Further research is needed to understand the role elevated intracranial pressure (ICP) plays in visual impairment observed during and following space missions. The long-term objective of this research is to noninvasively monitor ICP using 3-D ultrasound imaging by detecting changes in ocular structures and functioning of the eye that are correlated with elevated ICP. The project will lead to the development of tools to quantify inflight ocular changes, and thereby assess ICP. The new volumetric ultrasound imaging capability will provide user independent views of the entire ocular anatomy in a single scan with minimal crew time and ground guidance during image capture. A simplified ocular scan and new ocular metrics will provide the ability to track the short-term and long-term time course of ICP, determine the correlation of ICP with visual acuity changes in response to microgravity, and investigate effectiveness of potential countermeasures.
In the first two years of the grant, hardware was developed for 3-D ophthalmic imaging on the portable, high-resolution ultrasound platform (GE Vivid q) currently on board the International Space Station (ISS). A prototype mechanical 3-D ultrasound probe for ophthalmic scanning through a closed eyelid was integrated onto the Vivid q and several 2-D and Doppler imaging modes were implemented that control the acoustic output to remain below the FDA (Food and Drug Administration) limits for ophthalmic scanning. An external motor control unit was designed and fabricated to enable 3-D imaging with minimal changes to the Vivid q's hardware and software. Visualization and analysis tools were developed to automatically detect ocular structures within the ultrasound volumes, enhance standard and render new views of the ocular anatomy, enable new 3-D measurements, and align the ultrasound volumes with magnetic resonance images (MRI). These new capabilities were tested during ground-based human subject and animal studies in collaboration with a team from Wyle Integrated Science and Engineering with experience in the operational use of ophthalmic ultrasound. Safety tests were completed on the 3-D acquisition hardware at an external lab and the protocol for the human subjects' study was approved by NASA's IRB (Institutional Review Board).
An in vivo human subject study was conducted at Wyle's facility in Houston. In the first phase of the study, MRI and 3-D ultrasound data were acquired on 5 healthy volunteers. In the second phase of the study, 3-D ultrasound data were acquired on 11 healthy volunteers during head-down tilt (HDT) experiments. During the final year of the grant, the automatic image analysis and reconstruction algorithms were further refined, new structural and dynamic metrics were investigated, the animal study was completed, and the data from this study and the human study were analyzed. The computer algorithms automatically detect the optic nerve centerline and retina boundary within the 3-D ultrasound data. Knowledge of these anatomical landmarks enabled the contrast of the optic nerve sheath in standard longitudinal views to be enhanced and new cross-sectional views of the optic nerve to be generated. Additionally, new quantitative 3-D metrics of globe flattening were investigated to improve the repeatability of this traditionally subjective and highly user dependent metric when done solely with 2-D images. The image analysis algorithms were applied to both ultrasound and MRI volumes from the human study to demonstrate the ability to spatially align ocular structure across imaging modalities. Finally, new parameters related to intracranial dynamics were developed that quantify the periodic motion of structures near the optic nerve using tissue Doppler ultrasound. Analysis of the head-down tilt (HDT) data from the human study validated the 3-D ultrasound metrics, highlighted the individual variation in ONSD response to HDT even within the small number of healthy volunteers, and showed that 3-D globe flattening measures did not significantly change during the acute experiment. The elevated ICP animal study data demonstrated the feasibility to measure pulsatile motion of tissue near the optic nerve with ultrasound and allowed comparison of changes in the amplitude with mean ICP and ICP pulse pressure.
An advanced technology demonstration (ATD) of the 3-D ophthalmic ultrasound was conducted at the Space 4 Biomedicine to the National Space Biomedical Research Institute (NSBRI) leadership, the NSBRI user panel, and several NASA Johnson Space Center (JSC) researchers. The ATD provided the opportunity to walk the stakeholders through both the 3-D acquisition and the automated processing steps including some time for hands on scanning with the device during the demonstration. The team received helpful feedback on the usability of the technology in the space applications and applicability to the Vision Impairment and Intracranial Pressure (VIIP) problem from the group of experts.