Mechanisms Altering Electrical Conductivity & DTI in Epilepsy Surgery Patients

描述（申请人提供）：癫痫是一种常见的神经系统疾病，25% - 30%为难治性癫痫。对于那些不受控制的癫痫患者，如果脑电图可以定位到单一部位，一些人可能是癫痫神经外科手术的候选人。由于脑电导率的空间不均匀性，头皮脑电图在源定位方面存在局限性。本项目的目的是通过对癫痫手术患者的不同研究技术的整合，提高我们对影响脑电图源定位的大脑微观结构的理解。在初步研究中，我们证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。这些发现支持了我们测量脑电导率和DTI的目标，并将这些与改变的大脑结构联系起来，作为改进脑电图源定位方法的步骤。我们将实现我们的目标：1)测量平行于和垂直于脑皮层表面的皮层灰质和皮层下白质的电导率；2)通过对正常和异常脑动物模型进行体内和体外实验，验证脑电导率的离体测量在体内复制；3)使用术前DTI来确定脑回和皮质部位的水扩散张量和相关的主扩散系数（特征值）、主方向（特征向量）和FA，这些部位进行了电导率测量；3)测定与电导率和DTI测量相邻部位皮质失组织的组织病理学测量；4)使用结合电导和DTI等营养脑测量的模型对头皮EEG和MEG/MSI的脑电信号间期放电进行建模，并确定这些新方法是否与ECoG确定的脑电图源更接近。这些实验结果将为R01应用于开发针对个体患者的颅内脑电图源定位方法提供必要的初步数据。

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.