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High-resolution mapping of the human brainstem during continence and micturition: noninvasive in vivo 7 Tesla fMRI study

节制和排尿期间人类脑干的高分辨率绘图：无创体内 7 Tesla fMRI 研究

基本信息

批准号：
10330466
负责人：
Rose Khavari
金额：
$ 12.05万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-18 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10330466
关键词：
Affect Anatomy Arteries Benign Prostatic Hypertrophy Bladder Bladder Control Brain Brain Stem Budgets Catheters Cell Nucleus Collaborations Complement Complex Data Databases Evaluation Frequencies Functional Magnetic Resonance Imaging Functional disorder Future Grant Human Hydration status Incontinence Individual International Journals Knowledge Lead Location Lower urinary tract Magnetic Resonance Imaging Maps Mentored Patient-Oriented Research Career Development Award Multiple Sclerosis National Institute of Diabetes and Digestive and Kidney Diseases Noise Patients Pattern Peer Review Phase Pontine structure Protocols documentation Publishing Quality of life Research Research Support Resolution Resources Rest SECTM1 gene Scientist Secondary to Seminal Signal Transduction Surgeon Switching Complex Symptoms Techniques Therapeutic Time Urethra Urethral sphincter Urination Urine Urodynamics Urology Water consumption Woman Work blood oxygen level dependent cohort contrast imaging experience gray matter healthy volunteer imaging study improved in vivo innovation interest meetings men micturition urgency midbrain central gray substance mind control multiple sclerosis patient neural network neuroimaging neuroregulation novel programs prospective time use urinary bladder neck

项目摘要

The lower urinary tract (LUT) – bladder, bladder neck, urethra, and urethral sphincter – is controlled by a complex neural network. A delicate and complex switch/relay exists between storage of urine (continence) and voluntary voiding (micturition) and, in humans, control over this switch is located in the brainstem regions known as the pontine storage center (PSC), the pontine micturition center (PMC) and the periaqueductal gray (PAG). Over the last two decades, despite significant research in the brain control of LUT, our understanding of the brainstem in humans has remained rudimentary. 7Tesla magnetic resonance imaging (MRI) has demonstrated improved ability for mapping of the brainstem, a region historically posing challenges to obtain fMRI data due to its location close to many large arteries and ventricles, yet encompassing some of the most important regions of the bladder cycle, such as the PAG, PSC and PMC (Regions of Interest-RoIs for this study) highlighting the significance and the priority of this proposed research. The overall objective of this proposal is to use a noninvasive fMRI protocol that allows for evaluation of the brainstem during continence and micturition in real-time, using high-resolution neuroimaging (7T fMRI) in both men and women with the following two specific aims: Aim 1: Assessing activation patterns of brainstem RoIs during continence and micturition within and between cohorts of healthy men and women; and Aim 2: Comparing activation patterns of brainstem RoIs obtained in Aim 1 to our previous data from Multiple Sclerosis (MS) patients obtained on 3T and 7T MRI supported by my current K23 award. The proposed R03 project is a prospective two- year human trial that includes a novel and noninvasive micturition fMRI paradigm evaluating the brainstem at rest with empty bladder and with full bladder following accelerated hydration (noninvasive bladder filling by consuming water) and micturition using 7T fMRI in healthy men and women. Over the past five years, my research team has established a 3T fMRI brain-bladder platform and have successfully used it in healthy controls, patients with LUTD, including MS, and men with Benign Prostatic hyperplasia. I have the appropriate resources, collaboration, experience and expertise to complete the proposed study in time and within budget. Currently, I am in my final two years of her K23 Mentored Patient-Oriented Research Career Development Award from NIDKK and have successfully executed and published on aims 1 and 2 of my K23 proposal (Aim 3 is ongoing and with projected completion in 2021). This proposed R03 study will be the first 7T MRI study evaluating the brain and specifically brainstem control over LUT, creating the seminal 7 T database for future studies in patients with LUTD and providing a more accurate roadmap for potential therapeutic and neuromodulation options. The results from this study will complement my research to prepare strong preliminary data for future R01 studies to evaluate patients with lower urinary tract dysfunction (LUTD), specifically patients with underactive bladder.

下尿路（LUT）-膀胱、膀胱颈、尿道和尿道括约肌-由一个复杂的神经网络的在尿液储存（尿液储存）和自愿尿液储存之间存在一个微妙而复杂的开关/继电器。排尿（排尿），在人类中，控制这种开关位于脑干区域，称为脑桥储存中心（PSC）、脑桥排尿中心（PMC）和导水管周围灰质（PAG）。来在过去的二十年里，尽管在LUT的大脑控制方面进行了大量的研究，但我们对脑干的理解仍然存在。人类仍然是原始的。7特斯拉磁共振成像（MRI）已证明改善脑干的映射能力，该区域历史上对获得fMRI数据构成挑战，因为其位置靠近许多大动脉和心室，但包括一些最重要的区域，膀胱周期，如PAG、PSC和PMC（本研究的膀胱-ROI区域），突出显示这一研究的重要性和优先性。这项提案的总体目标是使用一种非侵入性的功能磁共振成像协议，允许评估的脑干在排尿和排尿的实时，使用高分辨率神经成像（7 T功能磁共振成像）在这两个目标1：评估脑干ROI的激活模式在健康男性和女性的队列内和队列之间的排尿和排尿期间;以及目标2：比较目的1中获得的脑干ROI激活模式与我们先前从多发性硬化（MS）患者获得的数据相比较在我目前的K23奖的支持下，在3 T和7 T MRI上获得。建议的R 03项目是一个前瞻性的两个- 一项为期一年的人体试验，包括一种新的和非侵入性的排尿功能磁共振成像范例，评估脑干在在加速水化后以空膀胱和充满膀胱的方式休息（通过饮水）和排尿功能。在过去的五年里，我研究小组建立了一个3 T功能磁共振成像脑膀胱平台，并成功地将其用于健康对照组、LUTD患者（包括MS）和良性前列腺增生男性。我有合适的资源、协作、经验和专门知识，以便在预算范围内及时完成拟议的研究。目前，我在我的最后两年，她的K23辅导病人为导向的研究职业发展奖从NIDKK，并成功地执行和发表了我的K23建议的目标1和2（目标3是正在进行中，预计2021年完成）。这项拟定的R 03研究将是首项7 T MRI研究评估大脑，特别是脑干对LUT的控制，为未来创建开创性的7 T数据库在LUTD患者中进行的研究，并为潜在的治疗和神经调节选项。这项研究的结果将补充我的研究，为初步的研究做好准备。用于评价下尿路功能障碍（LUTD）患者的未来R 01研究数据，特别是膀胱功能不全