Extravascular Molecular Transport in the Human Visual Pathway

Animal studies demonstrate that the glymphatic system plays a key role in the clearance of potential toxic waste products from the brain. However, the number of human studies is sparse due to technical difficulties. The observations in this thesis show that contrast enhanced magnetic resonance imaging may be utilized to safely study the glymphatic system in the visual pathway in humans. The contrast agent, gadobutrol (Gadovist™), serves as a surrogate for clearance of waste products through the glymphatic system. Furthermore, we demonstrate that the glymphatic system in the visual pathway is impaired in subjects with normal pressure hydrocephalus. The visual pathway is the connection between the eye and the visual cortex at the back of the brain. Damage in any segment of the visual pathway may thus impair the visual function. A potential mechanism is reduced clearance of toxic waste products. Reduced glymphatic clearance might thus play a part in the development of eye diseases, such as glaucoma. Our thesis can provide novel understanding of waste clearance in the visual pathway. Direct measurement of the intracranial pressure (ICP) necessitates the use of a sensor inserted into skull cavity. Although small, there is a risk of serious complications associated with invasive ICP measurement. In the last part of this thesis we show that optical coherence tomography (OCT) may be used as a non-invasive tool to predict elevated ICP. An OCT machine uses near infrared light and provides highly detailed images of the optic nerve head and the retina. This observation may reduce the need for invasive ICP measurement