ShuntCheck Clinical Validation and ShuntCheck-Micro-Pumper Assessment of CSF Shun

描述(由申请人提供)： 这项SBIR的目标是创建第一套全面的临床工具和非侵入性方法来诊断脑脊液(CSF)分流梗阻，并对它们进行验证，以使临床医生相信它们的临床价值。脑积水是一种常见的脑脊液积聚在脑室的情况，有可能导致脑损伤和死亡。可通过放置VP分流术将多余的脑脊液带走来纠正。虽然分流非常成功，但分流最终会失败，通常是因为阻塞。然而，分流梗阻的临床症状，主要包括头痛和恶心，是非特异性的，这使得分流失败的诊断具有挑战性。可疑的梗阻通常使用静态MRI和CT扫描进行调查，这两种检查都很昂贵，而且需要在序列图像中发现液体堆积的证据，从而无法预测分流失败。辐射暴露在接受分流手术的儿童中也很重要，他们每年可能需要进行几次分流检查。放射性核素研究提供了脑脊液分流的动态测量，具有侵入性，并带有感染的风险。由于间歇性分流--分流不连续导致高水平的假阳性读数，它们也降低了诊断的特异度。一种新的非侵入性分流检测，ShuntCheck，也由于间歇性分流而降低了特异度，导致该设备的准确性受到质疑。目前还没有区分间歇性分流和闭塞分流的工具。NeuroDx开发公司(NeuroDx)最近开发并进行了台架测试的“Micro-Pumper”，这是一种小型装置，在分流检查测试期间被固定在分流阀上。该装置向瓣膜提供特定的振动脉冲，产生流过瓣膜的受控水平的脑脊液。我们已经证明，微泵与分流检查结合使用可以区分非流动的分流和闭塞或部分闭塞的分流。该第一阶段项目的目标是通过与磁共振血流测试的比较，验证ShuntCheck血流/无血流测定的准确性，并在波士顿儿童医院的儿童脑积水患者的试点研究中测试Micro-Pumper/ShuntCheck组合。到第二阶段结束时，我们预计已经积累了足够的数据，能够向FDA提交Micro-Pumper的上市前通知(510(K))(与ShuntCheck一起)。这项工作的结果将是对目前用于管理脑积水患者的诊断算法的重要改变。考虑到对准确诊断分流失败的非侵入性方法的需求、与替代方法相比的潜在节省以及改善患者预后的可能性，本研究的数据将支持一种商业上可行且极其重要的诊断程序。 公共卫生相关性： 这项建议旨在满足医院或门诊环境中使用的诊断工具的需求，这些工具通过创建第一套全面的临床工具和非侵入性方法来诊断脑脊液(CSF)分流梗阻，并对其进行验证，以说服临床医生相信从ShuntCheck(R)(SC)和Micro-Pumper获得的宝贵信息，从而实时地确定分流功能。脑脊液分流阻塞是一种常见的并发症，目前通过放射成像技术(如CT扫描)或侵入性程序(如分流术)进行诊断。这些新工具将使分流梗阻得以诊断，并将为了解分流功能提供研究工具。

DESCRIPTION (provided by applicant): The goal of this SBIR is to create the first comprehensive set of clinical tools and noninvasive methods for diagnosing cerebrospinal fluid (CSF) shunt obstruction and to validate them to convince clinicians of their clinical value. 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, leading to questions about the device's accuracy. There are currently no tools for differentiating between intermittently flowing patent shunts and occluded shunts. NeuroDx Development (NeuroDx) has recently developed and bench tested "Micro-Pumper", a small device which is held against the shunt valve during the ShuntCheck test. The device provides specific vibration pulses to the valve, creating a controlled level of CSF flow through the valve. 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 validate the accuracy of the ShuntCheck flow/no-flow determination via comparison to MRI flow testing and to test the Micro-Pumper/ShuntCheck combination in a pilot study or pediatric hydrocephalus patients at Children's Hospital Boston. 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 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 diagnostic procedure which is commercially viable and extremely important. 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 creating the first comprehensive set of clinical tools and noninvasive methods for diagnosing cerebrospinal fluid (CSF) shunt obstruction and validating them to convince clinicians of the valuable information available from ShuntCheck(R) (SC) and Micro-Pumper. Obstruction of CSF shunts, a common complication, is currently diagnosed by radiation imaging techniques, such as CT Scan, or by invasive procedures, such as shunt tapping. These new tools will enable shunt obstruction to be diagnosed and will provide a research tool for understanding shunt function.