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

描述(由申请人提供)：膀胱过度活动(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，特别是对大脑因素的缺乏了解，治疗进展甚微。最近，正电子发射断层扫描(PET)和功能磁共振成像(FMRI)已经确定了与膀胱控制有关的关键脑区。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，其中岛叶记录膀胱的感觉，背侧前扣带回(DACC)提供排尿和运动输出的动力，前额叶皮质的区域管理膀胱控制。相比之下，当UUI患者面临巨大的膀胱容量和强烈的排尿欲望时，dACC、相关的辅助运动区和背外侧前额叶皮质的反应变得夸张，代表了神经的“紧迫感”；此外，作为膀胱控制的关键因素，内侧前额叶皮质也失活了。这些令人兴奋的数据表明，进一步研究大脑在尿路感染中的作用可能会带来新的治疗见解。然而，由于目前PET和fMRI技术固有的局限性，这一前景变得黯淡，这些限制阻碍了对大脑和膀胱/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，它不仅可以克服这些限制，而且可以实时、在排尿过程中和在门诊环境中研究个体(而不是一组)的脑膀胱/括约肌控制。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，在我们的模型中，可以从关键区域记录与膀胱/括约肌相关的激活变化。然而，尽管NIRS有很大的前景，但它的潜在好处在很大程度上仍未得到开发。为了解决这一问题，拟议的研究将评估fNIRS在研究与UUI相关的膀胱/括约肌功能方面的可行性、重复性和相关性：25例UUI患者和15名年龄匹配的对照组将同时接受fNIRS的尿动力学检查。在充盈、排尿和自发性膀胱事件期间，关键脑区的fNIR反应将被记录下来。将对患者和对照组的反应进行比较，以确定：(A)NIRS是否可以在已知与膀胱功能相关的大脑区域记录可重复的反应；(B)NIRS和fMRI的反应是一致的；以及(C)可以获得有关膀胱/括约肌激活的动态变化的新信息。这项拟议的研究将为更大规模的临床研究奠定基础。近红外光谱是一种新开发的方法学，可能成为研究膀胱问题和寻找新的治疗靶点的强有力的新工具。它还可以促进对UUI和OAB进行更有效的行为干预。 与公共卫生相关：在老年人中，失去膀胱控制是常见的、毁灭性的和代价高昂的(2007年为600亿美元)，然而几十年来治疗几乎没有改善，因为原因通常是未知的，治疗目标也不清楚。最近的研究表明，大脑异常可能起到重要作用，但目前大脑成像的局限性阻碍了进一步的深入研究。这项拟议的研究将调查一种新技术的潜在作用，如果被证明有效，不仅可能促进我们的理解，还可能导致更有效的治疗方法的开发。

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. 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.