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

项目总结/摘要 脑脊髓液流动（CSF）动力学的变化可能会发生与创伤性脑损伤，蛛网膜下腔出血， 和/或脑室内出血、脑肿瘤或中枢神经系统感染，并且都可能导致 颅内压（ICP）升高。神经外科医生通过放置脑室分流器治疗颅内压升高， 可以排出多余的脑脊液从而减轻脑部压力超过50%的分流器在第一次 一年，所有的分流最终都会失败。分流失败最常见于1岁以下的儿童， 占了超过10亿美元的住院费用。不幸的是，确认病人有分流 功能障碍在年轻患者中特别困难，因为症状是非特异性的（头痛，恶心， 疲劳）和现有的非侵入性测试（MRI和CT）是昂贵的并且不直接测量压力。只 出现这些症状的分流患者中有46%有功能障碍，而其余患者则发生 不必要的费用、暴露于辐射或可能导致脑损伤的侵入性检查。到 为了解决这个问题，我们建议创建iPPSIS（植入式无源压力传感器，使用（超） 声音），它是由一个被动的，微制造的压力传感器“目标”，偏转响应 增加的压力，并且可以用超声定量测量。我们假设重新思考 目前无线压力传感器的方法和消除对RF遥测的依赖将导致 无线传感器，无源（无电池），MRI兼容，长期临床监测稳定 （年）。根据《信息自由法》的要求，没有包括未发表的初步数据。然而，我们的分析 微加工目标设计和超声分辨率的计算，其基于 几十年的研究，证明了可行性和成功的可能性很高。我们将初步设计iPPSIS 对于儿科人群，考虑到显著的需求和由于颅骨缩小而降低的技术障碍， 厚在分流管放置过程中，将通过标准钻孔将传感器植入硬膜下 手术，并将继续运作，因为病人的头骨愈合和改革。目标1侧重于 一种新型、极其稳定的金属微压力传感器的构建和表征，该传感器将成为 对生理上的“恶劣环境”高度不受影响。目标2侧重于测试新操作员- 独立的超声测量和一种新的可穿戴超声换能器， 持续监测。目标3旨在严格测试iPPSIS在体外以及收集在体内的可行性数据， 猪肿瘤模型（n=2），其在几个月内经历快速ICP变化。证明了 我们的方法，我们已经组建了一个团队的个人与专业知识跨越微机电 系统设计、超声、神经外科和体内猪模型。完成后，iPPSIS将完全 功能齐全，可进行进一步的翻译测试。更广泛地说，这项工作为新范式铺平了道路 超声波询问生物传感器，这将使连续的，深层组织测量的第一次。

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.