Wireless Implantable Monitor for Improved Neuromodulation

用于改善神经调节的无线植入式监视器

• 批准号: 8840062
• 负责人: MARGOT S. DAMASER
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8840062
• 关键词: Algorithms; Ataxia; Autonomic Dysreflexia; Bladder; Bladder Control; Catheters; Cessation of life; Chronic; Clinical; Clinical Trials; Contact Dermatitis; Decubitus ulcer; Development; Devices; Effectiveness; Electric Stimulation; Equilibrium; Event; Extravasation; FDA approved; Feedback; Funding; Goals; Hyperreflexia; Individual; Infection; Kidney Failure; Lead; Methods; Monitor; Morphologic artifacts; Overactive Bladder; Pathway interactions; Patients; Positioning Attribute; Prevention; Reflex action; Research; Risk; Sensory; Sepsis; Septicemia; Signal Transduction; Skin; Sphincter; Spinal cord injury; Spinal cord injury patients; Stroke; System; Testing; Urinary Incontinence; Urine; Veterans; Wireless Technology; Work; bacterial resistance; base; design; habituation; high risk; implantation; improved; in vivo Model; neuroregulation; novel; pressure; research clinical testing; sensor

DESCRIPTION (provided by applicant): Control of urine leakage is of major importance after spinal cord injury (SCI) since SCI patients are highly susceptible to pressure ulcers. Pressure ulcers exposed to urine are more susceptible to infection since urine alters the pH balance of the skin and reduces resistance to bacterial invasion. Septicemia resulting from infected pressure ulcers is a major cause of rehospitalization or death among individuals with SCI. SCI patients characteristically develop detrusor overactivity and striated sphincter dyssynergia, leading to uncontrolled leakage of urine, putting the patient at increased risk for contact dermatitis and infected pressure ulcers. In addition, these bladder complications of SCI can lead to autonomic dysreflexia, renal failure, and stroke. Therefore, control of urine leakage is of major importance after SCI. Electrical stimulation of pudendal sensory pathways can arrest unwanted reflex bladder contractions in SCI patients. Open-loop continuous electrical stimulation can inhibit overactive bladder activity and several devices are approved by the FDA. However, patients must frequently return to the doctor to have their electrical stimulation system adjusted when its effectiveness wanes due to habituation or accommodation to an electrical stimulation signal that is always on. Conditional or closed-loop stimulation that only stimulates when triggered to do so has been shown to be more effective than open-loop continuous stimulation, resulting in greater bladder capacity and utilizing less power. However, conditional stimulation is presently only utilized acutely for research purposes using a catheter-based pressure-sensing system since a chronic bladder sensor is not currently available. During the initial VA Merit funding period of this project, we developed a miniature, implantable, wireless, catheter-free, battery-powered, rechargeable pressure monitor for chronic submucosal implantation which could provide the feedback for chronic conditional stimulation. We have achieved most of the objectives of the initial proposal period. However, several hurdles remain to be overcome for application of the pressure monitor to provide closed-loop control for prevention of urinary incontinence, including assessment of feasibility of implantation, optimization of the pressure monitor for chronic implantation, creation of an algorithm for differentiating important bladder events from artifacts, validating our micro-packaging method for chronic implantation, and testing of this novel system in a chronic in vivo model. The goal of this extensively revised design and development renewal proposal is to accomplish these goals, thereby optimizing our pressure monitor for chronic submucosal implantation in the bladder for closed-loop bladder control after SCI. Four specific objectives are designed to accomplish the necessary work: 1. Assess clinical aspects of pressure monitor implantation; 2. Optimize the implantable pressure monitor for chronic implantation; 3. Develop feature extraction methods for distinguishing important bladder events from artifact; and 4. Develop micro-packaging for chronic implantation of the pressure monitor. Completion of the proposed research will put us in a strong position to proceed to clinical testing of our closed loop control system, after which, we will begin clinical trials of our pressure monitor.

描述（由申请人提供）： 脊髓损伤（SCI）后控制尿液渗漏至关重要，因为SCI患者极易发生压疮。接触尿液的压疮更容易感染，因为尿液改变了皮肤的pH值平衡，降低了对细菌入侵的抵抗力。感染性压疮引起的败血症是SCI患者再次住院或死亡的主要原因。SCI患者的特征性发展为逼尿肌过度活动和横纹括约肌协同失调，导致尿液不受控制的渗漏，使患者接触性皮炎和感染性压疮的风险增加。此外，SCI的这些膀胱并发症可导致自主神经反射障碍、肾衰竭和中风。因此，SCI后尿漏的控制至关重要。 电刺激阴部感觉通路可以阻止SCI患者不必要的反射性膀胱收缩。开环连续电刺激可以抑制膀胱过度活动，并且FDA批准了几种设备。然而，当电刺激系统的有效性因习惯或适应始终开启的电刺激信号而减弱时，患者必须频繁地返回医生那里进行调整。只有在触发时才进行刺激的有条件或闭环刺激已被证明比开环连续刺激更有效，导致更大的膀胱容量和使用更少的功率。然而，由于慢性膀胱传感器目前不可用，因此条件刺激目前仅用于使用基于导管的压力感测系统的研究目的。 在该项目的最初VA Merit资助期间，我们开发了一种用于慢性粘膜下植入的微型、植入式、无线、无导管、电池供电、可充电压力监测器，可为慢性条件刺激提供反馈。我们已经实现了初步提案期的大部分目标。然而，对于压力监测器提供闭环控制以预防尿失禁的应用，仍有几个障碍有待克服，包括植入可行性的评估、用于慢性植入的压力监测器的优化、用于区分重要膀胱事件与伪影的算法的创建、验证我们用于慢性植入的微包装方法，以及在慢性体内模型中测试该新系统。这一广泛修订的设计和开发更新提案的目标是实现这些目标，从而优化我们的压力监测器，用于膀胱慢性粘膜下植入，用于SCI后的闭环膀胱控制。四个具体目标是为了完成必要的工作：1。评估压力监测器植入的临床方面; 2.优化植入式压力监测器用于慢性植入; 3.开发用于区分重要膀胱事件与伪影的特征提取方法;以及4.为压力监测器的长期植入开发微型包装。完成拟议的研究将使我们处于有利地位，继续进行我们的闭环控制系统的临床测试，之后，我们将开始我们的压力监测器的临床试验。

项目成果

Suburothelial Bladder Contraction Detection with Implanted Pressure Sensor.

使用植入压力传感器检测膀胱上皮下收缩情况。

• DOI: 10.1371/journal.pone.0168375
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Majerus,SteveJA;Fletter,PaulC;Ferry,ElizabethK;Zhu,Hui;Gustafson,KennethJ;Damaser,MargotS
• 通讯作者: Damaser,MargotS

Wireless Bladder Pressure Monitor for Closed-Loop Bladder Neuromodulation.

用于闭环膀胱神经调节的无线膀胱压力监测仪。

• DOI: 10.1109/icsens.2016.7808967
• 发表时间: 2016
• 期刊: Proceedings of IEEE Sensors. IEEE International Conference on Sensors
• 作者: Majerus,Steve;Basu,AnishaS;Makovey,Iryna;Wang,Peng;Zhui,Hui;Zorman,Christian;Ko,Wen;Damaser,MargotS
• 通讯作者: Damaser,MargotS

Automatic Drift Cancellation of Implanted Bladder Pressure Sensor.

植入式膀胱压力传感器的自动漂移消除。

• DOI: 10.1109/biocas.2015.7348430
• 发表时间: 2015
• 期刊: IEEE Biomedical Circuits and Systems Conference : healthcare technology : [proceedings]. IEEE Biomedical Circuits and Systems Conference
• 作者: Majerus,Steve;Damaser,MargotS
• 通讯作者: Damaser,MargotS

Implantable wireless battery recharging system for bladder pressure chronic monitoring.

用于膀胱压力长期监测的植入式无线电池充电系统。

• DOI: 10.1039/c5lc00821b
• 发表时间: 2015
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Young,DarrinJ;Cong,Peng;Suster,MichaelA;Damaser,Margot
• 通讯作者: Damaser,Margot

Wireless Implantable Pressure Monitor for Conditional Bladder Neuromodulation.

用于有条件膀胱神经调节的无线植入式压力监测器。

• DOI: 10.1109/biocas.2015.7348337
• 发表时间: 2015
• 期刊: IEEE Biomedical Circuits and Systems Conference : healthcare technology : [proceedings]. IEEE Biomedical Circuits and Systems Conference
• 作者: Majerus,Steve;Makovey,Iryna;Zhui,Hui;Ko,Wen;Damaser,MargotS
• 通讯作者: Damaser,MargotS