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

ShuntCheck-Micro-Pumper 的验证，一种非侵入性诊断程序

• 批准号: 8508322
• 负责人: Frederick J Fritz
• 金额: $ 101.78万
• 依托单位: NEURODX DEVELOPMENT, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8508322
• 关键词: Abdomen; Address; Adverse effects; Affect; American; Boston; Brain Death; Brain Injuries; Businesses; Cerebral Ventricles; Cerebrospinal fluid shunts procedure; Childhood; Clinic; Clinical; Clinical Management; Clinical Research; Collaborations; Complication; Contracts; Data; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic Sensitivity; Diagnostic Specificity; Diagnostic tests; Exposure to; FDA approved; Failure; Generations; Goals; Headache; Health Care Costs; Hospitals; Human; Hydrocephalus; Imaging Techniques; Infection; Laboratories; Legal patent; Manufacturer Name; Marketing; Measurement; Medical Device; Methods; Modeling; Nausea; Neurosurgeon; Notification; Obstruction; Outcome; Outpatients; Patients; Pediatric Hospitals; Performance; Phase; Pilot Projects; Procedures; Production; Pump; Radiation; Radioisotopes; Research; Risk; Roentgen Rays; Safety; Sales; Second Look Surgery; Series; Shunt Device; Small Business Innovation Research Grant; Specificity; Symptoms; System; Technology; Testing; Time; United States; United States National Institutes of Health; Validation; Work; X-Ray Computed Tomography; commercialization; design; experience; improved; innovation; neurosurgery; novel diagnostics; phase 1 study; prototype; rapid technique; response; sensor; subcutaneous; tool

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.

描述（由申请人提供）： 该 2 期 SBIR 将提供并临床验证第一个便携式、非侵入性诊断测试，用于区分间歇性流动的专利分流器与闭塞或部分闭塞的分流器 - ShuntCheck-Micro-Pumper。该设备将提供一种快速、非侵入性的方法来检测有症状患者的脑脊液分流阻塞，并有可能在症状出现之前识别即将发生的阻塞，从而改善脑积水的临床管理。脑积水是脑脊液积聚在脑室的一种常见病症，可通过放置 VP 分流器将多余的脑脊液排至腹部来纠正。分流器经常出现故障，通常是由于阻塞，但分流器故障的症状并不具体——头痛、恶心。分流器故障的诊断费用昂贵且存在风险（CT 扫描的辐射暴露、放射性核素测试的感染风险），并且不存在用于预测分流器故障的工具。目前还没有用于评估分流功能和故障的非侵入性、非放射技术。 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 的临床研究证明了流量/无流量测量的准确性，但它们表明“无流量”并不表示分流闭塞（因为分流流量可能是间歇性的），“流量”并不表示分流开放（因为部分闭塞分流可能导致 ICP 升高，同时允许脑脊液流动）。为了解决这个问题，NeuroDx 开发了微型泵，这是一种小型手持设备，可通过专利但不闭塞的分流器暂时增加脑脊液流量。 ShuntCheck 可以检测这种“微泵送”流量，作为分流容量的指示。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微型泵，可以在各种专利但不部分阻塞的分流阀中可靠地产生增加的脑脊液流量。重复微泵送不会对分流阀功能产生任何不利影响。目前正在波士顿儿童医院进行的 ShuntCheck-Micro-Pumper 试点临床研究表明，该程序对于儿科患者来说是可以接受的，并且在专利分流中产生可检测到的流量。在第二阶段，我们计划开发微型​​泵的生产就绪版本，优化与微型泵一起使用的 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约 310,000 次分流测试。 NeuroDx 该产品的商业模式主要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 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，本提案对此作出了回应。我们的提案直接响应了对在医院或门诊环境中使用实时定量确定分流功能的诊断工具的需求。

项目成果

Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study.

• DOI: 10.1093/neuros/nyaa128
• 发表时间: 2020-10-15
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Madsen JR;Boyle TP;Neuman MI;Park EH;Tamber MS;Hickey RW;Heuer GG;Zorc JJ;Leonard JR;Leonard JC;Keating R;Chamberlain JM;Frim DM;Zakrzewski P;Klinge P;Merck LH;Piatt J;Bennett JE;Sandberg DI;Boop FA;Hameed MQ
• 通讯作者: Hameed MQ