Ambulatory Bladder Monitoring After Spinal Cord Injury

It is frequently acknowledged that while much of spinal cord injury (SCI) scientific research community has focused their efforts on the restoration of walking abilities, there is insufficient attention paid to one of the most impactful consequences of SCI: bladder dysfunction. Bladder dysfunction has such a huge impact on quality of life after SCI, that many would prioritize the recovery of bladder function over the recovery of walking. Also, there are massive costs associated with managing secondary complications such as urinary tract infections, kidney stones, and - most importantly - chronic kidney failure. Currently, it is recommended that individuals living with SCI undergo an annual evaluation of their bladder with urodynamic studies (UDS), specifically filling cystometry. In filling cystometry, catheters are inserted into the bladder, which is then filled with water/saline, and bladder pressures are measured. While filling cystometry is the standard of care and the best urodynamics test currently available, it has many recognized limitations. Filling cystometry produces only a snapshot of bladder function based on a single fill-and-emptying cycle, and usually is done only once per year. Instead of the bladder filling naturally, it is artificially filled through the catheter, and at non-physiologically high rate, which itself can cause artefacts and may even induce autonomic dysreflexia. Finally, filling cystometry requires specialized personnel working in the expensive clinic setting that the person with SCI must then travel to. Such travel for able-bodied individuals may seem trivial, but to a person with SCI, it can be a huge challenge.

To overcome some of these limitations of filling cystometry, our multidisciplinary team representing neuroscience and spinal surgery (B. Kwon), biomedical engineering (M. Damaser, S. Majerus), and urology (L. Stothers, A. Kavanagh) proposes the translational development of the UroMonitor - a device conceived by Dr. Damaser that can be inserted into the bladder for wireless monitoring, even in the home setting. The UroMonitor would represent the first wireless, catheter-free bladder monitoring device and would provide physiologic monitoring of bladder function during natural bladder filling (versus the artificial retrograde filling of standard UDS), in the individual's home environment (versus the clinic), over a continuous period of time (versus a single bladder fill-and-emptying cycle). This will provide clinicians with a more comprehensive picture of the individual's physiologic bladder function and allow for more appropriate treatments.

While the field has depended upon rodent models of SCI for therapeutic development, such small animals are clearly inadequate for the development of novel human-sized devices such as the UroMonitor. Here, we will utilize our pig model of SCI to evaluate the UroMonitor device and prepare it for human use. The pig has a much larger bladder than the rat, making it far more suitable for the preclinical testing of such devices. Importantly, we are able to conduct filling cystometry in awake pigs using the same urodynamics equipment used clinically.

To develop the UroMonitor technology and bring it forward toward human SCI, we will conduct a preclinical study in the pig model of SCI and also a small human study. We first want to assess how well the UroMonitor measures and transmits pressure data in comparison to the 'gold standard' filling cystometry. The UroMonitor will be inserted and a filling cystometry study conducted to determine how well the pressures match. This comparison between the UroMonitor and filling cystometry will then be repeated after SCI. We also want to assess how well the UroMonitor measures and transmits data in the 'natural environment.' The pigs will also have a pressure monitoring device surgically implanted into the wall of the bladder that can transmit pressure data to a computer while the animal is awake and in its pen. By leaving the UroMonitor in place for 1 week and comparing it to this surgically implanted device, we will be able to determine how well the UroMonitor measures pressure while the animal is in its 'normal' environment. Finally, we will conduct a small pilot study in which the Uromonitor will be inserted into a small cohort of SCI individuals while they are having their annual urodynamic studies, to assess the safety, feasibility, and tolerability of UroMonitor insertion.

Our overall goal is to develop the UroMonitor device and conduct the first human testing of this novel technology. This project has considerable translational potential, as it aims to establish a novel, bladder monitoring sensor that would offer a paradigm-shift in how bladder function is assessed. From an impact perspective, this project has a chance to change the standard UDS paradigm of testing. Little has changed with UDS technology since its development after World War II, when pressure-based systems using artificial retrograde filling were first introduced. The UroMonitor offers a potential paradigm shift, by employing continuous, real-time monitoring of bladder pressure with natural filling. This is well-aligned with the FY18 SCIRP Focus Area of 'Bladder dysfunction, bowel dysfunction, and neuropathic pain,' which 'includes developing and testing interventions such as drugs, devices, and rehabilitation strategies.'