Short Title: Fluid Shifts - Stenger

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

The primary hypothesis of this proposal is that long duration space flight will induce a cephalad fluid shift and redistribution of fluid from intra- to extravascular space, resulting in increased facial interstitial thickness. This fluid redistribution will be more significant in a subset of astronauts that will also experience eye morphology changes and vision disturbances.

Specific Aim I: Determine distribution and compartmentalization of fluid volume (intracellular, extracellular, interstitial) during space flight and plasma volume after space flight.

Hypothesis 1: Plasma volume will be decreased post-flight compared to pre-flight.
Extracellular fluid volume will be decreased, intracellular fluid volume will be increased, and total body water will not change during long duration space flight.

Hypothesis 2: Ultrasound measures of fluid shift (interstitial thickness, venous diameter) and near infrared spectroscopy measures of tissue hydration will be elevated in the upper body and decreased in the lower body, during and after long duration space flight.

Specific Aim II: Determine effect of fluid distribution on visual acuity and its surrogates.

Hypothesis 3: Intraocular pressure, measured by tonometry, and optic nerve sheath diameter, a surrogate measure of intraocular pressure, will be increased with long duration space flight. The magnitude of this increase will be related to the magnitude of the measures of cephalad fluid shift.

Hypothesis 4: The magnitude of the changes in visual acuity will be related to the magnitude of the increase in optic nerve sheath diameter and tonometry measures of intraocular pressure.

Hypothesis 5: Recovery of visual acuity will be dependent on the recovery of optic nerve sheath diameter measures to preflight levels.

Specific Aim III: Correlate central venous pressure (CVP) to intraocular pressure as measured by tonometry and its surrogates.

Hypothesis 6: Central venous pressure will be elevated in those subjects who have elevated intraocular pressure after spaceflight, but not in subjects who do not have an elevation in intraocular pressure.

Specific Aim IV: Compare fluid shift measures and eye anatomy between acute 25 head down tilt and measures obtained during long duration space flight.

Hypothesis 7: The degree of pressure and anatomical changes to the eye during acute tilt will predict which subjects experience structural and functional changes during space flight.

Hypothesis 8: Post-bed flight acute tilts will reveal sub-clinical alterations that have occurred due to long duration space flight.

Specific Aim V: Compare the results obtained from space flight with those obtained from acute tilt and chronic head-down bed rest studies to assess whether bed rest is an adequate model of these space flight-induced adaptations. These comparisons will result from data sharing activities with bed rest measurements.

Hypothesis 9: The magnitude of the long duration space flight cephalad fluid shift on measures of fluid re-distribution can be predicted by the magnitude of similar responses during an acute pre-flight head-down tilt test.

Hypothesis 10: Observed magnitude in acute fluid shifts will be similar between spaceflight and bed rest, however the chronic distribution of that fluid between body compartments will be different between space flight and its analog. Changes in eye anatomy and function will be temporary in bed rest, while those observed during and following long-duration spaceflight will persist for months-years in some astronauts.

Short Title: Fluid Shifts - Dulchavsky

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
The primary hypothesis of this proposal is that long duration space flight will induce a cephalad fluid shift and redistribution of fluid from intra- to extravascular space, resulting in increased facial interstitial thickness. This fluid redistribution will be more significant in a subset of astronauts that will also experience eye morphology changes and vision disturbances.

Specific Aim I: Determine distribution and compartmentalization of fluid volume (intracellular, extracellular, interstitial) during space flight and plasma volume after space flight.

Hypothesis 1: Plasma volume will be decreased post-flight compared to pre-flight.
Extracellular fluid volume will be decreased, intracellular fluid volume will be increased, and total body water will not change during long duration space flight.

Hypothesis 2: Ultrasound measures of fluid shift (interstitial thickness, venous diameter) and near infrared spectroscopy measures of tissue hydration will be elevated in the upper body and decreased in the lower body, during and after long duration space flight.

Specific Aim II: Determine effect of fluid distribution on visual acuity and its surrogates.

Hypothesis 3: Intraocular pressure, measured by tonometry, and optic nerve sheath diameter, a surrogate measure of intraocular pressure, will be increased with long duration space flight. The magnitude of this increase will be related to the magnitude of the measures of cephalad fluid shift.

Hypothesis 4: The magnitude of the changes in visual acuity will be related to the magnitude of the increase in optic nerve sheath diameter and tonometry measures of intraocular pressure.

Hypothesis 5: Recovery of visual acuity will be dependent on the recovery of optic nerve sheath diameter measures to preflight levels.

Specific Aim III: Correlate central venous pressure (CVP) to intraocular pressure as measured by tonometry and its surrogates.

Hypothesis 6: Central venous pressure will be elevated in those subjects who have elevated intraocular pressure after spaceflight, but not in subjects who do not have an elevation in intraocular pressure.

Specific Aim IV: Compare fluid shift measures and eye anatomy between acute 25 head down tilt and measures obtained during long duration space flight.

Hypothesis 7: The degree of pressure and anatomical changes to the eye during acute tilt will predict which subjects experience structural and functional changes during space flight.

Hypothesis 8: Post-bed flight acute tilts will reveal sub-clinical alterations that have occurred due to long duration space flight.

Specific Aim V: Compare the results obtained from space flight with those obtained from acute tilt and chronic head-down bed rest studies to assess whether bed rest is an adequate model of these space flight-induced adaptations. These comparisons will result from data sharing activities with bed rest measurements.

Hypothesis 9: The magnitude of the long duration space flight cephalad fluid shift on measures of fluid re-distribution can be predicted by the magnitude of similar responses during an acute pre-flight head-down tilt test.

Hypothesis 10: Observed magnitude in acute fluid shifts will be similar between spaceflight and bed rest, however the chronic distribution of that fluid between body compartments will be different between space flight and its analog. Changes in eye anatomy and function will be temporary in bed rest, while those observed during and following long-duration spaceflight will persist for months-years in some astronauts.

Short Title: Fluid Shifts - Hargens

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
The primary hypothesis of this proposal is that long duration space flight will induce a cephalad fluid shift and redistribution of fluid from intra- to extravascular space, resulting in increased facial interstitial thickness. This fluid redistribution will be more significant in a subset of astronauts that will also experience eye morphology changes and vision disturbances.

Specific Aim I: Determine distribution and compartmentalization of fluid volume (intracellular, extracellular, interstitial) during space flight and plasma volume after space flight.

Hypothesis 1: Plasma volume will be decreased post-flight compared to pre-flight.
Extracellular fluid volume will be decreased, intracellular fluid volume will be increased, and total body water will not change during long duration space flight.

Hypothesis 2: Ultrasound measures of fluid shift (interstitial thickness, venous diameter) and near infrared spectroscopy measures of tissue hydration will be elevated in the upper body and decreased in the lower body, during and after long duration space flight.

Specific Aim II: Determine effect of fluid distribution on visual acuity and its surrogates.

Hypothesis 3: Intraocular pressure, measured by tonometry, and optic nerve sheath diameter, a surrogate measure of intraocular pressure, will be increased with long duration space flight. The magnitude of this increase will be related to the magnitude of the measures of cephalad fluid shift.

Hypothesis 4: The magnitude of the changes in visual acuity will be related to the magnitude of the increase in optic nerve sheath diameter and tonometry measures of intraocular pressure.

Hypothesis 5: Recovery of visual acuity will be dependent on the recovery of optic nerve sheath diameter measures to preflight levels.

Specific Aim III: Correlate central venous pressure (CVP) to intraocular pressure as measured by tonometry and its surrogates.

Hypothesis 6: Central venous pressure will be elevated in those subjects who have elevated intraocular pressure after spaceflight, but not in subjects who do not have an elevation in intraocular pressure.

Specific Aim IV: Compare fluid shift measures and eye anatomy between acute 25 head down tilt and measures obtained during long duration space flight.

Hypothesis 7: The degree of pressure and anatomical changes to the eye during acute tilt will predict which subjects experience structural and functional changes during space flight.

Hypothesis 8: Post-bed flight acute tilts will reveal sub-clinical alterations that have occurred due to long duration space flight.

Specific Aim V: Compare the results obtained from space flight with those obtained from acute tilt and chronic head-down bed rest studies to assess whether bed rest is an adequate model of these space flight-induced adaptations. These comparisons will result from data sharing activities with bed rest measurements.

Hypothesis 9: The magnitude of the long duration space flight cephalad fluid shift on measures of fluid re-distribution can be predicted by the magnitude of similar responses during an acute pre-flight head-down tilt test.

Hypothesis 10: Observed magnitude in acute fluid shifts will be similar between spaceflight and bed rest, however the chronic distribution of that fluid between body compartments will be different between space flight and its analog. Changes in eye anatomy and function will be temporary in bed rest, while those observed during and following long-duration spaceflight will persist for months-years in some astronauts.

Short Title: Direct ICP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim 1: Determine whether ICP in space is elevated in comparison to baseline ICP on Earth, and whether ICP after return to Earth differs from baseline values by measuring ICP in astronauts before, during, and after an ISS mission by invasive methods.

Specific Aim 2: Validate noninvasive ICP measurement methods and their correlation with invasive ICP before, during, and after spaceflight, and to quantify their error of measurement.

Specific Aim 3: Determine the correlation of ICP changes to other indicators of VIIP by collecting biomarkers of VIIP for correlation to ICP.

In addition to opening pressures, blood, urine, and cerebrospinal fluid (CSF) will be collected for biochemical and cytological analyses, including biomarkers unique to elevated ICP and choroid plexus and white matter damage. This study will be performed in conjunction with Zanello's "Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome."

Short Title: Biomarker Noninvasive ICP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim 1 (Hypothesis #1 and #2)

- To develop and validate a noninvasive ICP estimation (nICP) approach for a specific

population of crewmembers based on a noninvasive ICP framework (NICF). The anticipated

input parameters may include: arterial blood pressure (ABP), electrocardiogram signals, cerebral

blood flow velocity (CBFV), heart and ventilation rate, tympanic membrane displacement by

Cochlear and Cerebrospinal Fluid Pressure (CCFP), ophthalmic artery blood pressure by

Vittamed. The NICF has been only tested using ABP and CBFV data from brain injury patients.

The additional noninvasive data elements provide different aspects of cerebral physiology under

influence of ICP. Therefore, integrating them under the NICF is very likely to improve nICP

accuracy.

4

Specific Aim 2 (Hypothesis #2)

- To longitudinally estimate ICP in crew members before, during and after spaceflight using the

model developed in Aim 1.

Specific Aim 3 (Hypothesis #3)

- To use novel methods of mRNA and microRNA profiling to identify candidate urinary and

plasma biomarkers that align with VIIP-related physiologic variables.

Specific Aim 4 (Hypothesis #4)

-To measure and correlate novel biomarkers in urine and blood of crew members with measures

of estimated ICP, pre-, in- and post-flight.

-To use all noninvasive measures plus biomarkers as input to build a predictive model that will

inform the likelihood of a given crew member developing VIIP post flight.



This study will be performed in conjunction with Williams' "Zero G and ICP." It also informs gaps VIIP3, VIIP13, and CV7.

Short Title: CIPHER iSAFE

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

This proposal will identify if ocular structure and function alterations occur at a greater frequency and magnitude during one-year missions compared to six-month and six-week expeditions and whether the recovery profile is dependent upon mission duration. In addition, this project will determine if changes in vascular structure and function are greater after one-year missions and contribute to alterations in ocular structure and function. The identification of structural and functional changes will provide NASA the information necessary to inform the risk posture for future interplanetary expeditions with durations of up to three years and to identify possible countermeasures.

Aims:

1. Determine if ocular structural and functional changes develop to a greater degree (frequency or magnitude) during 1-year missions compared to shorter and if recovery is prolonged

2. Determine if ocular vascular structure and function is altered to a greater degree during 1YMs, and if recovery is more prolonged

3. Determine if ocular functional changes develop to a greater degree (frequency or magnitude) during 1-year missions compared to shorter and if recovery is prolonged

4. Determine if the vascular adaptations correlate with alterations in ocular structure and function.

Short Title: CSF Biomarkers - ISS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Objective:

To determine whether local vasoactive proteins and inflammatory cytokines in the CSF might provide useful biomarkers to monitor and address SANS.

Aims:

1. Identify biomarkers of ocular vascular vasomotor function in the CSF of astronauts - Test whether concentrations of 4 vasoactive proteins in the CSF are altered in ISS crew.

2. Identify biomarkers of vascular inflammation (inflammatory cytokines and products) in the CSF of astronauts.

3. Correlate findings with physiological variables (RNFL/choroidal thickness, IOP; mean arterial BP; IJV pressure).

Hypothesis:

Spaceflight-induced dysfunction in the ocular vasculature leads to symptoms of SANS and will be associated with markers of vascular dysfunction in the CSF of affected astronauts.

1. Long-duration spaceflight alters the levels of vasoactive biomarkers in the CSF that are linked to retinal vasomotor function, which will correlate with SANS symptoms.

2. Long-duration spaceflight alters the levels of inflammatory cytokine biomarkers in the CSF linked to venular permeability and lymphatic transport function, which will correlate with SANS symptoms.

Short Title: SANS OPTIMA

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Background:

One SANS hypothesis is that changes in the mechanical properties of the dural ONS can affect the optic nerve head. Another hypothesis is that choroid thickening leads to abnormally large mechanical strains on the anterior part of the optic nerve head.

Objective:

To use novel analysis methods that the PIs developed to evaluate these hypotheses in existing crew MRIs.

Aims:

1. Estimate optic nerve sheath (dura mater) structural stiffness in astronauts after long-duration space flight, and compare to structural stiffness in healthy control subjects.

2. Correlate optic nerve sheath structural stiffness in astronauts with severity of SANS.

3. Compute the magnitude of prelaminar retinal ganglion cell biomechanical insult due to choroidal swelling in flight (from pre and postflight OCTs), and correlate with severity of SANS in astronauts.

Short Title: Long-term Ocular & Brain Changes - ISS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Human Factors and Behavioral Performance (HFBP) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
To monitor ocular and brain changes induced by long-duration (ISS) flights for up to five years post-flight to determine:
1) Whether ocular and brain changes persist in some astronauts
2) If so, for how long
3) If there are any long-term health consequences

This study will use the same subjects (n=20 (standard duration and extended duration)) that are assigned to participate in the ISAFE study. In addition, 20 retired astronauts will be recruited for long term follow-up.

The lead PI on this study is Brandon Macias.  Additional PIs on this study are Eric Bershad, Mathias Basner, and Rachel Seidler.

Short Title: Gateway SANS Occupational & Research Monitoring

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

TBD

Aims:
TBD

Short Title: BRAIN-SANS

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Spaceflight Associated Neuro-ocular Syndrome (SANS) remains an important and unmitigated risk to long-duration spaceflight. Current hypotheses suggest that the lack of gravity leads to fluid shifting towards the head, resulting in congestion and/or elevated pressures in the cranial, vascular, and/or lymphatic compartments. NASA is proposing to conduct 30-day head-down tilt (HDT) experiments to test SANS countermeasures at the :envihab facility in Cologne, Germany. We propose to provide numerous key measurements in support of these planned 30-day missions. We will focus in particular on providing a toolkit for detailed neurophysiological and fluid shift assessment and monitoring suitable for measuring both SANS- and countermeasure-related changes. These tools will be designed to complement the standard ocular measures used for SANS diagnosis and monitoring (e.g., optical coherence tomography (OCT), ocular ultrasound (US), fundoscopy, visual acuity). Our proposed measures will include:

    • Intra-ocular pressure (IOP) tonometry, per our team’s prior SANS-relevant work.

    • Relative intracranial pressure (ICP) measurements via distortion product otoacoustic emissions (distortion product     otoacoustic emissions: DPOAE).

    • Blood volume shifts along the body axis via near-infrared spectroscopy (NIRS).

    • Intracranial blood inflow and outflow, via internal jugular vein (IJV) and carotid artery (CA) ultrasound cross-sectional     imaging and Doppler.

    • Cerebral pulsatility assessment, per our parabolic flight and SPACE-COT (Studying Physiological and Anatomical     Cerebral Effects of CO2 and Tilt) :envihab NIRS study.

    • Blood pressure at the level of the head via local, cuff less superficial temporal artery tonometry.

    • Sagittal sinus blood volume imaging and monitoring using diffuse optical tomography (DOT).

    • Cerebral edema assessment based on H2O concentration imaging, similar to that used in our previous altitude sickness     studies.

    • Cerebral electrical activity, via electroencephalogram (EEG) measurements.

    • Dynamic cerebral autoregulation (CAR) assessment during countermeasure (CM) challenges, which can be derived     from the NIRS signals used in the above measurements.

Our tools will be made fully compatible with the planned SANS countermeasures, as well as with those of other teams proposing specific CMs. Along with the measures, we will provide the necessary expertise and analysis to quantify physiological changes associated with SANS countermeasures deployed during the 30-day HDT campaigns at :envihab. Our specific aims are as follows:

    Aim 1: Develop an integrated collection of hardware to support multiple simultaneous, continuous brain monitoring/imaging capabilities, and ensure the hardware and measurements are fully compatible with whatever countermeasures are deployed during the :envihab missions.

    Aim 2: Characterize and quantify individual subjects’ physiological responses to each planned condition, including comparative assessment of SANS countermeasures.

    Aim 3: Relate neurophysiological changes over the 30-day HDT—both with and without SANS-CMs—to cognitive and operational performance, sleep, mood, and ocular measures. Given NASA’s plan to deploy Standard Measures during the study, we expect data will be collected from Cognition, Robotic On-Board Trainer for Research (ROBoT-r), psychological/mood surveys, and the standard ocular measures (OCT, fundoscopy). We will obtain these measures through data sharing so we can investigate the relationship of our neurophysiological measures to each of these outcome assessments. We will focus particular attention on neurophysiological relationships with operational performance ROBoT-r, the development of which was led by Dr. Strangman and which we have deployed in Human Exploration Research Analog (HERA), Neumayer Station in Antarctica, and onboard the International Space Station (ISS).

Jointly, the planned measures and Aims will enable NASA to quantitatively evaluate and compare the (neuro)physiological changes and fluid shifts associated with HDT and SANS countermeasures.

Short Title: CBS VNSCOR#3 Recovery Timeline of Spaceflight-Induced CNS Changes (Seidler)

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Factors and Behavioral Performance (HFBP) Element Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

SA1: Determine the recovery timeline of spaceflight-induced ocular changes (e.g., signs of SANS such as optic disc edema) and changes in brain structure, function, and fluid shifts, measuring out to five years post flight. Aim 1a will comprise prospective assessments, while Aim 1b will leverage follow up testing on crewmembers who participated in the PI’s Neuromapping flight study and those crewmembers who have existing retrospective pre and post flight MRI scans.

 

SA2:
Determine the associations between spaceflight-induced brain and

ocular structural and fluid changes with ocular function, cognitive function, sleep

quality and quality of life

Short Title: CBS VNSCOR#3 Long-Term Brain Structural and Functional Consequences of Spaceflight (Basner)

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Factors and Behavioral Performance (HFBP) Element Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

SA1: Determine long-term consequences of spaceflight on cognitive performance.

 

SA2: Determine long-term consequences of spaceflight on brain structural, functional and connectivity substrates of changes in cognitive performance.

Short Title: SANS Standards for maintaining inflight health to OCHMO

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Maturation

Aims:
The maturation task will

(1) review the findings of  the SANS data collected by multiple SANS-related ISS studies with the emphasis on SANS issues that develop in-flight; 
(2) develop/update standards for acceptable limits for inflight vision testing; and
(3) present the findings at boards to transition to appropriate operations stakeholders, as required 

Short Title: SANS Standards for Long Term Health to OCHMO

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Maturation

Aims:
The maturation task will

(1) review SANS data collected by research studies and as part of medical requirements (non-research) with the emphasis on SANS issues that continue postflight; 
(2) develop/update standards for acceptable limits for postflight vision testing; and
(3) present the findings at boards to transition to appropriate operations stakeholders, as required 

Short Title: Cephalad Fluid Redistribution

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
In order to fully characterize intracranial adaptation to long-term microgravity, we will use magnetic resonance imaging (MRI) which is the terrestrial gold standard. MRI allows direct visualization and functional characterization of the intracranial contents. Indeed, MR imaging is the clinical standard of care in evaluating patients with idiopathic intracranial hypertension. We will use a suite of advanced MRI sequences in conjunction with gadolinium contrast and a CO₂ challenge to: 1) characterize weightlessness-induced intracranial compartmental fluid volume changes at the macroscopic (brain, CSF), microscopic (brain tissue water) and vascular (venous) levels following adaptation to long-term spaceflight and 2) assess for potential resultant hemodynamic changes (cerebral perfusion) in the brain. This proposal represents the most relevant and advanced suit of MRI techniques for the characterization of intracranial compartmental fluid and hemodynamic changes induced by long-term microgravity. The specific sequences will be carried out by the recognized experts in each area and in most cases, the developer of the specific technique.

Short Title: Pull-Push Gz Fluid Shifts

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Terminated - A formerly active task that was stopped before its completion date due to deselection, descoping, reorganization etc.

Procurement Mechanism(s):

Aims:

Specific Aim 1: To determine the impact of sequential +1 Gz followed by -0.3 Gz stress

on cerebrovascular and ocular structure and function without the orthostatic intolerance

countermeasures normally applied in astronauts returning from space flight.

Hypothesis: Following +1.0 Gz exposure, –Gz exposure will increase jugular vein

distention and pressure, increase intraocular and intracranial pressure, and distend

optic nerve sheath diameter but not change cerebral blood flow velocity.

Specific Aim 2: To determine the effect of anti-orthostatic countermeasures (fluid

loading, gradient compression garments, legs up posture with foot pressure) on the +1

Gz to -0.3 Gz induced fluids shift and subsequent impact on cerebral and ocular

structure and function.

Hypothesis: The addition of the anti-orthostatic countermeasures will exacerbate ocular

and vascular effects induced by the HDT fluid shift and will overcome the ability of

cerebral autoregulation to minimize these changes resulting in clinically significant

elevations in ICP.

Short Title: Direct ICP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim 1: Determine whether ICP in space is elevated in comparison to baseline ICP on Earth, and whether ICP after return to Earth differs from baseline values by measuring ICP in astronauts before, during, and after an ISS mission by invasive methods.

Specific Aim 2: Validate noninvasive ICP measurement methods and their correlation with invasive ICP before, during, and after spaceflight, and to quantify their error of measurement.

Specific Aim 3: Determine the correlation of ICP changes to other indicators of VIIP by collecting biomarkers of VIIP for correlation to ICP.

In addition to opening pressures, blood, urine, and cerebrospinal fluid (CSF) will be collected for biochemical and cytological analyses, including biomarkers unique to elevated ICP and choroid plexus and white matter damage. This study will be performed in conjunction with Zanello's "Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome."

Short Title: Biomarker Noninvasive ICP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim 1 (Hypothesis #1 and #2)

- To develop and validate a noninvasive ICP estimation (nICP) approach for a specific

population of crewmembers based on a noninvasive ICP framework (NICF). The anticipated

input parameters may include: arterial blood pressure (ABP), electrocardiogram signals, cerebral

blood flow velocity (CBFV), heart and ventilation rate, tympanic membrane displacement by

Cochlear and Cerebrospinal Fluid Pressure (CCFP), ophthalmic artery blood pressure by

Vittamed. The NICF has been only tested using ABP and CBFV data from brain injury patients.

The additional noninvasive data elements provide different aspects of cerebral physiology under

influence of ICP. Therefore, integrating them under the NICF is very likely to improve nICP

accuracy.

4

Specific Aim 2 (Hypothesis #2)

- To longitudinally estimate ICP in crew members before, during and after spaceflight using the

model developed in Aim 1.

Specific Aim 3 (Hypothesis #3)

- To use novel methods of mRNA and microRNA profiling to identify candidate urinary and

plasma biomarkers that align with VIIP-related physiologic variables.

Specific Aim 4 (Hypothesis #4)

-To measure and correlate novel biomarkers in urine and blood of crew members with measures

of estimated ICP, pre-, in- and post-flight.

-To use all noninvasive measures plus biomarkers as input to build a predictive model that will

inform the likelihood of a given crew member developing VIIP post flight.



This study will be performed in conjunction with Williams' "Zero G and ICP." It also informs gaps VIIP3, VIIP13, and CV7.

Short Title: CSF Biomarkers - ISS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Objective:

To determine whether local vasoactive proteins and inflammatory cytokines in the CSF might provide useful biomarkers to monitor and address SANS.

Aims:

1. Identify biomarkers of ocular vascular vasomotor function in the CSF of astronauts - Test whether concentrations of 4 vasoactive proteins in the CSF are altered in ISS crew.

2. Identify biomarkers of vascular inflammation (inflammatory cytokines and products) in the CSF of astronauts.

3. Correlate findings with physiological variables (RNFL/choroidal thickness, IOP; mean arterial BP; IJV pressure).

Hypothesis:

Spaceflight-induced dysfunction in the ocular vasculature leads to symptoms of SANS and will be associated with markers of vascular dysfunction in the CSF of affected astronauts.

1. Long-duration spaceflight alters the levels of vasoactive biomarkers in the CSF that are linked to retinal vasomotor function, which will correlate with SANS symptoms.

2. Long-duration spaceflight alters the levels of inflammatory cytokine biomarkers in the CSF linked to venular permeability and lymphatic transport function, which will correlate with SANS symptoms.

Short Title: Telemetric ICP - ISS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

TBD

Aims:
This is a placeholder.

Specific Aims
Determine ICP during spaceflight.

Short Title: BRAIN-SANS

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Spaceflight Associated Neuro-ocular Syndrome (SANS) remains an important and unmitigated risk to long-duration spaceflight. Current hypotheses suggest that the lack of gravity leads to fluid shifting towards the head, resulting in congestion and/or elevated pressures in the cranial, vascular, and/or lymphatic compartments. NASA is proposing to conduct 30-day head-down tilt (HDT) experiments to test SANS countermeasures at the :envihab facility in Cologne, Germany. We propose to provide numerous key measurements in support of these planned 30-day missions. We will focus in particular on providing a toolkit for detailed neurophysiological and fluid shift assessment and monitoring suitable for measuring both SANS- and countermeasure-related changes. These tools will be designed to complement the standard ocular measures used for SANS diagnosis and monitoring (e.g., optical coherence tomography (OCT), ocular ultrasound (US), fundoscopy, visual acuity). Our proposed measures will include:

    • Intra-ocular pressure (IOP) tonometry, per our team’s prior SANS-relevant work.

    • Relative intracranial pressure (ICP) measurements via distortion product otoacoustic emissions (distortion product     otoacoustic emissions: DPOAE).

    • Blood volume shifts along the body axis via near-infrared spectroscopy (NIRS).

    • Intracranial blood inflow and outflow, via internal jugular vein (IJV) and carotid artery (CA) ultrasound cross-sectional     imaging and Doppler.

    • Cerebral pulsatility assessment, per our parabolic flight and SPACE-COT (Studying Physiological and Anatomical     Cerebral Effects of CO2 and Tilt) :envihab NIRS study.

    • Blood pressure at the level of the head via local, cuff less superficial temporal artery tonometry.

    • Sagittal sinus blood volume imaging and monitoring using diffuse optical tomography (DOT).

    • Cerebral edema assessment based on H2O concentration imaging, similar to that used in our previous altitude sickness     studies.

    • Cerebral electrical activity, via electroencephalogram (EEG) measurements.

    • Dynamic cerebral autoregulation (CAR) assessment during countermeasure (CM) challenges, which can be derived     from the NIRS signals used in the above measurements.

Our tools will be made fully compatible with the planned SANS countermeasures, as well as with those of other teams proposing specific CMs. Along with the measures, we will provide the necessary expertise and analysis to quantify physiological changes associated with SANS countermeasures deployed during the 30-day HDT campaigns at :envihab. Our specific aims are as follows:

    Aim 1: Develop an integrated collection of hardware to support multiple simultaneous, continuous brain monitoring/imaging capabilities, and ensure the hardware and measurements are fully compatible with whatever countermeasures are deployed during the :envihab missions.

    Aim 2: Characterize and quantify individual subjects’ physiological responses to each planned condition, including comparative assessment of SANS countermeasures.

    Aim 3: Relate neurophysiological changes over the 30-day HDT—both with and without SANS-CMs—to cognitive and operational performance, sleep, mood, and ocular measures. Given NASA’s plan to deploy Standard Measures during the study, we expect data will be collected from Cognition, Robotic On-Board Trainer for Research (ROBoT-r), psychological/mood surveys, and the standard ocular measures (OCT, fundoscopy). We will obtain these measures through data sharing so we can investigate the relationship of our neurophysiological measures to each of these outcome assessments. We will focus particular attention on neurophysiological relationships with operational performance ROBoT-r, the development of which was led by Dr. Strangman and which we have deployed in Human Exploration Research Analog (HERA), Neumayer Station in Antarctica, and onboard the International Space Station (ISS).

Jointly, the planned measures and Aims will enable NASA to quantitatively evaluate and compare the (neuro)physiological changes and fluid shifts associated with HDT and SANS countermeasures.

Short Title: CBS VNSCOR#3 Recovery Timeline of Spaceflight-Induced CNS Changes (Seidler)

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Factors and Behavioral Performance (HFBP) Element Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

SA1: Determine the recovery timeline of spaceflight-induced ocular changes (e.g., signs of SANS such as optic disc edema) and changes in brain structure, function, and fluid shifts, measuring out to five years post flight. Aim 1a will comprise prospective assessments, while Aim 1b will leverage follow up testing on crewmembers who participated in the PI’s Neuromapping flight study and those crewmembers who have existing retrospective pre and post flight MRI scans.

 

SA2:
Determine the associations between spaceflight-induced brain and

ocular structural and fluid changes with ocular function, cognitive function, sleep

quality and quality of life

Short Title: CBS VNSCOR#3 Long-Term Brain Structural and Functional Consequences of Spaceflight (Basner)

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Factors and Behavioral Performance (HFBP) Element Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

SA1: Determine long-term consequences of spaceflight on cognitive performance.

 

SA2: Determine long-term consequences of spaceflight on brain structural, functional and connectivity substrates of changes in cognitive performance.

Short Title: SANS Standards for Long Term Health to OCHMO

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Maturation

Aims:
The maturation task will

(1) review SANS data collected by research studies and as part of medical requirements (non-research) with the emphasis on SANS issues that continue postflight; 
(2) develop/update standards for acceptable limits for postflight vision testing; and
(3) present the findings at boards to transition to appropriate operations stakeholders, as required 

Short Title: Grav-Induced CV Changes - Lab

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim 1:
To generate dose-response relationships between cardiovascular and ocular parameters as a function of changes in the gravitational vector.

Specific Aim 2:
To develop a computational model to predict cardiovascular and ocular variables due to changes in the gravitational vector.

Specific Aim 3:
Identify, explore, and simulate the effects of countermeasures (i.e. Lower Body Negative Pressure, exercise) on cardiovascular and ocular parameters using both experimental results and modeling techniques.

Short Title: BRAIN-SANS

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Spaceflight Associated Neuro-ocular Syndrome (SANS) remains an important and unmitigated risk to long-duration spaceflight. Current hypotheses suggest that the lack of gravity leads to fluid shifting towards the head, resulting in congestion and/or elevated pressures in the cranial, vascular, and/or lymphatic compartments. NASA is proposing to conduct 30-day head-down tilt (HDT) experiments to test SANS countermeasures at the :envihab facility in Cologne, Germany. We propose to provide numerous key measurements in support of these planned 30-day missions. We will focus in particular on providing a toolkit for detailed neurophysiological and fluid shift assessment and monitoring suitable for measuring both SANS- and countermeasure-related changes. These tools will be designed to complement the standard ocular measures used for SANS diagnosis and monitoring (e.g., optical coherence tomography (OCT), ocular ultrasound (US), fundoscopy, visual acuity). Our proposed measures will include:

    • Intra-ocular pressure (IOP) tonometry, per our team’s prior SANS-relevant work.

    • Relative intracranial pressure (ICP) measurements via distortion product otoacoustic emissions (distortion product     otoacoustic emissions: DPOAE).

    • Blood volume shifts along the body axis via near-infrared spectroscopy (NIRS).

    • Intracranial blood inflow and outflow, via internal jugular vein (IJV) and carotid artery (CA) ultrasound cross-sectional     imaging and Doppler.

    • Cerebral pulsatility assessment, per our parabolic flight and SPACE-COT (Studying Physiological and Anatomical     Cerebral Effects of CO2 and Tilt) :envihab NIRS study.

    • Blood pressure at the level of the head via local, cuff less superficial temporal artery tonometry.

    • Sagittal sinus blood volume imaging and monitoring using diffuse optical tomography (DOT).

    • Cerebral edema assessment based on H2O concentration imaging, similar to that used in our previous altitude sickness     studies.

    • Cerebral electrical activity, via electroencephalogram (EEG) measurements.

    • Dynamic cerebral autoregulation (CAR) assessment during countermeasure (CM) challenges, which can be derived     from the NIRS signals used in the above measurements.

Our tools will be made fully compatible with the planned SANS countermeasures, as well as with those of other teams proposing specific CMs. Along with the measures, we will provide the necessary expertise and analysis to quantify physiological changes associated with SANS countermeasures deployed during the 30-day HDT campaigns at :envihab. Our specific aims are as follows:

    Aim 1: Develop an integrated collection of hardware to support multiple simultaneous, continuous brain monitoring/imaging capabilities, and ensure the hardware and measurements are fully compatible with whatever countermeasures are deployed during the :envihab missions.

    Aim 2: Characterize and quantify individual subjects’ physiological responses to each planned condition, including comparative assessment of SANS countermeasures.

    Aim 3: Relate neurophysiological changes over the 30-day HDT—both with and without SANS-CMs—to cognitive and operational performance, sleep, mood, and ocular measures. Given NASA’s plan to deploy Standard Measures during the study, we expect data will be collected from Cognition, Robotic On-Board Trainer for Research (ROBoT-r), psychological/mood surveys, and the standard ocular measures (OCT, fundoscopy). We will obtain these measures through data sharing so we can investigate the relationship of our neurophysiological measures to each of these outcome assessments. We will focus particular attention on neurophysiological relationships with operational performance ROBoT-r, the development of which was led by Dr. Strangman and which we have deployed in Human Exploration Research Analog (HERA), Neumayer Station in Antarctica, and onboard the International Space Station (ISS).

Jointly, the planned measures and Aims will enable NASA to quantitatively evaluate and compare the (neuro)physiological changes and fluid shifts associated with HDT and SANS countermeasures.

Short Title: Rodent CSF

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

This study will investigate the hypothesis that hindlimb suspension induces structural and functional changes in choroid plexus (where CSF is produced) and arachnoid granulations (where CSF is absorbed), including evidence of inflammation or fibrosis, changes in aquaporin level and changes in cell-cell adhesion protein expression. Such changes are hypothesized to occur concomitant with fluid shift caused by the positional change, which may affect the production and paracellular/ transcellular CSF outflow and thus, CSF homeostasis. Supraphysiologic pressures in the in vitro model also simulates this fluid shift and allows for direct measurement of changes in paracellular/transcellular CSF outflow through the arachnoid cell layer. This task will evaluate and investigate these measures in a cohort of hindlimb suspended rats. Task completion will contribute to closing the knowledge gap surrounding the etiology of the VIIP syndrome by characterizing and quantifying the observed physiological changes.

 

In consideration of the experimental design of the parent animal experiment and its organization in cohorts, this study proposes the following specific aims:

1. To perform genome-wide expression analysis in the CP and AV of rats subjected to HS and their normal posture controls, including analysis of the expression of aquaporins (water-selective channels) at various time points within each of the two cohorts available for tissue sharing.

2. To study and compare the ultrastructure of the CP and AG and the localization and distribution of aquaporins and of cellular junction proteins (tight junctions, desmosomes, adherens junctions) of the endothelial cell layer of the venous sinuses, in normal posture and in HR rats within each cohort.

*Note: Due to the fact that it is unlikely that frozen brain will be made available from cohort 1 (young male rats), we will not be able to investigate gender or age differences in the response to

HS. Only longitudinal comparisons will be possible within each cohort. Depending on the sequence of cohorts implemented in the parental animal study, we will be provided with tissue from old male rats or young female rats (cohort 3) and any one of young males, young females, or aged males, exposed to enriched CO2 (cohort 4).

 

Short Title: Rodent Vascular

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Background: Changes in retinal blood flow or pressure may contribute to the formation of cotton wool spots and optic disc edema. SANS sx may also result from ocular venous congestion and/or elevated venous compliance, disruption of the BRB, and/or reduction in ocular lymph flow.

 

Goal: Determine whether microgravity alters the structure and function of the ocular vasculature at the level of feed arteries, venous exchange and capacitance vessels, and lymph vessels.

Aims:

1. Evaluate the effects of microgravity on ocular artery structure/function - Will test whether CRA flow velocity and vasomotor function and structure of ophthalmic arteries are affected after exposure to spaceflight

2. Evaluate the effects of microgravity on ocular vein structure/function - Will test whether BRB integrity/microvascular hyperpermeability of venous exchange vessels and vascular reactivity of ophthalmic capacitance veins are affected

3. Evaluate the effects of microgravity on ocular lymphatic structure/function - Will test whether the ocular lymphatic network and the phasic and tonic contractile function and structure of the large ophthalmic collecting lymphatics are affected after flight.

Short Title: Rodent model for VIIP - Fuller

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
To determine if the cephalic fluid shift seen during microgravity exposure is the causative factor leading to the ocular changes seen in astronauts after long-term space flight (Watkins and Barr 2010) (Mader, Gibson et al. 2011). The Hind Limb Suspended (HLS) rat model of microgravity will be used to answer the following specific aims. The HLS rat model will allow us to approach these questions and more rapidly achieve the program objectives. A 90-day suspension experiment utilizing the rat model, which we have performed numerous times, is roughly equivalent to a 2.5-year exploration class mission, or bedrest study, in a human subject based on lifespans.

Specific Aim 1. To determine if the microgravity model of rat hindlimb suspension (HLS)
results in increased intracranial (IOP) and intraocular (IOP) pressures, as well as alterations in ophthalmic anatomy and/or function.

In order to answer this specific aim, we will test the following hypotheses:

Hypothesis 1a. HLS male rats will have a higher ICP and IOP than control male rats. Further, the HLS male rats will have altered ophthalmic morphology and function including, but not limited to, flattening of the globe, increased diameter of the optic nerve and alterations in retinal function.
Hypothesis 1b. Post-suspension, ICP and IOP will return to pre-suspension levels and ophthalmic morphology and function will also recover over time.

Specific Aim 2. To determine if there is a gender differences in the ophthalmic responses to increased ICP and IOP.

In order to answer this specific aim, we will test the following hypotheses:

2a. HLS will results in increased ICP, IOP and altered ophthalmic features in female animals compared to female controls, but the responses will not be different from HLS males studied in
Specific Aim 1.
2b. Post-suspension recovery of ICP, IOP and ophthalmic features in female rats will not have a longer time course compared to the HLS males of Specific Aim 1.

Specific Aim 3. To determine if aging increases the ophthalmic responses to increased ICP and IOP.

In order to answer this specific aim, we will test the following hypotheses:

3a. The effects of HLS on ICP, IOP and ophthalmic features will be greater in older animals compared to both age-matched controls and the younger HLS males of Specific Aim 1.
3b. Post-suspension recovery of ICP, IOP and ophthalmic features will have a longer time course in older rats compared to the younger HLS males of Specific Aim 1.

Specific Aim 4. To determine if elevated atmospheric carbon dioxide (CO2) levels affect the ophthalmic responses to increased ICP and IOP in male rats.

In order to answer this specific aim, we will test the following hypotheses:

4a. The effects of HLS in young male rats on ICP, IOP and ophthalmic features will be increased in a mildly hypercapnic environment compared both to hypercapnic controls and the HLS males of Specific Aim 1 in room air.

4b. Post-suspension recovery of ICP, IOP and ophthalmic features in young male rats will have a longer time course in male rats simultaneously exposed to HLS and increased CO2 levels, compared to controls and the recovery of HLS males in Specific Aim 1 in room air.

This study combines two studies from the 2011 NRA: C. Fuller and S. Zanello.

Short Title: Rodent Model for VIIP - Zanello

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
The awarded study was combined with a complementary analog study from 2011 NRA PI: Charles Fuller.

To determine if the cephalic fluid shift seen during microgravity exposure is the causative factor leading to the ocular changes seen in astronauts after long-term space flight (Watkins and Barr 2010) (Mader, Gibson et al. 2011). The Hind Limb Suspended (HLS) rat model of microgravity will be used to answer the following specific aims. The HLS rat model will allow us to approach these questions and more rapidly achieve the program objectives. A 90-day suspension experiment utilizing the rat model, which we have performed numerous times, is roughly equivalent to a 2.5-year exploration class mission, or bedrest study, in a human subject based on lifespans.

Specific Aim 1. To determine if the microgravity model of rat hindlimb suspension (HLS)
results in increased intracranial (IOP) and intraocular (IOP) pressures, as well as alterations in ophthalmic anatomy and/or function.

In order to answer this specific aim, we will test the following hypotheses:

Hypothesis 1a. HLS male rats will have a higher ICP and IOP than control male rats. Further, the HLS male rats will have altered ophthalmic morphology and function including, but not limited to, flattening of the globe, increased diameter of the optic nerve and alterations in retinal function.
Hypothesis 1b. Post-suspension, ICP and IOP will return to pre-suspension levels and ophthalmic morphology and function will also recover over time.

Specific Aim 2. To determine if there is a gender differences in the ophthalmic responses to increased ICP and IOP.

In order to answer this specific aim, we will test the following hypotheses:

2a. HLS will results in increased ICP, IOP and altered ophthalmic features in female animals compared to female controls, but the responses will not be different from HLS males studied in
Specific Aim 1.
2b. Post-suspension recovery of ICP, IOP and ophthalmic features in female rats will not have a longer time course compared to the HLS males of Specific Aim 1.

Specific Aim 3. To determine if aging increases the ophthalmic responses to increased ICP and IOP.

In order to answer this specific aim, we will test the following hypotheses:

3a. The effects of HLS on ICP, IOP and ophthalmic features will be greater in older animals compared to both age-matched controls and the younger HLS males of Specific Aim 1.
3b. Post-suspension recovery of ICP, IOP and ophthalmic features will have a longer time course in older rats compared to the younger HLS males of Specific Aim 1.

Specific Aim 4. To determine if elevated atmospheric carbon dioxide (CO2) levels affect the ophthalmic responses to increased ICP and IOP in male rats.

In order to answer this specific aim, we will test the following hypotheses:

4a. The effects of HLS in young male rats on ICP, IOP and ophthalmic features will be increased in a mildly hypercapnic environment compared both to hypercapnic controls and the HLS males of Specific Aim 1 in room air.

4b. Post-suspension recovery of ICP, IOP and ophthalmic features in young male rats will have a longer time course in male rats simultaneously exposed to HLS and increased CO2 levels, compared to controls and the recovery of HLS males in Specific Aim 1 in room air.

Short Title: Exploration ATM Bedrest

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

TBD

Aims:
After the completion of the AGBRESA study, we should know if CO2 plays a role in developing disc edema during bed rest, or if strict head down tilt alone is sufficient.  If CO2 does play a role, the next step will be to perform the CO2 dose-response study to determine the magnitude of the disc edema response to increasing magnitudes of CO2 atmosphere.  The duration and magnitude of CO2 doses is still TBD, but will likely be in the range of 4, 8 and 12 mmHg exposures for 2 to 4 weeks. 

Short Title: Thirty-day CO2 Bedrest - Alperin

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Behavioral Health & Performance (BHP) Element

Funding Status: Terminated - A formerly active task that was stopped before its completion date due to deselection, descoping, reorganization etc.

Procurement Mechanism(s):

Solicited

Aims:
1. Use novel technology that quantifies the degree of the globe distortions by MRI to assess the efficacy of head-down bed rest as a ground-based analog for VIIP. Detect and measure the magnitude of changes in globe flattening, optic nerve protrusion, visual acuity, and other related imaging measures that might be induced by subjects undergoing 30 days of head-down bed rest. The magnitude of the changes observed in bed rest will be compared to those measured in astronauts with and without signs of the VIIP syndrome.

2.  Assess the efficacy of bed rest as a behavioral, health, and performance stressor. Neurocognitive tests, some of which are similar to those performed aboard ISS, will be administered to the subjects and compared to available data from ISS to determine the efficacy of the bed-rest model as a ground-based analog for cognitive and behavioral modifiers.

Short Title: Transcutaneous CO2 - ISS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

TBD

Aims:

 

1. To determine if PtcCO2 levels compare and track with end-tidal PCO2 (PetCO2) during quiet breathing at rest before and during spaceflight.

2. To determine the range of PtcCO2 levels in crewmembers during spaceflight during various crew activities.

3. To compare daily and nightly PtcCO2 levels with outcomes related to sleep, cognitive performance, and SANS findings.

Short Title: Glymphatics: CO2 & HDT

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Aims:

Specific Aim 1: To measure the effects of HDT positioning on human glymphatic function.

Specific Aim 2: To assess the combined effect of breathing elevated CO2 and HDT on

human glymphatic function.

Short Title: 1C, PCOS, and VIIP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Directed

Aims:

1. Test for SNPs of each of 44 major genes (351 SNPs) involved in one-carbon metabolism in astronauts, and relate these to existing biochemical, vision and related medical data.
2. Gather ethnicity data from the crewmembers, and determine whether ethnicity is predictive of vision issues after long-duration space flight.
3. Compare biochemical, genetic, and ophthalmological data from PCOS patients and an age-matched control group.

 

Short Title: SANS Data Integration IMPALA

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Terminated - A formerly active task that was stopped before its completion date due to deselection, descoping, reorganization etc.

Procurement Mechanism(s):

Technology Development

Aims:
Task terminated (i.e. not completed) because the strategy for this task has changed. The task was incorporated into another larger task that is not funded by HHC.

Original Aim:
A collaboration effort between researchers, clinicians, and epidemiologists to look for relationships between various findings to determine what predisposes astronauts to SANS.

Short Title: metabolomic alterations

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Identify metabolomic profiles associated with simulated space flight induced

physiological outcomes.

Identify changes in metabolomic pathways associated with simulated space flight

induced physiological changes by applying metabolomic approaches described in Aim 1 on

longitudinally collected urine and serum samples.

Test whether plasma metabolites have the potential to regulate cellular

metabolism and if specific changes in metabolism may be a means of detecting the risk for or

monitoring the progression of physiological outcomes induced by a simulated space flight

Short Title: Ocular Monitoring Framework - Lab

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
Aim 1:
To develop novel computational tools to establish mappings between the observed ocular structure and visual function, pre-, in-, and postflight, in order to provide NASA scientists and clinicians with better means to investigate SANS etiology and its progression. 
Aim 2:
To integrate Contrast Sensitivity, Visual Fields, and our novel distortion assessment mechanism into a
validated and compact diagnostic tool to better measure ocular function.

Short Title: SANS CM Bedrest - B complex

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
Strict 6-degree HDT bed rest will be utilized to test countermeasures against SANS.  The overall bedrest study consists of 6 groups of 12 subjects.  For this study, the 12 subjects in the non-mechanical countermeasure group will receive a daily nutritional countermeasure while the 12 subjects in the control group will receive a placebo.  

Specific Aims

1. Determine whether provision of a non-mechanical countermeasure: supplementation
with bioactive B-vitamins: L-methyltetrahydrofolate (5-MTHF), pyridoxine,
methylcobalamin, and riboflavin; prevents or mitigates SANS pathology (significant
ΔTRT) compared to a placebo controlled group.

2. Determine one-carbon pathway SNP profiles in all subjects, and assess whether
individuals with 3-4 risk alleles for MTRR A66G and SHMT1 C1420T
polymorphisms have greater ΔTRT during and after 30-d HDT bed rest.

3. Determine whether subjects with 3-4 risk alleles exhibit differences in biomarkers of
endothelial function, compared to subjects with 0-2 risk alleles.

4. Determine viscoelastic properties of the posterior sclera before, during, and after bed
rest, and determine influence of genetics and B-vitamin status on these properties and
any changes due to bed rest.