Diversity supplement for noninvasive, wireless thermal sensors for the quantitative monitoring of ventricular shunt function in patients with hydrocephalus

摘要 脑积水是一种神经疾病，由过量的脑脊液积聚引起。 大脑中的液体(CSF)，并导致嗜睡、癫痫、昏迷或死亡。它是用 外科植入的导管，称为脑室分流术，可转移多余的脑脊液。 从大脑进入远端吸收部位，如腹部。不幸的是，由于 闭塞或定位错误，分流装置的故障率极高，两年内为51%，而98% 超过10年-通常需要进行矫正手术，即所谓的翻修手术。125,000人 分流植入术或整形手术每年在美国进行，费用为2美元 十亿美元。 由于分流故障的非特异性，诊断分流故障是极其困难的 症状。像CT这样的成像测试是常用的，尽管它们是长期辐射的 暴露风险和侵入性测试，如脑脊液抽吸和放射性核素示踪是痛苦的 并带有显著的感染风险。所有上述测试的诊断性能都很差， 敏感度(~80%)和特异度(~55%)低，很大程度上是因为它们不直接 测量流量动态，可以说是最重要和相关的分流性能指标。 植入物脑脊液流量的连续、无创、实时监测 分流代表着一种关键的未得到满足的需求。临床医生会将这些数据用于医疗护理点 诊断学，研究人员将使用它们来更好地了解分流故障，并阐明 常压性脑积水等知之甚少的疾病的病理生理学。 本提案通过利用现有无线传感器硬件来满足这一需求 开发第一款皮肤贴装无线产品，提供定量的脑脊液流量数据 植入分流装置。利用热传输的精确测量，我们将开发出新的 高精度地表征和量化通过基础分流的流量的算法。 初步的患者数据，桌面测试和计算机建模证实了 传感器可产生高质量的流量数据，同时不会对患者造成机械上的干扰。 第一阶段的活动将在大型动物模型上验证传感器，开发算法以 提供量化的流程数据，并实施质量管理系统来管理软件 开发，最终导致IRB批准用于临床试验。第二阶段活动将 最终通过人体试验验证传感器性能的临床诊断价值 导致向FDA提交了一份营销报告。

ABSTRACT Hydrocephalus is a neurological disorder caused by buildup of excess cerebrospinal fluid (CSF) in the brain, and leads to lethargy, seizures, coma, or death. It is treated with the surgical implantation of a catheter, known as a ventricular shunt, that diverts excess CSF away from the brain and into a distal absorptive site, such as the abdomen. Unfortunately, due to occlusion or mispositioning, shunts have extremely high failure rates - 51% in 2 years, and 98% over 10 years - and often require corrective surgical procedures, known as revisions. 125,000 shunt implantations or revisions are performed annually in the United States, at a cost of $2 billion. Diagnosing shunt failure is extremely difficult, due the non-specific nature of its symptoms. Imaging tests such as CT are commonly used despite their long-term radiation exposure risks and invasive tests such as CSF aspiration and radionuclide tracing are painful and carry significant infection risks. All the above tests have poor diagnostic performance, with low sensitivities (~80%) and specificities (~55%), in large part because they do not directly measure flow dynamics, arguably the most important and relevant shunt performance metric. The continuous, non-invasive, real-time monitoring of CSF flow through implanted shunts represents a critical unmet need. Clinicians would use these data for point-of-care diagnostics, and researchers would use them to better understand shunt failure, and elucidate the pathophysiology of poorly-understood conditions such as normal-pressure hydrocephalus. The present proposal addresses this need by capitalizing on existing wireless sensor hardware to develop the first skin mounted wireless product to give quantitative CSF flow data in implanted shunts. Using precise measurements of thermal transport, we will develop novel algorithms to characterize and quantify flow through underlying shunts with high accuracy. Preliminary patient data, benchtop tests, and computer modeling confirm the ability of the sensor to produce high-quality flow data while being mechanically unobtrusive to the patient. Phase I activities will validate the sensor on large animal models, develop algorithms to deliver quantitative flow data, and implement a quality management system to govern software development, ultimately leading to IRB approval for clinical testing. Phase II activities will validate diagnostic value of the sensor’s performance clinically through a human trial, ultimately leading to a marketing submission to the FDA.