Impact of bimonthly repeated total sleep deprivation and recovery sleep on cardiovascular indices.

Since short sleep duration adversely affects cardiovascular (CV) health, we investigated the effects of exposures to total sleep deprivation (TSD), and baseline (BL) and recovery (REC) sleep on CV measures. We conducted a 5-day experiment at months 2 and 4 in two separate studies (N = 11 healthy adults; 5 females). During these repeated experiments, CV measures [stroke volume (SV), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular ejection time, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) and mean arterial pressure (MAP)] were collected at three assessment time points after: (1) two BL 8 h time-in-bed (TIB) sleep opportunity nights; (2) a TSD night; and (3) two REC 8-10 h TIB nights. CV measures were also collected pre-study. TSD significantly increased SV and CI, and decreased SVRI, with large effect sizes, which importantly were reversed with recovery, indicating these measures are possible novel biomarkers for assessing the adverse consequences of TSD. Pre-study SV, CI, SVRI, HR, SBP, and MAP measures also significantly associated with TSD CV responses at months 2 and 4 [Pearson's r: 0.615-0.862; r2 : 0.378-0.743], indicating they are robust correlates of future TSD CV responses. Our novel findings highlight the critical impact of sleep on CV health across time.

Cardiovascular measures display robust phenotypic stability across long-duration intervals involving repeated sleep deprivation and recovery.

Introduction: We determined whether cardiovascular (CV) measures show trait-like responses after repeated total sleep deprivation (TSD), baseline (BL) and recovery (REC) exposures in two long-duration studies (total N = 11 adults). Methods: A 5-day experiment was conducted twice at months 2 and 4 in a 4-month study (N = 6 healthy adults; 3 females; mean age ± SD, 34.3 ± 5.7 years; mean BMI ± SD, 22.5 ± 3.2 kg/m2), and three times at months 2, 4, and 8 in an 8-month study (N = 5 healthy adults; 2 females; mean age ± SD, 33.6 ± 5.17 years; mean BMI ± SD, 27.1 ± 4.9 kg/m2). Participants were not shift workers or exposed to TSD in their professions. During each experiment, various seated and standing CV measures were collected via echocardiography [stroke volume (SV), heart rate (HR), cardiac index (CI), left ventricular ejection time (LVET), and systemic vascular resistance index (SVRI)] or blood pressure monitor [systolic blood pressure (SBP)] after (1) two BL 8h time in bed (TIB) nights; (2) an acute TSD night; and (3) two REC 8-10 h TIB nights. Intraclass correlation coefficients (ICCs) assessed CV measure stability during BL, TSD, and REC and for the BL and REC average (BL + REC) across months 2, 4, and 8; Spearman's rho assessed the relative rank of individuals' CV responses across measures. Results: Seated BL (0.693-0.944), TSD (0.643-0.962) and REC (0.735-0.960) CV ICCs showed substantial to almost perfect stability and seated BL + REC CV ICCs (0.552-0.965) showed moderate to almost perfect stability across months 2, 4, and 8. Individuals also exhibited significant, consistent responses within seated CV measures during BL, TSD, and REC. Standing CV measures showed similar ICCs for BL, TSD, and REC and similar response consistency. Discussion: This is the first demonstration of remarkably robust phenotypic stability of a number of CV measures in healthy adults during repeated TSD, BL and REC exposures across 2, 4, and 8 months, with significant consistency of responses within CV measures. The cardiovascular measures examined in our studies, including SV, HR, CI, LVET, SVRI, and SBP, are useful biomarkers that effectively track physiology consistently across long durations and repeated sleep deprivation and recovery.

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight.

Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.

Left Ventricular Ejection Time Measured by Echocardiography Differentiates Neurobehavioral Resilience and Vulnerability to Sleep Loss and Stress.

There are substantial individual differences (resilience and vulnerability) in performance resulting from sleep loss and psychosocial stress, but predictive potential biomarkers remain elusive. Similarly, marked changes in the cardiovascular system from sleep loss and stress include an increased risk for cardiovascular disease. It remains unknown whether key hemodynamic markers, including left ventricular ejection time (LVET), stroke volume (SV), heart rate (HR), cardiac index (CI), blood pressure (BP), and systemic vascular resistance index (SVRI), differ in resilient vs. vulnerable individuals and predict differential performance resilience with sleep loss and stress. We investigated for the first time whether the combination of total sleep deprivation (TSD) and psychological stress affected a comprehensive set of hemodynamic measures in healthy adults, and whether these measures differentiated neurobehavioral performance in resilient and vulnerable individuals. Thirty-two healthy adults (ages 27-53; 14 females) participated in a 5-day experiment in the Human Exploration Research Analog (HERA), a high-fidelity National Aeronautics and Space Administration (NASA) space analog isolation facility, consisting of two baseline nights, 39 h TSD, and two recovery nights. A modified Trier Social Stress Test induced psychological stress during TSD. Cardiovascular measure collection [SV, HR, CI, LVET, BP, and SVRI] and neurobehavioral performance testing (including a behavioral attention task and a rating of subjective sleepiness) occurred at six and 11 timepoints, respectively. Individuals with longer pre-study LVET (determined by a median split on pre-study LVET) tended to have poorer performance during TSD and stress. Resilient and vulnerable groups (determined by a median split on average TSD performance) showed significantly different profiles of SV, HR, CI, and LVET. Importantly, LVET at pre-study, but not other hemodynamic measures, reliably differentiated neurobehavioral performance during TSD and stress, and therefore may be a biomarker. Future studies should investigate whether the non-invasive marker, LVET, determines risk for adverse health outcomes.

Volumetric Ophthalmic Ultrasound for Inflight Monitoring of Visual Impairment and Intracranial Pressure.

OBJECTIVE: The objective is enhanced ophthalmic ultrasound imaging to monitor ocular structure and intracranial dynamics changes related to visual impairment and intracranial pressure (ICP) induced by microgravity. The goals are to improve the ease of use and reduce operator variability by automatically rendering improved views of the anatomy and deriving new metrics of the morphology and dynamics. MATERIALS AND METHODS: A prototype three-dimensional (3-D) probe was integrated onto a portable ultrasound scanner. Image analysis algorithms were developed to automatically detect the ocular anatomy and simultaneously render views of the optic nerve with improved sheath definition. Curvature metrics were calculated from 3-D retinal surfaces to quantify posterior globe flattening, and tissue velocity waveforms of the optic nerve were analyzed to assess intracranial dynamics. RESULTS: New 3-D structural measurements were evaluated in a head-down tilt study. The response of optic nerve sheath and globe flattening metrics were quantified in 11 healthy volunteers from baseline to moderately elevated ICP. The optic nerve measurements showed good correlation with existing two-dimensional (2-D) methods and an acute response to increased ICP, while globe flattening did not show an acute response. The tissue velocities were evaluated in a porcine model from baseline to significantly elevated ICP and correlated with invasive ICP readings in four animals. CONCLUSIONS: Volumetric ophthalmic imaging was demonstrated on a portable ultrasound system and structural measurements validated with existing methods. New 3-D structural measurements and dynamic measurements were evaluation during in vivo studies. Further investigations are needed to evaluate improvements in performance for non-experts and application to clinically relevant conditions.

Real-time Ultrasound Assessment of Astronaut Spinal Anatomy and Disorders on the International Space Station.

OBJECTIVES: Back pain is one of the most common conditions of astronauts during spaceflight and is hypothesized to be attributed to pathologic anatomic changes. Ultrasound (US) represents the only available imaging modality on the International Space Station, but a formal US protocol for imaging the structures of the spinal column does not exist. This investigation developed a method of acquiring diagnostic-quality images of the anterior lumbar and cervical regions of the spine during long-duration spaceflight. METHODS: Comprehensive spinal US examinations were conducted on 7 long-duration spaceflight astronauts before flight, in flight, and after flight and compared to preflight and postflight magnetic resonance imaging data. In-flight scans were conducted after just-in-time training assisted by remote expert tele-US guidance. RESULTS: Novice users were able to obtain diagnostic-quality spinal images with a 92.5% success rate. Thirty-three anomalous or pathologic findings were identified during the preflight US analysis, and at least 14 new findings or progressions were identified during the postflight US analysis. Common findings included disk desiccation, osteophytes, and qualitative changes in the intervertebral disk height and angle. CONCLUSIONS: Ultrasound has proven efficacy as a portable and versatile diagnostic imaging modality under austere conditions. We demonstrated a potential role for US to evaluate spinal integrity and alterations in the extreme environment of space on the International Space Station. Further investigations should be performed to corroborate this imaging technique and to create a larger database related to in-flight spinal conditions during long-duration spaceflight.

Preflight, In-Flight, and Postflight Imaging of the Cervical and Lumbar Spine in Astronauts.

BACKGROUND: Back pain is a common complaint during spaceflight that is commonly attributed to intervertebral disc swelling in microgravity. Ultrasound (US) represents the only imaging modality on the International Space Station (ISS) to assess its etiology. The present study investigated: 1) The agreement and correlation of spinal US assessments as compared to results of pre- and postflight MRI studies; and 2) the trend in intervertebral disc characteristics over the course of spaceflight to ISS. METHODS: Seven ISS astronauts underwent pre- and postflight US examinations that included anterior disc height and anterior intervertebral angles with comparison to pre- and postflight MRI results. In-flight US images were analyzed for changes in disc height and angle. Statistical analysis included repeated measures ANOVA with Bonferroni post hoc analysis, Bland-Altman plots, and Pearson correlation. RESULTS: Bland-Altman plots revealed significant disagreement between disc heights and angles for MRI and US measurements while significant Pearson correlations were found in MRI and US measurements for lumbar disc height (r2 = 0.83) and angle (r2 = 0.89), but not for cervical disc height (r2 = 0.26) or angle (r2 = 0.02). Changes in anterior intervertebral disc angle-initially increases followed by decreases-were observed in the lumbar and cervical spine over the course of the long-duration mission. The cervical spine demonstrated a loss of total disc height during in-flight assessments (∼0.5 cm). DISCUSSION: Significant disagreement but significant correlation was noted between US and MRI measurements of disc height and angle. Consistency in imaging modality is important for trending measurements and more research related to US technique is required.Harrison MF, Garcia KM, Sargsyan AE, Ebert D, Riascos-Castaneda RF, Dulchavsky SA. Preflight, in-flight, and postflight imaging of the cervical and lumbar spine in astronauts. Aerosp Med Hum Perform. 2018; 89(1):32-40.

Intraocular Lens Use in an Astronaut During Long Duration Spaceflight.

BACKGROUND: The purpose of this paper is to report the first use of an intraocular lens (IOL) in an astronaut during long duration spaceflight (LDSF). An astronaut developed a unilateral cataract and underwent phacoemulsification with insertion of an acrylic IOL. Approximately 15 mo later he flew on a Soyuz spacecraft to the International Space Station (ISS), where he successfully completed a 6-mo mission. CASE REPORT: Ocular examination, including ultrasound (US), was performed before, during, and after his mission and he was questioned regarding visual changes during each portion of his flight. DISCUSSION: We documented no change in IOL position during his space mission. This astronaut reported excellent and stable vision during liftoff, entry into microgravity (MG), 6 mo on the ISS, descent, and landing. Our results suggest that modern IOLs are stable, effective, and well tolerated during LDSF.Mader TH, Gibson CR, Schmid JF, Lipsky W, Sargsyan AE, Garcia K, Williams JN. Intraocular lens use in an astronaut during long duration spaceflight. Aerosp Med Hum Perform. 2018; 89(1):63-65.

Concept of Operations Evaluation for Using Remote-Guidance Ultrasound for Exploration Spaceflight.

BACKGROUND: Remote-guidance (RG) techniques aboard the International Space Station (ISS) have enabled astronauts to collect diagnostic-level ultrasound (US) images. Exploration-class missions will likely require nonformally trained sonographers to operate with greater autonomy given longer communication delays (> 6 s for missions beyond the Moon) and blackouts. Training requirements for autonomous collection of US images by non-US experts are being determined. METHODS: Novice US operators were randomly assigned to one of three groups to collect standardized US images while drawing expertise from A) RG only, B) a computer training tool only, or C) both RG and a computer training tool. Images were assessed for quality and examination duration. All operators were given a 10-min standardized generic training session in US scanning. The imaging task included: 1) bone fracture assessment in a phantom and 2) Focused Assessment with Sonography in Trauma (FAST) examination in a healthy volunteer. A human factors questionnaire was also completed. RESULTS: Mean time for group B during FAST was shorter (20.4 vs. 22.7 min) than time for the other groups. Image quality scoring was lower than in groups A or C, but all groups produced images of acceptable diagnostic quality. DISCUSSION: RG produces US images of higher quality than those produced with only computer-based instruction. Extended communication delays in exploration missions will eliminate the option of real-time guidance, thus requiring autonomous operation. The computer program used appears effective and could be a model for future digital US expertise banks. Terrestrially, it also provides adequate self-training and mentoring mechanisms.

Point of care ultrasound (POCUS) telemedicine project in rural Nicaragua and its impact on patient management.

BACKGROUND: Point of care ultrasound (POCUS) is a useful diagnostic tool in medicine. POCUS provides an easy and reproducible method of diagnosis where conventional radiologic studies are unavailable. Telemedicine is also a great means of communication between educators and students throughout the world. HYPOTHESIS: Implementing POCUS with didactics and hands-on training, using portable ultrasound devices followed by telecommunication training, will impact the differential diagnosis and patient management in a rural community outside the United States. MATERIALS AND METHODS: This is an observational prospective study implementing POCUS in Las Salinas, a small village in rural western Nicaragua. Ultrasound was used to confirm a diagnosis based on clinical exam, or uncover a new, previously unknown diagnosis. The primary endpoint was a change in patient management. International sonographic instructors conducted didactic and practical training of local practitioners in POCUS, subsequently followed by remote guidance and telecommunication for 3 months. RESULTS: A total of 132 patients underwent ultrasound examination. The most common presentation was for a prenatal exam (23.5 %), followed by abdominal pain (17 %). Of the 132 patients, 69 (52 %) were found to have a new diagnosis. Excluding pregnancy, 67 patients of 101 (66 %) were found to have a new diagnosis. A change in management occurred in a total of 64 (48 %) patients, and 62 (61 %) after excluding pregnancy. CONCLUSION: Implementing POCUS in rural Nicaragua led to a change in management in about half of the patients examined. With the appropriate training of clinicians, POCUS combined with telemedicine can positively impact patient care.

Point-of-care ultrasound in aerospace medicine: known and potential applications.

Since its initial introduction into the bedside assessment of the trauma patient via the Focused Assessment with Sonography for Trauma (FAST) exam, the use of point-of-care ultrasound has expanded rapidly. A growing body of literature demonstrates ultrasound can be used by nonradiologists as an extension of the physical exam to accurately diagnose or exclude a variety of conditions. These conditions include, but are not limited to, hemoperitoneum, pneumothorax, pulmonary edema, long-bone fracture, deep vein thrombosis, and elevated intracranial pressure. As ultrasound machines have become more compact and portable, their use has extended outside of hospitals to places where the physical exam and diagnostic capabilities may be limited, including the aviation environment. A number of studies using focused sonography have been performed to meet the diagnostic challenges of space medicine. The following article reviews the available literature on portable ultrasound use in aerospace medicine and highlights both known and potential applications of point-of-care ultrasound for the aeromedical clinician.

Detection of early diastolic alterations by tissue Doppler imaging in untreated childhood-onset essential hypertension.

The aim of the study was to determine the presence of preclinical diastolic dysfunction in hypertensive children relative to normotensive children by Tissue Doppler Imaging (TDI). We prospectively enrolled children with untreated essential hypertension in absence of any other disease and a matched healthy control group with normal blood pressure (BP); both groups confirmed by clinic BP and a 24-hour ambulatory BP monitoring. Echocardiographic diastolic parameters were determined using spectral transmitral inflow Doppler, flow propagation velocity, TDI, and systolic parameters were determined via midwall shortening fraction and ejection fraction. A total of 80 multiethnic children were prospectively enrolled for the study: 46 hypertensive (median age, 13 years; 72% males) and 34 control (median age, 14 years; 65% males). The only echocardiography parameters that had a statistically significant change compared with the control children, were regional mitral Ea, Aa, and the E/Ea ratio by TDI. In comparison with controls, hypertensive children had lower Ea and Aa velocities of anterior and posterior walls and higher lateral wall E/Ea ratio. The decrease in posterior wall Ea and Aa remained significant after adjustment for gender, age, body mass index, ethnicity, and left ventricular hypertrophy on multivariate analysis. The lateral and septal wall E/Ea ratios correlated significantly with fasting serum insulin levels on similar multivariate analysis. Decreased regional TDI velocities were seen with preserved left ventricular systolic function even when other measures of diastolic dysfunction remained unchanged in untreated hypertensive children. Hypertension and serum insulin levels had strong associations with preclinical diastolic alterations in children.

Doppler ultrasound of the central retinal artery in microgravity.

BACKGROUND: Ocular changes have been noted during long-duration spaceflight; we studied central retinal artery (CRA) blood flow using Doppler before, during, and after long-term microgravity exposure in astronauts compared with data from a control group of nonastronauts subjected to head-down tilt (HDT). METHODS: Available Doppler spectra of International Space Station (ISS) crewmembers were obtained from the NASA Lifetime Surveillance of Astronaut Health database, along with 2D ultrasound-derived measurements of the optic nerve sheath diameter (ONSD). CRA Doppler spectra and optic nerve sheath images were also obtained from healthy test subjects in an acute HDT experiment at 20 min of exposure (the ground-based analogue). RESULTS: HDT CRA peak systolic velocity in the ground-based analogue group increased by an average of 3 cm -s(-1) (33%) relative to seated values. ONSD at 300 of HDT increased by 0.5 mm relative to supine values. CRA Doppler spectra obtained on orbit were of excellent quality and demonstrated in-flight changes of +5 cm x s(-1) (50%) compared to preflight. ONSD increased in ISS crewmembers during flight relative to before flight, with some reversal postflight. DISCUSSION: A significant ONSD response to acute postural change and to spaceflight was demonstrated in this preliminary study. Increases in Doppler peak flow velocities correlated with increases in ONSD. Further investigations are warranted to corroborate the relationship between ONSD, intracranial pressure, and central retinal blood flow for occupational surveillance and research purposes.

New heights in ultrasound: first report of spinal ultrasound from the international space station.

BACKGROUND: Changes in the lumbar and sacral spine occur with exposure to microgravity in astronauts; monitoring these alterations without radiographic capabilities on the International Space Station (ISS) requires novel diagnostic solutions to be developed. STUDY OBJECTIVES: We evaluated the ability of point-of-care ultrasound, performed by nonexpert-operator astronauts, to provide accurate anatomic information about the spine in long-duration crewmembers in space. METHODS: Astronauts received brief ultrasound instruction on the ground and performed in-flight cervical and lumbosacral ultrasound examinations using just-in-time training and remote expert tele-ultrasound guidance. Ultrasound examinations on the ISS used a portable ultrasound device with real-time communication/guidance with ground experts in Mission Control. RESULTS: The crewmembers were able to obtain diagnostic-quality examinations of the cervical and lumbar spine that would provide essential information about acute or chronic changes to the spine. CONCLUSIONS: Spinal ultrasound provides essential anatomic information in the cervical and lumbosacral spine; this technique may be extensible to point-of-care situations in emergency departments or resource-challenged areas without direct access to additional radiologic capabilities.

Cardiac and vascular responses to thigh cuffs and respiratory maneuvers on crewmembers of the International Space Station.

BACKGROUND: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and under the influence of thigh occlusion cuffs available as a countermeasure device (Braslet cuffs). METHODS: Nine International Space Station crewmember subjects (expeditions 16-20) were examined in 15 experiment sessions 101 ± 46 days after launch (mean ± SD; 33-185). Twenty-seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs (162 parameter states/session). Quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by investigators from the NASA Telescience Center in Houston, TX, and the Mission Control Center in Korolyov, Moscow region, Russia. RESULTS: 14 of 81 conditions (27 parameters measured at baseline, Valsalva, and Mueller maneuver) were significantly different when the Braslet was applied. Seven of 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression. CONCLUSIONS: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient at the "microgravity bedside."

On-orbit prospective echocardiography on International Space Station crew.

OBJECTIVES: A prospective trial of echocardiography was conducted on six crew members onboard the International Space Station. The main objective was to determine the efficacy of remotely guided tele-echocardiography, including just-in-time e-training methods and determine what is "space normal" echocardiographic data. METHODS: Each crew member operator (n = 6) had 2-hour preflight training. Baseline echocardiographic data were collected 55-167 days preflight. Similar equipment was used in each 60-minute in-flight session (mean microgravity exposure--114 days [34--190]). On-orbit ultrasound (US) operators used an e-learning system within 24 hours of these sessions. Expert assistance was provided using US video downlink and two-way voice. Testing was repeated 5-16 days after landing. Separate ANOVA was used on each echocardiographic variable (n = 33). Within each ANOVA, three tests were made: (a) effect of mission phase (preflight, in-flight, postflight); (b) effect of echo technician (two technicians independently analyzed the data); (c) interaction between mission phase and technician. RESULTS: Eleven rejections of the null hypothesis (mission phase or technician or both had no effect) were found that could be considered for possible follow up. Of these, eight rejections were for significant technician effects, not space flight. Three rejections of the null hypothesis (aortic valve time velocity integral, mitral E-wave velocity, and heart rate) were attributable to space flight but determine to not be clinically significant. No rejections were due to the interaction between technician and space flight. CONCLUSION: Thus, we found no consistent clinically significant effects of long-duration space flight on echocardiographic variables of the given group of subjects.

Sonography for determining the optic nerve sheath diameter with increasing intracranial pressure in a porcine model.

OBJECTIVES: This study investigated whether it is feasible to use sonography to monitor changes in the optic nerve sheath diameter in a porcine model. METHODS: A fiber-optic intracranial pressure transducer was surgically placed through the frontal sinus directly into the brain parenchyma of adult Yorkshire pigs (n = 5). A second bolt was placed on the contralateral side for intraparenchymal fluid infusion. Optic nerve sheath diameter measurements were acquired by each of 2 ultrasound operators around the leading edge of the nerve, 3 to 5 mm distal from the origin of the optic nerve. To induce a change in diameter, intracranial pressure was manipulated by injecting normal saline into the intraparenchymal infusion catheter located in the symmetric contralateral position as the pressure-monitoring probe. RESULTS: Data from 1 pig were unusable because of a cerebrospinal fluid leak into the sinus and orbital fissure. Saline aliquots of 1 to 10 mL were able to generate intracranial pressures typically starting from 10 to 15 mm Hg and increasing to 75 to 90 mm Hg, which eventually evoked a Cushing response. Fluid injection was controlled to increase pressures by 60 mm Hg over a 15- to 20-minute period. Regression analysis of all animals showed that the optic nerve sheath diameter increased by 0.0034 mm/mm Hg of intracranial pressure; however, this slope ranged from 0.0025 to 0.0046, depending on the animal measured. There was no discernible effect of the ultrasound operator on the slope; however, measurements made by 1 operator were consistently higher than the others by about 8% of the overall diameter range. CONCLUSIONS: These results suggest that the use of the optic nerve sheath diameter to noninvasively confirm acute changes in intracranial pressure over 1 hour is feasible in a porcine model. We recommend that this method be validated in humans using direct intracranial pressure measurement where possible to confirm it as a screening tool for acute and chronically increased diameters secondary to elevated pressure in clinical settings.