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

iPPSIS：植入式无源压力传感器，通过（超）声音询问

• 批准号: 10196310
• 负责人: Brooks D Lindsey
• 金额: $ 45.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10196310
• 关键词: 1 year old; Address; Affect; Biosensor; Brain; Brain Injuries; Brain Neoplasms; Central Nervous System Infections; Cerebrospinal Fluid; Child; Childhood; Clinical; Common Cold; Data; Dependence; Development; Diagnosis; Environment; Equipment; Evaluation; Exposure to; Failure; Family suidae; Fatigue; Foreign Bodies; Functional disorder; Gases; Geometry; Glioblastoma; Goals; Headache; Hospitalization; Impaired cognition; Implant; In Vitro; Individual; Infiltration; Intracranial Hypertension; Intracranial Pressure; Investigation; Lead; Life; Magnetic Resonance Imaging; Measurement; Measures; Membrane; Memory impairment; Metals; Methods; Modeling; Monitor; Nausea; Neurological outcome; Neurosurgeon; Operative Surgical Procedures; Parietal bone structure; Patients; Permeability; Physiologic Monitoring; Physiological; Population; Probability; Procedures; Publishing; Radiation; Research; Resolution; Risk; Series; Shunt Device; Subarachnoid Hemorrhage; Symptoms; System; Telemetry; Testing; Thick; Time; Tissues; Training; Transducers; Traumatic Brain Injury; Trephine hole; Ultrasonic Transducer; Ultrasonography; Ventricular; Water; Wireless Technology; Work; accurate diagnosis; base; cost; cranium; design; experience; fluid flow; functional status; healing; high reward; in vitro testing; in vivo; innovation; intraventricular hemorrhage; metallicity; microsensor; neurosurgery; new technology; novel; porcine model; pressure; pressure sensor; research clinical testing; response; sensor; sound; success; tumor

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.

项目概要/摘要 脑外伤、蛛网膜下腔损伤可能会导致脑脊液流量 (CSF) 动力学发生变化 和/或脑室内出血、脑肿瘤或中枢神经系统感染，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术来治疗颅内压升高。 允许多余的脑脊液排出，减轻大脑的压力，因此超过 50% 的分流术在第一次就失败了。 分流失败最常见于 1 岁以下的儿童。 不幸的是，验证患者是否有分流的住院费用已超过 10 亿美元。 年轻患者的功能障碍尤其困难，因为症状不具有特异性（头痛、恶心或 ）和现有的非侵入性测试（MRI 和 CT）会造成疲劳，并且不直接测量压力。 出现这些症状的分流患者中 46% 存在功能障碍，而其余患者则出现功能障碍 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。 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询问（超） 声音），它由一个无源的、微制造的压力传感器“目标”组成，该传感器会响应于 压力增加，可以用超声波定量测量。 当前的无线压力传感器方法和消除对射频遥测的依赖将导致 无源（无电池）、MRI 兼容且稳定的无线传感器，可用于长期临床监测 （年）。根据 FOA 的要求，未包含未发布的初步数据。 微制造目标设计和超声分辨率的计算，其基础是 经过数十年的研究，证明了可行性和成功的可能性很高，我们将首先设计 iPPSIS。 对于儿科人群，由于头骨缩小，因此需求巨大且技术障碍较低 在分流器放置过程中，传感器将通过标准钻孔植入硬膜下。 手术，并将随着患者头骨的愈合和重塑而继续进行，目标 1 的重点是 一种新型、极其稳定的金属微压力传感器的构造和表征，该传感器将 高度不受生理“恶劣环境”的影响，目标 2 侧重于测试一种新颖的操作员- 独立的超声测量和新型可穿戴超声换能器可以实现长期 目标 3 旨在严格体外测试 iPPSIS 并收集体内可行性数据。 猪肿瘤模型 (n=2) 在几个月内经历 ICP 快速变化。 我们的方法是，我们组建了一支由具有微机电专业知识的个人组成的团队 系统设计、超声、神经外科和体内猪模型完成后，iPPSIS 将全面投入使用。 更广泛地说，这项工作为新范例铺平了道路。 超声波询问生物传感器将首次实现连续的深层组织测量。