VIIP Simulations of CSF, Hemodynamics and Ocular Risk (VIIP SCHOLAR)

Visual Impairment/Intracranial Pressure (VIIP) syndrome [Ed. note July 2018: now referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS)] occurs in a significant fraction of astronauts undergoing long-duration space flight, and is characterized by a spectrum of ophthalmic changes. Astronauts with VIIP can suffer permanent loss of visual acuity, and thus this condition is a major health concern for NASA. The pathophysiology of VIIP is poorly understood. However, evidence points to an important role for alterations in cerebrospinal fluid (CSF) and vascular flow dynamics/pressures in microgravity.

In view of the above, we hypothesize that the pathophysiology of VIIP involves alterations in biomechanical loads on the neural and connective tissues of the posterior globe/optic nerve due to changed CSF/blood pressures in microgravity. We further postulate that risk factors for VIIP can be identified through numerical modeling of these processes, and that such models can be used to evaluate proposed VIIP countermeasures.

In this proposal we will develop modeling tools that: (i) compute fluid shifts in microgravity; (ii) compute how these shifts lead to biomechanical insult to the optic nerve in astronauts; and (iii) estimate the effect that these insults have on optic nerve function. These tools will directly build upon, and interface with, models of ocular biomechanics and fluid shifts that we are currently developing in our NASA-funded MONSTR Sim project. Towards this end, we propose 4 specific aims:

SA1: Measure key physiologic parameters needed for modeling, including effects of intracranial pressure on optic nerve sheath diameter, optic nerve tortuosity, craniospinal volume, and cerebral blood flow.

SA2: Incorporate “quasi-1D” effects into existing compartment models, allowing us to evaluate the effects of microgravity and countermeasures on CSF and blood flows/pressures.

SA3: Extend finite element models of ocular biomechanics, specifically modeling: (i) optic nerve kinking, and (ii) compression of optic nerve fiber bundles in the lamina cribrosa; and relate kinking/compression to an index of axoplasmic insult/stasis.

SA4: Carry out parametric studies integrating the above models to identify individual-specific factors that: (i) predispose for the development of VIIP syndrome, and (ii) influence the efficacy of proposed countermeasures, both useful for risk profiling.

The resulting models will provide a powerful platform for better understanding individual-specific risks for VIIP and, eventually, for evaluating VIIP mitigation strategies, thus contributing to astronaut health. More specifically, these models will allow us to quantify the biomechanical environment of the optic nerve at the level of individual nerve fiber bundles, with outcome measures designed to predict the risk of two specific clinical features of VIIP: optic nerve kinking and papilledema.

This proposal directly addresses an explicit requirement of NASA Research Announcement NNJ15ZSA001N, namely to “...to develop and deliver detailed numerical models that quantify how CSF and vascular flow dynamics are altered in microgravity, and the propagative effects on the structure of the eye. The models must also be developed with the capability to interact with other pre-existing numerical models of the cardiovascular system, central nervous system, and eye ...”

The team assembled for this work has highly complementary skills that together address all relevant aspects of this complex, interdisciplinary problem. In addition to Ethier (Principal Investigator (PI) at Georgia Tech; expertise in modeling optic nerve head and ocular biomechanics), co-investigators include Myers (NASA Glenn; expertise in cephalad fluid shift models and space physiology); Samuels (Alabama; expertise in clinical ophthalmology and neuroscience); Oshinski (Georgia Tech/Emory; expertise in MR imaging of CSF and blood flow dynamics); and Martin (Idaho; expertise in modeling CSF dynamics).

May also help the understanding of idiopathic intracranial hypertension, an analogous condition that occurs in patients on Earth.

This is early/mid-stage (TRL 5) — the most realistic path in is NASA SBIR/STTR, which funds small businesses and research institutions to develop technology aligned with NASA's needs (equity-free, phased funding). Check whether a current SBIR/STTR solicitation topic overlaps with this project's technology area, or contact the project directly (above) to ask.

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