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%至40%的人口中无法通过药物控制。尽管癫痫动物模型的分子和细胞过程的知识越来越多，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和诊断和治疗难治性癫痫患者的创新方法。该项目的主要目标是使用互补的多模态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）标记物评估颞叶癫痫患者的神经炎症。假设当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的临床定义的癫痫发作区的位置; 2）炎症程度将与疾病严重程度的测量相关;和3）炎症区域将显示与其他脑区的异常网络连接，如通过功能性MRI评估的。通过提供癫痫局部炎症的神经影像学标志物，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致痫区，并最终提供一种监测癫痫患者癫痫发生的方法。基于候选人在癫痫功能性神经影像学和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的教育; 2）放射性配体PET方法学的培训; 3）对癫痫相关神经炎症的生物学机制的深刻理解。一个杰出的导师/顾问团队已经组装，以指导候选人，因为她承担这个多学科，基于实践的项目。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.