Noninvasive Intracranial Volume and Pressure Measurements Using Ultrasound

Prevention of secondary brain injuries following head can be accomplished most easily when intracranial pressure (ICP) is monitored. However, current measurement techniques are invasive and thus not practical in the combat environment. The Pulsed Phase Lock Loop (PPLL) devise, which was developed and patented, uses a unique, noninvasive ultrasonic phase comparison method to measure slight changes in cranial volume which occur with changes in ICP. Year one studies involved instrument improvements and measurement of altered intracranial distance with altered ICP in fresh cadavera. Our software was improved to facilitate future studies of normal subjects and trauma patients. Our bench studies proved that PPLL output correlated highly with changes in path length across a model cranium. Cadaveric studies demonstrated excellent compact, noninvasive devise for monitoring changes in intracranial distance may aid in the early detection of elevated ICP, decreasing risk of secondary brain injury and infection, and returning head-injured patients to duty

Transcapillary fluid shifts in head and neck tissues during and after simulated microgravity

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head down for 8 hr, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.2 +/- 5 mm Hg pre-HDT to 33.9 +/- 1.7 mm Hg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, while interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressures dropped significantly after 4 hr of HDT, suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 hr of seated recovery from HDT, microvascular pressures remained significantly elevated by 5 to 8 mm Hg above baseline values, despite a significant HDT diuresis and the orthostatic challenge of an upright, seated posture. During the control (baseline) period, urine output was 46.7 ml/hr; during HDT, it was 126.5 ml/hr. These results indicate that facial edema resulting from HDT is primarily caused by elevated capillary pressures and decreased plasma colloid osmotic pressures. Elevation of cephalic capillary pressures sustained for 4 hr after HDT suggests that there is a compensatory vasodilation to maintain microvascular perfusion. The negativity of interstitial fluid pressures above heart level also has implications for the maintenance of tissue fluid balance in upright posture

Experiment K-6-03. Gravity and skeletal growth, part 1. Part 2: Morphology and histochemistry of bone cells and vasculature of the tibia; Part 3: Nuclear volume analysis of osteoblast histogenesis in periodontal ligament cells; Part 4: Intervertebral disc swelling pressure associated with microgravity

Bone area, bone electrophysiology, bone vascularity, osteoblast morphology, and osteoblast histogenesis were studied in rats associated with Cosmos 1887. The results suggest that the synchronous animals were the only group with a significantly larger bone area than the basal group, that the bone electrical potential was more negative in flight than in the synchronous rats, that the endosteal osteoblasts from flight rats had greater numbers of transitional Golgi vesicles but no difference in the large Golgi saccules or the alkaline phosphatase activity, that the perioteal vasculature in the shaft of flight rats often showed very dense intraluminal deposits with adjacent degenerating osteocytes as well as lipid accumulations within the lumen of the vessels and sometimes degeneration of the vascular wall (this change was not present in the metaphyseal region of flight animals), and that the progenitor cells decreased in flight rats while the preosteoblasts increased compared to controls. Many of the results suggest that the animals were beginning to recover from the effects of spaceflight during the two day interval between landing and euthanasia; flight effects, such as the vascular changes, did not appear to recover

In vitro measurement of nucleus pulposus swelling pressure: A new technique for studies of spinal adaptation to gravity

Swelling of the intervertebral disc nucleus pulposus is altered by posture and gravity. We have designed and tested a new osmometer for in vitro determination of nucleus pulposus swelling pressure. The functional principle of the osmometer involves compressing a sample of nucleus pulposus with nitrogen gas until saline pressure gradients across a 0.45 microns Millipore filter are eliminated. Swelling pressure of both pooled dog and pooled pig lumbar disc nucleus pulposus were measured on the new osmometer and compared to swelling pressures determined using the equilibrium dialysis technique. The osmometer measured swelling pressures comparable to those obtained by the dialysis technique. This osmometer provides a rapid, direct, and accurate measurement of swelling pressure of the nucleus pulposus

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

Visual Impairment /Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure. The ITD works by providing up to 7 cm H2O (approximately 5 mmHg) resistance to inspiratory air flow, effectively turning the thorax into a vacuum pump upon each inhalation which lowers the intrathoracic pressure (ITP) and facilitates venous return to the heart. The ITD is FDA-approved and was developed to augment venous return to the central circulation and increase cardiac output during cardiopulmonary resuscitation (CPR) and in patients with hypotension. While the effect of ITD on CPR survival outcomes is controversial, the ITD's ability to lower ITP with a concomitant decrease in intracranial pressure (ICP) is well documented. A similar concept that creates negative ITP during exhalation (intrathoracic pressure regulator; ITPR) decreased ICP in 16 of 20 patients with elevated ICP in a hospital pilot study. ITP and central venous pressure (CVP) have been shown to decrease in microgravity however ITP drops more than CVP, indicating an increased transmural CVP. This could explain the paradoxical distention of jugular veins (JV) in microgravity despite lower absolute CVP and also suggests that JV transmural pressure is not dramatically elevated. Use of an ITD may lower JV pressure enough to remove or relieve cephalic venous congestion. During spaceflight experiments with Braslet thigh cuffs and modified (open-glottis) Mueller maneuvers, Braslets alone reduced cardiac preload but only reduced the internal JV (IJV) cross sectional area by 23%. The addition of Mueller maneuvers resulted in an IJV area reduction of 48%. This project will test if ITD essentially applies a Mueller maneuver with added negative ITP in every respiratory cycle, acting to: 1) reduce venous congestion in the neck and 2) potentially lower ICP. The expected mechanism of action is that in microgravity (or an analog) blood is relocated toward the heart from vasculature in the head and neck. Once validated, the ITD would be an exceptionally easy countermeasure to deploy and test on the ISS. Dosage could be altered though 1) duration of application and 2) inspiratory resistance set point. Effects could be additionally enhanced through co-application with other countermeasures such as thigh cuffs or LBNP

Simulated Microgravity Increases Cutaneous Blood Flow in the Head and Leg of Humans

The cutaneous micro-circulation vasodilates during acute 6 deg. head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body. We expected that relative magnitudes of and differences between upper and lower body cutaneous blood flow elevation would be sustained during initial acclimation to simulated microgravity. We measured cutaneous micro-vascular blood flow with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting). Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean + SE, p less than 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline throughout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p less than 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values. Because hydrostatic effects of HDT increase local arterial pressure at the carotid sinus, baroreflex-mediated withdrawal of sympathetic tone probably contributed to increased microvascular flows at the head and leg during HDT. In the leg, baroreflex effects combined with minimal stimulation of local veno-arteriolar and myogenic autoregulatory vasoconstriction to elicit relatively larger and more sustained increases in cutaneous flow during HDT. In the cheek, delayed myogenic vasoconstriction and/or humoral effects apparently compensated for flow elevation by 24 h of HDT. Therefore, localized vascular adaptations to gravity probably explain differences in acclimation of lower and upper body blood flow to HDT and actual microgravity

Noninvasive Monitoring of Elevated Intramuscular Pressure in a Model Compartment Syndrome via Quantitative Fascial Motion

Compartment syndromes, conditions of elevated intramuscular pressure (IMP) resulting from trauma or chronic overuse, frequently require invasive IMP monitoring for accurate diagnosis. Our objective was to test a noninvasive ultrasound technique For estimating IMP based on fascial displacement waveforms from arterial blood pressure pulses. IMP was increased in the legs of 23 healthy adult subjects LIP to 80 mmHg Using two blood pressure cuffs covering the region from the knee to the ankle. Receiver operator characteristic curves and recursive partitioning were used to determine the sensitivity and specificity of diagnosing elevated IMP using fascial displacement, For one curve. in which several ultrasonic measurement parameters were used along with subject body mass index and blood pressure, the sensitivity and specificity for diagnosing normal IMP (below 30 mmHg) from elevated IMP (30 mm Hg and up) was 0.61 and 0.94, respectively. Recursive partitioning, in which IMP was divided into three ranges (normal \u3c30 \u3emmHg, midrange of 30-40 mmHg, and elevated \u3e= 50 mmHg), resulted in improved diagnostic sensitivity (0.77) with almost no change in specificity (0.93). (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:489-494 200

Fluid Shifts: Otoacoustical Emission Changes in Response to Posture and Lower Body Negative Pressure

INTRODUCTION: The purpose of the NASA Fluid Shifts Study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to correlate these findings with vision changes and other elements of the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. Due to the invasive nature of direct measures of ICP, a noninvasive technique of monitoring ICP is desired for use during spaceflight. The phase angle and amplitude of otoacoustic emissions (OAEs) have been shown to be sensitive to posture change and ICP (1, 2), therefore use of OAEs is an attractive option. OAEs are low-level sounds produced by the sensory cells of the cochlea in response to auditory stimulation. These sounds travel peripherally from the cochlea, through the oval window, to the ear canal where they can be recorded. OAE transmission is sensitive to changes in the stiffness of the oval window, occurring as a result of changes in cochlear pressure. Increased stiffness of the oval window largely affects the transmission of sound from the cochlea at frequencies between 800 Hz and 1600 Hz. OAEs can be self-recorded in the laboratory or on the ISS using a handheld device. Our primary objectives regarding OAE measures in this experiment were to 1) validate this method during preflight testing of each crewmember (while sitting, supine and in head-down tilt position), and 2) determine if OAE measures (and presumably ICP) are responsive to lower body negative pressure and to spaceflight. METHODS: Distortion-product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were recorded preflight using the Otoport Advance OAE system (Otodynamics Ltd., Hatfield, UK). Data were collected in four conditions (seated, supine, 15 degrees head down tilt (HDT), and 15 degrees HDT with lower body negative pressure (LBNP)) to produce a range of ICP in each subject and test the susceptibility of OAEs to LBNP. LBNP was induced using the Russian Chibis suit to produce the same fit and pressures that would be experienced inflight during Chibis LBNP trials. Similar trials have occurred inflight on the ISS. A comparative analysis of preflight and inflight phase measurements and magnitudes was completed in both broad and narrow band frequency ranges. RESULTS: TEOAE data demonstrated notable phase shifts from 859-1640 Hz when the seated baseline condition is compared to supine, HDT, and HDT plus Chibis conditions. Changes were particularly pronounced at low frequencies and were consistent with the expected ICP changes. Preflight DPOAE magnitude data revealed changes consistent with increased ICP in two conditions at 1414 Hz, where a magnitude change (relative to the seated condition) was seen in the HDT position and in HDT plus Chibis. DISCUSSION: OAEs revealed systematic changes in phase and magnitude throughout all test conditions (including use of Chibis LBNP) that were consistent with ICP changes. Results indicate that OAEs may provide a rapid noninvasive means of monitoring ICP changes. The first two subjects are projected to complete inflight testing on the ISS in early 2016, with the full complement of 10 subjects scheduled to be complete in 2018

Regional cutaneous microvascular flow responses during gravitational and LBNP stresses

Due to the regional variability of local hydrostatic pressures, microvascular flow responses to gravitational stress probably vary along the length of the body. Although these differences in local autoregulation have been observed previously during whole-body tilting, they have not been investigated during application of artificial gravitational stresses, such as lower body negative pressure or high gravity centrifugation. Although these stresses can create equivalent G-levels at the feet, they result in distinct distributions of vascular transmural pressure along the length of the body, and should consequently elicit different magnitudes and distributions of microvascular response. In the present study, the effects of whole-body tilting and lower body negative pressure on the level and distribution of microvascular flows within skin along the length of the body were compared

Intramuscular pressure: A better tool than EMG to optimize exercise for long-duration space flight

A serious problem experienced by astronauts during long-duration space flight is muscle atrophy. In order to develop countermeasures for this problem, a simple method for monitoring in vivo function of specific muscles is needed. Previous studies document that both intramuscular pressure (IMP) and electromyography (EMG) provide quantitative indices of muscle contraction force during isometric exercise. However, at present there are no data available concerning the usefulness of IMP versus EMG during dynamic exercise. Methods: IMP (Myopress catheter) and surface EMG activity were measured continuously and simultaneously in the tibalis anterior (TA) and soleus (SOL) muscles of 9 normal male volunteers (28-54 years). These parameters were recorded during both concentric and eccentric exercises which consisted of plantarflexon and dorsiflexon of the ankle joint. A Lido Active Isokinetic Dynamometer concurrently recorded ankle joint torque and position. Results: Intramuscular pressure correlated linearly with contraction force for both SOL (r exp 2 = 0.037) and TA (R exp 2 = 0.716 and r exp 2 = 0.802, respectively). During eccentric exercises, SOL and TA IMP also correlated linearly with contraction force (r(exp 2) = 0.883 and r(exp 2) = 0.904 respectively), but SOL and TA EMG correlated poorly with force (r(exp 2) = 0.489 and r(exp 2) = 0.702 respectively). Conclusion: IMP measurement provides a better index of muscle contraction force than EMG during concentric and eccentric exercise. IMP reflects intrinsic mechanical properties of individual muscles, such as length tension relationships. Although invasive, IMP provides a more powerful tool and EMG for developing exercise hardware and protocols for astronauts exposed to long-duration space flight