This project focuses on assessing distortion product otoacoustic emissions (DPOAE) as a non-invasive measure of changes in intracranial pressure. It is hypothesized that visual acuity changes in spaceflight are caused by the long-term interaction between intracranial pressure (ICP) and the ocular globe. However, there is no noninvasive, easy-to-perform, on-orbit measure of ICP. Changes in DPOAE response have been shown to correlate with changes in ICP, potentially making them very useful as a proxy measure. We will statistically assess DPOAE as a tool to noninvasively measure ICP by isolating the effects of fluid shifts and changes in hydrostatic gradients, two separate response mechanisms, by altering body position (hydrostatic gradient) and lower body pressure (fluid shift). In conjunction with this work, we will also be collecting additional measures using MRI, ocular geometry/structures, and cardiovascular data to look for anatomical and physiological predictors for changes in the DPOAE maps.
Feasibility of DPOAE Mapping as an In-Flight Measure of Intracranial Pressure In Space (First Award Fellowship)
Allison Anderson, Ph.D.
Geisel School of Medicine at Dartmouth
Upon entering microgravity, astronauts experience a headward fluid shift, which could increase intracranial pressure (ICP) above seated levels. For long duration space flight, the interaction between ICP and intraocular pressure (IOP) is suspected to cause the visual acuity changes found in approximately 50% of astronauts. To understand the contribution of ICP to visual changes seen in long duration space flight, a noninvasive, easy-to-perform, on-orbit measure of ICP would be highly desirable.
Distortion product otoacoustic emission (DPOAE) level/phase mapping could be one such technique. DPOAEs have been shown to change in both amplitude and phase with alterations in body position, and with changes in intracranial pressure, potentially making them very useful as a proxy measure for ICP. The relative response of DPOAEs to fluid shifts and changes in hydrostatic gradients, however, has not been quantified. Since microgravity exposure not only produces a fluid shift but also removes all hydrostatic gradients, understanding the response caused by each of these variables separately is essential. Changes in tissue weight and alterations in hydrostatic gradients could also alter middle-ear compliance and the stiffness of the annular ligament, just as fluid shifts are postulated to do. Therefore, it cannot be known with certainty what the measurements in microgravity represent without understanding the relative contribution of fluid shifts and alterations in hydrostatic gradients.
We propose to isolate these two potential response mechanisms and evaluate the utility of DPOAEs as an in-flight measure of ICP. DPOAE probes the cochlea by emitting two sounds at different frequencies into the ear and measuring the response. The tones interact, creating two distortion products which interact with the cochlear hair cells, generating a newly emitted sound. These distortion products are sensitive to changes in intracranial pressure, which can change intralabyrinth pressure through several possible mechanisms. It is hypothesized that an increase in intracranial pressure and therefore intralabyrinth pressure causes an alteration in the position of the stapes and stiffness of the annular ligament at its base, leading to the dependency of the DPOAE response on intracranial pressure.
Our unique hardware measures many iterative DPOAES to crease response maps. DPOAEs are measured over a broad range of frequencies and varying ratios to create a map of responses. Additionally, both amplitude and phase measurements are taken, as both have been shown previously to change with posture. It was developed in conjunction with Creare, Inc. with support from the Office of Naval Research to evaluate noise-induced hearing loss in military personnel. Other studies on DPOAEs evaluate a narrow band of frequencies and ratios due to test duration and hardware limitations, rather than optimizing the test conditions to ensure the maximum response is recorded over a wide range of frequencies and ratios. We use an adaptive algorithm to create DPOAE maps to reduce testing time. DPOAE level/phase maps characterize the entire response space of the cochlea, since different frequencies and ratios probe different regions of the structure. This allows us to determine the most effective testing conditions under which DPOAEs may be administered in space, using DPOAE hardware planned for the International Space Station (ISS). This work will be done in conjunction with an existing NSBRI-funded set of experiments, Cranial Venous Modeling (CA03401).
We hypothesize that both fluid shifts and changes in hydrostatic gradients will alter DPOAE level/phase maps. The effects of the fluid shift and shifts in hydrostatic gradients will have different signatures in DPOAE level/phase mapping data. We will evaluate these hypotheses through three specific aims.
We will create DPOAE level/phase maps to characterize changes as a result of the isolated effects of fluid shifts and alterations in hydrostatic gradients. Subjects will be evaluated under seven experimental conditions to isolate the effects of hydrostatic gradients and fluid shifts on the body: seated baseline, prone, supine, supine with lower body negative pressure (LBNP), prone with LBNP, supine with lower body positive pressure (LBPP), and prone with LBPP. DPOAE level/phase maps will be created over a range of frequencies and ratios. Maps in each body orientation will be compared to determine difference in response from the seated baseline.
We will then statistically evaluate changes in DPOAE level/phase mapping to determine response signature of fluid shift and hydrostatic gradient . The maps from the experiment in Specific Aim 1 will be statistically analyzed to determine map regions where response is altered under each experimental condition. Regression, machine learning, and spatial analysis statistics will be used. Data will be analyzed within subjects to characterize individual changes and across subjects to determine signatures associated with changes in fluid shifts and alterations in hydrostatic gradients.
Finally, we will explore the relationship between ocular and cranial vascular measurements to changes seen in DPOAE level/phase maps. Subjects from experiment 1 will be placed in each of the seven experimental conditions described previously. Magnetic resonance imaging (MRI), optical coherence tomography (OCT), tonometry, and optical biometry will be used to measure cranial fluid flow and subject ocular anatomy. These parameters will be inputs to a cerebral hemodynamic model and physical model of the eye to calculate several additional metrics, such as ICP. Each of these anatomical, physiological, and calculated parameters will be statistically evaluated for correlations to changes in DPOAE level/phase maps.
This study will provide a novel way to make detailed DPOAE level/phase mapping measurements in association with multiple ocular and cranial vascular measurements. From this we propose to isolate the effects of changes in hydrostatic gradients (supine/prone) and fluid shifts (LBNP/LBPP) on DPOAE amplitude and phase across the cochlea. This information will be essential for using DPOAE measurement as a reflection of ICP on-orbit.
A non-invasive measure of ICP is useful for patients with idiopathic intracranial hypertension, where increased ICP shows similar visual acuity changes seen in astronauts. It could also be a useful monitoring tool for patients with traumatic brain injury where ICP is elevated. Our DPOAE mapping hardware is used for evaluating hear loss in patients with high noise exposure, such as members of the Navy, and with pathology, such as ototoxicity for cancer patients and HIV. Current studies include subjects in Tanania, China, Washington DC, and New Hampshire.