Deuterium Magnetic Resonance Imaging for Evaluation of Glymphatic Flow
Hunt R, Nagaraja T, Ding G, Knight R, Lee I, Ewing J, and Penning D. Deuterium Magnetic Resonance Imaging for Evaluation of Glymphatic Flow. J Neurosurg Anesthesiol 2022; 34(4):466-467.
J Neurosurg Anesthesiol
Background: In the 1905s, intraventricular deuterium (D2O) was used to study the absorption of cerebrospinal fluid (CSF) into the venous system in hydrocephalic children. Studies were limited by the lack of available methods to image the movement of D2O in the brain. The exact route by which CSF returns to the venous system has not yet been fully elucidated. More recently, the role of the glymphatic system has been defined and explored using tracers such as gadolinium to track the movement of CSF through the perivascular spaces and into the brain interstitium. Mathematical models of CSF movement into and out of the brain interstitium have not been consistent with observed behavior. A recent study using an isotope of water (H2-170) showed significantly increased rate of CSF flow into the glymphatic system as compared to a traditional gadolinium tracer. This difference may reasonably be explained by the fact that gadolinium is not blood-brain-barrier (BBB) soluble. Because the primary component of CSF is water, CSF likely behaves quite differently than many of the tracers historically used to track its flow. Due to both expense and toxicity profile, H2-170 is not an ideal tracer for translational studies. Recently, D2O-labeled glucose has been shown to produce a detectable magnetic resonance (MR) signal, suggesting D2O may hold promise as an imageable tracer for glymphatic studies. We hypothesized that D2O would provide a traceable MR signal for tracking movement of water 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. The coil itself consists of two separate resonant circuits with the proton coil using a butterfly design and the deuterium coil a 25 mm loop design with both circuits rated for 400 W maximum RF peak power. After prepping the animal, it was placed prone in a non-magnetic cradle, the 1H/2H coil was positioned over the head and entire setup will be moved into the MRI system. The proton coil was set first to set up for the proton frequency, adjusting magnetic field homogeneity, and to provide high-resolution reference images. Following the proton imaging, the system frequency was switched over for the deuterium coil before starting the D2O infusion. Images from the D20 signal were acquired 30 seconds after starting intravenous infusion of deuterated saline. Continuous infusion of deuterated saline was continued for 12 minutes with MRI images every two minutes to track the uptake and clearance of the deuterium signal.
Results: Deuterium produced a traceable MR signal in the brain after intravenous injection (Figure 1 and 2).
Conclusion: Deuterium MRI holds promise as a novel CSF tracer. Next steps include intrathecal infusion of D2O via spinal catheter with concurrent proton and deuterium MR imaging. (Figure Presented).