SUPRASPINAL TARGETS IN NEUROGENIC VOIDING DYSFUNCTION

神经源性排尿功能障碍的脊髓上靶点

基本信息

批准号：
10440022
负责人：
Rose Khavari
金额：
$ 10.02万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-17 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10440022
关键词：
Address Anisotropy Area Ataxia Bladder Bladder Control Bladder Dysfunction Brain Brain region Catheterization Catheters Clinical Clinical Trials Clinical trial protocol document Data Data Analyses Databases Department chair Development Development Plans Diagnostic Procedure Diffuse Diffusion Magnetic Resonance Imaging Etiology Exhibits Experimental Designs Faculty Failure Feasibility Studies Female Foundations Functional Magnetic Resonance Imaging Functional disorder Future Goals Hand Hematuria Human Individual Infection International Journals K-Series Research Career Programs Kidney Kidney Failure Lower Extremity Lower urinary tract Magnetic Resonance Imaging Measures Mentored Patient-Oriented Research Career Development Award Mentors Multiple Sclerosis National Institute of Diabetes and Digestive and Kidney Diseases Nature Neurogenic Bladder Neuropathy Neurosciences Outcome Study Pain Patients Pattern Peer Review Phase Program Development Protocols documentation Quality of life Questionnaires Relaxation Research Research Personnel Research Support Role SECTM1 gene Scientist Seminal Sepsis Signal Transduction Spasm Sphincter Stroke Surgeon Syndrome Therapeutic Time Trauma Urethra Urinary Retention Urinary tract infection Urodynamics Urology Work blood oxygen level dependent career development cohort cost design detrusor underactivity dexterity gray matter high risk improved interest meetings mind control multidisciplinary multiple sclerosis patient nervous system disorder neuroimaging neuroregulation novel diagnostics novel therapeutics patient oriented research pilot trial predicting response side effect therapy development urologic white matter

项目摘要

Project Summary/Abstract Dr. Khavari is in her final year of the Multidisciplinary K12 Urologic Research Career Development Program (Lamb: Director; Boone: Co-Director) from NIDDK and is applying for the Individual Career Development Award (K23) to support her transition into a fully independent surgeon-scientist in the fields of neurourology and voiding dysfunction. K23 award will specifically provide Dr. Khavari the support needed to develop expertise in 2 areas: (1) Advanced functional Magnetic Resonance Imaging (fMRI) protocol design and data analysis; (2) Application of Transcranial Rotating Permanent Magnet Stimulator (TRPMS) in a clinical trial. To achieve her goals, Dr. Khavari has assembled an expert multidisciplinary team of collaborators and advisors in neuroimaging (Karmonik), neuroscience (Masdeu and Helekar), neurourology (Chai and Daneshgari), and urologic research (Boone and Lamb). Dr. Boone, the chair of her Department, is a leading expert in neuro-urological research and has mentored many junior faculty to independent investigators and will serve as her Primary Mentor. Neurogenic voiding dysfunction (VD) is morbid, costly, and leads to urinary tract infections, stones, sepsis, and permanent renal failure. Currently, the only available therapy for VD is catheterization, which is a burden, especially in neurogenic patients, such as Multiple Sclerosis (MS), who commonly exhibit lower extremity spasms and compromised hand dexterity. The cost and morbid side effects (hematuria, pain, trauma, strictures, and infections) associated with catheterizations, urge us to look into potential therapeutic options beyond the bladder, such as supraspinal targets. Yet, the current understanding of supraspinal centers, and their roles in initiating or modulating voiding, is rudimentary in patients with neurogenic VD. Dr. Khavari will use preliminary data and the raw database from her established simultaneous fMRI and urodynamics platform to determine whether, in female MS subjects: Aim 1: Activation patterns of preselected grey matter Regions of Interest (ROI)s are different among MS patients with versus without VD, specifically those with Detrusor Sphincter Dyssenergia. Aim 2: Damage to preselected white matter tracts involved in bladder control provides an independent predictive measure for VD. Aim 3: Targeted cortical stimulation in ROIs in MS patients with VD causes changes in ROIs that better recapitulate the activation patterns in patients without VD or healthy controls. Aim 3 will be a pilot trial using an individualized TRPMS targeting personalized ROIs in selected MS patients with VD. Dr. Khavari’s ongoing research and current career development plans exemplify her commitment to becoming an independent investigator in patient-oriented research. Her project has the potential to improve our ability to understand brain control of bladder, suggest new diagnostic methods, and provide crucial steps towards therapeutic options for the morbid and intractable condition, VD, in patients with neurogenic (e.g. MS or Strokes) or non-neurogenic VD (e.g. underactive bladder or Fowler’s syndrome). This proposal, and the subsequent planed R01, will lay the foundation for future clinical trials addressing therapies for VD.

项目摘要/摘要 Khavari博士处于多学科K12泌尿外科研究职业发展计划的最后一年（羔羊：主任；布恩：联合导演）来自NIDDK，并正在申请个人职业发展奖（K23）支持她过渡到神经病学领域的完全独立的外科医生科学家功能障碍。 K23 Award将专门为Khavari博士提供在两个领域发展专业知识所需的支持：（1）高级功能磁共振成像（fMRI）协议设计和数据分析；（2）申请在临床试验中，经颅旋转永久磁铁刺激器（TRPM）为了实现她的目标，博士卡瓦里（Khavari （Karmonik），神经科学（Masdeu和Helekar），Neurourology（Chai and Daneshgari）以及泌尿科研究（布恩和羔羊）。她的部门主席Boone博士是神经神经研究研究的领先专家已经指导了许多初级教师到独立调查员，并将担任她的主要导师。神经源性空隙功能障碍（VD）病态，昂贵，导致尿路感染，石头，败血症和永久性肾衰竭。目前，VD的唯一可用疗法是导管插入术，这是一个负担，特别是在神经源性患者中，例如多发性硬化症（MS），他们通常表现出下肢痉挛和手动敏捷性妥协。成本和病态副作用（血尿，疼痛，创伤，狭窄，与导管相关的感染），敦促我们研究以外的潜在治疗选择膀胱，例如上脊柱靶标。然而，当前对脊柱上心的理解及其在神经源VD患者中，在启动或调节空隙中的作用是基本的。哈瓦里·威尔博士使用她已建立的简单fMRI和尿动力学平台的初步数据和RAW数据库确定在女性MS受试者中是否：目标1：提出的灰质区域的激活模式 MS患者与没有VD的MS患者的兴趣（ROI）不同，特别是那些有害的患者括约肌dyssenergia。目的2：对膀胱控制中涉及的白质区域的损坏提供 VD的独立预测度量。 AIM 3：MS患者的ROI的靶向皮质刺激导致ROI的变化可以更好地概括没有VD或健康对照的患者的激活模式。 AIM 3将是针对选定MS患者的个性化ROI的个性化TRPM的试点试验与VD。哈瓦里博士正在进行的研究和当前的职业发展计划体现了她对成为以患者为导向研究的独立研究者。她的项目有可能改善我们的能够理解大脑对膀胱的控制，提出新的诊断方法，并提供关键步骤神经源的患者（例如MS或MS或中风）或非神经发育VD（例如，膀胱不足或福勒综合征）。这个建议，以及随后计划的R01将为未来的临床试验奠定基础，以解决VD的疗法。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High spatial correlation in brain connectivity between micturition and resting states within bladder-related networks using 7 T MRI in multiple sclerosis women with voiding dysfunction.

DOI：
10.1007/s00345-021-03599-4
发表时间：
2021-09
期刊：
World journal of urology
影响因子：
3.4
作者：
Shi Z;Tran K;Karmonik C;Boone T;Khavari R
通讯作者：
Khavari R

Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial.

DOI：
10.1186/s40814-021-00825-z
发表时间：
2021-03-24
期刊：
Pilot and feasibility studies
影响因子：
1.7
作者：
Tran K;Shi Z;Karmonik C;John B;Rajab H;Helekar SA;Boone T;Khavari R
通讯作者：
Khavari R

Noninvasive brain stimulation in the treatment of functional urological and pelvic floor disorders: A scoping review.

无创脑刺激治疗功能性泌尿科和盆底疾病：范围界定审查。

DOI：
10.1002/nau.25205
发表时间：
2023
期刊：
Neurourology and urodynamics
影响因子：
2
作者：
Mazeaud,Charles;Salazar,BetsyH;Khavari,Rose
通讯作者：
Khavari,Rose

Disruption of specific white matter tracts is associated with neurogenic lower urinary tract dysfunction in women with multiple sclerosis.

特定白质束的破坏与多发性硬化症女性的神经源性下尿路功能障碍有关。

DOI：
10.1002/nau.25075
发表时间：
2023
期刊：
Neurourology and urodynamics
影响因子：
2
作者：
Choksi,Darshil;Schott,Bradley;Tran,Khue;Jang,Ryan;Hasan,KhaderM;Lincoln,JohnA;Jalali,Ali;Karmonik,Christof;Salazar,Betsy;Khavari,Rose
通讯作者：
Khavari,Rose

Low Interrater Reliability of Videourodynamic Diagnosis of Detrusor External Sphincter Dyssynergia.