Wireless Implantable Monitor for Improved Neuromodulation

描述(由申请人提供)： 脊髓损伤(SCI)后尿漏的控制是非常重要的，因为SCI患者对压疮非常敏感。暴露在尿液中的压疮更容易感染，因为尿液会改变皮肤的pH值平衡，降低对细菌入侵的抵抗力。感染压疮引起的败血症是脊髓损伤患者再次住院或死亡的主要原因。脊髓损伤患者的特点是出现逼尿肌过度活动和横纹括约肌协同失调，导致无法控制的尿漏，增加患者接触性皮炎和感染压疮的风险。此外，脊髓损伤的这些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，控制脊髓损伤后的尿漏是非常重要的。电刺激阴部感觉通路可以阻止脊髓损伤患者不想要的反射性膀胱收缩。开环持续电刺激可以抑制过度活跃的膀胱活动，FDA批准了几种设备。然而，当电刺激系统的有效性因适应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那里进行调整。仅在触发时才进行刺激的条件性刺激或闭环式刺激已被证明比开环持续刺激更有效，从而产生更大的膀胱容量和使用更少的能量。然而，由于慢性膀胱传感器目前还不可用，条件刺激目前仅被用于研究目的，使用基于导管的压力传感系统。在该项目最初的VA Merit资助期，我们开发了一种微型、可植入、无线、无导管、电池供电、可充电的慢性黏膜下植入压力监测仪，可以为慢性条件刺激提供反馈。我们已经实现了最初提议期间的大部分目标。然而，要应用压力监测器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器，创建区分重要膀胱事件和伪影的算法，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这一新系统。这项经过广泛修订的设计和开发更新方案的目标是实现这些目标，从而优化我们的压力监测仪，用于SCI后慢性粘膜下膀胱植入的闭环式膀胱控制。设计了四个具体的目标来完成必要的工作：1.评估压力监测仪植入的临床方面；2.优化用于慢性植入的植入式压力监测仪；3.开发用于区分重要的膀胱事件和伪影的特征提取方法；以及4.开发用于慢性植入的压力监测仪的微包装。拟议研究的完成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)患者的特点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(OAB)和无法控制的尿漏。这些患者患有压疮的风险很高，当持续接触尿液时，压疮可能会导致败血症，甚至可能死亡。此外，慢性膀胱反射亢进还会导致自主神经反射障碍和肾功能衰竭。目前在开环结构中使用电刺激来治疗OAB，但由于它必须持续开启，其有效性降低。我们开发了一种无线无导管压力监测仪，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，为脊髓损伤患者膀胱控制的电刺激系统的闭环控制提供必要的反馈。退伍军人占美国25万脊髓损伤患者的四分之一，每年有1万名新的脊髓损伤患者。因此，这项建议与退伍军人事务部具有很高的相关性。

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.