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

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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.