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

摘要 经颅磁刺激(TMS)是FDA批准的治疗耐药的方法 重度抑郁症(TRD)。然而，目前这种方法只有部分有效，部分原因是 到相对低效的目标定位方法。近几年来，有越来越多的 认识到TMS对重度抑郁障碍(MDD)的非享乐样症状的治疗最多 当靶向左侧背外侧前额叶皮质(L-DLPFC)区域时有效，即 与亚膝前扣带回皮质(SgACC)的最大反相关 静息状态功能连接磁共振成像(RsfcfMRI)。确定这一位置的理想方法 然而，对于个别受试者，仍然依赖于未经FDA批准的处理管道 并因此对TMS治疗社区是不可访问的。总的来说，3D大脑 重建可以使用传统的体积方法进行分析，也可以使用最近的方法 作为人类连接组项目(HCP)的一部分而开发的基于表面的方法 并导致了《HCP多模式脑图谱》(HCP MMP1.0)的出版。在体积中 已经实施了基于结构和功能的方法。在 基于表面的HCP MMP1.0方法，将结构和功能数据合并以识别 不同个体之间在功能上不连续的脑区。在这里，在第一阶段中，我们将首先开发一个 调查软件包(“TMS-TARGETS”)，将允许TMS研究人员利用 基于体积或表面的分析方法确定基于MR的个性化L DLPFC目标位置在线，并将创建一个并行离线虚拟神经导航工具来 允许神经导航的TMS，即使是对于无法访问在线神经的“社区”医生也是如此。 导航功能。在第二阶段，我们将创建图片存档和交流 符合系统(PACS)的临床就绪版本，我们在多中心随机评估 对耐TMS的TRD患者进行的对照试验。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)要求由 第二阶段结束，以实现510(K)或从头提交临床阳性的申请 结果。该项目建立在Soterix Medical Inc.(SMI)在 1)TMS和神经导航相结合的使用；2)自动化的发展 用于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)的研究人员展示了1)HCP MMP1.0包的反相关性 46在HCP样本中的个人之间使用sgACC，2)100%的应答率 耐TMS的TRD患者(n=10)接受靶向HCP MMP1.0包46的TMS治疗。 此外，有效的电休克治疗和有效的TMS都与rsfc有关。 涉及DLPFC包46和其他脑区的变化。这将是第一个 允许经FDA批准的TMS线圈放置的功能目标 结构信息，第一个允许虚拟和在线神经导航，以及第一个 评价表面包裹引导TMS的疗效与标准护理的比较研究。如果成功， 该项目将允许改善，有针对性的TMS目标位置跨个人，以及 实施个性化、针对MR的TMS，即使在社区治疗环境中也是如此。

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.