185 Deuterium MRI for CSF Studies in Normal and Hydrocephalic Rats

INTRODUCTION: The recent characterization of the glymphatic system has revived interest in the interaction of cerebrospinal fluid (CSF) with brain tissue via perivascular spaces. Traditional CSF tracers, such as gadolinium and iohexal, are large molecules that do not cross the blood brain barrier (BBB). The primary component of CSF, however, is water, which is BBB permeable. METHODS: Eight adult male rats underwent cisterna magna catheterization for intrathecal infusion. Brain MR images were obtained in a 7 tesla small-animal MRI system. Temporal T1-weighted images (T1WI) were obtained before, during, and after intrathecal infusion of D2O. Five rats then underwent ventricular kaolin injection for induction of hydrocephalus, after which repeat imaging with intrathecal D2O infusion was performed. RESULTS: Intrathecal deuterium infusion produced consistent changes on MRI imaging. Because conventional MRI does not sense deuterium, the T1WI showed a loss in proton signal with D2O infusion. Rapid D2O uptake of <2.5 minutes was noted in CSF spaces, brain tissue, and saggital and straight venous sinuses. CONCLUSIONS: Use of deuterium as an intrathecal contrast agent provides a physiologically realistic model of CSF behavior. Efforts are ongoing to quantify the relationship between MRI signal loss and deuterium tissue concentration for comparative analysis between healthy and hydrocephalic rats. The loss of MRI signal in the straight sinus after intrathecal infusion implicates the deep venous system in the clearance of CSF, suggesting that CSF is reabsorbed into the venous system via the brain tissue itself. Because traditional CSF tracers do not cross the BBB, the role of the brain tissue in the reabsorption of CSF has been overlooked.