MAPPING ELOQUENT CORTEX USING RESTING STATE CORTICAL PHYSIOLOGY

描述（由申请人提供）： 脑肿瘤手术治疗的一个挑战是在最大限度切除的同时保留脑功能的功能区。为此，当前的术前和术中脑映射技术需要患者积极参与，这限制了它们在大量患者（例如儿童）中的使用。这种限制妨碍了最佳切除。迫切需要开发可用于所有患者、可在术前和术中进行并可用于全身麻醉的脑映射方法。基于静息状态皮层生理学的新方法，如功能连接MRI（fcMRI）和慢速皮层电位映射（SCPM），正在成为识别运动和言语网络的技术。我们研究的长期目标是通过改善术前和术中标测，在更广泛的功能区皮质附近脑肿瘤患者人群中实现更有效的切除。本申请的总体目标是在神经胶质瘤患者体内确定静息状态方法确定的功能部位与更成熟的术前和术中定位方法确定的功能部位之间的对应关系。中心假设是，术前fcMRI和术中SCPM在麻醉下将确定功能皮层的解剖位置，这些位置与使用术前（基于任务的fMRI）和术中（直接皮层电刺激，德克斯）功能定位的金标准方法的部位一致，并且彼此一致。该提案的基本原理是，该项目将提供一种经验证的术前和术中脑标测方法，该方法可以在麻醉下和没有患者参与的情况下完成，这将为更明确的 未来的临床研究。我们将通过以下三个具体目标来检验我们的中心假设：1）使用术前静息状态功能连接性磁共振成像（fcMRI）识别接近脑肿瘤的运动和语言皮层，2）使用术中慢皮层电位映射（SCPM）在麻醉下识别接近脑肿瘤的运动和语言皮层，（3）在德克斯阳性位点的识别中，确定fcMRI和SCPM识别的功能区域之间的一致性。我们将通过招募20名新诊断的原发性胶质瘤成人受试者来实现这些目标，这些受试者将接受术中德克斯手术切除。使用我们实验室开发的方法，每位患者将获得术前fcfMRI和术中SCPM，然后将这些发现用于预测当前金标准技术定义的部位。该项目具有创新性，因为这些发现将提供一种全新的方法，该方法独立于患者状态，不需要德克斯，并且可以用于识别当前未映射的网络。因此，该项目是重要的，因为静息状态映射将满足患者参与/意识的需要，以成功地识别脑肿瘤背景下的关键功能部位。总之，这种能力将使更多的患者群体能够接受更有效的切除术，并减少脑肿瘤的个体和集体负担。 公共卫生相关性：这项拟议的研究与公共卫生有关，因为当脑肿瘤被诊断出位于大脑的关键部位时，如运动或语言区域，神经外科医生必须确切知道这些区域的位置，以避免在肿瘤切除过程中损坏它们。目前用于映射这些区域的方法仅限于能够配合检查的患者，并且不能在儿童或混乱或镇静的患者中进行。与国家癌症研究所的使命一致，通过开发仅使用不需要患者参与或意识的静息状态脑信号的脑映射技术，该项目将大大提高更有效的脑肿瘤手术治疗的能力，并适用于更广泛的患者群体。

DESCRIPTION (provided by applicant): A challenge in the surgical treatment of brain tumors is to preserve eloquent areas of brain function while maximizing extent of resection. To do so, current pre-operative and intra- operative brain mapping techniques require active patient participation, which limits their use in a significant number of patients (e.g. children). This limitation prohibits an optimal resection. There is an urgent need to develop brain mapping methodologies that can be used in all patients, can be performed both pre- and intra-operatively, and can be used in the setting of general anesthesia. New approaches based on resting state cortical physiology, such as functional connectivity MRI (fcMRI) and slow cortical potential mapping (SCPM), are emerging as techniques to identify motor and speech networks. The long-term goal of our research is to achieve more effective resections in a broader patient population with brain tumors near eloquent cortex by improving pre- and intra-operative mapping. The overall objective of this application is to define within patients with gliomas the correspondence between functional sites identified with resting state approaches to those areas identified by more established methods of pre-operative and intra-operative localization. The central hypothesis is that pre-operative fcMRI and intra-operative SCPM while under anesthesia will identify anatomic locations of eloquent cortex that are consistent with sites using the gold standard methods of pre-operative (task-based fMRI) and intra-operative (direct electrocortical stimulation, DECS) functional localization and with each other. The rationale that underlies this proposal is that this project wll provide a validated method of pre- and intra-operative brain mapping that can be done under anesthesia and in the absence of patient participation which will set the stage for more definitive clinical outcome studies in the future. We will test our central hypotheses with the following three specific aims: 1) Identify motor and language cortex in proximity to brain tumors using pre- operative resting state functional connectivity magnetic resonance imaging (fcMRI), 2) Identify motor and language cortex in proximity to brain tumors under anesthesia using intra-operative slow cortical potential mapping (SCPM), and 3) Define concordance between functional regions identified with fcMRI and SCPM in identifying DECS positive sites. We will implement these aims by enrolling 20 adults subjects with newly diagnosed primary gliomas that are to undergo surgical resection with intra-operative DECS. Using methods developed by our labs, each patient will get pre-operative fcfMRI and intra-operative SCPM and these findings will then be used to predict sites defined by current gold standard techniques. This project is innovative because these findings will provide a wholly new approach that is independent of patient state, does not require DECS, and can potentially be used to identify networks not currently mapped. Thus, this project is significant because resting-state mapping will obviate the need for patient participation/consciousness to successfully identify critical functional sites in the context of a brain tumor. In sum, such capabilities will make a larger patient population amenable to more effective resections and reduce individual and collective burden of brain tumors. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because when brain tumors are diagnosed in critical parts of the brain, such as the motor or language areas, it is important for the neurosurgeon to know exactly where these areas are located in order to avoid damaging them during the tumor resection. Current methods for mapping these regions are limited to patients than can cooperate with the exam and cannot be performed in children or in patients that are confused or sedated. Consistent with the National Cancer Institute's mission, by developing brain mapping techniques that use resting state brain signals alone which do not require patient participation or consciousness, this project will greatly enhance the ability for more effective surgical treatments of brain tumors and be applicable to a broader patient population.