Neuroimaging of Neuroinflammation in Temporal Lobe Epilepsy

Neuroimaging of Neuroinflammation in Temporal Lobe Epilepsy Project Summary/Abstract Epileptogenesis, a dynamic and adaptive process, is associated with focal neuroinflammation (NI). This, in turn, is accompanied by glial activation and corresponding focal temperature increases. Methods of visualizing NI have been tested mostly in animal models of epilepsy and are not readily translatable to in vivo human imaging. Advanced positron emission tomography (PET) has been used for human in vivo NI visualization. However, advanced PET methods are underdeveloped, unreliable for identification of NI, riddled with many technical, genetic and logistical obstacles, expensive, and readily available to only few investigators. A less technically challenging technique of in vivo NI visualization is greatly needed. We, thus, propose to investigate and validate a technique called magnetic resonance spectroscopic imaging and thermometry (MRSI-t) {via biomarkers in brain tissue and peripheral blood. MRSI-t measures} in vivo brain temperature (T) increases in response to focal NI; it relies on measuring the location of creatine (CRE) and H2O peaks on the ppm chemical shift distribution in multiple and relatively small voxels encompassing the whole brain. While the location of the CRE peak is stable on the ppm spectrum, the location of the H2O peak changes with temperature (TCRE) fluctuations. The first step towards implementing MRSI-t as a tool for in vivo assessment of NI is to determine the degree of focal TCRE elevation in treatment-resistant temporal lobe epilepsy (TR-TLE) and whether MRSI-t can differentiate TR-TLE from controlled TLE (C-TLE). It is also important to show that the TCRE measures are stable over time. Finally, the key is to examine the relationship between the results of MRSI-t and biomarkers of NI in the resected brain tissue from epilepsy surgery and in peripheral blood. To address this, we propose three specific aims: AIM 1: To quantify the TCRE distribution patterns in TR-/C-TLE participants and compare them to healthy controls, AIM 2: To assess the 12-week stability of the focal TCRE measurements in patients with TR-/C-TLE, and AIM 3: To determine the relationship between focal increase in TCRE and 1). Focal changes in NI biomarkers in surgically resected temporal lobe tissue and 2). Blood biomarkers of inflammation. Via completion of this project, we will determine the utility of MRSI-t for detecting TCRE elevations as a proxy for chronic low-grade NI that is the underlying cause of treatment resistance in TLE and the stability of the MRSI-t signals in TR-/C-TLE over time. We expect that this will lead to further development of MRSI-t as a biomarker for treatment resistance and allow for development of MRSI-t as a method for monitoring treatment response in focal TR-/C-TLE and its use in the presurgical evaluation of patients with TR-TLE.