TSPO-PET and MRI Imaging as Novel Imaging Tools for Autoimmune Epilepsy

项目摘要 自身免疫性癫痫的免疫调节治疗在临床观察中取得了良好的效果。 研究，但自身免疫性癫痫的诊断和治疗仍然存在问题。神经的价值 自身抗体作为癫痫自身免疫性病因的诊断和治疗生物标记物的作用有限 由于敏感性不高，与临床病程缺乏相关性。在这项提案中，我们建议在 利用新的成像方法在这一领域的诊断和治疗生物标记物的差距 适用的工具和帮助阐明这组患者疾病的神经炎症机制，这些患者可能 成为病因学靶向治疗的候选对象。在目标1中，我们将使用一种新的TSPO-PET成像技术 放射性配基([11C]ER176)，用于定量和可视化确定自身抗体患者的小胶质细胞激活 自身免疫性癫痫阳性，临床怀疑但抗体阴性的自身免疫性癫痫，以及 将它们与疾病对照组(已知结构原因的局灶性癫痫)和健康对照组进行比较。在目标2中，我们 将执行传统的和新型的DCE MRI以量化和可视化血脑屏障(BBB)的破坏 与疾病和健康对照组相比，确定的和临床怀疑的自身免疫性癫痫组相同。 在一个小的验证队列中，我们还将执行脑脊液与血清白蛋白的比率来验证我们的成像 血脑屏障中断的测量。在目标3中，我们将在标准护理后重复TSPO-PET和DCE-MRI 对确诊为自身免疫性癫痫和相关改变的受试者进行免疫调节1) TSPO摄取和2)DCE-MRI测量的血脑屏障破坏，并伴有亚急性癫痫结果。这些目标 将通过癫痫科和高级成像中心之间的合作实现 纽约大学的创新和研究，包括癫痫专家、临床神经放射科医生和影像科学家。通过 使用新的成像方法来测量不同的神经炎症机制，我们将超越 单纯依靠神经自身抗体诊断自身免疫性癫痫并开发潜在的替代物 疾病的标记物，可能不仅能够检测到，而且能够跟踪治疗过程中的疾病活动。

Project Summary Autoimmune epilepsy has been treated with immunomodulation with promising results in clinical observational studies, but the diagnosis and treatment of autoimmune epilepsy remains problematic. The value of neural autoantibodies as diagnostic and therapeutic biomarkers of an autoimmune etiology of seizures has been limited because of imperfect sensitivity and lack of correlation with clinical course. In this proposal, we propose to bridge the diagnostic and therapeutic biomarker gap in this field by using novel imaging methods that could be broadly applicable tools and help elucidate neuroinflammatory mechanisms of disease in this group of patients who may be candidates for etiology-targeted treatment. In aim 1, we will perform TSPO-PET imaging, with a novel radioligand ([11C]ER176), to quantify and visualize microglial activation in patients with definite autoantibody positive autoimmune epilepsy, and clinically suspected but antibody negative autoimmune epilepsy, and compare them to disease controls (focal epilepsy of known structural cause) and healthy controls. In aim 2, we will perform traditional and novel DCE MRI to quantify and visualize blood-brain barrier (BBB) disruption in the same definite and clinically suspected autoimmune epilepsy groups, compared to disease and healthy controls. In a small validation cohort, we will also perform CSF to serum albumin ratios to validate our imaging measurements of BBB disruption. In aim 3, we will repeat TSPO-PET and DCE-MRI after standard of care immunomodulation is administered to subjects with definite autoimmune epilepsy and correlate changes in 1) TSPO uptake and 2) BBB disruption as measured by DCE-MRI, with subacute seizure outcomes. These aims will be achieved through a collaboration between the Division of Epilepsy and the Center for Advanced Imaging Innovation and Research at NYU, including epileptologists, clinical neuroradiologists, and imaging scientists. By using novel imaging methods that measure different neuroinflammatory mechanisms, we will move beyond the sole reliance on neural autoantibodies for the diagnosis of autoimmune epilepsy and develop potential surrogate markers of disease that may be able to not only detect, but track disease activity in the context of treatment.