Development of Novel Cystometrics for Overactive Bladder

Aim 1. Validate an Urgency Meter and quantify urgency-volume relationship. Test the
hypothesis that the tension sensor output of urinary urgency can be objectively measured and
is reflected by the input of filling volume.

Aim 2. Quantify the bladder geometry-urgency relationship. Test the hypothesis that bladder
geometry (wall thickness, surface area, and shape) affects the load on the detrusor tension
sensor as reflected by objective changes in the output of urgency.

Aim 3. Quantify the dynamic compliance-urgency relationship. Test the hypothesis that dynamic
compliance (strain-history and activation-history dependent compliance) affects the load on
the detrusor tension sensor as reflected by objective changes in the output of urgency.

Aim 4. Quantify the spontaneous rhythmic contraction-urgency relationship. Test the
hypothesis that spontaneous rhythmic contractions affect the load on the detrusor tension
sensor as reflected by objective changes in the output of urgency.

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 is 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), an objectively 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 assess bladder geometry,
dynamic compliance, and spontaneous rhythmic contractions during the filling phase of
micturition. Our new cystometrics will include 1) a sliding scale Urgency Meter that will
allow patients to continuously record the tension sensor output of 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 output (urgency) of the detrusor
tension sensor, will be tested in clinical experiments involving accelerated hydration,
abbreviated cystometrics, and repeat-fill cystometrics, and extended-hold cystometrics.
Successful completion of this multi-PI proposal involving the combined skill sets of a
neuro-urologist and a mechanical engineer will allow for the development of novel cystometric
tests for the improved diagnosis and treatment of OAB and for the potential identification of
novel mechanistic targets in the pathophysiology of OAB.

Inclusion Criteria:

Study 1:

- Inclusion for Control Subjects:

- No urgency defined as scoring a "0" on the screening question 5A of ICIQ-OAB survey
instrument.

- Above 21 years of age.

- Healthy enough to undergo testing

- No Cognitive Impairment

- No vulnerable population

Inclusion for Heightened Urgency Group:

- Answer greater than or equal to 3 on question 5a of ICIQ-OAB survey instrument.

- Above 21 years of age.

- Healthy enough to undergo testing.

- Have no cognitive impairment.

- Not vulnerable population

Study 2, 3 and 4:

- Scheduled to undergo cystoscopy examinations for clinically indicated condition.

- Over 21 years of age.

- No cognitive impairment.

- No vulnerable population

Exclusion Criteria:

Study 1:

Exclusion for Control Participants:

- Prescription medications.

- Significant medical conditions.

- 21 years of age or younger

- Cognitive impairment.

- Vulnerable population.

- Scoring anything other than "0" on all screening questions on the ICIQ-OAB.

- Score less than or equal to 3 on question 5a of ICIQ--OAB.

Exclusion for Heightened Urgency Group:

- Significant medical conditions.

- 21 years of age or younger.

- Cognitive impairment.

- Vulnerable population.

- Score less than 3 on question 5a of ICIQ-OAB.

Study 2, 3, and 4:

- Not undergoing standard of care cystoscopy examinations for clinically indicated
conditions.

- 21 years of age or younger.

- Have cognitive impairment.

- Vulnerable population