Imaging inflammation in focal epilepsy

描述（由申请人提供）：癫痫影响世界人口的0.5%至1%，并且在30-40%的人口中不受药物控制。尽管对癫痫动物模型中的分子和细胞过程的了解不断增加，但对人类癫痫的发生和维持仍然知之甚少。由于这些原因，需要新的模型来理解人类癫痫和创新的方法来诊断和治疗难治性癫痫患者。该项目的总体目标是利用互补的多模态神经成像技术来确定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，本项目将使用激活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病灶区域，并且1)这些炎症区域将对应于患者临床定义的癫痫发作区域的位置；2)炎症程度与疾病严重程度相关；3)通过功能性MRI评估，炎症区域将表现出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影像学标记，本研究的结果可以在癫痫手术的临床评估中帮助识别患者的癫痫发生区，并最终为有癫痫发生风险的患者提供一种监测癫痫发生的方法。根据候选人在癫痫功能神经影像学和临床培训方面的研究背景，我们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的指导；2)放射学和PET方法学培训；3)对癫痫相关神经炎症的生物学机制有深入的了解。一个杰出的导师/顾问团队已被召集来指导候选人，因为她承担这个多学科，翻译为基础的项目。这项研究将通过更好地了解和治疗人类癫痫来改善公众健康。

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.