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

摘要 经颅磁刺激（TMS）是FDA批准的治疗难治性 重度抑郁症（TRD）。然而，目前这种做法只是部分有效，部分原因是 相对无效的目标定位方法。近年来， 意识到TMS对重度抑郁症（MDD）的快感缺失样症状是最重要的， 当靶向左背外侧前额叶皮层（L-DLPFC）区域时有效， 与膝下前扣带皮层（sgACC）的最大反相关性， 静息态功能连接MRI（rsfcfMRI）。确定此位置的理想方法 然而，对于个体受试者，仍然依赖于未经FDA批准的处理管道 因此TMS治疗社区无法获得。一般来说，3D大脑 可以使用传统的体积方法或最近的方法来分析重建 开发了基于表面的方法，作为人类连接体项目（HCP）的一部分 并导致HCP多模态脑图谱（HCP MMP 1.0）的出版。置于容量 基于结构和功能的方法都已实施。在 基于表面的HCP MMP 1.0方法，结构和功能数据被合并以识别 功能离散的大脑包裹。在此，在第一阶段，我们将首先开发一个 研究软件包（“TMS目标”），将允许TMS研究人员利用 基于体积或表面的分析方法，用于确定基于MR的个性化L- DLPFC目标位置在线，并将创建并行离线虚拟神经导航工具， 允许神经导航TMS，即使是“社区”从业者，也无法访问在线神经导航系统， 导航能力。在第二阶段，我们将创建一个图片库和通信 系统（PACS）兼容的临床就绪版本，我们在多中心随机 在TMS耐药TRD个体中进行对照试验。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， II期结束，以便能够继续进行510（k）或重新申报，并获得阳性临床试验 结果。该项目建立在Soterix医疗公司的长期利益基础上。(SMI)在 1)TMS和神经导航相结合的使用，以及2）自动化的开发 非侵入性脑刺激的靶向软件;以及校长最近的研究 哥伦比亚大学（CU）研究人员证明了1）HCP MMP 1.0包裹的反相关性 HCP样本中46例sgACC患者，2）HCP样本中100%的应答率 TMS耐药TRD患者（n=10）接受靶向HCP MMP 1.0包裹46的TMS治疗。 此外，有效的电休克治疗和有效的TMS都与rsfc相关 涉及DLPFC包裹46和其他大脑区域的变化。这将是第一个软件 允许FDA批准的TMS线圈放置的功能目标， 结构信息，第一个允许虚拟以及在线神经导航和第一个 评价基于表面的包裹引导TMS与标准治疗的有效性的研究。如果成功， 该项目将允许改进TMS目标位置的针对性， 即使在社区治疗环境中，也可以实施个性化的MR靶向TMS。

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 (“TMS-Targets”) 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 (CU) 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.