Many of the long duration astronauts experience visual impairment and findings suggesting elevated intracranial pressure (ICP) while in microgravity. This condition has the potential for seriously impacting space flight operations, due to the effect on vision, and may not be fully reversible upon return to Earth. Currently, the ICP can only be measured by placing invasive catheters into the brain, or by performing a lumbar puncture (spinal tap). These methods carry significant risks, and therefore there is an urgent need to develop a non-invasive modality. Dr. Eric M. Bershad and colleagues are conducting a research project to validate the Vittamed Two Depth Transcranial Doppler (Vittamed, Kaunas, Lithuania) for minimally invasive ICP measurement in the astronauts. This device uses ultrasound technology to measure the difference in blood flow through two segments of the ophthalmic (eye) artery, while gradually applying pressure to the orbital tissues to balance the extracranial and intracranial artery segments. If the device operating characteristics including repeatability, reproducibility and accuracy are confirmed, this technology may find broad applications not only in the astronauts, but also in patients with traumatic brain injury, strokes, brain hemorrhages, and hydrocephalus in the global health care setting.
The Suitability of the Vittamed Two-Depth Transcranial Doppler for the Non-Invasive Assessment of Intracranial Pressure in Astronauts Before and After Spaceflight
Eric M. Bershad, M.D.
Baylor College of Medicine
Microgravity results in multiple physiologic changes including changes in cerebrovascular fluid dynamics. Since NASA has focused on longer space missions, up to six months, at least 30% of astronauts have returned with visual changes, including optic nerve edema (papilledema), a narrowed visual field, choroidal folds, cotton-wool spots, dilated optic nerve sheaths, and hyperopic refractive shift as great as 1.75 diopters suggestive of elevated ICP. As part of their diagnostic evaluation, lumbar puncture (LP) performed on selected astronauts returning from prolonged missions have demonstrated ICP as high as 28 cm H20 (normal ranges 7-18 cm H2O). Given that the direct measurements of ICP have only been determined post-flight while in Earth gravity conditions, intra-flight ICP may be higher due to cephalad fluid shifting, increased carbon dioxide exposure, and other spaceflight related factors which may impact cerebral hemodynamic and CSF pathways. In some cases, the ICP has remained elevated in post-mission astronauts for months or even years.
There is a need for quantitative non-invasive methods for measuring ICP. Although post-flight LP data suggests that astronauts may be developing elevated ICP, there is currently no reliable way to assess in-flight ICP, or understand how environmental factors may dynamically change ICP. In addition, LPs are not routinely performed on crew pre and post flight as part of their medical requirements due to the inherent risks. Direct measurement of ICP using invasive LP poses significant risks if they are to be performed in the space environment. Complications may include headaches, CSF leaks, and rarely, infection, which could be catastrophic to the mission objectives and astronaut health. Therefore, an accurate, quantitative non-invasive method for measuring ICP would enable the identification of astronauts at risk for developing visual impairments, establish a time course of ICP changes in flight, determine the effect of environmental factors, and assess efficacy of treatments. Various non-invasive modalities for estimating ICP have been developed which assess pressure waves in the skull using indirect approaches that have not been validated as being quantitative, accurate, or reproducible.
The Two-Depth Transcranial Doppler (TCD) developed by Vittamed, LLC holds promise for quantitatively and directly assessing ICP, but further validation is required to determine the precision, reproducibility, and accuracy of the device.
The two-depth TCD determines the ICP based on simultaneous analysis of two contiguous segments of the ophthalmic artery (OA) by two ultrasonic (2 mHZ) emitters. The intracranial (IC) OA passes through the subarachnoid space, and thus the arterial flow is modulated by transmural pressure from ICP; whereas the extracranial (EC) OA is outside the dura, and not modulated by ICP. Therefore, at baseline an imbalance between the OA arterial blood flow velocities exists. By using this approach, and comparing two contiguous segment of the OA, one can factor out systematic physiological variables affecting flow in a single segment such as blood pressure, auto regulation, viscosity, hematocrit, etc. Therefore, no calibration of the device to external reference data is required. The two-depth TCD procedure attempts to balance the morphological appearance of the arterial flow velocities between IC and EC OA segments by external application of gentle pressure to the orbit at small (4 mmHg) pressure steps, until a close correlation of OA segments is observed.
The overall aim of the project is to evaluate the two-depth TCD for non-invasive ICP assessment. In order to achieve these goals we will test the two-depth TCD in two populations: healthy subjects and patients undergoing lumbar puncture. These populations will be tested sequentially in two phases.
Specific Aim 1: The purpose of this aim will be to assess the training requirements for novice operators, assess inter-operator reproducibility, intra-operator repeatability, and assess whether ICP measurement is reasonable and affected by body position. The body position can be manipulated using a tilt table to add additional hydrostatic pressure. For example, in supine position the expected ICP range is 5 to 15 mmHg, whereas additional hydrostatic pressure column can be added by head down tilt.
Specific Aim 2: The purpose of this aim will be to assess the accuracy of the Two Depth TCD in patients who are undergoing invasive ICP measurement, so that we can make simultaneous ICP measurements with the two-depth TCD. To assess the device's accuracy across a wide range of ICP values, we will include patients with a variety of neurological conditions as long as they have no obstruction of the ventricular or subarachnoid space. We expect that the primary conditions of the patients will include: demyelinating disease, infections, headaches, and idiopathic intracranial hypertension (IIH).
The project timeline of 1 year will allow for completion of phase 1 and 2, and determine whether the device is suitable for implementation to measure baseline and post-flight ICP in the astronauts. Further development would then focus on improving the user interface to reduce the need for specialized operators, and also miniaturizing the hardware platform to conform to the space limitations on the International Space Station. Other future aims would also include measurement of ICP in other ground-based analogs including carbon dioxide exposure, hypoxia, altitude, centrifuge, and during resistive exercise.
This research may facilitate this technology being adopted for broad applications not only in the astronauts, but also in patients with traumatic brain injury, strokes, brain hemorrhages, and hydrocephalus in the global health care setting.