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

摘要 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，尚未得到很好的理解。新的神经生理学实验，以解决知识差距正在进行清醒，行为的动物，而不是在麻醉下，但监测膀胱功能在慢性实验仍然是一个挑战。目前的技术可用于通过外科手术放置的耻骨上导管无线监测膀胱压力，但这些技术是有限的，因为它们不测量膀胱体积，这是一个重要的变量;导管可能刺激膀胱并混淆数据;接收器线圈不是便携式的，这需要动物保持在密闭空间中进行数据收集;并且该技术不能扩展到未来的人类应用。一个无线的，无导管的膀胱压力和体积传感器是需要在清醒的，行为动物或人类的慢性实验，以阐明LUT功能在健康和疾病的神经生理学。 我们已经开发出一种小型无线无导管压力传感器的原型，该传感器可充电并可传输连续的压力数据。我们正在通过增加体积传感和修改膀胱内膀胱放置的包装来建立这一成功。这种新的设备，有意识活动的泌尿监测器（UroMOCA），将能够连续测量和无线传输压力和体积数据从膀胱内到一个小的，可穿戴的接收器单元。我们已经在动物膀胱中测试了潜在的包装形状因子，以证明其不会排泄，也不会阻碍膀胱排空。我们还测试了一种估计体积的电导方法，其中在两个外电极之间通过非常小的电流，并且在膀胱中包含的尿液内的两个内电极之间测量电压，我们使用该方法根据欧姆定律确定电导。通过了解电导率、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，并且该方法可以并入UroMOCA。 本提案的目标是开发和验证UroMOCA。本研究的中心假设是，UroMOCA将通过无线方式为未来的神经生理学实验提供准确的膀胱压力和容量测量，并通过标准尿动力学工具和有意识行走动物的测试进行验证。拟定工作的目的是（1）通过在我们之前的设计中增加体积测量并将器械重新包装为新的形状因子，开发用于膀胱内压力和体积测量的UroMOCA;（2）通过在急性非存活和慢性非卧床动物实验中进行测试，确认器械的生物相容性和功能。此外，我们正在利用我们的无线传感器平台开发一种肠道传感器系统，该系统将确定用于研究和诊断应用的肠道充盈度和活动。对于肠道传感，该项目将重点关注确定适当的感觉方式，传感器形状因子和确定肠道状态的策略。完成拟议的研究目标将提供重要的工具，可以与神经，心电图，肌电图或其他记录，用于研究下尿路或肠道的神经控制的研究人员在有意识的走动实验。它还将为下一代神经调节治疗的设计提供信息，以改善或恢复LUT功能，例如通过提供闭环LUT控制。

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.