Conscious ambulatory bladder monitoring to understand neural control of lower urinary tract function

有意识的动态膀胱监测以了解下尿路功能的神经控制

• 批准号: 10008010
• 负责人: DENNIS BOURBEAU
• 金额: $ 36.98万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10008010
• 关键词: Activities of Daily Living; Acute; Address; Ambulatory Monitoring; Anesthesia procedures; Animal Experiments; Animals; Biological Markers; Biomechanics; Bladder; Catheters; Chronic; Collaborations; Computer software; Confined Spaces; Conscious; Data; Data Collection; Detection; Development; Devices; Diagnostic; Disease; Electric Conductivity; Electrocardiogram; Electrodes; Electromyography; Electronics; Epithelial; Failure; Family Felidae; Felis catus; Future; Goals; Growth; Health; Human; Implant; In Vitro; Intestines; Investigation; Knowledge; Laws; Lower urinary tract; Measurement; Measures; Methods; Michigan; Microbial Biofilms; Modality; Monitor; Nerve; Operative Surgical Procedures; Organ; Pathology; Peripheral; Peripheral Nerves; Peripheral Nervous System; Preparation; Pressure Transducers; Request for Applications; Research; Research Personnel; Sensory; System; Technology; Testing; Time; Universities; Urethra; Urine; Urodynamics; Validation; Wireless Technology; Work; awake; biomaterial compatibility; data acquisition; design; experimental study; human subject; implantation; improved; innovative technologies; intravesical; irritation; neurophysiology; neuroregulation; next generation; pre-clinical; pressure; programs; prototype; relating to nervous system; response; sensor; success; tool; urologic; voltage

ABSTRACT Mechanisms underlying neural control of the lower urinary tract (LUT) in health and disease, including mechanisms of pathology development, are not well understood. New neurophysiology experiments to address knowledge gaps are being conducted in awake, behaving animals, rather than under anesthesia, but monitoring bladder function during chronic experiments remains a challenge. Current technologies can be used to wirelessly monitor bladder pressure via a surgically placed suprapubic catheter, but these technologies are limited because they do not measure bladder volume, which is an important variable; the catheter may irritate the bladder and confound the data; the receiver coil is not portable, which requires the animal to remain in a confined space for data collection; and the technology does not scale up to future human applications. A wireless, catheter-free bladder pressure and volume sensor is needed for chronic experiments in awake, behaving animals or humans to elucidate the neurophysiology of LUT function in health and disease. We have developed a prototype for a small, wireless, catheter-free pressure transducer that is rechargeable and can transmit continuous pressure data. We are building on this success by adding volume sensing and modifying the packaging for intravesical bladder placement. This new device, the Urological Monitor of Conscious Activity (UroMOCA), will be able to continuously measure and wirelessly transmit pressure and volume data from within the bladder to a small, wearable receiver unit. We have tested a potential packaging form factor in an animal bladder to demonstrate that it is not voided, nor does it obstruct bladder emptying. We have also tested an electrical conductance method of estimating volume wherein a very small current is passed between two outer electrodes and voltage is measured between two inner electrodes within the urine contained in the bladder, which we use to determine conductance from Ohm’s Law. By knowing the conductance, the conductivity of the urine, and the spacing between our electrodes, we were able to estimate bladder volume and this method can be incorporated into the UroMOCA. The goal of this proposal is to develop and validate the UroMOCA. The central hypothesis of this research is that the UroMOCA will wirelessly provide accurate bladder pressure and volume measurements for future neurophysiology experiments as validated by standard urodynamics tools and testing in conscious ambulating animals. The objectives of the proposed work are to (1) develop the UroMOCA for intravesical pressure and volume measurements by adding volume measurement to our previous design and repackaging the device into a new form factor and (2) validating the biocompatibility and function of the device by testing in acute nonsurvival and chronic ambulatory animal experiments. In addition, we are leveraging our wireless sensor platform to develop a bowel sensor system that will determine bowel fullness and activity for use in research and diagnostic applications. For bowel sensing, this project will focus on identifying appropriate sensory modalities, sensor form factor, and a strategy for determining bowel state. Completion of the proposed research objectives will provide important tools, which could be used in conjunction with nerve, electrocardiogram, electromyography or other recordings, for use by investigators studying the neural control of the lower urinary tract or bowel during conscious ambulatory experiments. It will also inform the design of next generation neuromodulation therapies to improve or restore LUT function, such as by providing closed-loop LUT control.

抽象的 健康和疾病中下尿路（LUT）的神经控制机制，包括病理发展机制，目前尚不清楚，但旨在解决知识差距的新神经生理学实验是在清醒、有行为能力的动物身上进行的，而不是在麻醉下进行的。慢性实验期间的膀胱监测功能仍然是一个挑战。目前的技术可通过手术放置的耻骨上导管来无线监测膀胱压力，但这些技术具有局限性，因为它们不能测量膀胱体积，而膀胱体积是导管可能会刺激的一个重要变量。这膀胱并混淆数据；接收器线圈不是便携式的，这需要动物留在有限的空间内进行数据收集；并且该技术无法扩展到未来的人类应用。需要对清醒、有行为能力的动物或人类进行长期实验，以阐明 LUT 在健康和疾病中的功能的神经生理学。 我们开发了一种小型、无线、无导管压力传感器原型，该传感器可充电，可以传输连续压力数据。我们在这一成功的基础上，添加了容量传感功能并修改了膀胱内放置的包装。意识活动泌尿监测仪 (UroMOCA) 将能够连续测量膀胱内的压力和体积数据并将其无线传输到小型可穿戴接收器单元。我们已经在动物膀胱中测试了一种潜在的包装形式，以证明它的可行性。不是我们还测试了一种估计体积的电导方法；在两个外部电极之间通过非常小的电流，并在膀胱内的尿液内测量两个内部电极之间的电压。根据欧姆定律确定电导 通过了解电导、尿液的电导率以及电极之间的间距，我们能够估计膀胱体积，并且该方法可以合并到 UroMOCA 中。 该提案的目标是开发和验证 UroMOCA。这项研究的中心假设是，UroMOCA 将为未来的神经生理学实验提供准确的膀胱压力和体积测量，并通过标准尿动力学工具和在有意识的行走动物中进行测试来验证。建议的工作包括 (1) 通过在我们之前的设计中添加体积测量并将设备重新包装成新的外形尺寸，开发用于膀胱内压力和体积测量的 UroMOCA；(2) 验证通过在急性非存活和慢性流动动物实验中测试该设备的生物相容性和功能，我们正在利用我们的无线传感器平台开发肠道传感器系统，该系统将确定肠道饱满度和活性，用于肠道研究和诊断应用。传感，该项目将重点关注确定感觉模式、传感器形状因素以及确定适当肠道状态的策略，完成拟议的研究目标将提供重要的工具，可与神经、心电图、肌电图或其他记录结合使用。 ,供研究人员在有意识的动态实验中研究下尿路或肠道的神经控制时使用，它还将为下一代神经调节疗法的设计提供信息，以改善或恢复 LUT 功能，例如通过提供闭环 LUT 控制。