The Detrusor Tension Sensor: A Model for Novel Cystometrics in Overactive Bladder

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 DESCRIPTION (provided by applicant): Urinary urgency is the key symptom in Overactive Bladder (OAB) that occurs during the filling phase of micturition, and increased detrusor wall tension is thought to be a critical factor in the pathophysiology of OAB. However, because pressure increases little during bladder filling and does not reflect changes in detrusor wall tension, true filling phase physiology cannot be evaluated during clinical cystometrics. Thus, objective assessments of OAB using standard clinical cystometric testing are difficult or impossible. Furthermore, evaluation of OAB using verbal sensory thresholds recommended by the International Continence Society are subjective and poorly defined. Thus, there is a pressing need for a mechanistically relevant diagnostic test of OAB that incorporates objective metrics for the direct evaluation of detrusor wall tension. Using a systems model of the filling phase of micturition, the detrusor smooth muscle and its in-series tension sensitive afferent nerves can be represented as a tension sensor with a definable input (volume), a continuously measurable output (urgency), and objectively measurable biomechanical parameters that affect the load on the tension sensor. Based on our previous investigations and the work of others, we have identified the following biomechanical parameters that can directly affect the load on the detrusor tension sensor during filling: bladder geometry, dynamic compliance, and spontaneous rhythmic contractions. In the current proposal, we will develop novel cystometric tests to identify 3 new tension-mediated OAB sub- categories (geometry-mediated, dynamic compliance-mediated, and spontaneous rhythmic contraction mediated) and a non-tension-medicated sub-category due to alterations in nervous system processing. Our new cystometrics will include 1) a sliding scale Urgency Meter that will allow patients to continuously record the tension sensor output of acute urgency, 2) two and three dimensional bladder ultrasonography to provide real- time measurements of bladder geometry that will be used to measure the effect of geometry and used for dynamic compliance calculations, and 3) Fast Fourier Transform (FFT) analysis to objectively measure filling phase spontaneous rhythmic contractions. These new metrics will provide a quantitative mechanistic link between OAB symptomatology and detrusor function, and we will use these new metrics to identify tension- mediated and non-tension mediated sub-groups of OAB. In this proposal, our central hypothesis, that measurable biomechanical parameters can directly affect the load on the detrusor tension sensor, will be tested in clinical extended cystometrics experiments on subjects with no, low, and high urgency. Successful completion of this multi-PI proposal involving the combined skill sets of a neuro-urologist and a mechanical engineer will lead to the development of novel cystometric tests for improved OAB diagnosis and treatment and for the potential identification of novel mechanistic targets in the pathophysiology of OAB.