Imaging inflammation in focal epilepsy

描述(申请人提供)：癫痫影响世界人口的0.5%到1%，并且不能通过药物控制在30%到40%。尽管对癫痫动物模型中的分子和细胞过程的了解越来越多，但人类癫痫的发生和维持仍然知之甚少。出于这些原因，需要了解人类癫痫的新模型，以及诊断和治疗难治性癫痫患者的创新方法。这个项目的广泛目标是使用互补的多模式神经成像技术来识别人类癫痫和癫痫发生的神经生物学机制。基于癫痫动物模型中的神经炎症可能是癫痫发作的原因和后果的证据，该项目将使用激活的小胶质细胞的正电子发射断层扫描(PET)标记来评估颞叶癫痫患者的神经炎症。假设在癫痫发作后不久进行PET扫描时，将检测到异常炎症的局部区域，并且1)这些炎症区域将对应于患者临床定义的癫痫发作起始区的位置；2)炎症的程度将与疾病严重程度的测量相关；以及3)通过功能MRI评估，炎症区域将显示与其他大脑区域的异常网络连接。通过提供癫痫局部炎症的神经成像标记物，这项研究的结果可以在癫痫手术的临床评估背景下帮助识别患者的致痫区域，并最终可能提供一种监测有癫痫风险的患者的癫痫发生的方法。基于候选人在功能神经成像和癫痫临床培训方面的研究背景，设计了一个教育计划，为她提供：1)临床研究和应用生物统计学指导方面的教育；2)放射配基PET方法学培训；以及3)对癫痫相关神经炎症的生物学机制的扎实理解。一支杰出的导师/顾问团队已被召集起来，指导候选人进行这一以翻译为基础的多学科项目。这项研究将通过更好地了解和治疗人类癫痫来改善公共健康。

DESCRIPTION (provided by applicant): Epilepsy affects 0.5 to 1% of the world's population, and is not controlled by medications in 30-40%. Despite increasing knowledge of molecular and cellular processes in animal models of epilepsy, the genesis and maintenance of epilepsy in humans remains poorly understood. For these reasons, new models for understanding human epilepsy and innovative approaches to the diagnosis and treatment of patients with medically-refractory epilepsy are needed. The broad objective of this project is to use complementary multimodal neuroimaging techniques to identify neurobiological mechanisms underlying epilepsy and epileptogenesis in humans. Building upon evidence that neuroinflammation in animal models of epilepsy may be both cause and consequence of seizures, this project will assess neuroinflammation in patients with temporal lobe epilepsy using a Positron Emission Tomography (PET) marker of activated microglia. It is hypothesized that focal regions of abnormal inflammation will be detected when PET scanning is performed shortly after seizures, and that 1) these regions of inflammation will correspond to the location of a patient's clinically-defined seizure onset zone; 2) degree of inflammation will correlate with measures of disease severity; and 3) regions of inflammation will demonstrate abnormal network-connectivity with other brain areas, as assessed through functional MRI. By providing a neuroimaging marker of localized inflammation in epilepsy, results from this research could aid identification of a patient's epileptogenic zone in the context of clinical evaluations for epilepsy surgery, and could eventually provide a method for monitoring epileptogenesis in patients at risk of developing epilepsy. Building upon the candidate's research background in functional neuroimaging and clinical training in epilepsy, an educational program has been designed to provide her with: 1) education in the conduct of clinical research and applied biostatistics; 2) training in radioligand PET methodology; and 3) a solid understanding of biological mechanisms of epilepsy-related neuroinflammation. A distinguished team of mentors/advisors has been assembled to guide the candidate as she undertakes this multidisciplinary, translationally-based project. This research will improve public health through better understanding and treatment of human epilepsy.