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: 8203341
• 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/8203341
• 关键词: Acute; Algorithms; Ataxia; Autonomic Dysreflexia; Bladder; Bladder Control; Catheters; Cessation of life; Chronic; Clinical; Clinical Trials; Consumption; Contact Dermatitis; Decubitus ulcer; Detection; Development; Device Designs; Devices; Effectiveness; Electric Stimulation; Equilibrium; Event; Extravasation; FDA approved; Feedback; Frequencies; Funding; Future; Goals; Hyperreflexia; Individual; Infection; Kidney Failure; Lead; Medical; Methods; Modeling; Monitor; Morphologic artifacts; Nerve; Overactive Bladder; Pathway interactions; Patient Monitoring; Patients; Performance; Positioning Attribute; Prevention; Radio; Rattus; Reflex action; Research; Risk; Sampling; Sensory; Sepsis; Septicemia; Signal Transduction; Skin; Sphincter; Spinal cord injury; Spinal cord injury patients; Stress; Stroke; Surface; System; Techniques; Testing; Time; Urinary Incontinence; Urine; Veterans; Wireless Technology; Work; bacterial resistance; base; body system; design; digital; high risk; human subject; implantation; implanted sensor; improved; in vivo; in vivo Model; migration; neuroregulation; novel; pressure; research clinical testing; response; sensor; transmission process

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. PUBLIC HEALTH RELEVANCE: Spinal cord injury (SCI) patients characteristically develop detrusor overactivity and striated sphincter dyssynergia, leading to overactive bladder (OAB) and uncontrolled leakage of urine. These same patients are at high risk for pressure ulcers, which can lead to sepsis and potentially death when in continuous contact with urine. In addition, chronic bladder hyperreflexia can also lead to autonomic dysreflexia and renal failure. Electrical stimulation is currently used in an open loop configuration to treat OAB but the effectiveness is reduced because it must be on continuously. We have developed a wireless catheter-free pressure monitor for submucosal implantation in the bladder. In the proposed project, we will further develop it to provide the necessary feedback for closed loop control of electrical stimulation systems for bladder control in SCI patients. Veterans constitute one quarter of the 250,000 people with SCI in the U.S. and there are 10,000 new SCI patients each year. Therefore this proposal is of high relevance to the VA.

描述（由申请人提供）： 由于脊髓损伤（SCI）患者极易发生压疮，因此控制尿液渗漏非常重要。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。 公共卫生相关性： 脊髓损伤（SCI）患者的特征性发展逼尿肌过度活动和横纹括约肌协同失调，导致膀胱过度活动症（OAB）和不受控制的漏尿。这些患者患压疮的风险很高，当持续接触尿液时，压疮可能导致败血症和潜在的死亡。此外，慢性膀胱反射亢进也可导致自主神经反射障碍和肾功能衰竭。电刺激目前用于开环配置以治疗OAB，但有效性降低，因为它必须连续进行。我们已经开发了一种无导管的无线压力监测器，用于膀胱粘膜下植入。在拟议的项目中，我们将进一步开发它，为SCI患者膀胱控制电刺激系统的闭环控制提供必要的反馈。退伍军人占美国25万SCI患者的四分之一，每年有1万名新的SCI患者。因此，这一建议与退伍军人事务部具有高度相关性。