Virtual neuro-navigation system for personalized,community-based TMS

用于个性化、基于社区的 TMS 的虚拟神经导航系统

• 批准号: 10474577
• 负责人: Dennis Quangvinh Truong
• 金额: $ 45.19万
• 依托单位: SOTERIX MEDICAL,INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10474577
• 关键词: 3-Dimensional; Address; Adoption; Affect; Algorithms; Anterior; Antidepressive Agents; Area; Atlases; Award; Base of the Brain; Biological Markers; Brain; Brain region; Brain scan; Clinic; Clinical; Collaborations; Communities; Computer software; Data; Development; Devices; Disease remission; Electroconvulsive Therapy; Electroencephalography; Ensure; Equipment; FDA approved; Favorable Clinical Outcome; Feasibility Studies; Generalized seizures; Hand; Head; Human; Image; Individual; Interstitial Collagenase; Investigation; Ketamine; Left; Location; Magnetic Resonance Imaging; Magnetism; Major Depressive Disorder; Marketing; Measures; Medical; Medical center; Mental Depression; Morphology; Motor Cortex; Neuronavigation; Neurosciences; Outcome; Patients; Persons; Pharmaceutical Preparations; Phase; Picture Archiving and Communication System; Pilot Projects; Positioning Attribute; Prefrontal Cortex; Principal Investigator; Procedures; Provider; Publications; Randomized Clinical Trials; Randomized Controlled Trials; Research; Research Personnel; Resistance; Rest; Sampling; Scalp structure; Site; Standardization; Surface; Symptoms; System; Technology; Transcranial magnetic stimulation; Universities; Validation; Variant; awake; base; brain tissue; cingulate cortex; clinical decision support; clinical practice; connectome; efficacy evaluation; improved; in silico; interest; multimodality; neuropsychiatry; noninvasive brain stimulation; programs; reconstruction; repetitive transcranial magnetic stimulation; response; severe mental illness; side effect; software development; standard of care; tool; treatment-resistant depression; virtual

ABSTRACT Transcranial magnetic stimulation (TMS) is an FDA-approved treatment for treatment-resistant major depression (TRD). However, at present the approach is only partially effective, due in part to relatively ineffective targeting approaches. Over recent years, there has been increasing realization that TMS for anhedonic-like symptoms of major depressive disorder (MDD) is most effective when targeted at the region of left dorsolateral prefrontal cortex (L-DLPFC) that is maximally anti-correlated with subgenual anterior cingulate cortex (sgACC) as determined using resting-state functional connectivity MRI (rsfcfMRI). Ideal approaches for identifying this location for individual subjects, however, still depend on processing pipelines that are not FDA cleared and thus and are not accessible to the TMS treatment community. In general, 3D brain reconstructions can be analyzed using either traditional, volumetric approaches, or more recently developed surface-based approaches developed as part of the human connectome project (HCP) and leading to publication of the HCP multimodal brain atlas (HCP MMP1.0). In volumetric approaches, structurally and functionally based approaches have both been implemented. In the surface-based HCP MMP1.0 approach, structural and functional data are merged to identify functionally discrete brain parcels across individuals. Here, during phase I we will first develop an investigational software package (“TMSMap”) that will permit TMS researchers to utilize either volumetric or surface-based analytic approaches for determining MR-based personalized L-DLPFC target locations on-line, and will create a parallel off-line virtual neuro-navigation tool to permit neuro-navigated TMS even for “community” practioners without access to on-line neuro-navigation capabilities. During phase II we will create a Picture Archiving and Communication System (PACS) compliant clinic-ready version, which we evaluate in a multicenter randomized controlled trial in TMS-resistant TRD individuals. We will ensure that all device (software developed to medical standards) and data (clinical validation) requirements are complete by Phase II end, to enable pursuing either a 510(k) or de-novo submission with positive clinical outcome. The project builds both from the long-standing interest of Soterix Medical Inc.(SMI) in 1) the use of combined TMS and neuro-navigation, and 2) the development of automated targeting software for non-invasive brain stimulation; and from recent research by the principal investigator at Columbia University Irving Medical Center (CUIMC) demonstrating 1) anti-correlation of HCP MMP1.0 parcel 46 with sgACC across individuals within the HCP sample and 2) 100% response rate among TMS-resistant TRD patients (n=10) treated with TMS targeted to HCP MMP1.0 parcel 46. Moreover, both effective electroconvulsive therapy and effective TMS were associated with rsfc changes involving DLPFC parcel 46 and additional brain regions. This will be the first software to permit FDA-cleared functional targeting of TMS coil placement using functional as well as structural information, the first to permit virtual as well as on-line neuro-navigation and the first study to evaluate efficacy of surface-based parcel-guided TMS vs. standard of care. If successful, this project will permit improved, targeting of TMS target location across individuals, as well as implementation of personalized, MR-targeted TMS even within community treatment settings. 1

摘要 经颅磁刺激（TMS）是FDA批准的治疗难治性抑郁症的方法 （TRD）。然而，目前这一方法只是部分有效，部分原因是目标相对无效 接近。近年来，越来越多的人认识到，TMS用于治疗 重度抑郁症（MDD）是最有效的，当针对左背外侧前额叶区域 与膝下前扣带皮层（sgACC）最大反相关的皮层（L-DLPFC）， 使用静息状态功能连接MRI（rsfcfMRI）确定。确定这一点的理想方法 然而，个体受试者的位置仍然取决于未经FDA批准的处理管道， TMS治疗社区无法获得。通常，可以分析3D大脑重建， 使用传统的体积法或最近开发的基于表面的方法 作为人类连接体计划（HCP）的一部分开发，并导致HCP多模式 脑图谱（HCP MMP 1.0）。在体积方法中，基于结构和功能的方法同时具有 已实施。在基于表面的HCP MMP 1.0方法中，结构和功能数据被合并， 识别个体之间功能离散的脑区。在此，在第一阶段，我们将首先开发一个 研究软件包（“TMSMap”），将允许TMS研究人员利用体积或 用于在线确定基于MR的个性化L-DLPFC目标位置的基于表面的分析方法， 并将创建一个并行的离线虚拟神经导航工具，以允许神经导航TMS， “社区”从业者无法访问在线神经导航功能。在第二阶段，我们将创建 一个符合PACS标准的临床就绪版本，我们在 在TMS耐药TRD个体中进行的多中心随机对照试验。我们将确保所有设备（软件 根据医疗标准制定）和数据（临床验证）要求在第二阶段结束时完成， 能够继续进行510（k）或重新分类申报，并获得积极的临床结局。该项目同时构建 Soterix Medical Inc.的长期利益。(SMI)在1）组合TMS和神经导航的使用中， 以及2）用于非侵入性脑刺激的自动靶向软件的开发;以及从最近的 哥伦比亚大学欧文医学中心（CUIMC）首席研究员的研究表明： HCP样品中个体间HCP MMP 1.0包裹46与sgACC的反相关性，以及2）100% TMS耐药TRD患者（n=10）接受靶向HCP MMP 1.0包裹46的TMS治疗的缓解率。 此外，有效的电休克治疗和有效的TMS都与rsfc的变化有关 涉及DLPFC包裹46和另外的脑区域。这将是第一个允许FDA批准的软件 使用功能和结构信息对TMS线圈放置进行功能定位，这是第一个允许 虚拟和在线神经导航以及第一项评估基于表面的包裹引导的有效性的研究 TMS与标准治疗。如果成功，该项目将允许改进TMS目标位置， 个人，以及实施个性化，MR靶向TMS，即使在社区治疗 设置. 1