MAPPING ELOQUENT CORTEX USING RESTING STATE CORTICAL PHYSIOLOGY

描述(由申请人提供)： 脑肿瘤外科治疗的一个挑战是在最大限度地扩大切除范围的同时，保留脑功能的有说服力的区域。为此，目前的术前和术中脑地形图技术需要患者的积极参与，这限制了它们在相当数量的患者(如儿童)中的使用。这一限制妨碍了最佳切除。迫切需要开发一种可用于所有患者、可在术前和术中进行、并可用于全身麻醉设置的脑电地形图方法。基于静息状态皮层生理学的新方法，如功能连接磁共振成像(FcMRI)和慢皮质电位标测(SCPM)，正在作为识别运动和语音网络的技术出现。我们研究的长期目标是通过改善术前和术中的标测，在更广泛的脑肿瘤患者群体中实现更有效的切除。这项应用的总体目标是在胶质瘤患者中确定与静息状态方法确定的功能部位之间的对应关系，以确定通过更成熟的术前和术中定位方法确定的区域。中心假设是，术前fcMRI和术中SCPM在麻醉状态下将识别口才皮质的解剖位置，这些解剖位置与术前(基于任务的fMRI)和术中(直接皮质刺激，DECS)功能定位的黄金标准方法以及彼此之间的位置一致。这项提议背后的理论基础是，这个项目将提供一种经过验证的术前和术中脑成像方法，这种方法可以在麻醉下进行，在没有患者参与的情况下进行，这将为更明确地进行奠定基础。 未来的临床结果研究。我们将通过以下三个具体目标来验证我们的中心假设：1)使用术前静息状态功能连接磁共振成像(FcMRI)识别靠近脑肿瘤的运动和语言皮质；2)使用术中慢皮质电位标测(SCPM)识别麻醉下脑肿瘤附近的运动和语言皮质；以及3)确定fcMRI和SCPM识别DECS阳性部位的功能区之间的一致性。我们将通过招募20名新诊断为原发性胶质瘤的成人受试者来实现这些目标，这些受试者将接受手术切除，术中使用DECS。使用我们实验室开发的方法，每个患者都将得到术前fcfMRI和术中SCPM，然后这些结果将被用来预测当前金标准技术所确定的部位。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DECS，并且可能用于识别当前未绘制的网络。因此，这个项目意义重大，因为静息状态图将不再需要患者的参与/意识来成功识别脑瘤背景下的关键功能部位。总而言之，这种能力将使更多的患者群体更容易接受更有效的切除，并减轻脑瘤的个人和集体负担。 公共卫生相关性：拟议的研究与公共健康相关，因为当脑肿瘤在大脑的关键部位被诊断出来时，如运动区或语言区，神经外科医生必须准确地知道这些区域的位置，以避免在肿瘤切除过程中对它们造成损害。目前绘制这些区域图的方法仅限于能够配合检查的患者，不能在儿童或困惑或服用镇静剂的患者中执行。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成像技术，该项目将极大地提高更有效地手术治疗脑瘤的能力，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.