Micro-Pumper method for improving the specificity of CSF shunt patency testing

描述（由申请人提供）：该1期SBIR将开发一种便携式、非侵入性工具，用于提高小儿脑积水患者动态分流管通畅测试（包括放射性核素研究或ShuntCheck测试）的诊断准确性。这将改善小儿脑积水患者疑似分流功能障碍的临床护理。脑积水是脑脊液在脑室积聚的一种常见疾病，可能导致脑损伤和死亡。通过放置VP分流器将多余的CSF带走来纠正。尽管取得了巨大的成功，但分流术最终还是会失败，通常是由于阻塞。然而，分流管阻塞的临床症状，主要包括头痛和恶心，是非特异性的，使得分流管失败难以诊断。可疑的梗阻通常使用静态MRI和CT扫描进行调查，这是昂贵的，并且需要在连续图像中发现液体积聚的证据，从而排除了对分流失败的预测。在分流的儿童中，暴露于辐射也很重要，他们可能需要每年进行几次分流检查。放射性核素研究提供了脑脊液分流流的动态测量，是侵入性的，有感染的风险。由于间歇性分流血流，它们的诊断特异性也降低了——专利分流器不能连续流动，导致高水平的假阳性读数。一种新的、无创的分流检测方法ShuntCheck，由于间歇性分流，其特异性也降低了。目前还没有工具来区分间歇流动的通畅分流管和闭塞分流管。NeuroDx开发公司（NeuroDx）最近开发并测试了一种工具，该工具可以通过专利分流器产生可重复的脑脊液流量。与放射性核素研究或ShuntCheck测试结合使用，这种新设备可以提高两种测试方法的诊断特异性。NeuroDx“微型泵”是一种小型装置，在放射性核素或ShuntCheck测试期间，将其固定在分流阀上。该装置向阀门提供特定的振动脉冲，通过阀门产生可控水平的CSF流量。通过脑脊液流动的台架模型，我们已经证明Micro-Pumper与ShuntCheck结合使用可以区分不流动的未闭分流管和闭塞或部分闭塞的分流管。第一阶段项目的目标是扩展这些初步发现，开发出临床可用的微型泵设备原型，并验证其在实验模型中提高ShuntCheck特异性的能力。在第二阶段，我们将在一系列人体研究中测试Micro- Pumper/ShuntCheck组合，从一项30例患者的试点研究开始，到一项300例患者的临床验证研究结束，将ShuntCheck通畅结果与儿童医院急诊科出现症状的儿科患者的临床结果进行比较。到第二阶段结束时，我们预计已经积累了足够的数据，可以向FDA提交Micro-Pumper（与ShuntCheck一起）的上市前通知（510(k)）。这项工作的结果将是一个重要的改变，诊断算法目前用于管理症状性脑积水患者。考虑到需要一种非侵入性方法来准确诊断分流失败，与其他方法相比，潜在的节省和改善患者预后的潜力，这项研究的数据将支持一种具有商业可行性和极其重要的产品。

DESCRIPTION (provided by applicant): This Phase 1 SBIR will develop a portable, non-invasive tool which will improve the diagnostic accuracy of kinetic shunt patency testing, including radionuclide studies or ShuntCheck tests, in pediatric hydrocephalus patients. This will improve clinical care for pediatric hydrocephalus patients with suspect shunt malfunction. Hydrocephalus is a common condition in which CSF accumulates in the brain ventricles, potentially leading to brain damage and death. It is corrected by placing a VP shunt that carries excess CSF away. Although enormously successful, shunts eventually fail, usually by obstruction. However, the clinical symptoms of shunt obstruction, primarily including headache and nausea, are non-specific, making shunt failure challenging to diagnose. Suspected obstruction is typically investigated using static MRI and CT scans which are expensive, and require evidence of fluid accumulation in serial images, precluding prediction of shunt failure. Exposure to radiation is also significant in shunted children, who may require several shunt investigations annually. Radionuclide studies, which provide dynamic measures of shunt CSF flow, are invasive and carry the risk of infection. They also have reduced diagnostic specificity due to intermittent shunt flow - patent shunts do not flow continuously leading to a high level of false positive readings. A new, non-invasive test for shunt flow, ShuntCheck, also suffers from reduced specificity due to intermittent shunt flow. There are currently no tools for differentiating between intermittently flowing patent shunts and occluded shunts. NeuroDx Development (NeuroDx) has recently developed and bench tested a tool which generates a reproducible level of CSF flow through patent shunts. Used in conjunction with radionuclide studies or ShuntCheck testing, this new device can improve diagnostic specificity of both test methods. The NeuroDx "Micro-Pumper" is a small device which is held against the shunt valve during the radionuclide or ShuntCheck test. The device provides specific vibration pulses to the valve, creating a controlled level of CSF flow through the valve. Using a bench model of CSF flow, we have shown that the Micro-Pumper, used in combination with ShuntCheck can differentiate between non-flowing patent shunts and occluded or partially occluded shunts. The goal of this Phase 1 project is to extend these preliminary findings to develop a clinic-ready prototype Micro-Pumper device and to verify its ability to improve ShuntCheck's specificity in our bench model. In Phase 2, we will test the Micro- Pumper/ShuntCheck combination in a series of human studies, beginning with a 30 patient pilot study and concluding with a 300 patient clinical validation study comparing ShuntCheck patency results to clinical outcomes of symptomatic pediatric patients who present at the Emergency Departments of Children's Hospitals. By the end of Phase 2, we anticipate having accumulated sufficient data to enable submission of a pre-market notification (510(k)) to the FDA for the Micro-Pumper (in conjunction with ShuntCheck). The result of this work will be an important change in the diagnostic algorithm currently used to manage symptomatic hydrocephalus patients. Given the need for a non-invasive method to accurately diagnose shunt failure, the potential savings over alternative methods and the potential for improved patient outcomes, the data from this study will support a product which is commercially viable and extremely important. PUBLIC HEALTH RELEVANCE: This proposal supports the development of a portable, non-invasive tool which will improve the diagnostic accuracy of CSF shunt patency testing such as radionuclide studies and ShuntCheck tests. This will improve clinical care for pediatric hydrocephalus patients with suspect shunt malfunction and could lead to an important change in the standard diagnostic pathway currently used to manage symptomatic hydrocephalus patients.