346 Development of Deuterium Magnetic Resonance Imaging for Cerebrospinal Fluid Studies

Abstract

INTRODUCTION: Over the past ten years, the role of the glymphatic system has been defined and explored using various cerebrospinal fluid (CSF) tracers to track the movement of CSF through the perivascular spaces and into the brain interstitium. Glymphatic studies most commonly use gadolinium as a CSF tracer, which is not blood-brain-barrier (BBB) soluble. The primary component of CSF is water, however, which is BBB permeable. Cerebrospinal fluid may behave differently than large molecule tracers. Heavy water (D2O) is an isotope of water often used in physiology studies. We hypothesized that D2O would provide a traceable MR signal in the brain, allowing for more physiologically realistic models of CSF flow within the glymphatic system. METHODS: Two adult male rats underwent deuterium enhanced MR imaging. Images were obtained using a custom-made RF transmit/receive coil from Rapid MR International that is dual tuned to both proton (1H, 300.3 MHz) and deuterium (2H, 46.1 MHz) resonant frequencies for use in a 7 Tesla Bruker MRI system. After appropriate system calibration for optimization of deuterium MR signal with intravenous D2O infusion, the rats underwent spinal catheter implantation for intrathecal infusion. Images were taken during and after D2O infusion to evaluate uptake and clearance. RESULTS: Deuterium produced a imageable MR signal in the brain with intravenous and intrathecal infusion. Complete signal washout was noted within 10 minutes of stopping the intrathecal infusion. CONCLUSIONS: Deuterium MRI holds promise as a physiologic CSF tracer. As the technique is refined, it can be used for further CSF physiology studies. The rapid clearance of intrathecal D2O as compared to previous models using gadolinium supports our theory that CSF behaves differently than the large molecule tracers historically used to characterize its flow.