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 其病理发展机制尚不清楚。新的神经生理学实验需要解决 知识差距是在清醒的、行为正常的动物中进行的，而不是在麻醉下进行的，但是 在慢性实验期间监测膀胱功能仍然是一个挑战。可以使用当前的技术 通过手术放置的耻骨上导管无线监测膀胱压力，但这些技术 有限，因为它们不测量膀胱体积，这是一个重要的变量；导管可能会刺激 膀胱和混乱的数据；接收器线圈不能携带，这要求动物留在一个 数据收集的空间有限；而且这项技术不能扩大到未来的人类应用。一个 在清醒状态下进行慢性实验需要无线、无导管的膀胱压力和容量传感器， 表现为动物或人类，以阐明LUT在健康和疾病中的神经生理学功能。 我们已经开发了一种小型、无线、无导管压力传感器的原型 可充电，可传输连续压力数据。我们正在通过增加销量来巩固这一成功 感测和修改包装以放置膀胱内。这种新的设备，泌尿外科 意识活动监测器(UroMOCA)，将能够连续测量并无线传输 将压力和容量数据从膀胱内传输到一个小型可穿戴接收器单元。我们已经测试了一个 动物膀胱中的潜在包装形状因数，以证明它没有排出尿液，也没有阻塞 膀胱排空。我们还测试了一种估算体积的电导法，其中非常 小电流在两个外电极之间传递，而电压在两个内电极之间测量 在膀胱中的尿液中，我们用它来根据欧姆定律来确定电导。通过 知道电导、尿液的电导率和电极之间的间距，我们就能够 该方法可应用于UroMOCA。 这项提案的目标是制定和验证UroMOCA。这项研究的中心假设是 UroMOCA将为未来提供准确的膀胱压力和容量测量 由标准尿流动力学工具和意识行走测试验证的神经生理学实验 动物。拟议工作的目标是(1)开发用于膀胱内压力和 通过在我们以前的设计中添加体积测量并重新包装设备来进行体积测量 转化为新的外形因素；(2)通过急性毒性试验验证该装置的生物兼容性和功能 不存活和慢性非活动性动物实验。拟议研究的完成将提供一个 重要的工具，可与神经、心电图、肌电图仪或其他 录音，供研究清醒时下尿路神经控制的研究人员使用 流动实验。它还将为下一代神经调节疗法的设计提供信息，以改进 或者例如通过提供闭环LUT控制来恢复LUT功能。

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. Completion of the proposed research will provide an important tool, 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 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.