Microfabricated Implantable Flowmeter for CSF Shunts Phase II

描述(由申请人提供)： 一种植入式无线流量传感器系统正在开发中，该系统将能够测量脑脊液(CSF)通过脑室腹膜分流术(VP)的流量，该分流术目前用于治疗脑积水患者。脑脊液流量是分流功能的重要指标，目前尚无原位测量分流功能的方法，导致缺乏直接评估分流功能或预测分流功能失败的临床方法。使用MEMS微制造方法，所提出的流量传感器将被制造成足够小的尺寸，足以与植入的VP分流器集成在一起。流量计中的关键元件是电容式结构，它会随着脑脊液流量的变化而改变特性。内部无源电路和外部手持电路之间的电磁耦合允许植入流量传感器，而不需要植入电池或经皮导线。拟议的第二阶段项目将建立在第一阶段令人鼓舞的结果的基础上，该阶段展示了概念验证MEMS传感器的无线询问，以及存在易于测量的流量与传感器共振的关系。在第二阶段，将制造全功能的流量传感MEMS芯片，以及根据已知的流量和共振之间的关系，显示和输出流量的改进的手持单元。体外测试将为传感器植入物建立校准，并将在整个脑脊液流动的生理范围内、长时间内和适当的体模模型上证明测量的准确性。同时，将准备一个慢性绵羊脑积水模型，并在传感器植入原型中实施适当的包装、生物兼容性和灭菌性，以及考虑MR兼容性。动物试验方案的性能应从以下方面对传感器进行评估：(1)检测血流阻塞的灵敏度和特异度；(2)脑脊液流量测量的准确性；(3)对分流通畅的影响。 公共卫生相关性： 美国每年大约进行23,000次分流手术，以纠正用于治疗脑积水患者的脑室腹膜分流术(VP)相对常见的失败。然而，仍有儿童死于分流失败，研究表明，早期发现将挽救很大一部分儿童。植入式无线脑脊液流量计将使临床医生能够在常规就诊期间监测分流功能(而不是等待脑积水症状再次出现)，从而能够检测到即将发生的分流失败，避免在紧急情况下进行挽救生命的治疗，并降低与VP分流失败相关的死亡率。

DESCRIPTION (provided by applicant): An implantable wireless flow sensor system has been under development that would enable measurement of the flow of cerebrospinal fluid (CSF) through the ventriculoperitoneal (VP) shunt, currently used to treat hydrocephalus patients. CSF flow is a key indicator of shunt function, and there is currently no way to measure it in situ, resulting in the absence of clinical methods to directly assess shunt function or to predict its failure. Using MEMS microfabrication methods, the proposed flow sensor will be manufactured at a size small enough to be integrable with implanted VP shunts. The key elements in the flow meter are capacitive structures that change properties with change in CSF flow. Electromagnetic coupling between the internal passive circuitry and an external handheld circuit allows implantation of the flow sensor without the need for implanted batteries or transcutaneous wires. The proposed Phase II project will build on the encouraging results of Phase I, which demonstrated the wireless interrogation of proof-of-concept MEMS sensors and the presence of a readily measurable relationship of flow to the resonance of the sensor. In Phase II, fully-function flow-sensing MEMS chips will be manufactured, as well as a revised handheld unit that will display and output flow, based on the known relationship between flow rate and resonance. In vitro testing will establish calibration for the sensor implants, and will demonstrate measurement accuracy over the full physiological range of CSF flow, over long periods of time, and with appropriate phantom models. In parallel, a chronic sheep hydrocephalus model will be in preparation, along with implementation of appropriate packaging, biocompatibility, and sterilizability into the sensor implant prototypes, as well as consideration of MR compatibility. Performance of an animal test protocol shall evaluate the sensor in regard to (1) sensitivity and specificity with regard to detection of flow obstruction, (2) CSF flow measurement accuracy, and (3) effect on shunt patency. PUBLIC HEALTH RELEVANCE: Every year there are approximately 23,000 shunt revisions performed in the U.S., in order to correct the relatively common failure of ventriculoperitoneal (VP) shunts used to treat hydrocephalus patients. However, children are still dying from shunt failure, and studies indicate that earlier detection would save a large fraction of these children. An implantable, wireless CSF flow meter would enable the clinician to monitor shunt function during routine office visits (rather than waiting for the re-appearance of hydrocephalus symptoms), allowing detection of impending shunt failure, avoidance of lifesaving treatment on an emergency basis, and reduction of mortality associated with VP shunt failure.