Continuous Real Time CSF Shunt Flow Monitor ShuntCheck

描述(由申请人提供)： 这一阶段的SBIR将开发连续实时(CRT)分流检查，这是第一个便携式、非侵入性设备，用于实时、连续监测脑脊液分流中的流量。该设备将提供一种快速和非侵入性的方法来检测有症状患者的脑脊液分流阻塞，并监测和研究无症状患者的分流功能，从而改善脑积水的临床治疗。脑积水是一种常见的脑脊液积聚在脑室的情况，可通过放置VP分流术将多余的脑脊液排入腹部来纠正。分流管经常出现故障，通常是由于阻塞，但分流管故障的症状是非特异性的-头痛、恶心。分流功能故障的诊断费用昂贵，存在风险(CT扫描暴露于辐射，放射性核素测试有感染风险)，分流患者常规的、持续的临床管理复杂(由于缺乏工具来调查脑脊液过度引流，评估特定分流阀和虹吸控制装置的性能，以及简化可编程分流阀的调整)。一种新的非侵入性分流热稀释测试ShuntCheck由于分流的间歇性--分流不连续，导致高水平的假阳性读数，降低了诊断的特异性。目前还没有非侵入性、非放射学的技术来评估分流功能和故障。这一阶段项目的目标是开发一种通过热稀释连续监测脑脊液流量的原型设备，并在实验台上进行验证，并在脑脊液流量的动物模型中进行验证。该计划基于我们的热稀释技术的一项突破性创新，该技术允许长期、连续的脑脊液流量测量(如脑脊液流量的Holter测试)。我们的第二阶段目标将是进行一项全面的临床研究，以评估我们的非侵入性测试在确定脑积水患者分流功能障碍方面的诊断准确性和实用性。该项目的另一个重要成果可能是更好地了解脑积水患者的分流和脑脊液流动行为的新工具。仅在美国，分流故障和管理测试每年就构成大约60万次分流测试。NeuroDx这种产品的商业模式主要是通过持续销售用于这些测试的一次性传感器来产生收入。NIH的公告“脑脊液分流的先进工具和技术”(PA-09-206)强调了对管理脑积水患者的新诊断工具的需求，本提案正在对此做出回应。我们的建议直接响应了医院或门诊环境中使用的诊断工具的要求，这些工具可以实时工作以定量确定分流功能。 公共卫生相关性： 该方案提供了第一台便携式非侵入性设备，用于连续监测脑脊液分流中的流量，从而满足了医院或门诊使用的实时工作以定量确定分流功能的诊断工具的需求。脑脊液分流阻塞是脑积水的常见并发症，目前通过放射成像技术(如CT扫描)或侵入性检查(如分流手术)进行诊断。这一新工具将帮助神经外科医生区分间歇性分流和阻塞性分流，并将为了解分流功能提供有价值的研究工具。

DESCRIPTION (provided by applicant): This Phase 1 SBIR will develop Continuous Real Time (CRT) ShuntCheck, the first portable, non- invasive device for real time, continuous monitoring of flow in CSF shunts. This device will result in improved clinical management of hydrocephalus by providing a rapid and non-invasive method for detecting CSF shunt obstruction in symptomatic patients, and for monitoring and researching shunt function in asymptomatic patients. Hydrocephalus, a common condition in which CSF accumulates in the brain ventricles, is corrected by placing a VP shunt that drains excess CSF to the abdomen. Shunts frequently malfunction, usually by obstruction, but the symptoms of shunt failure are unspecific - headache, nausea. Diagnosis of shunt malfunction is expensive and presents risks (exposure to radiation from CT Scans, risk of infection from radionuclide testing) and regular, ongoing clinical management of shunted patients is complex (due to a lack of tools for investigating CSF over drainage, for assessing the performance of specific shunt valves and siphon control devices and for streamlining the adjustment of programmable shunt valves). A new, non-invasive thermal dilution test for shunt flow, ShuntCheck, has reduced diagnostic specificity due to intermittent shunt flow - patent shunts do not flow continuously, leading to a high level of false positive readings. There are currently no non-invasive, non-radiologic technologies for assessing shunt function and malfunction. The goal of this Phase 1 project is to develop a prototype device which continuously monitors CSF flow via thermal dilution, and to verify it in a bench and validate it in an animal model of CSF flow. The program is based upon a breakthrough innovation in our thermal dilution technology which allows for long term, continuous CSF flow measurement (like a Holter test for CSF flow). Our Phase 2 goal will be to conduct a full scale clinical study to assess the diagnostic accuracy and utility of our non-invasive test in identifying shunt malfunction in hydrocephalus patients. An important additional outcome of this project will likely be a new tool for better understanding shunt and CSF flow behavior in hydrocephalus patients. Shunt malfunction and management testing constitute approximately 600,000 shunt flow tests annually in the United States alone. NeuroDx's business model for this product involves the generation of revenue primarily from the ongoing sale of single- use, disposable sensors for these tests. The need for new diagnostic tools for managing hydrocephalus patients is highlighted by the NIH announcement "Advanced Tools and Technologies for Cerebrospinal Fluid Shunts" (PA-09-206), to which this proposal is responding. Our proposal directly responds to the request for Diagnostic tools for use in a hospital or outpatient setting that work in real-time to quantitatively determine shunt function. PUBLIC HEALTH RELEVANCE: This proposal addresses the need for diagnostic tools for use in a hospital or outpatient setting that work in real-time to quantitatively determine shunt function by providing the first portable, non-invasive device for continuous monitoring of flow in CSF shunts. Obstruction of CSF shunts, a common complication in hydrocephalus, is currently diagnosed by radiation imaging techniques, such as CT Scan, or by invasive procedures, such as shunt tapping. This new tool will help neurosurgeons differentiate between intermittently flowing and obstructed shunts and will provide a valuable research tool for understanding shunt function.