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%至30%患有难治性癫痫。在那些不受控制的癫痫患者中，如果脑电可以定位在一个单一的部位，一些人可能会接受癫痫神经外科手术。由于大脑电导率的空间不均匀，头皮脑电在来源定位方面存在局限性。本项目的目标是通过整合癫痫手术患者的不同研究技术，提高我们对影响脑电源定位的脑微结构的理解。在初步研究中，我们证明了皮质电导性是方向性的，并且取决于病理类型。此外，脑电导率的测量与弥散张量成像(DTI)MRI测量的脑水扩散率之间也存在关系。这些发现支持我们的目标，即测量大脑电导率和DTI，并将它们与大脑结构的改变联系起来，以此作为改进脑电源定位方法的步骤。我们将通过以下方式实现我们的目标：1)测量与软膜表面平行和垂直的皮质灰质和皮质下白质的电导率；2)通过在正常和异常脑的动物模型上进行体内和体外实验，验证体外脑电导率测量方法重复活体条件；3)使用术前DTI从执行电导率测量的脑回和皮质部位确定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；3)确定用于电导率和DTI测量的邻近部位皮质电导率紊乱的组织病理学测量；以及4)使用模型来模拟头皮EEG和MEG/MSI的EEG发作间歇放电，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由ECoG确定的EEG来源。这些实验的结果将为R01的应用提供必要的初步数据，以开发针对个别患者的颅内EEG来源定位方法。 公共卫生相关性：三分之一的癫痫患者有不受药物控制的癫痫发作，并面临癫痫导致死亡和精神发育迟缓的风险。手术是治疗失控癫痫的一种选择，但由于EEG和MRI技术的限制，只有不到一半的人是候选的。这笔赠款将通过研究癫痫患者的电信号在大脑中的移动方式是否不同，电信号的变化是否可以使用新的MRI技术来估计，以及电信号和MRI的变化是否来自大脑皮层的紊乱，来改进这些工具。

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.