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

描述（由申请方提供）：本1期SBIR将开发一种便携式、无创工具，可提高小儿脑积水患者动力学分流通畅性试验（包括放射性核素研究或ShuntCheck试验）的诊断准确性。这将改善疑似分流故障的小儿脑积水患者的临床护理。脑积水是一种常见的疾病，其中CSF积聚在脑室中，可能导致脑损伤和死亡。通过放置VP分流管将多余的CSF带走来纠正。尽管分流术取得了巨大的成功，但最终还是失败了，通常是由于阻塞。然而，分流阻塞的临床症状，主要包括头痛和恶心，是非特异性的，使得分流失败的诊断具有挑战性。通常使用静态MRI和CT扫描来研究疑似阻塞，这是昂贵的，并且需要在连续图像中有液体积聚的证据，从而排除了分流失败的预测。接受分流术的儿童暴露于辐射的情况也很严重，他们每年可能需要接受几次分流术检查。放射性核素研究提供了分流CSF流量的动态测量，具有侵入性并存在感染风险。由于间歇性分流，它们也降低了诊断特异性-专利分流不连续流动，导致高水平的假阳性读数。一种新的、非侵入性的分流测试ShuntCheck也由于间歇性分流而降低了特异性。目前还没有区分间歇性流动的通畅分流和闭塞分流的工具。NeuroDx Development（NeuroDx）最近开发并台架测试了一种工具，该工具可通过专利分流器产生可再现水平的CSF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”是一种小型器械，在放射性核素或分流检查测试期间抵靠分流阀固定。该器械向阀提供特定的振动脉冲，从而通过阀产生受控水平的CSF流量。使用CSF流动的实验室模型，我们已经证明，与ShuntCheck结合使用的微型泵可以区分非流动的通畅分流和闭塞或部分闭塞的分流。该第1阶段项目的目标是扩展这些初步研究结果，以开发临床就绪的原型微型泵装置，并验证其在我们的实验室模型中提高ShuntCheck特异性的能力。在第2阶段，我们将在一系列人体研究中测试微型泵/ShuntCheck组合，从30名患者的初步研究开始，并以300名患者的临床验证研究结束，该研究将ShuntCheck通畅性结果与儿童医院急诊科的症状性儿科患者的临床结局进行比较。到第2阶段结束时，我们预计已经积累了足够的数据，可以向FDA提交微型泵（与ShuntCheck一起）的上市前通知（510（k））。这项工作的结果将是目前用于管理症状性脑积水患者的诊断算法的重要变化。考虑到需要一种非侵入性方法来准确诊断分流失败，替代方法的潜在节省以及改善患者结局的潜力，本研究的数据将支持一种商业上可行且极其重要的产品。 公共卫生相关性：该提案支持开发一种便携式、非侵入性工具，该工具将提高CSF分流通畅性检测（如放射性核素研究和ShuntCheck检测）的诊断准确性。这将改善疑似分流功能障碍的小儿脑积水患者的临床护理，并可能导致目前用于管理症状性脑积水患者的标准诊断途径发生重要变化。

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.