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

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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.