NOTE: End date changed to 3/31/2016 per NSBRI report submission (Ed., 5/8/14)

NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/18/14)

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.

Aim 1 – The prototype 3-D acquisition hardware and visualization and analysis tools for enhanced ocular scanning were demonstrated to members of the NSBRI and NASA research communities. This included a 3-D optic nerve sheath measurement workflow consisting of a single button press for the 3-D acquisition on the Vivid q, semi-automated image analysis of ultrasound 3-D volumes to produce multiple optic nerve sheath views with improved image quality and contrast, and integration with GE EchoPAC review software for optic nerve sheath diameter and area measurements. The 3-D information enabled multiples longitudinal views and new cross-sectional views of the optic nerve anatomy to be generated from a single 3-D ultrasound acquisition.

Aim 2 – The 3-D image analysis algorithms developed are applicable to both 3-D ultrasound and MRI ocular scans. The image analysis algorithms were used to spatially align ultrasound and MRI volumes acquired on a healthy volunteer to demonstrate the complementary structural information across imaging modalities from co-registered data sets.

Aim 3 – The optic nerve measurements with the prototype 3-D acquisition hardware and reconstruction software were validated with measurements from the current 2-D protocol in healthy subjects during moderately elevated ICP (n=11). The feasibility to use the results of the image analysis to generate 3-D posterior globe flattening metrics was demonstrated on data from the same healthy volunteers.

Aim 4 – The feasibility of a new ultrasound-based measure related to the pulsatility of the intracranial dynamics was demonstrated in an elevated ICP animal study. A response with ICP level was observed in the initial animal study (n=4) with further research needed to repeat the measure in human subjects and understand the clinical utility of the new parameter.

NOTE: End date changed to 3/31/2016 per NSBRI report submission (Ed., 5/8/14)

NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/18/14)

In the first two years of the grant, hardware was developed for 3-D ophthalmic imaging on the GE Vivid q ultrasound system with prototype mechanical 3-D ultrasound probes and in vivo studies started. Several 2-D imaging and Doppler modes were implemented on the Vivid q for imaging with the prototype 3-D probes below the FDA's (Food and Drug Administration) acoustic output limits for ophthalmic scanning. Safety tests were completed on the 3-D acquisition hardware at an external lab and the protocol for the human subjects study approved by NASA's Institutional Review Board (IRB). The ultrasound acquisition on the Vivid q was optimized for ocular scanning and computer algorithms developed for visualizing the 3-D ultrasound data.

An in vivo human subject study is being conducted at Wyle Integrated Science and Engineering in Houston. In the first phase of the study magnetic resonance and 3-D ultrasound data were acquired on 5 subjects. In the second phase of the study, 3-D ultrasound data will be acquired on 10 subjects during head-down tilt experiment during the final month of the current grant year. Additionally, a plan for integrating the prototype 3-D ophthalmic probe with NASA's next generation flexible ultrasound system was developed and reviewed with NASA and National Space Biomedical Research Institute (NSBRI). In the final year of the research project, the performance of 3-D ocular metrics for tracking changes in ICP will be evaluated using the in vivo data being collected and ultrasound parameters related to cerebral dynamics will be explored. The data collected during the in vivo human studies will be used to further develop automated image analysis algorithms for registering MR and ultrasound volumes and 3-D measurements of optic nerve sheath size and globe flattening. For the 3-D ultrasound ocular measurements, the repeatability with ultrasound probe position and the sensitivity to changes in ICP will be quantified on the data collected during the in vivo studies. In addition to the ocular structural metrics, new ultrasound-derived parameters of cerebral dynamics will be investigated as part of an in vivo animal study in the final year of the research project.

Image Quality – The acquisition parameters for the prototype mechanical 3-D probes were optimized for ophthalmic imaging through several in vivo scanning sessions with the engineering team at GE Global Research and the clinical team at Wyle Integrated Science and Engineering. A down-selection between two prototype probe designs was performed resulting in the probe with a slightly smaller aperture and shallower focus providing better imaging performance and being selected to be used for the subsequent in vivo evaluation.

Visualization – The 3-D ultrasound data collected with the volume acquisition hardware is generated by first extracting separate volume sweeps from standard DICOM (Digital Imaging and Communications in Medicine) files stored on the Vivid q ultrasound system and then converting the ultrasound volume data into multiple files formats compatible with different rendering software. Several rendering and display methods were investigated for visualizing the 3-D ocular data. These methods included orthogonal cuts through the 3-D data, parallel slices aligned with and perpendicular to the optic nerve, arbitrary slices through the volume, and surface rendering of the retinal boundary.

Image Analysis – Image analysis algorithms have started to be developed to automatically identify ocular landmarks, such as the optic nerve centerline and retinal boundary, for registering multiple ultrasound and MRI (magnetic resonance imaging) volumes acquired on a single subject. These landmarks will be used to generate consistent slices through the ultrasound volume data for making standard measurements of the optic nerve sheath and globe shape, as well as providing inputs for automatic algorithms for 3-D measurement of the same ocular structures.

In Vivo Data Collection – A protocol and supporting design and safety documentation were submitted to NASA's IRB and approval obtained for a human study to evaluate the performance of the 3-D ophthalmic acquisition and ocular measurements. The in vivo human subject study is currently being conducted at Wyle Integrated Science and Engineering in Houston.

In the first phase of the study magnetic resonance and 3-D ultrasound data were acquired on 5 subjects. In the second phase of the study, 3-D ultrasound data will be acquired on 10 subjects during head-down tilt experiment during the final month of the current grant year.

NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/18/14)

In the first year of the grant, a prototype mechanical 3-D ultrasound probe for ophthalmic scanning through a closed eyelid has been integrated with the current portable, high-resolution medical ultrasound scanner on the International Space Station (ISS) (GE Vivid q). An external motor control unit has been designed and developed to enable 3-D imaging on the current ISS ultrasound scanner with minimal changes to the Vivid q ultrasound system. First in vitro images of an ultrasound imaging phantom were acquired with the prototype probes and Vivid q ultrasound system. Electrical safety tests and acoustical output measurements for ophthalmic use were completed on the prototype probe and Vivid q ultrasound system, and a protocol submitted to NASA's Institutional Review Board (IRB) for human subject scanning starting in year 2.

The proposed research plan for upcoming year focuses on transitioning the technology development to in vivo evaluation of the volumetric prototype probe on human subjects. Sonographs of the optic nerve and globe will be extracted from the volumetric ultrasound data, and new 3-D measurement techniques for the size and shape of these structures will be developed to serve as indirect measures of ICP. The new ultrasound hardware and measurement techniques will be tested during ground-based in vivo human subject in collaboration with flight surgeon, sonographer, and technical team from Wyle Integrated Science and Engineering in Houston. Initial in vivo imaging will be performed to optimize the image quality for ocular structure with the prototype probe and the Vivid q ultrasound system. The first phase of the in vivo human subject evaluation includes MR (magnetic reonance) and volumetric ultrasound scans on 5 subjects to develop algorithms and evaluate the accuracy of multimodality registration and repeatability of 3-D ocular structure measurements. The second phase of the in vivo human subject evaluation includes volumetric ultrasound scans on 10 subjects during head-down tilt experiments to quantify the sensitivity of 3-D ocular metrics to mild changes in intracranial pressure. Additionally, discussions will continue with NASA Glenn Research Center on compatibility of the design with the next generation flexible ultrasound system, as well as with other mechanical 3-D ultrasound probes.

Design - Computer simulation studies of acoustic array designs for ophthalmic imaging applications were conducted to guide selection of two prototype volumetric ultrasound probes for in vivo evaluation. Several options for implementing the volumetric imaging functionality on the Vivid q system were explored and a hardware design implemented that requires minimal modifications to the ultrasound system.

Hardware - New hardware was developed and fabricated enabling volumetric imaging by interfacing to the Vivid q ultrasound system and controlling the stepper motor in the volumetric ultrasound probe. This motor control unit consists of a commercially available field-programmable gate array (FPGA) processor evaluation board, USB interface board, and two custom printed circuit boards to route the probe control signals. Additional connections between the motor control unit and the Vivid q through the USB and ECG ports were implemented. Firmware was written for the FPGA processor to generate the signal for controlling the stepper motor in the volumetric probe, responding to user inputs, and generating timing waveforms required for the reconstruction of the volume data.

Integration – The properties of the prototype volumetric probes were characterized and the relevant parameters entered into probe specification tables on the Vivid q. The prototype probes were integrated with the acoustic model on the Vivid q enabling real-time display of acoustic output levels. Imaging applications were created on the Vivid q for the prototype probes specifying acquisition parameters for the ultrasound imaging modes that will be used in the in vivo evaluation. The Vivid q's acoustic output levels were set to the lower FDA limits for ophthalmic use for all imaging modes with the prototype probes (B-mode, M-Mode, Spectral Doppler, and Color Flow). Once integrated, the acoustic output of the prototype volumetric probes and Vivid q software were measured at an outside laboratory to verify the acoustic output levels were below the ophthalmic limits for the high acoustic output settings in each imaging modes.

Evaluation – First images of an ultrasound imaging phantom were acquired with the prototype probes and Vivid q. Initial MR data collected on the same ultrasound imaging phantom allowed the initial development of the volumetric visualization and registration algorithms. The electrical and acoustic safety tests were completed and a protocol submitted the NASA's IRB for human subject scanning starting in year 2.

An ultrasound probe for ophthalmic scanning through a closed eyelid will be developed and integrated with a portable, high-resolution medical ultrasound scanner. The new volumetric ultrasound system will provide user independent views of the entire ocular anatomy in a single scan with minimal crew time and ground guidance during image capture. Volumetric ultrasound data taken preflight, post-flight, and inflight will be aligned with preflight and post-flight magnetic resonance scans allowing inflight changes in the ocular anatomy to be tracked over time. Sonographs of the optic nerve and globe will be extracted from the volumetric ultrasound data, and reliable measurement techniques for the size and shape of these structures will be developed to serve as indirect measures of ICP. Ultrasound ophthalmic scanning will also be used to measure fluctuations in the ICP and the blood flow in the retinal vessels to monitor the body's ability to compensate for changes in the ICP.

This research will lead to the development of tools to non-invasively monitor ICP and the body's ability to compensate for increases in ICP. The simplified ocular scan and new ocular metrics will provide the ability to track the short-term and long-term time course of ICP with minimal burden on the crew, to determine the correlation of ICP with visual acuity changes in response to microgravity, and to investigate effectiveness of potential treatments. In addition to inflight monitoring of crew health during space missions, these techniques are applicable to many clinical applications where ICP plays a key role, such as monitoring patients with head trauma.