SUPRASPINAL TARGETS IN NEUROGENIC VOIDING DYSFUNCTION

神经源性排尿功能障碍的脊髓上靶点

• 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
• 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

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.

项目概要/摘要 Khavari 博士正处于多学科 K12 泌尿学研究职业发展计划的最后一年 （Lamb：主任；Boone：联合主任）来自 NIDDK，正在申请个人职业发展奖 (K23) 支持她转变为神经泌尿学和排尿领域完全独立的外科医生科学家 功能障碍。 K23 奖项将专门为 Khavari 博士提供在以下两个领域发展专业知识所需的支持： （1）先进功能磁共振成像（fMRI）协议设计和数据分析； （二）申请 经颅旋转永磁刺激器（TRPMS）在临床试验中的应用。为了实现她的目标，博士。 Khavari 组建了一个由神经影像领域的合作者和顾问组成的多学科专家团队 (Karmnik)、神经科学 (Masdeu 和 Helekar)、神经泌尿学 (Chai 和 Daneshgari) 以及泌尿学研究 （布恩和兰姆）。布恩博士是该系主任，是神经泌尿学研究领域的领先专家， 为独立调查人员指导了许多初级教师，并将担任她的主要导师。 神经源性排尿功能障碍 (VD) 是病态的、昂贵的，并会导致尿路感染、结石、败血症和 永久性肾功能衰竭。目前，VD唯一可用的治疗方法是导管插入术，这是一种负担， 尤其是神经源性患者，例如多发性硬化症（MS），他们通常表现出下肢 痉挛和手部灵活性受损。费用和病态副作用（血尿、疼痛、创伤、狭窄、 和感染）与导管插入术相关，敦促我们研究除导管之外的潜在治疗选择 膀胱，例如脊髓上的目标。然而，目前对脊髓上中枢及其作用的认识 启动或调节排尿的作用，对于神经源性 VD 患者来说还处于初级阶段。卡瓦里博士将 使用来自她建立的同步功能磁共振成像和尿动力学平台的初步数据和原始数据库 确定女性多发性硬化症受试者中是否： 目标 1：预选灰质区域的激活模式 患有 VD 的 MS 患者与不患有 VD 的 MS 患者之间的兴趣 (ROI) 不同，特别是那些患有逼尿肌的患者 括约肌无力。目标 2：对参与膀胱控制的预选白质束的损伤提供了 VD 的独立预测指标。目标 3：对患有 VD 的多发性硬化症患者的 ROI 进行靶向皮质刺激 引起 ROI 的变化，更好地概括没有 VD 的患者或健康对照的激活模式。 目标 3 将是一项试点试验，使用个性化 TRPMS，针对选定的 MS 患者实现个性化 ROI 与VD。 Khavari 博士正在进行的研究和当前的职业发展计划体现了她对 成为以患者为导向的研究的独立研究者。她的项目有潜力改善我们的 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 针对神经源性（例如 MS 或 MS）患者的病态和难治性病症 VD 的治疗选择 中风）或非神经源性 VD（例如膀胱活动不足或福勒综合征）。该提案以及 随后计划的 R01 将为未来针对 VD 治疗的临床试验奠定基础。

项目成果

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.

在多发性硬化症女性中使用7 t MRI，在膀胱相关网络中排尿和静息状态之间的大脑连通性高空间相关性。

• 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

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

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

Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial.

• DOI: 10.1097/ju.0000000000002297
• 发表时间: 2022-03
• 期刊: JOURNAL OF UROLOGY
• 影响因子: 6.6
• 作者: Khavari, Rose;Tran, Khue;Helekar, Santosh A.;Shi, Zhaoyue;Karmonik, Christof;Rajab, Hamida;John, Blessy;Jalali, Ali;Boone, Timothy
• 通讯作者: Boone, Timothy