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

脑成像加尿动力学研究大脑对膀胱的控制

WERNER SCHAEFER Show email (2011-08-15 to 2013-07-31) $124,230

Project ID: R03AG038583 (NIA)

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Abstract

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. PUBLIC HEALTH RELEVANCE: In older adults, loss of bladder control is common, devastating, and costly (>$60 billion in 2007), yet treatment has improved little in decades because the causes are often unknown and therapeutic targets unclear. Recent studies suggest that brain abnormalities may play a major role, but limitations of current brain imaging hinder further insights. The proposed study will investigate the potential role of a new technique which, if proven effective, may not only advance our understanding but also lead to development of more effective treatment.

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，由于对其病因学认识不足，特别是大脑因素的理解不足，治疗在50年内几乎没有改善。最近，正电子发射断层扫描（PET）和功能磁共振成像（fMRI）已经确定了涉及膀胱控制的关键脑区域。这种成像使我们能够设计正常脑 - 膀胱控制系统的工作模型，其中岛叶记录膀胱感觉，背前扣带皮层（dACC）提供空洞和运动输出的动机，以及前额皮质的区域控制膀胱控制。相比之下，当患有UUI的患者受到大量膀胱体积和强烈的排空欲望的挑战时，dACC，相关辅助运动区域和背外侧前额叶皮层的反应被夸大，代表“紧迫性”的神经相关性;此外，是内侧前额叶皮质的停用，这是膀胱控制的关键因素。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，这一承诺因目前PET和fMRI技术固有的局限性而变暗，这些技术可防止同时研究大脑和膀胱/括约肌的变化，并完全排除对许多受试者的评估。功能性近红外光谱（fNIRS）是一种新方法，不仅可以克服这些局限性，还可以实现个体（仅针对一组）的脑 - 膀胱/括约肌控制，实时，排尿期间和动态设置。因此，fNIRS可以成为尿动力学和神经成像技术的有力补充，使研究人员能够更好地研究有助于OAB和UUI的中心和外周因素。此外，令人兴奋的新初步数据证实，可以从我们模型中的关键区域记录膀胱/括约肌相关的激活变化。尽管有很大的希望，但是NIRS的潜在利益仍然很大程度上尚未开发。为了解决这个问题，拟议的研究将评估fNIRS与UUI相关的膀胱/括约肌功能调查的可行性，可重复性和相关性：25名UUI患者和15名年龄匹配的对照者将同时接受fNIRS的尿动力学。在填充，排尿和自发膀胱事件期间将记录关键脑区域中的fNIRS反应。将比较患者和对照中的反应以确定：（a）NIRS是否可以记录fMRI已知与膀胱功能相关的大脑区域的可重现反应;（b）NIRS和fMRI反应是一致的;以及（c）新信息可以获得关于膀胱/括约肌激活的动态变化。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，可成为研究膀胱问题和确定新治疗靶点的有力新工具。它还可以促进为UUI和OAB开发更有效的行为干预措施。公共卫生相关性：在老年人中，膀胱失控是常见的，破坏性的和昂贵的（2007年> 600亿美元），但治疗几十年来几乎没有改善，因为其原因往往是未知的，治疗目标尚不清楚。最近的研究表明，大脑异常可能起主要作用，但目前大脑成像的局限性阻碍了进一步的见解。拟议的研究将调查新技术的潜在作用，如果证明有效，它不仅可以促进我们的理解，还可以促进更有效的治疗方法的发展。