Brain Imaging plus Urodynamics to Investigate the Brain's Control of the Bladder

脑成像结合尿动力学研究大脑对膀胱的控制

• 批准号: 8316107
• 负责人: Werner Schaefer
• 金额: $ 6.21万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8316107
• 关键词: Address; Age; Anterior; Area; Behavior; Behavior Therapy; Bladder; Bladder Control; Brain; Brain imaging; Brain region; Cerebrum; Claustrophobias; Clinical Research; Complement; Data; Development; Dorsal; Elderly; Electronics; Elements; Esthesia; Etiology; Evaluation; Event; Exclusion Criteria; Female; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Head; Image; Imaging technology; Implant; Incontinence; Individual; Insula of Reil; Investigation; Lateral; Lead; Lower urinary tract; Medial; Metals; Methodology; Methods; Micturition Reflex; Modeling; Monitor; Motivation; Motor; Motor output; Near-Infrared Spectroscopy; Noise; Overactive Bladder; Patients; Peripheral; Play; Positron-Emission Tomography; Prefrontal Cortex; Publishing; Radioactive; Records; Reproducibility; Research Personnel; Resolution; Role; Sensitivity and Specificity; Signal Transduction; Sphincter; Staging; Supine Position; System; Techniques; Technology; Testing; Time; Urinary Incontinence; Urodynamics; Work; base; c new; cingulate cortex; effective therapy; improved; insight; mind control; neuroimaging; new therapeutic target; novel; novel therapeutics; prevent; relating to nervous system; response; therapeutic target; tool

DESCRIPTION (provided by applicant): Overactive bladder (OAB) and urge urinary incontinence (UUI) are common, morbid, and costly. Yet, treat- ment has improved little in 50 years, impeded by poor understanding of their etiology, especially of the cerebral factors. Recently, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have identified key brain areas involved in bladder control. Such imaging has enabled us to devise a working model of the normal brain-bladder control system, in which the insula records bladder sensations, the dorsal anterior cingulate cortex (dACC) provides the motivation to void and motor output, and regions of the prefrontal cortex govern bladder control. By contrast, when patients with UUI are challenged with a large bladder volume and strong desire to void, responses in the dACC, associated supplementary motor area, and dorsolateral prefrontal cortex become exaggerated, representing the neural correlate of "urgency"; in addition, there is deactivation of the medial prefrontal cortex, a crucial element of bladder control. These exciting data suggest that further study of the brain's role in UUI may lead to new therapeutic insights. The promise is dimmed, however, by the limitations inherent in current PET and fMRI technology, which prevent simultaneous study of brain and bladder/sphincter changes and exclude evaluation of many subjects entirely. Functional near-infrared spectroscopy (fNIRS) is a new method that may not only overcome these limitations, but also enable investigation of brain-bladder/sphincter control in individuals (vs. only a group), in real time, during voiding, and in ambulatory settings. Thus, fNIRS could become a powerful complement to urodynamic and neuroimaging techniques, allowing investigators to better study central and peripheral factors that contribute to OAB and UUI. Moreover, exciting new preliminary data confirm that bladder/sphincter related changes in activation can be recorded from key regions in our model. Despite its substantial promise, however, NIRS' potential benefit remains largely unexplored. To address this, the proposed study will evaluate fNIRS' feasibility, reproducibility, and relevance for investigation of bladder/sphincter function associated with UUI: 25 patients with UUI and 15 age-matched controls will undergo urodynamics with concurrent fNIRS. fNIRS responses in key brain regions will be recorded during filling, voiding, and spontaneous bladder events. Responses in patients and controls will be compared to determine whether: (a) NIRS can record reproducible responses in brain regions known from fMRI to be relevant for bladder function; (b) NIRS and fMRI responses are consistent; and (c) new information can be obtained about dynamic changes in bladder/sphincter activation. The proposed study will set the stage for a larger clinical study. fNIRS, a newly developed methodology could become a powerful new tool for investigation of bladder problems and identification of new therapeutic targets. It also could facilitate development of more effective behavioral interventions for both UUI and OAB.

描述（由申请人提供）：膀胱过度活动症（OAB）和急迫性尿失禁（UUI）是常见的、病态的和昂贵的。然而，50年来，由于对其病因，特别是脑因素的认识不足，治疗进展甚微。最近，正电子发射断层扫描（PET）和功能性磁共振成像（fMRI）已经确定了参与膀胱控制的关键脑区。这种成像使我们能够设计出一个正常的脑-膀胱控制系统的工作模型，其中，小脑记录膀胱感觉，背侧前扣带皮层（dACC）提供排尿和运动输出的动机，前额叶皮层的区域控制膀胱控制。相比之下，当UUI患者面临膀胱容量大和强烈排尿欲望的挑战时，dACC、相关辅助运动区和背外侧前额叶皮质的反应会变得放大，代表“紧迫性”的神经相关性;此外，内侧前额叶皮质（膀胱控制的关键因素）失活。这些令人兴奋的数据表明，进一步研究大脑在UUI中的作用可能会带来新的治疗见解。然而，由于当前PET和fMRI技术固有的局限性，这一前景变得暗淡，这些局限性阻止了对大脑和膀胱/括约肌变化的同时研究，并完全排除了对许多受试者的评估。 功能性近红外光谱（fNIRS）是一种新的方法，不仅可以克服这些局限性，而且还可以在真实的时间内，在排尿期间和在门诊环境中对个体（与仅一组）的脑膀胱/括约肌控制进行研究。因此，fNIRS可以成为尿动力学和神经影像学技术的有力补充，使研究人员能够更好地研究导致OAB和UUI的中枢和外周因素。此外，令人兴奋的新的初步数据证实，膀胱/括约肌相关的激活变化可以从我们的模型中的关键区域记录。然而，尽管近红外光谱有很大的前景，但其潜在的好处在很大程度上仍未得到探索。为了解决这个问题，拟议的研究将评估fNIRS的可行性，再现性和与UUI相关的膀胱/括约肌功能研究的相关性：25例UUI患者和15例年龄匹配的对照将接受尿动力学检查，同时进行fNIRS。将在充盈、排尿和自发性膀胱事件期间记录关键脑区域中的fNIRS反应。将比较患者和对照组的反应，以确定：（a）NIRS是否可以记录从fMRI已知与膀胱功能相关的脑区域中的可再现反应;（B）NIRS和fMRI反应是否一致;以及（c）是否可以获得关于膀胱/括约肌激活动态变化的新信息。拟议的研究将为更大规模的临床研究奠定基础。fNIRS是一种新开发的方法学，可能成为研究膀胱问题和识别新治疗靶点的强大新工具。它也可以促进开发更有效的行为干预UUI和OAB。