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）： 脊髓损伤 (SCI) 后控制漏尿至关重要，因为 SCI 患者极易患压疮。接触尿液的压疮更容易受到感染，因为尿液会改变皮肤的 pH 平衡并降低对细菌入侵的抵抗力。感染压疮引起的败血症是 SCI 患者再住院或死亡的主要原因。 SCI 患者的特征是逼尿肌过度活动和横纹括约肌协同失调，导致尿液不受控制地漏出，使患者患接触性皮炎和感染性压疮的风险增加。此外，SCI 的膀胱并发症可导致自主神经反射障碍、肾功能衰竭和中风。因此，SCI后控制漏尿尤为重要。 阴部感觉通路的电刺激可以阻止 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，多种设备已获得 FDA 批准。然而，当电刺激系统的有效性由于习惯或适应始终开启的电刺激信号而减弱时，患者必须经常返回医生处调整其电刺激系统。仅在触发时进行刺激的条件或闭环刺激已被证明比开环连续刺激更有效，从而产生更大的膀胱容量并使用更少的功率。然而，由于目前还没有慢性膀胱传感器，因此条件刺激目前仅广泛用于使用基于导管的压力传感系统的研究目的。 在该项目最初的 VA Merit 资助期间，我们开发了一种微型、植入式、无线、无导管、电池供电、可充电压力监测器，用于慢性粘膜下植入，可为慢性条件刺激提供反馈。我们已经实现了最初提案期间的大部分目标。然而，应用压力监测仪为预防尿失禁提供闭环控制仍有几个障碍需要克服，包括评估植入的可行性、优化慢性植入的压力监测仪、创建区分重要膀胱事件和伪影的算法、验证我们的慢性植入微包装方法，以及在慢性体内模型中测试这种新颖的系统。这项经过广泛修改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，用于膀胱中慢性粘膜下植入，以实现 SCI 后的闭环膀胱控制。设计了四个具体目标来完成必要的工作： 1. 评估压力监测器植入的临床方面； 2.优化慢性植入植入式压力监测仪； 3. 开发区分重要膀胱事件和伪影的特征提取方法； 4. 开发用于压力监测器长期植入的微封装。完成拟议的研究将使我们处于有利地位，可以继续对我们的闭环控制系统进行临床测试，之后，我们将开始对我们的压力监测器进行临床试验。 公共卫生相关性： 脊髓损伤（SCI）患者的特征是出现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，如果持续接触尿液，可能会导致败血症，甚至可能导致死亡。此外，慢性膀胱反射亢进还可导致自主神经反射障碍和肾功能衰竭。目前，电刺激采用开环配置来治疗 OAB，但由于必须持续进行，因此效果会降低。我们开发了一种无线无导管压力监测器，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 患者膀胱控制的电刺激系统闭环控制提供必要的反馈。美国 25 万 SCI 患者中四分之一是退伍军人，并且每年新增 10,000 名 SCI 患者。因此，该提案与 VA 具有高度相关性。