Development of 21st Century Concepts and Tools for Quantifying Urethral Failure Mechanisms that Cause Urinary Incontinence

开发 21 世纪量化导致尿失禁的尿道衰竭机制的概念和工具

基本信息

批准号：
10449216
负责人：
JAMES Anthony ASHTON-MILLER
金额：
$ 113.51万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-18 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10449216
关键词：
3-Dimensional Accelerometer Adult Affect Age American Anatomy Assessment tool Atlases Bladder Blood Vessels Catheters Cells Childbirth Communities Complex Computer Models Data Development Diabetes Mellitus Disease Distress Elderly Elements Equipment Event Failure Female urethral structure Genetic Image Imaging technology In Vitro Incontinence Individual Injury Maps Measurement Measures Modeling Morphologic artifacts Muscle National Institute of Diabetes and Digestive and Kidney Diseases Organ Physics Physiological Play Probability Process Race Research Research Personnel Resolution Resources Role Scanning Science Sensory Site Sphincter Stigmatization Stress Stress Urinary Incontinence Structure Structure-Activity Relationship System Technology Testing Time Ultrasonography United States National Institutes of Health Urethra Urethral sphincter Urge Incontinence Urinary Incontinence Woman Work advanced disease age effect cost design elastography experience in vivo intravesical kinematics mechanical properties new therapeutic target next generation novel pressure sensor sensor technology social stressor therapeutic target tool ultrasound urinary

项目摘要

Abstract Approximately “one in ten U.S. adults suffer from daily urinary incontinence; most of those affected are women” (NIDDK). Hence 12.6 million American women are afflicted by this distressing and socially stigmatizing problem, at a cost of $88.2 billion dollars annually. Despite the importance of this condition, cure rates in NIH- sponsored trials for stress and urge incontinence remain at 50% or lower. Why? The current conceptual framework on which treatments are based maintains that 1) stress incontinence is caused by poor urethral support, and 2) urge incontinence is caused by abnormal bladder contractility. Paradigm-shifting research by our group shows that the urethral sphincter complex, long overlooked as a causal factor, is responsible for 50% of stress incontinence and also plays a critical role in urge incontinence. Progress in understanding how the urethral closure mechanism works is currently hindered by two factors: 1) current testing strategies that are based on outmoded, simplistic, and artifact-prone 1960s technology, and 2) the lack of a detailed understanding of urethral structure-function relationships needed to guide research. AIM 1: Develop a state-of-the-art battery of urethral sensorimotor and vascular assessment tools: We will produce and validate novel measurement strategies using state-of-the-art sensor and advanced imaging strategies. These tools will include: a) an ultraflexible, microscale, multisite urethral pressure catheter; b) a physiologic urethral sensory testing apparatus; and c) a miniature wearable uroflowmeter and a daily activity monitor. AIM 2: Develop advanced ultrasound imaging equipment and strategies: The structure and function of the urethra is easily accessed by ultrasound, yet strategies and equipment to evaluate it are limited. In this Aim, we will develop: B-mode for dynamic anatomy, Doppler for vascular flow quantification, and elastography for urethral wall mechanical properties to measure real-time urethral kinematics that can be used by AIMS 1 & 3. AIM 3: Develop a multiscale 3D anatomical atlas and high-fidelity urethral multiphysics computer model for simulating how changes in individual structures and the effects of age and disease processes affect urethral function. We will a) produce the first in vitro 3D multiscale probability map and in vivo high-resolution MR scans of the female urethra. These data, along with emerging data from AIMS 1 & 2, will be used to b) create and validate the first finite element multiphysics urethral model that can be used by researchers to investigate how changes in individual urethral structural and functional parameters affect urethral closure pressure. The technical and conceptual tools provided by this work will stimulate research and launch hypothesis testing to clarify how the continence margin is determined and how age, diabetes, childbirth, race, genetics, and other factors affect urethral failure in women. This work will reveal currently unexplored therapeutic targets and bring science to the urethra's critical, but long overlooked, aspect of continence function.

抽象的大约“十分之一的美国成年人患有日常尿失禁；其中大多数是女性” (NIDDK) 因此，有 1260 万美国女性遭受着这种痛苦和社会耻辱的折磨。尽管这种情况很重要，但 NIH 的治愈率却高达 882 亿美元。为什么压力性尿失禁和急迫性尿失禁的赞助试验比例仍保持在 50% 或更低？当前治疗所依据的概念框架认为：1) 压力性尿失禁是尿道支撑不良引起；2）急迫性尿失禁是膀胱收缩力异常引起的。我们小组的范式转变研究表明，长期以来被忽视的尿道括约肌复合体造成 50% 压力性尿失禁的原因，并且在急迫性尿失禁中也起着关键作用。目前，两个因素阻碍了对尿道闭合机制工作原理的理解：1) 当前的测试策略基于过时、简单且容易出现伪影的 20 世纪 60 年代技术，以及 2) 缺乏对指导研究所需的尿道结构与功能关系的详细了解。目标 1：开发一套最先进的尿道感觉运动和血管评估工具：我们将使用最先进的传感器和先进的成像技术制定并验证新颖的测量策略这些工具将包括：a) 超柔韧、微型、多部位尿道压力导管；b) a) 生理尿道感觉测试仪；和 c) 微型可穿戴尿流量计和日常活动监视器。目标2：开发先进的超声成像设备和策略：超声成像设备的结构和功能超声波很容易进入尿道，但评估尿道的策略和设备有限。将开发：用于动态解剖学的 B 模式、用于血管流量量化的多普勒、以及用于尿道壁机械特性，用于测量可由 AIMS 1 和 3 使用的实时尿道运动学。目标 3：开发多尺度 3D 解剖图谱和高保真尿道多物理场计算机模型模拟个体结构的变化以及年龄和疾病过程的影响如何影响尿道我们将 a) 生成第一个体外 3D 多尺度概率图和体内高分辨率 MR 扫描。这些数据以及来自 AIMS 1 和 2 的新数据将用于 b) 创建和验证第一个有限元多物理场尿道模型，研究人员可以使用该模型来研究如何个体尿道结构和功能参数的变化会影响尿道闭合压力。这项工作提供的技术和概念工具将刺激研究并启动假设检验澄清如何确定节制裕度，以及年龄、糖尿病、分娩、种族、遗传和其他因素如何影响这项工作将揭示目前尚未探索的治疗靶点并带来影响女性尿道衰竭的因素。科学对尿道的失禁功能至关重要但长期被忽视的方面进行了研究。