Fig 3
PPLL output voltage as a function of displacement amplitude and oscillation frequency. A linear relationship of approximately 1.5 mV pm-' exists over the clinically relevant range. Electronic noise and mechanical limitations degrade the results at displacements less than 3 pm.
Source publication
Intracranial pressure (ICP) may be an important contributor to symptoms of space adaptation syndrome during the initial days of microgravity exposure. The temporary nature of these symptoms suggests that some physiologic adaptation or compensation occurs. Fluid shifts similar to those in microgravity can be simulated on Earth using head-down tilt (...
Context in source publication
Context 1
... in vitro calibration studies demonstrated that the PPLL instrument output voltage (peak-to-peak) was proportional to displacement amplitude as measured over a dimensional range of 1-50 pm (Fig. 3). The output voltage amplitude tracked the displacement os- cillations, increasing when path length increased and decreasing during path length reduction. A linear rela- tionship was found .between the output voltage and displacement amplitude with sensitivity to displace- ments as small as 3 pm (1.5 mV . pm-', R~ = 0.99). The measurement. was reproducible over the frequency range of 0.5,1, and 2 Hz, which simulates heart rates of 30,60, and 120 ...
Citations
... The distension of the ONSSA or the immediate rise in ICP during HDT has been demonstrated in human subjects and animal models 47,48 . Gradual return toward the pre-HDT baseline has been noted in several studies 39,48,49 . ...
... The distension of the ONSSA or the immediate rise in ICP during HDT has been demonstrated in human subjects and animal models 47,48 . Gradual return toward the pre-HDT baseline has been noted in several studies 39,48,49 . Permanent changes after longduration spaceflight have also been observed 3,4,6,50 . ...
The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm ² (95% CI: 0.13 to 0.76 mm ² , P = 0.001), 0.45 mm ² (95% CI: 0.15 to 0.75 mm ² , P = 0.001), and 0.46 mm ² (95% CI: 0.15 to 0.76 mm ² , P < 0.001), respectively, and recovered immediately after HDT on R + 2. Such small changes in the ONSSA were below the lateral resolution limit of ultrasound (0.4 mm) and may not be clinically relevant, possibly due to ONS hysteresis causing persistent ONS distension. Future research can explore advanced quantitative portable ultrasound-based techniques and establish comparisons containing the pre-HDT measurements to deepen our understanding of SANS.
... In HDBR, having the head tilted below the feet also results in fluid shifts towards the head because of a change in the gravitational vector direction 6 . It has been hypothesized that these fluid shifts lead to increased intracranial pressure 16,17 , as well as redistribution of fluids within the skull 18 . ...
The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.
... TCD waveform analysis, owing to its sensitivity to detect changes in cerebral blood flow, has been investigated as a noninvasive ICP estimator. [15][16][17][18][19][20][21][22][23][24][25][26][27][28] In these methods, the insonated compliant middle cerebral artery (MCA) is interpreted as a ''biological'' pressure transducer, with walls that can be deflected by transmural pressure (equivalent to cerebral perfusion pressure [CPP]), modulating accordingly the pulsatile waveform of cerebral blood flow velocity (FV). Transmission of this ''transducer,'' its linearity, stability in time, and calibration coefficients are unknownand these factors mainly contribute to limited accuracy of TCDbased methods. ...
Elevation of intracranial pressure (ICP) may occur in many diseases, and therefore the ability to measure it noninvasively would be useful. Flow velocity signals from transcranial Doppler (TCD) have been used to estimate ICP; however, the relative accuracy of these methods is unclear. This study aimed to compare four previously described TCD-based methods with directly measured ICP in a prospective cohort of traumatic brain-injured patients. Noninvasive ICP (nICP) was obtained using the following methods: 1) a mathematical "black-box" model based on interaction between TCD and arterial blood pressure (nICP_BB); 2) based on diastolic flow velocity (nICP_FVd); 3) based on critical closing pressure (nICP_CrCP); and 4) based on TCD-derived pulsatility index (nICP_PI). In time domain, for recordings including spontaneous changes in ICP greater than 7 mm Hg, nICP_PI showed the best correlation with measured ICP (R = 0.61). Considering every TCD recording as an independent event, nICP_BB generally showed to be the best estimator of measured ICP (R = 0.39; p < 0.05; 95% confidence interval [CI] = 9.94 mm Hg; area under the curve [AUC] = 0.66; p < 0.05). For nICP_FVd, although it presented similar correlation coefficient to nICP_BB and marginally better AUC (0.70; p < 0.05), it demonstrated a greater 95% CI for prediction of ICP (14.62 mm Hg). nICP_CrCP presented a moderate correlation coefficient (R = 0.35; p < 0.05) and similar 95% CI to nICP_BB (9.19 mm Hg), but failed to distinguish between normal and raised ICP (AUC = 0.64; p > 0.05). nICP_PI was not related to measured ICP using any of the above statistical indicators. We also introduced a new estimator (nICP_Av) based on the average of three methods (nICP_BB, nICP_FVd, and nICP_CrCP), which overall presented improved statistical indicators (R = 0.47; p < 0.05; 95% CI = 9.17 mm Hg; AUC = 0.73; p < 0.05). nICP_PI appeared to reflect changes in ICP in time most accurately. nICP_BB was the best estimator for ICP "as a number." nICP_Av demonstrated to improve the accuracy of measured ICP estimation.
... A head-ward fluid shift and accompanying increase in ICP is believed to play a role in the headache and nausea experienced by most astronauts during the initial hours or days in weightlessness (37). These symptoms appear to resolve after hours or days, which is consistent with head-down tilt weightlessness-simulation studies, indicating attenuation of the increase in ICP (35). Adaptive mechanisms to weightlessness include a reduction in blood and total fluid volume (19), altered cerebral autoregulation (6), and changes in compliance of vasculature, membranes and bony structures (29,42). ...
... Adaptive mechanisms to weightlessness include a reduction in blood and total fluid volume (19), altered cerebral autoregulation (6), and changes in compliance of vasculature, membranes and bony structures (29,42). Gabrion et al. (16) found that a head-ward fluid shift induced by either weightlessness (9 and 14 days during NASA STS 40 and 56 missions) or (9 or 14 days) tail suspension of rats caused similar changes in the choroidal plexus, indicating reduced CSF formation, which could attenuate ICP during long term head-down tilt or weightlessness (35). Shortly after return to earth or termination of tail-suspension (within 8 h), the rats displayed return towards normal choroidal differentiation (16). ...
We evaluated postural effects on intracranial pressure (ICP) and cerebral perfusion pressure (CPP: mean arterial pressure (MAP) - ICP) in neurosurgical patients undergoing 24-hour ICP monitoring as part of their diagnostic workup. We identified 9 patients (5 women, age 44±20 yrs.; mean±SD) who were "as normal as possible" i.e. without indication for neurosurgical intervention (e.g. focal lesions, global edema, abnormalities in ICP-profile or cerebrospinal fluid dynamics). ICP (tip-transducer probe, Raumedic) in the brain parenchyma (N=7) or in the lateral ventricles (N=2) and cardiovascular variables (Nexfin) were determined from 20° head-down tilt to standing up. Compared to the supine position, ICP increased during 10° and 20° of head-down tilt (from 9.4±3.8 to 14.3±4.7 and 19±4.7 mmHg, P<0.001). Conversely, 10° and 20° head-up tilt reduced ICP to 4.8±3.6 and 1.3±3.6 mmHg and ICP reached -2.4±4.2 mmHg when standing up (P<0.05). Concordant changes in MAP maintained CPP at 77±7 mmHg regardless of body position (P=0.95). During head-down tilt, the increase in ICP corresponded to a hydrostatic pressure gradient with reference just below the heart, likely reflecting the venous hydrostatic indifference point. When upright, the decrease in ICP was attenuated, corresponding to formation of a separate hydrostatic gradient with reference to the base of the skull, likely reflecting the site of venous collapse. ICP therefore seems to be governed by pressure in the draining veins and collapse of neck veins may protect the brain from being exposed to a large negative pressure when upright. Despite positional changes in ICP, MAP keeps CPP tightly regulated.
... TCD waveform analysis, owing to its sensitivity to detect changes in cerebral blood flow, has been investigated as a noninvasive ICP estimator. [15][16][17][18][19][20][21][22][23][24][25][26][27][28] In these methods, the insonated compliant middle cerebral artery (MCA) is interpreted as a ''biological'' pressure transducer, with walls that can be deflected by transmural pressure (equivalent to cerebral perfusion pressure [CPP]), modulating accordingly the pulsatile waveform of cerebral blood flow velocity (FV). Transmission of this ''transducer,'' its linearity, stability in time, and calibration coefficients are unknownand these factors mainly contribute to limited accuracy of TCDbased methods. ...
Elevation of intracranial pressure (ICP) may occur in many diseases and therefore the ability to measure it non-invasively would be useful. Flow velocity signals from Transcranial Doppler (TCD) have been used to estimate ICP, however the relative accuracy of these methods is unclear. This study aimed to compare 4 previously described TCD-based methods with directly measured ICP in a prospective cohort of head injured patients. Non-invasive ICP (nICP) was obtained using the following methods: I) a mathematical “black-box” model based on interaction between TCD and ABP (nICP_BB); II) based on diastolic FV (nICP_FVd); III) based on critical closing pressure (nICP_CrCP) and IV) based on TCD-derived pulsatility index (nICP_PI).
In time domain, for recordings including spontaneous changes in ICP greater than 7 mmHg, nICP_PI showed the best correlation with measured ICP (R=0.61). Considering every TCD recording as an independent event, nICP_BB generally showed to be the best estimator of measured ICP (R=0.39, p
... It has been shown to alter bone metabolism (Trappe et al. 2001), cardiac functions (Trappe et al. 2006), and other physiological changes (Kanikowska et al. 2008) that have been observed in astronauts after long-term space flights, and thus can be studied in more detail under conventional laboratory conditions, e.g. during the 60-day HDT WISE study in women (Beller et al. 2011 Mester et al. 1988). The mechanism behind this effect remains unclear but may be a consequence of an upward shift of body fluids, resulting, for example, in higher intracranial pressure or swelling of the mucosa tissue, although nasal airway resistance has been reported not to be changed with HDT bedrest (Steinbach et al. 2005). The effect appears to be stronger under the low salt diet for unknown reasons. ...
Altered olfactory functions in patients with eating disorders have been reported with obesity, during hunger, following food ingestion and after bariatric surgery, but subsequent data have remained controversial. Methods : We investigated olfactory function (threshold, identification, discrimination) by Sniffin Sticks® in six independent studies: At baseline and 24 h and 48 h after a zero-calorie fasting (Study 1); fasted and after a 3810 kJ mixed meal (Study 2); twice after a 2510 kJ mixed meal supplemented with either 40 g saturated or unsaturated fatty acids (Study 3); prior to and after rotation-induced nausea (Study 4); at baseline and after a 5-day 6° head-down tilt bedrest (HDT-BR) and a high (7.7 mmol/kg BW/d) and low (0.7 mmol/kg BW/d) sodium diet (Study 5). We also compared odor sensitivity before and 12 months after bariatric (sleeve) surgery in patients with morbid obesity (Study 6). Results : Fasting (Study 1) did not alter olfactory functions, and a highcalorie diet (Study 2) moderately improved odor discrimination only; saturated fatty acids (Study 3) marginally improved odor identification, while the induction of nausea (Study 4) did not affect olfaction. HDT-BR (Study 5) significantly reduced the olfactory thresholds as well as the total score, mainly due to the bedrest component. Bariatric surgery (Study 6) did not change odor sensitivity, but some morbidly obese patients exhibited abnormally low olfactory functions prior to and after surgery. Conclusions : Manipulation of the hunger/satiety state has only marginal effects on olfactory functions in normal healthy volunteers and obese patients.
... The PPLL technique has been utilized in several applications, including intracranial pressure (ICP) tracking (Ueno et al 1998, 2003, Steinbach et al 2005. The variable frequency PPLL has proven sensitive to phase changes due to changes in the ultrasound TOF. ...
Ultrasound has been widely used to nondestructively evaluate various materials, including biological tissues. Quantitative ultrasound has been used to assess bone quality and fracture risk. A pulsed phase-locked loop (PPLL) method has been proven for very sensitive tracking of ultrasound time-of-flight (TOF) changes. The objective of this work was to determine if the PPLL TOF tracking is sensitive to bone deformation changes during loading. The ability to noninvasively detect bone deformations has many implications, including assessment of bone strength and more accurate osteoporosis diagnostics and fracture risk prediction using a measure of bone mechanical quality. Fresh sheep femur cortical bone shell samples were instrumented with three 3-element rosette strain gauges and then tested under mechanical compression with eight loading levels using an MTS machine. Samples were divided into two groups based on internal marrow cavity content: with original marrow, or replaced with water. During compressive loading ultrasound waves were measured through acoustic transmission across the mid-diaphysis of bone. Finite element analysis (FEA) was used to describe ultrasound propagation path length changes under loading based on µCT-determined bone geometry. The results indicated that PPLL output correlates well to measured axial strain, with R(2) values of 0.70 ± 0.27 and 0.62 ± 0.29 for the marrow and water groups, respectively. The PPLL output correlates better with the ultrasound path length changes extracted from FEA. For the two validated FEA tests, correlation was improved to R(2) = 0.993 and R(2) = 0.879 through cortical path, from 0.815 and 0.794 via marrow path, respectively. This study shows that PPLL readings are sensitive to displacement changes during external bone loading, which may have potential to noninvasively assess bone strain and tissue mechanical properties.
... However, the symptoms of early space sickness appear to resolve after several days in microgravity and the reason for this adaptation is likewise unknown. Re-adaptation of ICP to upright control posture has been shown to occur in a 30-d bed rest model of microgravity (131). ...
Long-duration space missions, as well as emerging civilian tourist space travel activities, prompted review and assessment of data available to date focusing on cardiovascular risk and available risk mitigation strategies. The goal was the creation of tools for risk priority assessments taking into account the probability of the occurrence of an adverse cardiovascular event and available and published literature from spaceflight data as well as available risk mitigation strategies.
An international group of scientists convened in Bellagio, Italy, in 2004 under the auspices of the Aerospace Medical Association to review available literature for cardiac risks identified in the Bioastronautics Critical Path Roadmap (versions 2000, 2004). This effort led to the creation of a priority assessment framework to allow for an objective assessment of the hazard, probability of its occurrence, mission impact, and available risk mitigation measures.
Spaceflight data are presented regarding evidence/ no evidence of cardiac dysrhythmias, cardiovascular disease, and cardiac function as well as orthostatic intolerance, exercise capacity, and peripheral resistance in presyncopal astronauts compared to non-presyncopal astronauts. Assessment of the priority of different countermeasures was achieved with a tabular framework with focus on probability of occurrence, mission impact, compliance, practicality, and effectiveness of countermeasures. Special operational settings and circumstances related to sensitive portions of any mission and the impact of environmental influences on mission effectiveness are addressed. The need for development of diagnostic tools, techniques, and countermeasure devices, food preparation, preservation technologies and medication, as well as an infrastructure to support these operations are stressed. Selected countermeasure options, including artificial gravity and pharmacological countermeasures need to be systematically evaluated and validated in flight, especially after long-duration exposures. Data need to be collected regarding the emerging field of suborbital and orbital civilian space travel, to allow for sound risk assessment.
Introduction:
Spaceflight-Associated Neuro-ocular Syndrome (SANS) was linked to increased intracranial pressure (ICP) attributable to the combined effects of microgravity and environmental conditions encountered during spaceflight. Microgravity countermeasures as lower body negative pressure (LBNP) are potential interventions for SANS. Our aim is to provide a comprehensive qualitative analysis of literature contrasting simulation and spaceflight studies, focusing on the pathophysiology of SANS, and highlighting gaps in current knowledge.
Evidence acquisition:
We systematically searched PubMed electronic database for English primary research published until February 2019 discussing intracranial changes in spaceflight or simulated microgravity, excluding animal and experimental studies. Two authors screened all the abstracts with a third author resolving disagreements. The full-text manuscripts were analyzed in pilot-tested tables.
Evidence synthesis:
19 studies were reviewed. 13 simulation, and two out of six spaceflight studies were prospective. ICP changes were investigated in 11 simulation studies, where eight demonstrated a significant increase in ICP after variable periods of head-down tilt. three showed a significant increase in intraocular pressure (IOP) in conjunction with ICP elevation. With increasing ambient CO2: one showed an increase in IOP without further increase in ICP, while another showed a slight further decrease in ICP. LBNP demonstrated no significant effect on ICP in one and a decrease thereof in another study. After spaceflight, increased ICP on lumbar puncture was demonstrated in five studies.
Conclusions:
Exposure to microgravity increases ICP possibly precipitating ocular changes. Whether other factors come into play is the subject of investigation. Further randomized studies and methods of direct ICP measurement during spaceflight are needed.
