A s reviewed in part I (1), the glymphatic system is a network unique to the central nervous system that allows for the dynamic exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) and has an essential role in normal homeostasis and clearance of interstitial solutes. The different compartments include the intracranial interstitial extracellular space (iECS), the paravascular space (PVS), defined here as between the endothelial basement membranes and the glial limitans of parenchymal perforating vessels that are continuous with the basal lamina of capillaries, and the CSF spaces with their transdural and transvenous efflux pathways. The anatomy and physiology of these multiple components present several challenges when designing techniques to clinically image glymphatic function, including length scales of the interstitium being orders of magnitude smaller than the spatial resolution of CT or MRI, the inability of conventional CT or MRI contrast agents to cross an intact blood-brain barrier (BBB) to access the PVS, and the slow transport velocities involved. In the following review, our attention turns to evaluation of the glymphatic system with imaging techniques, many of which are in the development phase but likely to advance to clinical use soon (Table). We also discuss the role of glymphatic function in the pathology of several common neurologic diseases, which supports the

Normal physiologic function of organs requires a circulation of interstitial fluid to deliver nutrients and clear cellular waste products. Lymphatic vessels serve as collectors of this fluid in most organs; however, these vessels are absent in the central nervous system. How the central nervous system maintains tight control of extracellular conditions has been a fundamental question in neuroscience until recent discovery of the glial-lymphatic, or glymphatic, system was made this past decade. Networks of paravascular channels surrounding pial and parenchymal arteries and veins were found that extend into the walls of capillaries to allow fluid transport and exchange between the interstitial and cerebrospinal fluid spaces. The currently understood anatomy and physiology of the glymphatic system is reviewed, with the paravascular space presented as an intrinsic component of healthy pial and parenchymal cerebral blood vessels. Glymphatic system behavior in animal models of health and disease, and its enhanced function during sleep, are discussed. The evolving understanding of glymphatic system characteristics is then used to provide a current interpretation of its physiology that can be helpful for radiologists when interpreting neuroimaging investigations.

Ethanol poisoning is endemic the world over. Morbidity and mortality depend on blood ethanol levels which in turn depend on the balance between its rates of absorption and clearance. Clearance of ethanol is mostly at a constant rate via enzymatic metabolism. We hypothesized that isocapnic hyperpnea (IH), previously shown to be effective in acceleration of clearance of vapour anesthetics and carbon monoxide, would also accelerate the clearance of ethanol. In this proof-of-concept pilot study, five healthy male subjects were brought to a mildly elevated blood ethanol concentration (~ 0.1%) and ethanol clearance monitored during normal ventilation and IH on different days. IH increased elimination rate of ethanol in proportion to blood levels, increasing the elimination rate more than three-fold. Increased veno-arterial ethanol concentration differences during IH verified the efficacy of ethanol clearance via the lung. These data indicate that IH is a nonpharmacologic means to accelerate the elimination of ethanol by superimposing first order elimination kinetics on underlying zero order liver metabolism. Such kinetics may prove useful in treating acute severe ethanol intoxication.