Microgravity physiologi and intracranial pressure for understanding spaceflight induced intracranial hypertension and vision alteration

Project description

Visual Impairment / Intracranial Pressure (VIIP) is a syndrome identified in astronauts who have had long duration mission on the space station. The identified visual symptoms can cause permanent problems for the astronauts and jeopardizes future planned space activities such as long duration stays at the Space Station or missions towards Mars. For the diseased astronauts the visual symptoms are often associated with an increased intracranial pressure (ICP).

The researchers currently working towards understanding the onset of the disease generally have a background as flight surgeons or physiologists with focus on physiological responses to gravitational changes in human cardiovascular, respiratory and musculoskeletal functions, or ophthalmologists with focus on the visual symptoms and signs. This means that they have large knowledge in their field but not necessary specialists in cerebrospinal fluid dynamics (CSF dynamics) and ICP physiology. Our multi disciplinary research group in hydrocephalus has dedicated decades to development of measurement methods and models to analyze and understand ICP variation and CSF dynamics, since disturbed CSF dynamics are the main pathophysiological hypothesis in hydrocephalus. We also have experience in pressure measurement and biomechanics of the intraocular system. This means that we approach the VIIP problem from a different background and we are confident that we have a unique opportunity to contribute new and vital knowledge in this important space related research field.

By describing the CSF system and the venous system together, in a single model, we believe that we can produce a description of what controls ICP, and which components in that control that link to gravitational phenomena. Preliminary results imply that such a model can predict ICP at different body positions, and thus at different hydrostatic loads. We plan to develop this preliminary model to include additional aspects of the venous intracranial drainage and arterial blood supply, and adjust it for input from different measurement techniques. Additonally, we will develop a corresponding model for the intraocular system, and evaluate both models at different body posture, in both patients with CSF dynamic disturbances and healthy. Knowing how these systems work, and how they are influenced by gravity we can then anticipate what will happen in microgravity, and from that suggest a physiologically based explanation to why the absence of gravity will induce the VIIP symptoms.

In this project we will perform a study on healthy volunteers with measurement of IOP and detailed Ultrasound Imaging (USI) assessment of cerebral venous drainage and venous collapse with respect to upper body tilt angles. This is to understand the venous outflow pathways and how they can differ between individual and patient groups. We will further evaluate suggested models by performing combined infusion and tilt studies with patients that has Idiopathic Intracranial Hypertension (same symptoms as VIIP), Hydrocephalus patients and healthy volunteers, using an extensive protocol that includes assessment of ICP, IOP, as well as Ultrasound

Imaging for assess cerebral venous drainage at the level of the neck, and MRI for cerebral venous system characterization. With that comprehensive data from all system we can analyze the differences in characteristics between patient groups and healthy with goal of understanding why IIH patients (i.e.VIIP model) develop increased ICP and visual symptoms. The goal is to formulate a specific hypothesis for the effects of microgravity on the intracranial and intraocular systems and how this may lead to VIIP.

VIIP is a physiological phenomenon which is related to microgravity. It is probable that all astronauts develop this, but to different extents depending on the properties of their CSF, venous and intraocular systems. As an ultimate goal we aim to use the developed model for how these systems interact, and an identified combination of properties that is likely to produce a brain and eye that is vulnerable to VIIP. This way we hope to develop a method that could be used to identify astronaut candidates at risk.

The NASA has declared VIIP as the largest medical obstacle for long-time stay on the Moon or for trips to Mars. A major research grant was announced 2012 in the U.S. solely for research on VIIP. Our research group is internationally renowned and has a background in research on pressures and flows of the brain. Therefore, we believe that our new hypothesis that is presented in this research plan has the potential to become a breakthrough in VIIP research, explaining why astronauts develop the syndrome in space, and why the syndrome persists upon return to Earth. Our research will contribute to an increased knowledge of VIIP, to the creation of an explanation model that can be tested on the international space station and finally, a model for a pre-flight identification and exclusion of individuals at risk for developing VIIP based on physiological bio-fluid dynamic parameters. The counterpart of VIIP on Earth is a disease called idiopathic intracranial hypertension. Research on IIH is neglected, and our research will provide spin-off effects that may help young and obese women with IIH, to avoid the development of blindness.