Validation of ShuntCheck-Micro-Pumper, a non-invasive diagnostic procedure for de

描述(由申请人提供)： 该二期SBIR将提供并在临床上验证首个便携式、非侵入性诊断测试，用于区分间歇性流动的未闭分流和闭塞或部分闭塞的分流--ShuntCheck-Micro-Pumper。该设备将提供一种快速和非侵入性的方法来检测有症状的患者的脑脊液分流障碍，并有可能在症状出现之前识别即将到来的闭塞，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成本很高，而且存在风险(暴露于CT扫描的辐射，放射性核素测试的感染风险)，而且目前还没有预测分流功能故障的工具。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。NeuroDx开发了一种名为ShuntCheck的非侵入性设备，它使用热稀释来检测皮下分流中的脑脊液流量。虽然ShuntCheck的临床研究证明了血流/无血流测量的准确性，但它们表明，“无血流”并不意味着闭塞的分流(因为分流可以是间歇性的)，“流动”并不意味着明显的分流(因为部分闭塞的分流可以在允许脑脊液流动的同时导致颅内压升高)。为了解决这个问题，NeuroDx开发了Micro-Pumper，这是一种小型手持设备，可以通过专利而不是闭塞分流来暂时增加脑脊液流量。这种“微泵”流量可以通过ShuntCheck检测到，作为分流流量的指示。在我们的第一阶段研究中，我们开发了操作参数和实验室原型Micro-Pumper，在各种专利但不是部分堵塞的分流阀中可靠地产生更多的脑脊液流量。反复微泵对分流瓣功能无不良影响。目前正在波士顿儿童医院进行的一项关于ShuntCheck-Micro-Pumper的试点临床研究表明，该程序可以被儿科患者接受，并在专利分流中产生可检测到的流量。在第二阶段，我们计划开发可用于生产的Micro-Pumper版本，优化用于Micro-Pumper的ShuntCheck设计，并在人体临床研究中验证组合程序的准确性。仅在美国，儿科分流故障和管理测试每年就构成了大约310,000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。

DESCRIPTION (provided by applicant): This Phase 2 SBIR will provide and clinically validate the first portable, non-invasive diagnostic test for differentiating intermittently flowing patent shunts from occluded or partially occluded shunts - ShuntCheck- Micro-Pumper. 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, potentially for identifying oncoming occlusion before symptoms emerge. 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 no tools exist for predicting shunt malfunction. There are currently no non-invasive, non-radiologic technologies for assessing shunt function and malfunction. NeuroDx has developed a non-invasive device called ShuntCheck which uses thermal dilution to detect CSF flow in subcutaneous shunts. While clinical studies of ShuntCheck demonstrated the accuracy of flow/no-flow measurements, they showed that "no-flow" does not indicate an occluded shunt (since shunt flow can be intermittent) and "flow" does not indicate a patent shunt (since a partially occluded shunt can cause elevated ICP while allowing CSF flow). To address this problem, NeuroDx developed the Micro-Pumper, a small, handheld device which generates a temporary increase in CSF flow through patent but not occluded shunts. This "micro-pumped" flow can be detected by ShuntCheck as an indication of shunt flow capacity. In our Phase 1 studies, we developed operating parameters and a laboratory prototype Micro-Pumper that reliably generates increased CSF flow in a wide variety of patent, but not partially-obstructed, shunt valves. Repeated micro-pumping did not result in any adverse effects on shunt valve function. A pilot clinical study of the ShuntCheck-Micro-Pumper, currently underway at Children's Hospital Boston, indicates that the procedure is acceptable to pediatric patients and generates detectable flows in patent shunts. In Phase 2, we plan to develop a production ready version of the Micro-Pumper, optimize the ShuntCheck design for use with the Micro-Pumper and validate the accuracy of the combined procedure in human clinical studies. Pediatric shunt malfunction and management testing constitute approximately 310,000 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.