TSPO-PET and MRI imaging as novel imaging tools for autoimmune epilepsy

TSPO-PET 和 MRI 成像作为自身免疫性癫痫的新型成像工具

• 批准号: 10412595
• 负责人: Claude Steriade
• 金额: $ 56.19万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10412595
• 关键词: Aftercare; Albumins; Animal Model; Antibodies; Autoantibodies; Autoimmune; Autoimmune encephalitis; Binding; Biological Markers; Blood - brain barrier anatomy; Cerebrospinal Fluid; Chronic; Classification; Clinical; Clinical Trials; Collaborations; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disease Marker; Encephalitis; Ensure; Epilepsy; Epileptogenesis; Etiology; Exhibits; Functional disorder; Genetic; Human; Image; Imaging Device; Immune; Inflammation; Intervention Studies; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Methodology; Observational Study; Outcome; Partial Epilepsies; Pathologic Processes; Patients; Persons; Phenotype; Positron-Emission Tomography; Proteins; Radial; Recovery; Research; Seizures; Serum; Serum Albumin; Signs and Symptoms; Site; Surrogate Markers; Techniques; Temporal Lobe Epilepsy; Testing; Update; Validation; Variant; biomarker-driven; blood-brain barrier disruption; blood-brain barrier permeabilization; clinical diagnosis; cohort; contrast enhanced; cost estimate; diagnostic biomarker; disorder control; imaging biomarker; imaging modality; imaging scientist; imaging study; immunoregulation; improved; innovation; neuroimaging; neuroinflammation; novel; patient population; radioligand; regional difference; relating to nervous system; standard of care; targeted treatment; therapeutic biomarker; tool; treatment planning; treatment response; uptake

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.

项目摘要 免疫调节治疗自身免疫性癫痫在临床观察中具有良好的效果 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病因学的诊断和治疗生物标志物是有限的 因为不完全的敏感性和缺乏与临床过程的相关性。在这份提案中，我们建议 通过使用新的成像方法，可以广泛地 适用的工具，并帮助阐明这组患者的疾病神经炎症机制， 成为病因靶向治疗的候选者。在目标1中，我们将使用一种新的 放射性配体（[11 C] ER 176），用于定量和可视化明确自身抗体患者中的小胶质细胞活化 自身免疫性癫痫阳性和临床疑似但抗体阴性的自身免疫性癫痫，以及 将其与疾病对照（已知结构性原因的局灶性癫痫）和健康对照进行比较。在目标2中，我们 将进行传统和新型的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，相同的明确和临床疑似自身免疫性癫痫组。 在一个小的验证队列中，我们还将进行CSF与血清白蛋白的比值，以验证我们的成像 测量BBB破坏。在目标3中，我们将在标准治疗后重复TSPO-PET和DCE-MRI 对患有明确的自身免疫性癫痫的受试者施用免疫调节， 通过DCE-MRI测量TSPO摄取和2）BBB破坏，具有亚急性癫痫发作结局。这些目标 将通过癫痫科和高级成像中心之间的合作来实现 纽约大学的创新和研究，包括癫痫学家，临床神经放射学家和成像科学家。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替代药物 疾病标志物不仅能够检测，而且能够在治疗过程中跟踪疾病活动。