Research

Biomechanics and Neuromuscular Control of the Lower Urinary Tract and Female Pelvic Floor:

In the Urological Biomechanics Laboratory, we investigate the causes of and potential treatments for pelvic floor dysfunction. Our primary focus is the investigation of stress urinary incontinence (SUI), the unwanted leakage of urine due to increased abdominal pressure such as when laughing or coughing. SUI is a disabling condition that is endemic among older women, primarily those who have given birth vaginally. Treatments include diapers, pelvic floor muscle exercises (Kegels), injections of collagen and bulking agents, and surgery. Ten percent of all women will undergo surgeries for pelvic floor disorders and one-third of those surgeries will need to be revised. Therefore, there is a need for new treatments and preventative measures for SUI and other pelvic floor disorders of women.

Models of Stress Urinary Incontinence:

We are working with several different rat models of SUI to determine the mechanisms of injury that occur in vaginal delivery of children and devise methods of treating and/or preventing development of SUI. These methods could include facilitation of innate stem cell homing to the pelvic floor organs and tissues; treatment of blockers of AGE accumulation in diabetics; hormonal supplementation; or use of neuroregenerative agents. All these methods are presently under investigation in the laboratory.

In collaboration with the laboratory of Firouz Daneshgari, M.D., we are investigating possible mechanisms of SUI development in women with diabetes. Diabetic women have a higher incidence of incontinence than either diabetic men or women without diabetes. We have hypothesized that this is because of a decreased ability to recover from traumatic injuries to the pelvic floor during vaginal delivery of children. We are presently investigating the biochemical and molecular events that lead to slowed recovery in diabetics and that could be reversed with targeted treatments.

Genetic Mouse Models of Female Pelvic Floor Disorders:

We are using a knock-out mouse models that demonstrate symptoms of female pelvic floor disorders to investigate the role of elastin in development of these conditions. Elastin homeostasis is disrupted in mice genetically missing the enzyme Loxl1. These mice develop pelvic organ prolapse and associated voiding dysfunction in a pattern strikingly similar to that in women: after deliver of pups or when aged. We are characterizing this mouse model and investigating its potential for use in identifying those patients most at risk for pelvic floor disorders as well as in development of new treatments for female pelvic floor disorders.

Functional Virtual Reality Model of the Female Pelvic Floor:

We are in the initial stages of developing a functional, patient specific model of the female pelvic floor.  Current research in this area is focused in three main areas:

• Identifying optimal Magnetic Resonance Imaging techniques for acquiring high quality images of the structures of the pelvic floor
• Development of semi-automatic techniques to segment out the anatomical data of the pelvic floor structures for use in the construction of patient specific three dimensional models of these structures
• Functional modeling of the mechanics of the organs and musculature of the pelvic floor

The resulting virtual reality model will serve as a tool for use in teaching, research, and surgical simulation  

Novel Methods of Monitoring Lower Urinary Tract Function:

We have begun development of a bladder sensor which will enable wireless, catheter-free, ambulatory Urodynamics measurements; and development of the wireless intracavity micro-manometer (WIMM) for pressure measurement in a variety of organs.

Investigation of Fecal Incontinence:

Fecal incontinence is a debilitating condition which affects men and women. However, it is more common in women and often occurs in conjunction with urinary incontinence. Women are more likely to have fecal incontinence due to direct or stretch injury to the anal sphincter and pudendal nerve injury from birth trauma incurred during vaginal delivery. Other causes include direct trauma, trauma during various rectal and anal procedures, birth defects, stroke, spinal cord injuries, irradiation to the anal area and pelvis, dementia and multiple sclerosis.

The rat anal internal sphincter is surprisingly similar to that of the human internal anal sphincter which makes this animal very suitable for this kind of study. We are currently conducting a research investigation in this area and our review of literature showed that there were no existing studies using animal models to test therapeutic options. We are investigating use of the rat to study the effects of direct anal sphincterotomy and pudendal nerve injury on anal sphincter structure and function.

The long term goal of this project is to develop clinical treatment protocols that can be used for incontinent patients based on preclinical testing performed on these animal models.