Project Summary: There is growing recognition that overactive bladder (OAB) is not a single clinical entity but may actually represent points on a continuous spectrum. The underlying mechanisms behind the OAB spectrum are poorly understood and likely multifactorial. In addition, the prevalence of OAB is staggering, affects large portions of the adult population, and contributes to significant morbidly and quality of life impact. Multi-channel urodynamics (UDS) have been the gold standard for the evaluation of OAB and other lower urinary tract symptoms for decades. However, UDS are invasive, non-physiologic, and poorly reproducible. In addition, the test provides only limited information regarding the function of the detrusor muscle during the filling phase of the micturition cycle. In our previous R01, we developed ultrasound metrics to improve OAB sub-typing based on bladder biomechanical factors of shape, compliance, and rhythm and showed how these factors can affect the underlying detrusor tension sensor. However, critical research objectives remain and include the: 1) development less- invasive and more physiologic next-generation urodynamics, and 2) development of novel tools to provide improved information about detrusor muscle function and its position on a dynamic elasticity spectrum. Our preliminary data demonstrates how ultrasound can be used to measure biomechanical bladder properties and provide a non-invasive means to quantify bladder wall micromotion. In addition, we have shown how extrinsic strain applied to the bladder wall or intrinsic bladder wall muscle activity work in opposition in the regulation of bladder wall tone, a process that we term the “dynamic elasticity equilibrium.” According to our conceptual model, extrinsic strain acts as a break to acutely decrease detrusor wall tone, and intrinsic muscle activity acts as an accelerator to acutely increase detrusor wall tone. In this proposal, we will use a multi-disciplinary approach combining urology and mechanical engineering to achieve our critical research objectives and test our dynamic equilibrium hypothesis using a pre-clinical approach using in-vitro and in-vivo porcine bladders in two aims which will 1) Develop novel techniques to quantify dynamic elasticity in response to extrinsic strain applied to the bladder wall, and 2) Develop novel techniques to quantify dynamic elasticity in response to intrinsic muscle activity within the bladder wall. Data from these preclinical studies will then be leveraged in future translational studies in human urodynamics. SPECIFIC AIMS: There is growing recognition that overactive bladder (OAB) is not a single clinical entity but may represent points on a continuous spectrum1-3. The underlying mechanisms behind the OAB spectrum are poorly understood and likely multifactorial4. In addition, OAB prevalence is staggering5,6, affects large portions of the population, and contributes to morbidity and quality of life impact7. Multi-channel...