Physiological Testing of Lower Urinary Tract Function
Although conducting lower urinary tract testing in animals, particularly rats, is relatively common, many tests are not standardized, and test selection is usually ad-hoc and incomplete. Thus, the objective of this project is to develop a comprehensive and repeatable testing suite for characterizing lower urinary tract function in rats.
In future work, this comprehensive testing suite will be used to characterize lower urinary tract function in a variety of rat models such as older rats, diabetic rats, hypertensive rats, etc. These efforts will help us understand the types of urinary tract dysfunction that are implicitly being chosen when using each of these models. With good physiological characterization, we can begin to explore the relationship between physiological measurements and gene expression, which will support efforts to simplify and improve phenotyping approaches in humans. Additionally, by improving our understanding of these models, we can better understand physiological conditions that are indicative of the success and failure of various therapeutic modalities.
Abstracts
Braun J, Hokanson JA. Initial Experience Conducting Void Spot Assay in Rats. SUFU 2023, March 7–11, Nashville, TN
He W, Hokanson JA. Impact of Bladder Filling Rate on Cystometric Variables in Anesthetized Rats. SUFU 2023, March 7–11, Nashville, TN
Predicting Urinary Continence Status
Treatment plans for various forms of urinary dysfunction in humans typically are not patient specific. Instead, patients proceed from one therapy to another until they find something that works. This is because most relevant treatments are designed to treat symptoms, as opposed to a specific underlying pathophysiology. As a result, treatment of urinary dysfunction can be frustrating for patients and time consuming and increases healthcare costs.
The use of machine learning and advanced statistical methods promises to improve the way we diagnose and treat urinary dysfunction. In this project, PDAT Lab is reanalyzing data from large multi-site randomized clinical trials that examined the use of sacral nerve electrical stimulation (neuromodulation) and the injection of botulinum toxin (Botox) into the bladder (intravesical) for treatment of urinary urgency incontinence. Specifically, PDAT will be evaluating data from the ROSETTA and ABC trials.
With the ROSETTA data, PDAT is also examining what utility urodynamics data (physiological testing of the bladder) provides beyond that which we glean from looking at other standard clinical variables such as age and weight. More specifically, urodynamics consists of time-series data (e.g., bladder pressure over time/bladder volume) rather than single measurements (e.g., weight at the time of surgery). We believe these signals may contain multiple “features” that may be indicative of how someone responds to treatment that can be extracted using signal processing techniques. The utility of urodynamics in guiding the treatment of non-cancerous, idiopathic urological conditions, particularly incontinence, is hotly debated. Thus, a critical question we are asking with this study is whether this physiological testing improves our ability to predict how someone would respond to sacral neuromodulation and intravesical Botox treatments.
This project is sponsored by a K01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). As a training grant, the K01 also supports Dr. Hokanson's efforts to establish himself, more generally, in the field of non-cancerous pelvic health.
Representative Publications
Organ-Based Phenotyping
PDAT Lab also participates in NIDDK’s Lower Urinary Research Tract Network, also known as LURN, which is a multi-site study that focuses on trying to improve phenotyping of patients. A subset of that project, LURN Organ, focuses on physiological testing to differentiate women with and without urinary urgency and urinary urgency incontinence. Testing at sites has begun, and PDAT is playing a critical role in data analysis, particularly with respect to urodynamics data. We expect these efforts will help us better understand why patients have symptoms and how we might improve treatments by better targeting of specific patient specific pathologies.This project is sponsored by a U01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) via a subcontract with Duke University.