Mechanisms Altering Electrical Conductivity & DTI in Epilepsy Surgery Patients

描述（由申请人提供）：癫痫是一种常见的神经系统疾病，25%至30%的患者患有难治性癫痫。在那些癫痫不受控制的患者中，如果EEG可以定位到单个部位，有些可能是癫痫神经外科手术的候选者。由于大脑电导率的空间非均匀性，头皮EEG在源定位方面具有局限性。本研究的目的是通过整合不同的研究技术，提高我们对癫痫手术患者脑微结构影响脑电源定位的理解。在初步研究中，我们表明，皮质电导率是定向特异性的，并取决于病理类型。此外，通过扩散张量成像（DTI）MRI测量的脑电导率和脑水扩散率之间存在关系。这些发现支持我们的目标，测量脑电导率和DTI，并将这些与改变的脑结构作为改善EEG源定位方法的步骤。我们将通过以下方式实现我们的目标：1）测量平行和垂直于软膜表面的皮质灰质和皮质下白色物质的电导率; 2）通过在正常和异常脑的动物模型中进行体内和体外实验来验证脑电导率的体外测量在体内条件下的复制; 3）术前DTI测定水扩散张量及相关的主扩散系数（特征值），主方向（本征向量）和FA，其中在所述脑回和皮层位点上执行电导率测量; 3）确定与用于电导率和DTI测量的部位相邻的部位中的皮质紊乱的组织病理学测量;（4）用头皮EEG和MEG模拟EEG发作间期放电。MSI使用模型，该模型结合了来自电导率和DTI的等营养脑的测量，并确定这些新方法是否更接近地确定EEG由ECoG确定的来源。这些实验的结果将为R 01应用程序提供必要的初步数据，以开发针对个体患者的颅内EEG源定位方法。 公共卫生相关性：三分之一的癫痫患者的癫痫发作不受药物控制，并且有癫痫发作引起的死亡和智力迟钝的风险。手术是治疗不受控制的癫痫发作的一种选择，但由于EEG和MRI技术的限制，只有不到一半的人是候选人。这项拨款将通过研究癫痫患者的电信号是否以不同的方式通过大脑来改善这些工具，是否可以使用新的MRI技术来估计电信号变化，以及电和MRI变化是否来自大脑皮层的紊乱。

DESCRIPTION (provided by applicant): Epilepsy is a frequent neurological disorder, and 25% to 30% have therapy-resistant epilepsy. Of those with uncontrolled epilepsy, some may be candidates for epilepsy neurosurgery if the EEG can be localized to a single site. Scalp EEG has limitations with regard to source localization because of spatial non-uniformity of the brain's electrical conductivity. The goals of this project are to improve our understanding of the brain micro-structure that effect EEG source localization by integrating different research techniques in epilepsy surgery patients. In Preliminary Studies, we demonstrate that cortical electrical conductivities are directionally specific and depend on the type of pathology. Also, there is a relationship between measures of brain electrical conductivity and brain water diffusivity measured by Diffusion Tensor Imaging (DTI) MRI. These findings support our goal of measuring brain electrical conductivity and DTI, and relating these to altered brain structure as steps toward improving methods of EEG source localization. We will accomplish our goals by: 1) Measuring the electrical conductivity of cortical gray matter and subcortical white matter parallel and perpendicular to the pial surface; 2) validate that ex vivo measures of brain electrical conductivity replicate in vivo conditions by performing in vivo and ex vivo experiments in animal models of normal and abnormal brains; 3) use presurgical DTI to determine the water diffusion tensor and the associated principal diffusivities (eigenvalues), principal directions (eigenvectors) and FA from the gyri and cortical sites on which the electrical conductivity measures are performed; 3) determine histopathologic measures of cortical disorganization in sites adjacent to those used for the electrical conductivity and DTI measurements; and 4) model EEG interictal discharges from scalp EEG and MEG/MSI using models that incorporate measures of isotrophic brain from electrical conductivity and DTI and determine if these new methods more closely determine EEG sources as determined by ECoG. The results of these experiments will provide the necessary Preliminary data for an R01 application to develop methods of intracranial EEG source localization that will be individual patients. PUBLIC HEALTH RELEVANCE: One-third of epilepsy patients have seizures that are not controlled by drugs, and are at risk for seizure- induced death and mental retardation. Surgery is an option to treat uncontrolled seizures, but less than half are candidates because of limitations of EEG and MRI techniques. This grant will improve these tools by studying if electrical signals move through the brain differently in epilepsy patients, whether electrical signal changes can be estimated using new MRI techniques, and if the electrical and MRI changes are from disorganization of the cerebral cortex.