Novel Assessment Techniques for in vivo Bladder Physiology

Neurological and functional bladder disorders cause significant morbidity and detriment to the quality of life. These disorders cause lower urinary tract symptoms which affect up to 45.7% of the world population. Neurological bladder disorders due to spinal cord injury and multiple sclerosis in some cases cause life-threatening urological complications. Functional bladder disorders in the absence of nervous system pathology present with moderate-to-severe symptoms in 34.9% of patients. Assessment of these disorders are often challenging, with various examination methods employed including symptom scores, bladder diary, uroflowmetry and urodynamics.

Urodynamics is commonly used to describe a combination of tests aimed to elucidate the underlying pathophysiology of the lower urinary tract disorder. One routine urodynamic test, filling cystometry, continuously measures bladder pressure in response to filling of the bladder. Another test, pressure flow study, records this pressure during voiding along with other parameters. Urodynamics using telemetry from implanted sensors in primates provides recording for long periods without anesthesia. Surgery to implant the telemetric sensors precludes usage in humans, therefore ambulatory urodynamics in patients for clinical problems is still limited to urethral catheters.

To further clarify bladder (dys)function, pressure measurements are combined with measurement of electrical muscle activity (electromyography) and x-ray bladder imaging. This investigation is commonly referred to as video urodynamics. However, measurements with this method only reflect summation of total bladder activity, and is unable to discern differential contribution from various parts of the bladder.

The bladder has contrasting roles in voiding and storage phases of the micturition cycle. During voiding, bladder contraction is observed as a synchronous contraction of the entire organ. In contrast, during the storage phase the bladder functions as a flexible compliant vessel for urine storage. Studies during this phase have shown that separate parts of the bladder exhibit localized contractions and elongations with variable propagation. This autonomous activity of the bladder has been observed in ex-vivo animal models. Furthermore, in-vivo studies have shown alterations in autonomous myogenic activity may play a role in the pathogenesis of urgency symptoms.

Two different sensors will be used to study the bladder in this project. A miniature sensor in form of a pill, which can be implanted through minimally invasive endoscopy (cystoscopy) has been developed. This sensor allows ambulatory monitoring without surgical implantation. The newest design of this sensor will feature wireless powering and communication system thus reducing the components on the pill and consequently its size.

The second sensor is an accelerometer in biocompatible packaging implantable in the bladder submucosa. This sensor has successfully been used to acquire acceleration signals of the heart. Therefore, we expect application of this sensor in the bladder will provide mechanical insight into bladder wall motion with 3 dimensional data.

A suitable animal model for testing these microelectronic sensors should closely resemble the human lower urinary tract. Gottingen minipigs are purpose bred and widely used in research. Micturition volume of these animals closely resemble human data. The aim of this thesis is to study the application of the wireless pressure sensor and acceleration sensor in animal models of normal physiology and pathological conditions.