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.

项目摘要 特发性震颤（ET）是一种常见的神经系统疾病，是功能性和心理性震颤的主要原因。 口服药物难以抑制的残疾，其中许多药物具有相当大的副作用 限制了足够的剂量。结果，高达20%的ET患者不能达到令人满意的控制他们的 症状，必须考虑干预措施。腹部的聚焦超声消融（FUSA） 中间核（Vim）是一种FDA批准和Medicare报销的ET耐药程序， 可以选择性地消融与震颤相关的大脑区域而无需手术的药物 切口或麻醉。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，这一目标因三个方面的技术挑战而变得复杂 手术的关键阶段：计划（确定Vim位置和延伸）;输送（消融Vim 具有足够准确性的体积）;和监测（通过可靠的术中成像确认Vim消融）。 我们建议在3-D纤维束成像的支持下推进Vim-FUSA，这是一种神经成像技术， 代表大脑中的神经束。我们假设3-D纤维束成像Vim-FUSA将改善Vim 与标准Vim-FUSA相比，消融术的安全性和可行性在临床环境中得到了证明。我们还假设 术中磁共振（i-MR）监测将区分消融组织和即刻消融组织， 病灶周围水肿，并准确预测Vim-FUSA的临床结果。 目标1。估计和表征使用3-D纤维束成像实现的Vim消融改善 实验对照动物研究中的Vim-FUSA与标准Vim-FUSA。通过实验 在动物研究中，我们将描述在一个半球中使用3-D纤维束成像Vim-FUSA进行的Vim消融的特征 （实验组）与对侧半球中的标准Vim-FUSA（对照组）。 目标2.测试3-D纤维束成像的安全性、可行性和初步疗效，并估计其效应量 Vim-FUSA在一项II期、两组、干预前后人体研究中的应用。在人类研究中，我们将测试 消融70%的Vim体积同时检查术中副作用的安全性和可行性 临床试验震颤评估将在基线和12周时进行录像，并进行比较， 时尚，年龄性别匹配的对照组随机选择的两个FDA监管的视频库， 在基线和12周时的标准Vim-FUSA研究。 目标3（探索性）。评估i-MR在区分组织消融和即刻消融方面的准确性 病灶周围水肿及其在预测Vim-FUSA临床结局中的效用。在实验动物中 研究中，我们将估计和比较传统和非传统i-MR在区分 病灶周围水肿导致的组织坏死。在介入性人体研究中，我们将评估i-MR在以下方面的效用： 预测Vim-FUSA临床结局。