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

摘要 脑积水是一种神经系统疾病所造成的积累过量脑脊液（CSF） 会导致嗜睡癫痫昏迷甚至死亡它是用外科手术治疗的。 植入导管，称为脑室分流，将多余的CSF从 脑并进入远端吸收部位，如腹部。不幸的是，由于闭塞或 错误定位，分流有极高的失败率- 51%在2年内，98%以上10 通常需要进行矫正手术，称为翻修术。125，000分流器 在美国，每年都要进行修正或修改，费用为20亿美元。 诊断分流失败是非常困难的，由于其症状的非特异性。 尽管CT等成像检查存在长期辐射暴露风险， 侵入性检查，如脑脊液抽吸和放射性核素示踪是痛苦的， 重大感染风险。所有上述测试都具有较差的诊断性能， 敏感性（~80%）和特异性（~55%），在很大程度上是因为它们不直接测量 流动动力学，可以说是最重要和最相关的分流性能指标。的 通过植入的分流器连续、无创、实时监测CSF流量， a critical关键unmet满足need需求.临床医生将使用这些数据进行即时诊断， 研究人员将利用它们来更好地了解分流失败，并阐明 病理生理学的了解甚少的条件，如正常压力脑积水。 本提案通过利用现有的无线传感器硬件来解决这一需求 开发第一个皮肤安装的无线产品，以提供定量CSF流量数据， 植入分流器通过对热传输的精确测量，我们将开发新的 高精度地表征和量化通过底层分流器的流量的算法。 初步的患者数据、台架试验和计算机建模证实了 传感器产生高质量的流量数据，同时在机械上不干扰患者。 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， 量化流程数据，并实施质量管理体系来管理软件 开发，最终导致IRB批准临床试验。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 从而向食品药品监督管理局提交上市申请

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.