Flow dynamics of cerebrospinal fluid between the intracranial cavity and the subarachnoid space of the optic nerve- an experimental and clinical approach

Background: Impaired cerebrospinal fluid (CSF) dynamics plays an important role in many pathologies in the central nervous system and the optic nerve (ON). Glaucoma is one of the most frequent causes of blindness worldwide. Elevated intraocular pressure (IOP) is a well-established risk factor. Idiopathic intracranial hypertension (IIH) is a neurological disease that presents with headaches and tinnitus. Papilledema can lead to vision loss and even blindness. Common for these both ophthalmological diseases is the fact that the pathophysiology is not yet fully understood. It is hypothesized that altered intracranial pressure and impaired CSF flow may play a major role in the progression of these diseases. Until now it is not possible to perform non-invasive quantitative measures of the absolute CSF flow velocity and the intracranial pressure. Aim: Over three years period we want to investigate the CSF flow velocity and pressure non-invasively using i) patient MRI measurements, ii) computer simulations and iii) different flow conditions in laboratory setting. New information will be gained and results will be matched to gain better knowledge of the very complex slow-flow CSF dynamics in the subarachnoid space (SAS) of the ON. Methods: First, a realistic 3D model of the SAS of ON will be created. Second, 3D model of the ON will then be produced using a high-resolution 3D printer and tested in laboratory conditions for different flow-conditions. As a third step, computer simulations of the flow and pressure conditions in SAS of the ON using this model as a starting point will be conducted. Simultaneously, the non-invasive already existing MR methodology will be applied clinically to glaucoma and papilledema patients. At last, the 3D model will be imaged in MRI and all the results will be compared and conclusions drawn as a means to better understand the complex slow flow conditions of dynamic CSF flow in the SAS of the ON. Relevance of this research: Today no non-invasive method to quantitatively measure pressure condition intracranial or to study the absolute flow conditions in SAS of the ON exists. To explore the pathophysiology in different ophthalmological diseases through CSF dynamics is gaining its popularity; however, proper methods are still missing. The understanding of the pathophysiology in glaucoma and papilledema patients is of great importance as in these patients visual impairment progresses and can result in blindness.