The Detrusor Tension Sensor: A Model for Novel Cystometrics in Overactive Bladder

逼尿肌张力传感器：膀胱过度活动症的新型膀胱测压模型

• 批准号: 8965037
• 负责人: Adam Philip Klausner
• 金额: $ 31.04万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-20 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8965037
• 关键词: Acute; Affect; Age; Anatomy; Animal Model; Area; Biological Models; Biomechanics; Bladder; Boxing; Categories; Chronic; Clinical; Comorbidity; Constipation; Deterioration; Development; Diagnosis; Diagnostic tests; Disease; Engineering; Evaluation; Figs - dietary; Fourier Transform; Functional disorder; Future; Geometry; Goals; Gold; High Prevalence; Human; International; Investigation; Knowledge; Laws; Lead; Link; Measurable; Measurement; Measures; Mechanics; Mediating; Methods; Modeling; Morbidity - disease rate; Nervous system structure; Obesity; Output; Overactive Bladder; Patients; Phase; Physiology; Population; Process; Property; Quality of life; Radial; Recording of previous events; Reporting; Sensory Thresholds; Series; Severities; Shapes; Slide; Smooth Muscle; Societies; Stretching; Surface; Symptoms; System; Testing; Time; Ultrasonography; Urination; Urologist; Urology; Work; afferent nerve; base; detrusor muscle; effective therapy; functional disability; human subject; imaging modality; improved; interdisciplinary approach; meter; micturition urgency; non-invasive imaging; novel; pre-clinical; pressure; public health relevance; research study; sensor; skills; temporal measurement; yellow-1

 DESCRIPTION (provided by applicant): 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 are 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), a continuously 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 identify 3 new tension-mediated OAB sub- categories (geometry-mediated, dynamic compliance-mediated, and spontaneous rhythmic contraction mediated) and a non-tension-medicated sub-category due to alterations in nervous system processing. Our new cystometrics will include 1) a sliding scale Urgency Meter that will allow patients to continuously record the tension sensor output of acute 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 load on the detrusor tension sensor, will be tested in clinical extended cystometrics experiments on subjects with no, low, and high urgency. Successful completion of this multi-PI proposal involving the combined skill sets of a neuro-urologist and a mechanical engineer will lead to the development of novel cystometric tests for improved OAB diagnosis and treatment and for the potential identification of novel mechanistic targets in the pathophysiology of OAB.

 描述（由申请人提供）：尿急是膀胱过度活动症（OAB）的关键症状，发生在排尿充盈期，逼尿肌壁张力增加被认为是OAB病理生理学的关键因素。然而，由于压力增加很少在膀胱充盈，并不反映逼尿肌壁张力的变化，真正的充盈期生理不能在临床膀胱测压评估。因此，使用标准临床膀胱测压测试客观评估OAB是困难的或不可能的。此外，OAB的评价使用的语言感觉阈值推荐的国际大陆协会是主观的和不明确的。因此，迫切需要一种机械相关的OAB诊断测试，结合客观的指标，直接评估逼尿肌壁张力。使用排尿的充盈阶段的系统模型，逼尿肌平滑肌及其串联的张力敏感传入神经可以表示为具有可定义的输入（音量）、连续可测量的输出（紧迫性）和影响张力传感器上的负载的客观可测量的生物力学参数的张力传感器。根据我们以前的调查和其他人的工作，我们已经确定了以下生物力学参数，可以直接影响在充盈过程中的逼尿肌张力传感器上的负载：膀胱几何形状，动态顺应性，和自发的节律性收缩。在目前的建议中，我们将开发新的膀胱测压测试，以确定 3个新的张力介导的OAB子类别（几何结构介导、动态顺应性介导和自发节律性收缩介导）和一个由于神经系统处理改变而引起的非张力给药子类别。我们的新膀胱测量将包括1）滑动标度尿急计，其将允许患者连续记录急性尿急的张力传感器输出，2）二维和三维膀胱超声检查，以提供膀胱几何形状的真实的实时测量，其将用于测量几何形状的影响并用于动态顺应性计算，和3）快速傅立叶变换（FFT）分析，以客观地测量充盈期自发节律性收缩。这些新指标将提供OAB症状和逼尿肌功能之间的定量机制联系，我们将使用这些新指标来识别张力介导和非张力介导的OAB亚组。在这个建议中，我们的中心假设，即可测量的生物力学参数可以直接影响逼尿肌张力传感器上的负载，将在临床扩展膀胱测压实验中进行测试，受试者没有，低，高紧迫性。成功完成这项涉及神经泌尿科医生和机械工程师的综合技能的多PI提案将导致开发新的膀胱测压测试，以改善OAB的诊断和治疗，并在OAB的病理生理学中识别新的机制靶点。