3-D Tractography Focused Ultrasound Ablation for Essential Tremor

3-D 纤维束成像聚焦超声消融治疗特发性震颤

• 批准号: 10344274
• 负责人: Vibhor Krishna
• 金额: $ 77.66万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10344274
• 关键词: 3-Dimensional; Ablation; Age; American; Anatomy; Anesthesia procedures; Animals; Area; Atlases; Autopsy; Blinded; Brain; Cell Nucleus; Climacteric; Clinical; Control Groups; Controlled Clinical Trials; Data; Dependence; Diffusion Magnetic Resonance Imaging; Dose; Eating; Edema; Essential Tremor; FDA approved; Focused Ultrasound Therapy; Glass; Goals; Histopathology; Hygiene; Image; Image-Guided Surgery; Intervention; Intraoperative Monitoring; Lesion; Life; Location; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Medicare; Modeling; Monitor; Nerve; Neurologic Deficit; Operative Surgical Procedures; Oral; Outcome; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phase; Procedures; Protocols documentation; Randomized; Recurrence; Resistance; Resolution; Risk; Sensitivity and Specificity; Standardization; Structure; Surgical incisions; Symptoms; Techniques; Temperature; Testing; Thermography; Tissue Differentiation; Tissues; Tremor; Ultrasonic Therapy; Videotape; Visualization; brain surgery; brain tissue; disability; drinking; experimental group; human study; improved; necrotic tissue; nervous system disorder; neuroimaging; porcine model; post intervention; psychologic; repository; research clinical testing; response; safety and feasibility; safety testing; sex; side effect; success; tractography; ultrasound

PROJECT SUMMARY Essential tremor (ET) is a common neurological disorder and a leading cause of functional and psychological disabilities that can be difficult to suppress with oral medications, many of which have considerable side effects limiting adequate dosing. As a result, up to 20% of ET patients cannot achieve satisfactory control of their symptoms and must consider interventional options. Focused ultrasound ablation (FUSA) of the ventral intermediate nucleus (Vim) is an FDA-approved and Medicare-reimbursed procedure for ET resistant to medications that can selectively ablate the brain area associated with tremor without the need for surgical incisions or anesthesia. The success of Vim-FUSA depends on the ability to accurately ablate 70% of the Vim volume without lesioning neighboring structures, a goal that is complicated by technical challenges in three critical phases of the procedure: planning (identifying the Vim location and extension); delivery (ablating the Vim volume with adequate accuracy); and monitoring (confirming Vim ablation with reliable intraoperative imaging). We propose to advance Vim-FUSA with the support of 3-D tractography, a neuroimaging technique to visually represent nerve tracts within the brain. We hypothesize that 3-D tractography Vim-FUSA will improve the Vim ablation compared to standard Vim-FUSA and prove safe and feasible in the clinical setting. We also hypothesize that intraoperative magnetic resonance (i-MR) monitoring will differentiate ablated tissue from immediate perilesional edema and accurately predict the Vim-FUSA clinical outcomes. Aim 1. Estimate and characterize the improvement in Vim ablation achieved with 3-D tractography Vim-FUSA vs. standard Vim-FUSA in an experimental controlled animal study. Through an experimental animal study, we will characterize the Vim ablation delivered with 3-D tractography Vim-FUSA in one hemisphere (experimental group) vs. standard Vim-FUSA in the opposite hemisphere (control group). Aim 2. Test safety, feasibility, and preliminary efficacy, and estimate effect size of 3-D tractography Vim-FUSA in a phase-II, two-groups, pre-post interventional human study. In a human study, we will test the safety and feasibility of ablating 70% of the Vim volume while checking for side effects with intraoperative clinical testing. Tremor assessments will be videotaped at baseline and 12 weeks and compared, in a blinded fashion, with age-sex matched controls randomly selected from the video repository of the two FDA-regulated studies of standard Vim-FUSA at baseline and 12 weeks. Aim 3 (Exploratory). Assess the accuracy of i-MR in differentiating tissue ablation from immediate perilesional edema and its utility in predicting Vim-FUSA clinical outcomes. In the experimental animal study, we will estimate and compare the accuracy of conventional and non-conventional i-MR in differentiating tissue necrosis from perilesional edema. In the interventional human study, we will evaluate the utility of i-MR in predicting Vim-FUSA clinical outcomes.

项目总结 特发性震颤(ET)是一种常见的神经系统疾病，是功能性和心理性疾病的主要原因 用口服药物难以抑制的残疾，其中许多有相当大的副作用 限制适当的剂量。因此，高达20%的ET患者无法实现满意的控制 出现症状，必须考虑介入治疗。腹侧聚焦超声消融术(FUSA) 中间核(Vim)是FDA批准并由医疗保险报销的ET耐药手术 药物可以选择性地消融与震颤相关的大脑区域，而不需要手术 切开或麻醉。Vim-Fusa的成功取决于能否准确消融70%的Vim 体积而不损害邻近结构，这一目标因三个技术挑战而变得复杂 程序的关键阶段：规划(确定Vim位置和扩展)；交付(消融Vim 容量足够准确)；监测(通过可靠的术中成像确认Vim消融)。 我们建议在三维纤维束成像技术的支持下推进Vim-Fusa，这是一种视觉上的神经成像技术 代表大脑内的神经束。我们假设三维摄影Vim-Fusa将改善Vim 消融与标准Vim-Fusa相比，在临床环境中被证明是安全和可行的。我们还假设 术中磁共振(I-MR)监测将区分消融组织和即刻组织 并准确预测Vim-Fusa的临床结果。 目的1.评估和表征3-D纤维束造影术对Vim消融的改善 VIM-FUSA与标准VIM-FUSA在实验对照动物研究中的比较。通过一项实验性的 动物研究，我们将描述在单侧大脑半球应用三维纤维束造影术进行Vim消融的特征 (实验组)与对侧大脑半球标准Vim-Fusa比较(对照组)。 目的2.测试3-D纤维束造影术的安全性、可行性和初步疗效，并估计其效果大小 VIM-FUSA为II期，两组，介入前的人体研究。在一项人体研究中，我们将测试 术中检查副作用的同时消融70%Vim体积的安全性和可行性 临床测试。震颤评估将在基线和12周被录制下来，并进行盲法比较 时尚，年龄和性别匹配的对照组从FDA监管的两个视频存储库中随机选择 基线和12周时的标准Vim-Fusa研究。 目标3(探索性)。评价I-MR区分组织消融与即刻消融的准确性 皮损周围水肿及其在预测Vim-Fusa临床结果中的作用。在实验动物中 研究中，我们将评估和比较常规和非常规I-MR在鉴别诊断中的准确性 皮损周围水肿性组织坏死。在介入性人体研究中，我们将评估I-MR在 预测Vim-Fusa临床结果。