Doctor of Philosophy

dissertationPelvic floor disorders (PFD) affect one in four women in the United States. Elevated intra-abdominal pressure (IAP) during daily activity or strenuous physical activity has been identified as a risk factor in the prevalence of PFD. However, the relationship between IAP and physical activity remains poorly understood. Despite the lack of scientific evidence, clinicians oftentimes prescribe long-term activity restrictions to urogynecologic postoperative patients to minimize IAP, which is thought to lessen the load on the pelvic floor. Since many health benefits are associated with exercise, it is necessary to understand how IAP changes with activity in order to reduce risk to the pelvic floor while allowing women to be physically active. Current methods of measuring IAP include invasive catheters in the vagina, rectum, bladder, or stomach that are tethered to laboratory equipment and have been shown to have poor dynamic response. These characteristics limit the potential for tracking IAP during daily physical activity away from the clinic. The objectives of this research were to determine how intra-abdominal routine that may be adapted for postsurgical patients. Three phases of this work included (1) development of a wireless gel-filled intravaginal pressure sensor to accurately track intra-abdominal pressure, (2) testing the newly developed intravaginal sensor in benchtop and in vivo settings to determine the utility of sensors in real-world deployments, and (3) using the wireless intravaginal pressure sensor to characterize IAP during exercise and, based upon results, create a low intra-abdominal pressure routine that can be used to exercise while minimizing pressure load on the pelvic floor

Effect of Heavy Lifting with a Head Strap on the Pelvic Floor across the Menstrual Cycle

Background: Pelvic organ prolapse (POP) occurs in 10% of women in Nepal, even 6% of nulliparous women have symptomatic POP.1 This may be linked to the heavy lifting tasks performed by women using a head strap.2 This study explored the impact of hormonal changes on the pelvic floor when performing these tasks during each phase of the menstrual cycle. Methods: The study included 22 female Nepali participants with a mean age of 27.4(3.6) years; all were from rural villages and frequently carried with a head strap. Using intravaginal pressure transducers (IVT), the mean change in intraabdominal pressure (IAP) was found to be 37.1(4.3) cmH20 when lifting a load with a mean weight of 19.8(3.2)kg using a head strap. Lifting tasks were simulated with isometric ballistic lifts against a head strap secured to the plith with the participant lying supine. The mean increase in IAP from rest was 31.6(2.1)cmH20. Displacement of the pelvic floor was measured by transperineal ultrasound. Mean displacement of the pelvic floor at ovulation was 5.1(0.4)mm and a mean of 5.9(0.4)mm during the early follicular phase (p 0.03). Conclusion: during the early follicular phase, when basal body temperature and beta estrogen are lowest, the compliance of the pelvic floor is greatest. Repetitive lifting during this time may predispose some woman to POP

Biomechanics and Electromyography Inassessing Female Stress Urinary Incontinence

Introduction: Stress urinary incontinence (SUI), the involuntary urinary leakage associated with increases in intra-abdominal pressure, has a prevalence of 25–50% in U.S. women and the number of those who will undergo surgery will increase by half in the next forty years. SUI negatively affects the patient’s quality of life and places a great burden to the society. The functional anatomy of the continence mechanism remains vaguely understood. Hence my dissertation aims at offering a complete description of the pelvic floor muscles (PFM), the key contributor to the continence, thorough biomechanical and neurophysiological approaches. Methods: The biomechanical approach involves the development of a subject-specific finite element (FE) model of the female pelvic floor region. Subsequent computer simulations are targeted at finding the most contributive muscle to the urethral support function and evaluating current treatment strategies using a mini-sling. The neurophysiological approach involves the implementation of a novel surface electromyography (EMG) probe to acquire bioelectrical information of PFMs and the assessment of their innervations in healthy subjects and patients. Results: An FE pelvic floor model was developed which incorporates 40+ anatomical structural in the pelvis, representing the most complete model in the field. Simulation results showed that the vaginal walls, puborectalis, and pubococcygeus are the most important structures and that mid-distal post-urethral implantation represents the optimal location. Innervation zones of PFMs have been successfully identified and described for multiple PFMs. An high-density surface EMG-based motor unit number estimation approach was developed, providing a novel tool to evaluate the condition of neurologically impaired PFM. Conclusions: The combined information greatly advances our understanding of the physiology of PFM and would lay a firm foundation to novel, non-invasive, patient-specific interventional strategies in the future.Biomedical Engineering, Department o

IMPACT OF VAGINAL SYNTHETIC PROLAPSE MESHES ON THE MECHANICS OF THE HOST TISSUE RESPONSE

The vagina helps support the bladder, urethra, uterus, and rectum. A lack of support leads to pelvic organ prolapse, and vaginal delivery is a prevalent risk factor; however, there is little research on vaginal biomechanical properties. Despite numerous complications, clinical practice involves surgical repair with synthetic meshes. Complications can be partially attributed to our lack of knowledge regarding the mesh-tissue complex (MTC) after implantation. However, it is difficult to perform rigorous studies without utilizing animal models. Therefore, we evaluated how parity affected the mechanical properties of vaginal tissue in three animal models: rodent, sheep, and non-human primate (NHP) to compare their mechanically properties to parous women who typically undergo prolapse surgery. Parity negatively impacted the mechanical properties of the vagina in NHP, which were biomechanically similar to parous women, making it a suitable model for studying the effects of mesh implantation. Second, we examined the textile and structural properties of commonly used meshes (Gynemesh, UltraPro, SmartMesh, Novasilk, and Polyform) utilizing uniaxial and ball-burst tests. These meshes had significantly different porosity and structural properties. To investigate the host response, three meshes were implanted into the abdominal wall of the rodent and NHP, and on the vagina in the NHP. The MTC was removed, and the tissue contribution was calculated. We did not observe notable changes in the tissue properties following mesh implantation in the rodent; however, implantation of the stiffest mesh (Gynemesh) in the NHP resulted in an exhibition of a stress-shielding response manifested by inferior biomechanical properties of the abdominal and vaginal tissues. Less stiff meshes (UltraPro and SmartMesh) resulted in preservation of tissue properties. To gain insight into how mesh properties affect the tissue contribution, we began developing a finite element model. Utilizing the co-rotational theory with a fiber-recruitment stress-strain relationship, we could describe the behavior of SmartMesh and UltraPro. While an in-depth characterization of these meshes revealed multiple fiber populations, further development of modeling may be instrumental in closing the current knowledge gap. Ultimately, understanding the mesh-tissue interaction will improve clinical outcomes by identifying mesh properties that are essential for providing structural support while maintaining tissue integrity

Lower Urinary Tract Dysfunction

Lower urinary tract dysfunction (LUTD) is an umbrella diagnosis that covers the abnormalities of anatomy and function in the bladder, urethra, and, in men, the prostate. People with LUTD face a number of social, mental, and physical health effects due to the symptoms. Despite the increasing evidence in the assessment and management of lower urinary tract symptoms, it remains a challenge to bridge the gap between research evidence and clinical practice. In this book, each and every one of the authors presents a remarkable work for how to apply the evidence to clinical practice from different aspects. I hope this book is a key for every reader to open the door to LUTD

Integration of novel diagnostic techniques and in-depth characterisation of anorectal (dys)function in studies of healthy volunteers and patients with faecal incontinence

Introduction Large overlap in the range of values seen in health and disease limit the clinical utility of investigations which describe pathophysiological findings in faecal incontinence (FI). Aims The aims of this thesis were to: 1. investigate the prevalence of major disorders of anal motor and rectal sensory function in FI; 2. better describe stress FI; 3. expand knowledge of normal ranges and develop novel metrics to evaluate anorectal function using both contemporary and emerging diagnostic tests (Rapid Barostat Bag [RBB] pump and the functional lumen imaging probe [EndoFLIP®]); 4. develop understanding of (the role of) parity on anorectal function in health and FI; 5. investigate the interaction of continence mechanisms in healthy individuals. Methods Research methods used in this thesis include systematic review and meta-analysis, retrospective case-control and cohort studies, and a prospective study of anorectal function in health using contemporary and new technologies. Results Anal hypocontractility is the most common pathophysiological finding in FI, but rectal sensory dysfunction remains important, especially in men. Further, assessment of the cough response and amplitude of anal slow waves revealed subtle anal motor dysfunction not appreciated by traditional metrics. Stress FI is poorly researched but common, and appears to represent a more severe FI phenotype. For the first time, normal ranges for rectal compliance, capacity and sensation were generated using the RBB, and distensibility of the anal canal using EndoFLIP®. Prospective studies in health demonstrated limited impact of parity on individual metrics. Conclusion While routine clinical tests of anorectal function are useful for evaluating FI, identification of characteristics or metrics associated with progressive decline in function may prove useful for detecting individuals at risk of FI. Research in healthy populations remains relevant to maintain pace with advancing technology; the concept of normality is still an important part of clinical care

Design and Testing Novel Wearable Instrumentation for Assessing Pelvic Floor Function and Exploring Continence Mechanisms

Urinary incontinence (UI) and fecal incontinence (FI) affect 20% of North Americans, with a higher prevalence in women and the elderly. The prevention and treatment of these conditions unfortunately leaves much to be desired, despite the $88B and$49B annual U.S. costs associated with managing UI and FI, respectively. Recent research suggests that the major problem lies with the sphincters themselves, rather than other structures. More needs to be learned about how age, injury and disease affect these sphincters. The literature is reviewed in Chapter 1, knowledge gaps are identified and testable hypotheses formulated. In Chapter 2, we describe the first subject-specific, 3-D, biomechanics model of the urethra capable of contracting the three individual muscle layers along their lines of action. This was developed to better understand how the different layers contribute to urethral closure during activities of daily living. Exploratory studies of the vascular plexus suggest a role in affecting functional urethral length. While this model helps one to understand which muscles contribute to continence, it could not provide insights into the amount of urine leaked which, after all, is what bothers women the most. In Chapter 3, we describe a novel approach for quantifying urine leakage both in and out of the clinic. While one can presently obtain micturition flowmetry in the seated posture in the clinic, this precludes the possibility of any information being gathered on leakage during activities of daily living (ADL). Instead, a patient must keep a leakage diary for several days, which unfortunately is prone to recall bias and other errors. Therefore, a novel wearable personal uroflowmeter (PUF) was invented and developed to attach over the urethral meatus in women to collect urine flow rate and leakage data during ADL leakage episodes. This was connected with a waist-mounted inertial measurement unit (IMU) to provide data on the pose and ADL associated with the volume of each leakage episode. Chapter 4 describes the first-in-human testing of the PUF in women in and outside the clinic, demonstrating the feasibility of wearable uroflowmetry. Moreover, theoretical studies of labia majora coaptation suggest that the labia can inadvertently form a potential reservoir for urine leakage during a sneeze or cough. This insight will help eliminate the confusion over the relationship between the ADL causing the passage of urine through the urethra (i.e., a cough) and that which later causes urine to leak from the labial reservoir (i.e., rising from a chair). A few incidents of this phenomenon were measured for the first time while testing the PUF in women. In terms of anorectal function, Chapter 5 reports the design and development of a disposable point-of-service instrumented anorectal manometry glove (“digital manometry”, DM) for testing anal sphincter and anorectal function at an order of magnitude lower cost than the standard high resolution anorectal manometry (HR-ARM). Chapter 6 reports first-in-human testing of the DM device in patients with and without FI and chronic constipation. Comparisons of the DM and HR-ARM results show reasonable agreement. In addition, the DM also provided myoelectric information useful for identifying paradoxical contraction of the anorectal muscle in patients with dyssynergic defecation. In summary, the dissertation provides novel and inexpensive approaches for a clinician or researcher to better document and understand incontinence.PHDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163121/1/attari_1.pd

Rethinking the artificial urinary sphincter : from current knowledge to the development of a new smart device

Background: Urinary incontinence (UI) plagues millions of women and men worldwide, leading to social stigma, low self-esteem, poor quality of life, and affects their loved ones. In women, frequent causes include childbirth, and in men prostate surgery for benign or malignant disease. In both genders congenital anomalies, neurological diseases, pelvic surgery, and radiation therapy are incriminating factors. Many patients struggle daily with pads and/or diapers, often unaware of the existence of a surgical cure. Since the seventies, the AMS 800Ô (Boston Scientific - Marlborough, Massachusetts, USA) artificial urinary sphincter (AUS) has been the reference to treat severe male stress UI (SUI) secondary to intrinsic sphincter deficiency (ISD). In women, it constitutes a second-line option, the mid-urethral sling (MUS) being recommended as first-line surgical therapy in moderate to severe cases. However, although efficient, it has several drawbacks, namely poor ergonomics, untailored status to patients’ physical activities, high revision and explantation rates. Aims: To solve the above issues, a novel electronic AUS was incepted in France in 2007. This thesis tells the modern developmental journey of this device for severe SUI treatment. The objective is three- fold: to conduct a review of the current AMSÔ in both genders to identify potential literature gaps to identify and analyze data resulting from bench tests and clinical studies, and to conduct pre-clinical feasibility, performance and safety studies on human cadavers and animals prior to FIM studies. The 6 constituent papers present the results of the process rethinking the current AMS 800Ô known today, from State of the Art (papers I-III) to the design stages (paper IV) and subsequent pre-clinical implantation phases (papers V and VI) prior to the First in Man study, which eventually leads to the obtention of CE marking. Material, Methods, and Results: In Paper I, a systematic literature review of AMS 800Ô implantation in women with non-neurogenic severe SUI, non-extant to date, was performed. The 12 articles included showed a very low level of evidence, result heterogeneity in performance and safety outcomes and highlighted the need for post- market studies. Paper II addressed the absence of standardized continence outcome measurement tool, essential to homogenize functional reported outcomes data, but also crucial for defining the primary outcomes of the FIM study. We retrospectively assessed the 24- hour pad weight test in 180 men treated with primary AUS for PPUI. Secondarily, its correlation to quality-of-life was analyzed. Thirdly (Paper III), we retrospectively evaluated long-term continence and safety results of transscrotal versus transperineal (TP) primary AUS implantation in 183 men with PPUI in a single center. No statistical difference in performance outcomes was seen; however, the TP technique appeared to present worse long-term safety results. In Paper IV, we dimensioned the novel AUS by prospectively measuring the exact in vivo volume taken by the AMS 800Ô occlusive cuff after its pressurization at implantation. We found that the larger the cuff, the greater the accommodated volume, which did not surpass 1 cc. Therefore, the final prototype could be designed, an essential developmental milestone. In paper V the usability and performance of the novel AUS was established, in accordance with current FDA and European regulations on AIMDs in development. The device’s usability and performance were shown in 8 anatomical subjects, using randomly obtained urodynamic maximum urethral closure pressure ranges, equivalent to those of the AMS 800Ô. In Paper VI, we ascertained the novel device’s feasibility of implantation and histopathological safety in an animal pilot study using two wether models. The study showed the suitability of the models, the device’s ease of implantation and the absence of peri-or postoperative, and histopathological adverse events. We could therefore safely consider a Pivot study. Conclusion: Developing a novel AUS is a lengthy, expensive, and regulatory challenging process. In the ‘State of the Art’, essential to assess the ‘Gold standard’, we identified three literature gaps relevant for the risk analysis and evaluated similar competing devices. We showed a fine example of the application of ‘in vivo’ clinical study to the design of the smart AUS device. These initiated the required pre- clinical studies prior to FIM trials, demonstrating device feasibility, performance, and safety. the importance of post-market studies was also highlighted, and we strive to soon deliver a safe and efficient electronic device, tailored to the patient’s needs, whilst abiding to current regulations