteries), MRI compatible, and stable for long-term clinical monitoring (years). As requested in the FOA, no unpublished preliminary data is included. However, our analytical calculations of both the microfabricated target design and ultrasound resolution, which are grounded in decades of research, demonstrate feasibility and a high probability of success. We will initially design iPPSIS for pediatric populations given the significant need and lower technical barriers due to the reduced skull thickness. The sensor will be implanted subdurally through a standard burr hole during a shunt placement procedure, and will continue to operate as the patient's skull heals and reforms. Aim 1 focuses on the construction and characterization of a novel, extremely stable, metallic micro-pressure sensor that will be highly impervious to the physiological “harsh environment”. Aim 2 focuses on the testing of a novel operator- independent ultrasound measurements and a new wearable ultrasonic transducer that would enable long-term continuous monitoring. Aim 3 seeks to rigorously test iPPSIS in vitro as well collect in vivo feasibility data in a porcine tumor model (n=2) that experiences rapid ICP changes over several months. Attesting to the rigor of our approach, we have assembled a team of individuals with expertise spanning micro-electro-mechanical systems design, ultrasound, neurosurgery, and in vivo porcine models. Upon completion, iPPSIS will be fully functional and ready for further translational testing. More broadly, this work paves the way for a new paradigm of ultrasound interrogated biosensors that will enable continuous, deep-tissue measurements for the first time.