HRR - Risk - Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

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Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

Short Title: SANS Last Published: 07/31/19 10:05:29 AM (Central)

Element: Human Health Countermeasures (HHC)

Evidence: Report

Risk Master Logic Diagram: Not Available

Point of Contact: Michael Stenger

HRP Risk Status:

Risk Ratings and Dispositions per Design Reference Mission (DRM) Category

DRM Categories	Mission Duration	Operations		Long-Term Health
DRM Categories	Mission Duration	LxC	Risk Disposition *	LxC	Risk Disposition *
Low Earth Orbit	6 months	3x2	Accepted	3x2	Accepted
Low Earth Orbit	1 year	3x2	Accepted	3x3	Accepted
Deep Space Sortie	1 month	3x1	Accepted	3x1	Accepted
Lunar Visit/ Habitation	1 year	3x2	Accepted	3x3	Accepted
Deep Space Journey/Habitation	1 year	3x4	Requires Mitigation	3x4	Requires Mitigation
Planetary	3 years	3x4	Requires Mitigation	3x4	Requires Mitigation
Note: LxC is the likelihood and consequence rating. This risk title has been updated by HRP and is pending document update at the HSRB. The current HSRB risk title is “Risk of Spaceflight-Induced Intracranial Pressure/Vision Alterations” (VIIP).

Risk Statement

Given that the microgravity environment causes cephalad fluid shift in astronauts, there is a probability that astronauts will have intracranial pressure changes to some degree, and if left untreated, could lead to vision alterations and potentially other deleterious health effects.

Context

Astronauts on long duration ISS missions have experienced increased intracranial pressure (as measured post flight), ophthalmic anatomical changes and visual performance decrements of varying degrees. Presently, these symptoms have manifested themselves as changes in eye structure such as optic disc edema, globe flattening, choroidal folds, cotton wool spots (CWS), increased retinal nerve fiber layer and/or decreased near vision along with post mission spinal opening pressures ranging between 21 - 28.5 cm H2O for symptomatic astronauts. Present pre, in and post flight data indicate that after approximately 6 months of space flight, 24 of 64 US crewmembers that have been evaluated have shown symptoms of Spaceflight-Induced Intracranial Hypertension (SIIH). The cases are identified based on the criteria in the Spaceflight-Induced Intracranial Hypertension Clinical Practice Guideline. The signs considered are refractive change, changes in globe flattening, choroidal folds, cotton wool spots (CWS) and/or increased retinal nerve fiber layer along with the severity of optic disc edema (using the Frisen Scale). Prevalence to date have shown a rate of 37.5% of those tested with a16% rate for the cases with frank disc edema.

A preliminary occupational surveillance trial performed on space shuttle astronauts showed changes to the optic nerve diameter, Optical Coherence Tomography (OCT) parameters and visual acuity, even after the short 14 day mission. Although the crewmembers did not complain of fulminant changes in vision, and optic disc edema was not present, it was apparent on MRIs that changes were occurring but had not reached a particular threshold to cause significant visual disturbance.

Over 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short and long-duration missions, respectively, experienced a degradation in distant and near visual acuity.

Some of these vision changes and elevated ICP have remained unresolved years after flight. The mechanisms that cause Intracranial Hypertension (IHT) in microgravity are not known, and the processes by which eye structure changes occur as a result of IHT are not clearly understood. The impact of multiple missions or of cumulative time in space is not yet established, but suggest a dose response. Greater understanding of the mechanisms for IHT and eye structure changes is necessary to understand and mitigate the hazard and treat the resultant conditions.

Mitigation Strategy

Since 2009, medical requirements include more comprehensive pre-, in-, and postflight assessment of ocular parameters, including OCT, ocular ultrasound, fundus imaging, and visual acuity testing. Ultimately, the goal of both Space Medicine Operations and Human Research Program (HRP) is to identify and implement a set of preventative and treatment countermeasures for SANS. The SANS Research and Clinical Advisory Panel (RCAP), comprised of experts in the fields of glaucoma, vascular function, intracranial hypertension, retinal specialists, etc. monitors progress and provides guidance to NASA.

Space Medicine Operations manages the risk from a clinical perspective, monitoring and treating crewmembers as needed. The HRP conducts research to determine the cause and contributing factors to the syndrome as well as its eventual countermeasure development. In its pursuit to understand SANS etiology and risk factors, the research team depends on retrospective and prospective data sharing from the Space Medicine Operations group. Likewise, results of research investigations will inform Space Medicine Operations and may include recommendations from the research team regarding preflight susceptibility parameters to screen for in crewmembers, benefits of monitoring new parameters in-flight so that the onset of SANS signs and symptoms can be discovered (and eventually treated) much earlier, and eventually the most suitable countermeasures to use.

The current state of technology is continually surveyed (techwatch activities) so that the SANS team, comprised of Space Medicine Operations and HRP representatives, can optimize the diagnostic tools available onboard ISS. Since 2009, several modalities for improved in-flight measurements of ocular structure and function have been developed and launched (i.e. visual acuity testing software, ocular ultrasound, improved fundoscopy, and optical coherence tomography (OCT)).

The SANS research plan has been compiled from input from the summit results and RCAP guidance. Project gaps include 1) determining the etiology and risk factors for the VIIP syndrome, 2) acquiring suitable diagnostic tools, 3) identifying analogs and models for the syndrome, and 4) countermeasure development. Current efforts are mostly focused on determining etiology and risk factors and acquiring suitable diagnostic tools, with a concurrent effort underway to identify appropriate analogs and models. Progress on closing these gaps will facilitate countermeasure development. Medical Standards and Clinical Practice Guidelines are used by Space Medicine Operations to protect the safety of the crew, and as research progresses, findings will be transferred to Operations.

Gaps (4)

SANS1: We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight.

Responsible Element: Human Health Countermeasures (HHC)

Status: Open

Description

Initial State:

Limited data are available to definitively establish the underlying etiological mechanisms and contributing risk factors for SANS. Current efforts include crew data mining and occupational surveillance activities as well as terrestrial and in-flight studies to characterize these aspects. The leading hypothesis is that SANS is caused by increased intracranial pressure resulting from a cephalad (headward) fluid shift resulting from microgravity exposure and elevated CO₂ levels. Microgravity-induced cephalad fluid shift is known to occur but has not been fully quantified. The degree of cephalad fluid shift (and cerebral venous drainage) is hypothesized to vary based on individual levels of vascular compliance, which can be influenced by environmental and/or individual risk factors that are, as yet, insufficiently understood.

The spectrum of SANS signs and symptoms spans a range from mild (choroidal folds, globe flattening, and change in refraction) to more clinically significant (optic disc edema, scotomas, and visual field changes such as an enlarged blind spot). These observations suggest that SANS signs and symptoms develop along a clinical continuum, and if discovered early could be mitigated with the application of suitable countermeasures to minimize long-term health concerns. Successful countermeasure development is dependent on a thorough understanding of the cause and progression of this syndrome, including the identification of the most prevalent environmental and individual risk factors that contribute to its onset. Since etiology and risk factors are inextricably linked and are studied together, this gap addresses both aspects concurrently. The primary research goal is to understand the cause and progression of SANS and the risk factors that most significantly influence its development.

Target for closure:
Establish the etiology of SANS development and the impact of the hypothesized risk factors (as determined by the RCAP) to direct and focus countermeasure development.

Interim steps:

Define the time course of in-flight and postflight changes to ocular structure and function as compared to a preflight baseline (20%)
Quantify the time course and relative change in preflight, in-flight, and postflight intracranial pressure (20%)
Characterize the degree of spaceflight-induced cephalad fluid shift and establish whether a correlation exists between individual degrees of vascular and/or spinal compliance and changes in ocular structure and function (15%)
Define the correlation, if one exists, between in-flight and postflight ocular structure and function changes and central nervous system structure and function changes. (10%)
Characterize the relative contributions of the following hypothesized risk factors to the development of SANS: (25%)
1. Duration of microgravity exposure (cumulative, multiple, and single)
2. Environmental CO2 levels
3. Diet (specifically sodium consumption)
4. Individual anatomy
5. Genetic predisposition
6. Effects of medications used by crewmembers pre-, in-, and postflight
7. Effects of exercise
8. Other predisposing health parameters
As interim steps progress and major questions are answered, update the SANS Evidence Report to reflect and integrate the current state of knowledge. (5%)
Target closure will be recommended by a SANS advisory panel (i.e. the Research and Clinical Advisory Panel) following a review of the collective results of ground and in-flight studies and data mining efforts. Closure will be indicated by an advisory panel recommendation that identifies which risk factors and etiology mechanisms to target during countermeasure development efforts. (5%)

Research Approach:

The rVIIP project considers the SANS 1 knowledge gap to be its highest priority and, as such, current research efforts are predominately directed at this gap. Much of the planned work in SANS research plan cross-informs both etiology and risk factors. As progress is made on one interim stage, the other stages are informed. Activities to-date have included retrospective data mining, prospective occupational surveillance, and flight and ground studies to identify the numerous aspects of SANS outlined above. Importantly, many questions regarding etiology and risk factors can only be answered using actual space flight exposure. As such, preflight, in-flight, and postflight crew testing is planned and required to close this gap. Space Medicine Operations Division (i.e. non HRP) funded and managed tasks not covered by the SANS Research Plan include in-flight monitoring of visual health as part of the Medical Requirements Integration Document (MRID) mandated testing.

Target for Closure

No Target for Closure Available.

Tasks (43)

Prospective Observational Study of Ocular Health in ISS Crews [OCULAR HEALTH/OTTO/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Macias, Brandon

Short Title: Ocular Health (Ocular Health Study)

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):

Directed

Aims:
The International Space Station (ISS) Ocular Health Study aims to systematically gather physiological data to characterize the Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations on crewmembers assigned to long-duration (6-12 month) ISS increments. The data collected will mirror Medical Requirements Integration Documents (MRID) requirements and testing performed during annual medical exams. The frequency of in-flight and postflight testing will be increased to more accurately assess changes that occur in the visual, vascular, and central nervous systems upon exposure to microgravity and induction of fluid shifting. Monitoring in-flight changes, in addition to postflight recovery, is the main focus of this protocol. A data sharing plan with Medical Operations will reduce redundancy of data acquisition. Preflight, in-flight and postflight measures include: tonometry, ocular ultrasound, fundoscopy, visual acuity, and optical coherence tomography (OCT); while magnetic resonance imaging (MRI), and bio-microscopy will be captured preflight and postflight exclusively. Three additional, non-MRID measures, will be collected preflight, in-flight and postflight, including blood pressure and cardiac output to assess vascular compliance, and transcranial Doppler (TCD) for Pulsatility Index (PI) to assess a surrogate measure of ICP. Data collection will begin one year prior to flight, continue in-flight approximately every 30 days, and continue through to one year postflight. In circumstances where abnormalities may persist beyond one year, postflight data will continue to be collected, but as per the MRID requirements (MedB 1.10) and Visual Impairment/Intracranial Pressure (VIIP) clinical practice guidelines.

Resources (Flight)

Deliverables (1)

Risk of visual impairment and intracranial hypertension after space flight: Evaluation of the role of polymorphism of enzymes involved in one-carbon metabolism [ONE-CARBON METABOLISM/SMITH/COMPLETED]

Task Book: Entry
Principal Investigator: Smith, Scott

Short Title: One-Carbon Metabolism

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
In evaluating data collected from the Nutritional Status Assessment Supplemental Medical Objective (SMO), we have identified elevations in 4 metabolites of the one-carbon metabolism pathway in affected crew members studied to date. These elevations and related data strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the affected crew members. The incidence of such polymorphisms in the general population is relatively high, and they have been associated on Earth with increased risk of stroke and other cardiovascular, and specifically cerebrovascular, events. Therefore it is within the realm of plausibility, given the number and ethnic background of the affected astronauts, that these polymorphisms could be causing the cerebrovascular and optical medical issues in astronauts. This evidence demands follow-up to more clearly define this relationship. The proposed study will accomplish this. We expect that, at a minimum, the results of the proposed effort will provide a guiding path for other research to be conducted that would allow this problem to be defined and resolved.

This task will also contribute to gap closure of N7.3 by identifying the role of one-carbon pathway polymorphisms in VIIP related issues and determining if an initial relationship is found and requires further gaps and or tasks.

Resources (Flight)

Deliverables (1)

SD-OCT Analysis of The Optic Nerve Head and Surrounding Structures in Long Duration ISS Crew Members Compared to Terrestrial Bound Normals [SD-OCT ANALYSIS/PASS/COMPLETED

Task Book: Entry Unavailable
Principal Investigator: Pass, Anastas

Short Title: SD-OCT Analysis

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
To assess morphological ocular changes measured with spectral domain optical coherence tomography (SD-OCT) in the optic nerve head, peripapillary structures (retinal pigmented epithelium and choroid) and general choroidal thickness seen in International Space Station crewmembers exposed to long duration zero gravity and compared to matched normals and pseudotumor and increased intracranial hypertension patients.

Specifically, utilizing the data obtained and stored in the Zeiss Cirrus SD-OCT to assess optic discometry (disc size, elevation, cup and volume of the nerve), retinal thickness, retinal nerve fiber layer thickness (total and at specific points), choroidal thickness (peripapillary and sub-macular) and retinal pigmented epithelium angle.

Resources (Flight)

Deliverables (1)

Are Medications Involved in Vision and Intracranial Pressure Changes Seen in Spaceflight? [VIIP PHARM/WOTRING/COMPLETED]

Task Book: Entry Unavailable
Principal Investigator: Wotring, Virginia

Short Title: VIIP Pharm

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
To determine if affected crewmembers use medications known to be associated with cardiovascular, visual changes and ICP elevations in terrestrial medical practice and to assess the likelihood of medications as causal agents in spaceflight-associated visual changes and ICP elevation by using a large terrestrial database to model correlations.

Resources (Flight)

Deliverables (1)

Distribution of Body Fluids during Long Duration Space Flight and Subsequent Effects on Intraocular Pressure and Vision Disturbance [FLUID SHIFTS / STENGER / ACTIVE]

Task Book: Entry
Principal Investigator: Stenger, Michael

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.

Resources (Flight)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Description:
The deliverable will be a final report that 1) characterizes fluid distribution and compartmentalization before, during, and after long duration spaceflight, 2) reports any correlation between in-flight alterations of eye structure, ocular vascular parameters, and vision changes with headward fluid shifts, vascular dimensions, and flow patterns, 3) determines systemic and ocular factors of individual susceptibility to the development of ICP elevation and/or vision alterations, and 4) evaluates the patterns of fluid distribution in astronaut subjects on the ISS during mechanical interventions. It will contribute to the VIIP 1, VIIP 13, and CV 7 gaps by addressing the role of individual risk factors (VIIP 1), characterizing fluid redistribution inflight (CV 7), and evaluating the potential efficacy of mechanical countermeasures (VIIP 13).

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Microgravity Associated Compartmental Equilibration (MACE) [FLUID SHIFTS / DULCHAVSKY / ACTIVE]

Task Book: Entry
Principal Investigator: Dulchavsky, Scott

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.

Resources (Flight)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Fluid Distribution before, during and after Prolonged Space Flight-NNX13AJ12G [FLUID SHIFTS / HARGENS / ACTIVE]

Task Book: Entry
Principal Investigator: Hargens, Alan

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

Resources (Flight)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Human Cerebral Vascular Autoregulation and Venous Outflow in Response to Microgravity-Induced Cephalad Fluid Redistribution [CEPHALAD FLUID REDISTRIBUTION/ROBERTS/ACTIVE]

Task Book: Entry
Principal Investigator: Roberts, Donna

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.

Resources (Flight)

Deliverables (1)

Association of Diffusion Tensor Imaging Parameters of Optic Tracts and Cerebral White Matter Tracts with Visual Impairment and Structural Changes of the Eyes and Optic Nerves in Long-Duration Microgravity Exposure [DTI/RIASCOS/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Riascos-Castaneda, Roy

Short Title: DTI

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

The study uses diffusion tensor MRI of the brain to investigate alterations in nerve structure in correlation with intracranial pressure and compliance measures in astronauts pre- and post- microgravity exposure. The examination of brain microstructure has not been investigated in this context before and may reveal alterations to the brains of crewmembers.

The hypothesis that will be tested is that the degree of alteration in diffusion tensor (DT) metrics, including fractional anisotropy (FA) and mean diffusivity (MD), in cerebral optic and corticospinal (CST) tracts in astronauts correlates with the presence, severity, and duration of symptoms. This hypothesis will be tested using the following specific aims:

1. Quantify pre- and postflight diffusion tensor (DT) metrics, in the optic and corticospinal tracts of approximately 10 short duration (space shuttle missions) crewmembers, whose images are available for analysis.

2. Quantify pre- and postflight diffusion tensor (DT) metrics, in the optic and corticospinal tracts of approximately 10 long-duration (ISS missions) crewmembers whose images are available for analysis, starting with those scanned in 2010 and ending with those completing their mission by June 2013.

3. Determine and compare the presence of a significant alteration in DT metrics in those with and without in-flight and postflight signs/symptoms known to be secondary to microgravity exposure, and evaluate degree of correlation between DT metrics alteration and symptom/sign presence, severity and duration.

4. Obtain noninvasive MR measurement of intracranial compliance and pressure (MRICP) and evaluate the degree of correlation between DT metrics alteration and MRICP results.

5. Utilize all results to introduce an optimized conventional and diffusion MR imaging protocol.

Resources (Flight)

Deliverables (1)

Retrospective Pre and postflight measurement of cerebrospinal fluid (CSF) dynamics [MR-ICP CSF DYNAMICS RETROSPECTIVE/ALPERIN/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Alperin, Noam

Short Title: MR-ICP CSF Dynamics Retrospective

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
This retrospective study will evaluate pre and postflight MRI data from long-duration (15) and short-duration (10) crew members to determine cerebrospinal fluid (CSF) dynamics, to identify potential changes due to space flight and the relationship with the VIIP syndrome.

Resources (Flight)

Deliverables (1)

Effects of Long Duration Spaceflight on Venous and Arterial Compliance in Astronauts [VASCULAR COMPLIANCE/PLATTS/ACTIVE]

Task Book: Entry
Principal Investigator: Platts, Steven

Short Title: Vascular Compliance

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

1. Determine whether noninvasive measures of venous and arterial compliance are altered by long-duration spaceflight exposure in ISS astronauts and whether these changes are related to the development of the VIIP Syndrome.

2. Using 14-days of 6° head-down tilt bed rest as a model of spaceflight, evaluate the effect of aging on vascular compliance using a subject population similar to younger (25-35 yrs) and older (45-55 yrs) astronaut cohorts.

3. Determine whether previous spaceflight experience or training in high performance jet aircraft predispose astronauts to lower venous compliance and/or the development of the VIIP syndrome.

Resources (Ground Analog, Flight)

Deliverables (1)

Effects of Microgravity on Intracranial Pressure [MICROGRAVITY ICP/LEVINE/ACTIVE]

Task Book: Entry
Principal Investigator: Levine, Benjamin

Short Title: Microgravity ICP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

The primary objective of this study is to directly measure intracranial pressure, cerebral hemodynamics, and structure of the visual apparatus during changes in hydrostatic gradients (parabolic flight) that mimic microgravity exposure. To accomplish this objective the following hypotheses will be tested.

Hypothesis 1: The transition from the upright to the supine posture increases intracranial and right atrial pressures without a clinically significant change in ocular structure. The location of the intracranial hydrostatic indifference point (where rotation around that Gy axis in the Gz plane causes no change in hydrostatic pressure) determines the magnitude of the increase in ICP during changes in posture and in microgravity; if so, this characteristic could be a testable a risk factor for visual impairment in space.

Hypothesis 2: Microgravity-induced changes (via parabolic flight) in cerebral pressures and flow will be greater than those observed during bed rest.

To test these hypotheses, we will accomplish the following specific aims:

Specific Aim 1: We will recruit adult patients whom, because of prior medical treatment, have a brain access port from which ICP can be measured with little risk to the patient. Importantly, the selected patients will have no intracranial or cardiovascular pathology, and thus ICP can be measured accurately. Simultaneous measurement of right atrial pressure and arterial pressure will be combined with echo/Doppler measures of the middle cerebral artery, carotid and jugular vessels, and ocular ultrasound for central retinal and ciliary artery blood flow, globe size, shape and optic sheath diameter during 24 hours of head down tilt bedrest. These measures will allow a comprehensive assessment of cerebrovascular hemodynamics during routine gravitational transients. The hydrostatic indifference point will be determined in each volunteer.

Additional measurements will be made with modest increases in carbon dioxide concentrations, and during strength exercise to determine the independent and additive effects of these confounding stimuli. Finally, after the 24 hour measurements are completed, ICP will be monitored as the subject does a series of head maneuvers including lifting the head up on a pillow, and inflation of braslets to see if these simple interventions alter intracranial pressure.

Specific Aim 2: Subjects from Aim 1 will be exposed to parabolic flight (on a separate day) to achieve brief periods of microgravity. This protocol will allow comparison between real microgravity, and usual terrestrial changes in hydrostatic gradients during daily life (e.g., from supine to upright). Similar to aim 1, measurements will be obtained at rest, during exercise, and during small increases in carbon dioxide concentrations (10 parabolas each). The study of intracranial and cardiocerebral hemodynamics in microgravity has been largely unexplored. Only a careful dissection of the pathophysiology will allow the development of effective countermeasures that could ultimately lead to reducing the risk of visual impairments during space flight. Thus, this project will serve as the essential science base required to address a potential critical impediment to safe, long-duration space flight.

Resources (Ground Analog)

Deliverables (2)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Description:
The evaluation of a space flight analog environment to study transient ICP changes

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Category:
Subcategory:

Description:

Internal Customers:
None External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Pre & Postflight MRV review (central venous congestion) [VIIP MRV/RIASCOS/COMPLETED]

Task Book: Entry Unavailable
Principal Investigator: Riascos-Castaneda, Roy

Short Title: VIIP MRV

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:
NASA JSC’s Space Medicine group has added magnetic resonance venography (MRV) to the clinical monitoring protocol to evaluate central venous congestion and stenosis in astronauts pre and postflight. The MRVs will be collected as part of the standard medical requirements testing performed on all crew members using medical operations resources.

Resources (Flight)

Deliverables (1)

Brain Gene Expression Signatures from Cerebrospinal Fluid Exosome RNA Profiling [CSF EXOSOME GROUND/ZANELLO/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: CSF Exosome Ground

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:
This study will investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension –IIH). Our target population will be preferentially individuals with moderate ICP increase since their condition resembles more closely that of the astronauts exposed to microgravity in long duration spaceflight.

Resources (Other)

Deliverables (1)

A gene expression and histological approach to the study of cerebrospinal fluid production and outflow in rats [RODENT CSF/ZANELLO/ACTIVE]

Task Book: Entry
Principal Investigator: Zanello, Susana

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).

Resources (Other)

Deliverables (1)

Influence of Exercise Modality on Cerebral-Ocular Hemodynamics and Pressures [EXERCISE MODALITY/SCOTT/ACTIVE]

Task Book: Entry
Principal Investigator: Scott, Jessica

Short Title: Exercise Modality

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

Characterize the impact of 3 exercise modalities used by astronauts on cerebral blood flow, ICP, and IOP. Use head down tilt (HDT), a ground based analog that is well established to elicit similar cephalad fluid shifts as spaceflight. Evaluate 3 HDT sessions: 1) HDT + resistance exercise, 2) HDT + moderate intensity aerobic exercise, and 3) HDT + high intensity aerobic exercise. During and following each HDT session cerebral blood flow, IOP, and ICP will be measured.

Resources (None Listed)

Deliverables (1)

Effects of short term hypercapnia during head-down tilt on ocular structures, cerebral blood flow, and visual acuity in healthy human subjects [CO2 TILT/LAURIE/ACTIVE]

Task Book: Entry
Principal Investigator: Vizzeri, Gianmarco

Short Title: CO2 Tilt

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:
1. Investigate changes in IOP and ocular structures induced by short-term exposure to head-down bed rest and hypercapnia;

2. Investigate changes in cerebral blood flow and indirectly estimate ICP;

3. Evaluate the relationships between the measured ocular and cerebral outcomes.

Resources (Ground Analog)

Deliverables (1)

Integrative physiology of VIIP: cardiopulmonary, sleep, and cognitive function assessment during hypercapnic bed rest [Thirty-day CO2 Bedrest/LAURIE/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Steven Laurie

Short Title: Thirty-day CO2 Bedrest - Laurie

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Behavioral Health & Performance (BHP) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim I

Determine if changes consistent with VIIP develop during 30 days of BR combined with 0.5% CO₂ and determine if physiologic changes such as an increase in P_ETCO₂, PCO₂ sensitivity, or noninvasive estimates of intracranial pressure (nICP) occur and correlate with VIIP symptoms.

Specific Aim II

Determine if 30 days of BR combined with 0.5% CO₂ causes changes in cognitive function, mood, or anxiety and if these changes correlate with the development of VIIP symptoms. We will use two cognitive function assessment tools: the Cognition battery, which is currently undergoing testing in other NASA analog environments and on ISS, and the Defense Automated Neurobehavioral Assessment (DANA), an additional tool to assess cognitive changes, mood, and anxiety that includes a normative database based on testing with active military personnel and athletes.

Specific Aim III

Determine if 30 days of BR combined with 0.5% CO₂ causes sleep disruption, alters circadian and ultradian rhythms, and if these changes correlate with the development of VIIP symptoms.

Resources (Ground Analog)

Deliverables (1)

Zero G and ICP: Invasive and Noninvasive ICP Monitoring of Astronauts on the ISS [DIRECT INTRACRANIAL PRESSURE MEASUREMENT/WILLIAMS/ACTIVE]

Task Book: Entry
Principal Investigator: Williams, Michael

Short Title: Direct Intracranial Pressure Measurement

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."

Resources (Flight)

Deliverables (1)

Pilot study to evaluate a novel non-invasive technology to estimate peripheral and central venous pressure

Task Book: Entry Unavailable
Principal Investigator: Martin, David

Short Title: PVP Pilot Study

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
To confirm the relation between compression sonography as a non-invasive measure of peripheral venous pressure and an invasive measure and to identify which vein or veins are best suited for the measurement of peripheral venous pressure. Anatomical and individual differences influencing the size and quality of the veins and the tissues surrounding them may impact the ability of the sonographers to obtain reproducible measures in clinical and research environments. Information collected in this project will add to a greater understanding of this hardware and its utility in the measurement of peripheral venous pressure and the estimation of central venous pressure. A non-invasive methodology is critical for the estimation of central venous pressure safely in a large number of astronauts before, during, and after space flight. Central venous pressure is one of the primary factors which have been hypothesized to contribute to the development of elevated intracranial pressure in astronauts during and after space flight.

Resources (Other)

Deliverables (1)

A data mining project to identify cardiovascular related factors that may contribute to changes in visual acuity within the astronaut corps

Task Book: Entry Unavailable
Principal Investigator: Platts, Steven

Short Title: CV Data Mining for VIIP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
The overall aim for this project was to compile and analyze existing multi-system data obtained from astronauts before, during and after space missions to identify and characterize associations between crew who experienced changes in vision and elevated opening CSF pressures compared with those who did not.

Resources (None Listed)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Description:
A final report was delivered to the project on 10/3/11. Findings: In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown. However, using traditional theory, a higher total peripheral resistance combined with lower vascular compliance is generally associated with greater pathological changes to the cardiovascular system and potentially to the surrounding tissues. This information contributed to gap closure by informing the evidence base.

Internal Customers:
None External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Hindlimb suspension (HS) as an analog model of ocular alterations associated with cephalad fluid shifts: resveratrol as a countermeasure

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: Microgravity-HS-Retina

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
This project aims at testing the overall hypothesis that cephalad fluid shifts elicited by either microgravity or hindlimb suspension (HS) represent a stress factor that induces optic disc neuroanatomical changes, as well as retinal cell deterioration and loss via oxidative stress. The first specific aim of this pilot project is to perform histological and gene expression analysis of retinas collected from mice flown in STS-133 and STS-135 and from their ground control counterparts. The second specific aim is to perform similar analysis in retinas from hindlimb suspended rats, focusing on pathways consistent with cellular and oxidative stress, thus validating this ground analog animal model for the study of retinal stress in microgravity. The third specific aim will explore the potential efficacy of reversatrol and EGCG as a nutritional countermeasure to mitigate the risks or retinal oxidative stress and degeneration in conditions of simulated microgravity.

These experiments constitute tissue sharing endeavors among collaborators within and also external to NASA. Dr. Zanello leads the JSC efforts and has collected the eyes of the animals from both of these experiments in order to be used for histological and gene expression analysis.

Resources (None Listed)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Description:
a) Analog validation: this pilot experiment will determine i) The usefulness of the mouse model in microgravity to study degenerative processes in the retina; ii) The hindlimb suspension model as a analog that recapitulates the ocular changes associated with the fluid shifts in microgravity as observed in crewmembers.

b) Countermeasure: this pilot experiment will investigate whether the protective effects of resveratrol on other organ systems are also observed in the eye of rats subjected to the stress elicited by hindlimb suspension.

A final report titled “Effects of microgravity in the rodent retina and hindlimb suspension (HS) as an analog model of ocular alterations associated with cephalad fluid shifts” was delivered to the VIIP project on 3/5/2013.

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Spaceflight effects on the mouse retina: Histological, gene expression and epigenetic changes after flight on STS-135

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: Spaceflight - Retina

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
This task will pursue the following aims: Specific Aim 1 will perform histological and gene expression analysis of retinas collected from C57BL/6 mice flown in STS-135 (and from their ground control counterparts) and compare these results to similar analyses performed on BALB mice from STS-133. Histological and gene expression outcomes will be focused on cellular stress, oxidative stress, DNA damage and cellular death and survival, but will also investigate genome-wide changes by expression microarray analysis. Specific Aim 2 will investigate whether retinal gene expression differences between STS135-flown mice and their gound counterparts may have an epigenetic basis, by analyzing DNA methylation in specific target genes. Using the same methodological approach. Specific Aim 3 plans to address a question related to the risk of circadian disruption. This aim will interrogate whether the expression of the non-visual photorreceptor "melanopsin", which is a major protein responsible for light-entrainment, remains intact during spaceflight (under the combined influence of space environmental factors as described above). Under this objective, we will compare the expression of melanopsin (Opsn4) in intrinsically photorreceptive retinal ganglion cells (ipRGC) in mouse retinas after spaceflight and in their ground controls, in both BALB (flight STS133) and CB57Bl/6 mice (flight STS135). Demonstrating that melanopsin expression remains unaffected by spaceflight is of high importance as additional evidence to support blue light as a countermeasure to prevent and mitigate circadian disruption in spaceflight crews.

Resources (None Listed)

Deliverables (1)

Combined effects of gamma radiation and high dietary iron on oxidative damage and antioxidant status in rat eyes

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: Iron-radiation-eye

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
Using a rat model, this task will pursue the following aims:

Specific Aim 1 will determine the individual and combined effects of gamma radiation and elevated iron on markers of oxidative damage and antioxidant status in various eye structures, namely, retina, cornea and lens.

Specific Aim 2 will investigate the relationship between the extent of oxidative stress damage and indexes of cellular functional status, namely apoptosis, inflammation and stress signaling pathways, measured by gene expression profiling and immunohistochemistry.

Resources (None Listed)

Deliverables (1)

rVisual Impairment and Intracranial Pressure Project Data Mining

Task Book: Entry Unavailable
Principal Investigator: Otto, Christian

Short Title: rVIIP Data Mining

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
The overall aim for this project is to compile and analyze existing multi-system data obtained from astronauts before, during and after space missions to identify and characterize associations between crew who experienced changes in vision and elevated opening CSF pressures compared with those who did not.

Resources (None Listed)

Deliverables (1)

Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations Evidence Report

Task Book: Entry Unavailable
Principal Investigator: Otto, Christian

Short Title: VIIP Evidence Report

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:

Over the last 40 years there have been reports of visual acuity impairments associated with spaceflight through testing and anecdotal reports. Until recently, these changes were thought to be transient, but a comparison of pre and postflight ocular measures has identified a potential risk of permanent visual changes as a result of microgravity exposure. There are limited pre and postflight measures to define the risk and very few in-flight measures. These data show that there is a subset of crewmembers that experience visual performance decrements, cotton wool spot formation, choroidal fold development, papilledema, optic nerve sheath distention and/or posterior globe flattening with varying degrees of severity and permanence. These changes define the visual impairment/intracranial pressure (VIIP) syndrome. It is thought that the ocular structural and optic nerve changes are caused by events precipitated by the cephalad fluid shift crewmembers experience during long-duration spaceflight. It is believed that some crewmembers are more susceptible to these changes due to genetic/anatomical predisposition or lifestyle (fitness) related factors. Three important systems, ocular, cardiovascular, and central nervous, will be evaluated to understand the risk of developing the VIIP syndrome. Several hypotheses have been proposed to explain the identified visual acuity and structural changes including increased intracranial pressure, localized ocular changes such as ocular hypotony, decreased venous compliance, and alterations in cerebrospinal fluid dynamics. As there is little data to determine the extent or cause of the VIIP syndrome, there is a knowledge gap related to etiology of the changes and the postflight resolution. This lack of knowledge gives the basis for increased pre, in-, and postflight monitoring to characterize the risk. It will be very important to determine the risk of developing the VIIP syndrome and if there is an increase in severity corresponding to mission duration for exploration class missions.

The VIIP evidence book will capture the current evidence for the risk and outline potential hypothesis and future research areas.

Resources (None Listed)

Deliverables (1)

Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome [BIOMARKER NONINVASIVE ICP/ZANELLO/ACTIVE]

Task Book: Entry
Principal Investigator: Zanello, Susana

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.

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.

Resources (Other)

Deliverables (1)

VIIP and One-Carbon Metabolism: Expanded Polymorphism Evaluation and Polycystic Ovary Syndrome Pilot Study [1C-PCOS/SMITH/ACTIVE]

Comparing Globe Distortions Following Head-Down Bed Rest to those Measured in Astronauts in Short and Long-Duration Spaceflights [Thirty-day CO2 Bedrest/ALPERIN/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Alperin, Noam

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.

Resources (Ground Analog)

Deliverables (1)

Gravitational dose and multi-system physiologic response

Task Book: Entry Unavailable
Principal Investigator: Ploutz-Snyder, Lori

Short Title: AG dose

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Characterize the relationship between gravitational dose and acute physiologic responses of the cardiovascular, cerebrovascular, ocular, muscular, and sensorimotor systems.

Resources (Ground Analog)

Deliverables (1)

Impact of +Gz and -Gz induced fluid shifts on ocular and cerebral parameters during simulated Orion re-entry.

Task Book: Entry Unavailable
Principal Investigator: Stenger, Michael B.

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.

Resources (None Listed)

Deliverables (1)

VIIP Simulations of CSF, Hemodynamics and Ocular Risk (OPHTHALMIC MODELING CHANGES 2)

Task Book: Entry Unavailable
Principal Investigator: Ethier, Christopher

Short Title: Ophthalmic Modeling Changes 2

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

The aim is to develop modeling tools that: (i) compute fluid shifts in microgravity; (ii) compute how these shifts lead to biomechanical insult to the optic nerve in astronauts; and (iii) estimate the effect that these insults have on optic nerve function. These tools will directly build upon, and interface with, models of ocular biomechanics and fluid shifts that are currently being developed in

the NASA-funded MONSTR Sim project. Four specific aims were proposed:

SA1: Measure key physiologic parameters needed for modeling, including effects of intracranial pressure on optic nerve sheath

diameter, optic nerve tortuosity, craniospinal volume and cerebral blood flow.

SA2: Incorporate “quasi-1D” effects into existing compartment models, allowing us to evaluate the effects of microgravity and

countermeasures on CSF and blood flows/pressures.

SA3: Extend finite element models of ocular biomechanics, specifically modeling: (i) optic nerve kinking, and (ii) compression of optic

nerve fiber bundles in the lamina cribrosa; and relate kinking/compression to an index of axoplasmic insult/stasis.

SA4: Carry out parametric studies integrating the above models to identify individual-specific factors that: (i) predispose for the

development of VIIP syndrome, and (ii) influence the efficacy of proposed countermeasures, both useful for risk profiling

Resources (None Listed)

Deliverables (1)

Endothelial Dysfunction NRA

Task Book: Entry Unavailable
Principal Investigator: TBD

Short Title: Endothelial Dysfunction NRA

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Planned-Unfunded - Task not within current budget

Procurement Mechanism(s):

Solicited

Aims:

The purpose of this solicitation will be to further inform the impact of endothelial dysfunction on SANS. The blood-brain barrier is a target of particular interest.

Resources (None Listed)

Deliverables (1)

Venous Congestion Countermeasure Study

Task Book: Entry Unavailable
Principal Investigator: Stenger, Michael

Short Title: SANS CMs

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Directed

Aims:

The purpose of this proposal is to determine which individual or combination of countermeasures (CMs) most effectively acutely reverses the headward fluid shift and if it is possible to sustain the effects for up to 4 hours.

Specific Aims:

Determine if a single or combination of mechanical countermeasures, including lower body negative pressure (LBNP), veno-constrictive thigh cuffs (VTC), and breathing through an impedance threshold device (ITD), will acutely reverse a seated-to-supine posture headward fluid shift and sustain it for up to 30 min. Outcomes will include noninvasive measures of intracranial pressure (ICP), internal jugular vein cross sectional area (IJVA), internal jugular vein cross sectional pressure (IJVP), choroid thickness, and intraocular pressure.
Determine if the most effective combination of CMs to reverse vascular outcomes in specific aim #1 also reverses the cerebral spinal fluid (CSF) shift by quantifying intraventricular volumes using magnetic resonance imaging (MRI).
Determine if up to 8 hours of daily LBNP during sleep can prevent the headward fluid shift-induced changes during 3 days of head-down tilt bedrest.

Resources (Other)

Deliverables (1)

Eye Vein Pressure Device

Task Book: Entry Unavailable
Principal Investigator: Sit, Arthur

Short Title: Eye Vein Pressure Device

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Technology Development

Aims:
This project will include development and production of a minimally invasive device to measure and analyze episcleral venous pressure in human subjects. The device will be capable of making measurements in subjects positioned in the seated, supine, and head-down tilt postures.

Resources (Other)

Deliverables (1)

Self-Generated LBNP for Deep-Space Missions

Task Book: Entry Unavailable
Principal Investigator: Hargens, Alan

Short Title: Self-Generated LBNP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Goals:
Evaluate a novel, self-generated LBNP device as a SANS CM. A physiologically-integrated exercise hardware that is safe, low mass, low volume, low power and simple for deployment on a small, confined deep-space vehicle.

Elucidate how the interplay between and alleviation of increased IOP, ICP, and venous congestion alter the development of SANS
Determine the dosing and effectiveness of a novel, Self-Generated and Exercise Powered LBNP device to reproduce daily, Earth-like postures and activities in order to prevent cephalad fluid shifts and SANS development.

Aims:

Determine the immediate effects of 30 minutes of pulsatile, self-generated LBNP on cardiovascular, cerebral and ocular systems – N=12, males and females combined. Device specific data such as pressure fluctuations inside the chamber and footward reaction forces will be monitored. Will quantify central cardiovascular parameters such as HR and BP, leg fluid shifts, leg muscle activity, head and neck venous volumes, cerebral and ocular volumes, internal jugular vein pressures during and after 30 minutes of supine posture, 30 minutes of activity in the self-generated LBNP device, and 30 minutes of passive LBNP exposure.
Characterize the intermediate timescale responses in a 3 days of supine bedrest and determine dose-response
Parabolic flight

Resources (Ground Analog)

Deliverables (1)

Effects of microgravity on ocular vascular hydrodynamics (Flight)

Task Book: Entry Unavailable
Principal Investigator: Zawieja, David

Short Title: Mice Vascular Hydrodynamics

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:

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
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
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.

Resources (Flight)

Deliverables (1)

Investigating Structure and Function of the Eye (Flight)

Task Book: Entry Unavailable
Principal Investigator: Macias, Brandon

Short Title: 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:

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
Determine if ocular vascular structure and function is altered to a greater degree during 1YMs, and if recovery is more prolonged
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
Determine if the vascular adaptations correlate with alterations in ocular structure and function.

Resources (Flight)

Deliverables (1)

SPACE-CENT: Studying the Physiological and Anatomical Cerebral Effects of CENTrifugation and Head Down Tilt Bed Rest

Task Book: Entry Unavailable
Principal Investigator: Bershad, Eric

Short Title: Intermittent Rotation AGBRESA - Bershad

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
In this proposal, the effects of a 60-day exposure to simulated microgravity (6° head down tilt

bedrest, HDBR) on the cerebral, ocular and vestibular systems with and without the intervention

of intermittent artificial gravity (AG, short-arm centrifugation) will be evaluated. Our

overarching objective is to reveal the effects of HDBR-induced headward fluid shifts as well as

the reversal of these hydrostatic pressure gradients with AG using innovative, integrated

techniques to provide novel insights into the physiological adaptations during simulated

microgravity.

Aims:

To determine the between-group effects of 60 days HDBR alone versus HDBR with AG (2 different regimens) on the cerebral, ocular, and sensorimotor systems.
To determine the within-group effects of the experimental conditions (60 days HDBR +/- AG) on the cerebral, ocular and sensorimotor systems compared to pre HDBR baseline.
Assess the within and between group transient effects of AG (intervention groups) on cerebral and ocular systems using non-invasive technologies in the peri-centrifuge period.

Additional measures and data collections are also being performed on the subjects to create a non-CO2 control group for comparison to the Thirty-day CO2 Bedrest (VAPER) study (PI: S. Laurie).

Resources (Ground Analog)

Deliverables (1)

SANS Data Integration using IMPALA

Task Book: Entry Unavailable
Principal Investigator: Stenger, Michael

Short Title: SANS Data Integration IMPALA

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Technology Development

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

Resources (None Listed)

Deliverables (1)

Effects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits

Task Book: Entry Unavailable
Principal Investigator: Mao, Xiao Wen

Short Title: Tissue Sharing Flagship

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Radiation (SR) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

The objectives of this application are to characterize the impact of radiation doses and qualities on retinal vasculature and tissue remodeling and to study the role of mitochondria in regulating oxidative stress-induced cellular damage and alteration of cell-cell interactions in the function of blood-retina-barrier (BRB). Archived ocular tissues samples at dose ranges from 0.1 Gy to 1 Gy with multiple particle types and energies across multiple animal species will be available for sharing from three NASA funded investigators. We will evaluate radiation –induced retinal vascular and tissue remodeling at multiple time points. Our study will elucidate the spectrum of radiation-induced structural and functional alteration in retinal BRB function and the mechanisms by which these

changes are mediated.

Specific Aim 1:
Define the relationships between radiation-induced oxidative stress in ROS expression, retinal vascular remodeling, and BRB function. We will correlate cellular oxidative status with changes in retinal vascular topology, vascular endothelial cells (ECs), and BRB integrity using immunohistochemistry (IHC), stereological and automated image analyses, and magnetic resonance imaging diffusion tensor imaging (DTI-MRI). The observed changes in mice will be compared with that of rats and rabbits.

Specific Aim 2:
Determine whether radiation-induced oxidative damage in retina is mediated through photoreceptor mitochondrial ROS production. We will examine mitochondrial associated-oxidative stress and apoptosis and mitochondrial integrity in retinal photoreceptor using Western blot assays and histopathology.

Resources (None Listed)

Deliverables (1)

Markers of Vascular Risks Associated with Spaceflight Associated Neuro-ocular Syndrome

Task Book: Entry Unavailable
Principal Investigator: Zawieja, David

Short Title: CSF Markers

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:

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

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.
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.

Resources (Flight)

Deliverables (1)

Changes of the optic nerve dura mater in astronauts and SANS (OPTIMA)

Task Book: Entry Unavailable
Principal Investigator: Ethier, Christopher

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:

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

Resources (Flight)

Deliverables (1)

SANS 3: We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function.

Responsible Element: Human Health Countermeasures (HHC)

Status: Open

Description

Initial State:

We need an in-flight tool to measure intracranial pressure (ICP). We need optimal diagnostic tools to measure ocular structure and function.

There are currently (as of spring, 2014) six devices in-use on ISS to measure ocular structure or function: a hand-held tonometer (Tono-Pen), an ultrasound machine (GE Vivid Q), a fundoscope (Merge EyeScan), a Snellen chart (for measuring near vision), Acuity Pro software (Amsler grid and distance vision measurement), and optical coherence tomography (OCT) unit (Spectralis, Heidelberg Engineering). OCT provides high resolution 3D images of optical structure and tissue morphology. Technology to evaluate peripheral visual fields in-flight is also in work. Development and upgrade of in-flight ocular hardware is being led by Medical Operations (non HRP) but is of interest to the research community and is therefore being closely followed by the SANS research team.

As of spring 2014, the only hardware available onboard the ISS that is capable of providing a surrogate evaluation of ICP is an ultrasound device, capable of measuring both optic nerve sheath diameter (ONSD) and transcranial Doppler (TCD), both of which have been shown terrestrially to correlate with ICP. Further development of ICP measurement techniques and devices is outlined below.

Target for closure:

Compile a set of flight-validated, in-flight techniques and/or tools to characterize and quantify intracranial pressure, ocular structure, and ocular function.

Interim steps:

Survey the market for non-invasive technologies that are potentially capable of providing an accurate measure of intracranial pressure. (10%) - COMPLETE
Continuously review current technologies for the capability to monitor and measure ocular structures and function. (10%)
Determine the efficacy of the selected devices to obtain the desired measurement in the relative environment (e.g. ground and spaceflight) and its suitability for flight certification (15%)
Because even currently mature technologies that noninvasively measure ICP have limited testing correlating them to gold-standard invasive measurements, test the selected device(s) to verify the strength of correlation between indirect measures of intracranial pressure and invasive measurements of ICP (i.e. determine precision and accuracy of non-invasive modalities). (60%)
Flight-certify the final hardware selection. (10%)
Complete in-flight testing and validation of selected hardware. (5%)

Research Approach:

The identification and implementation of enhanced clinical/operational capabilities is a joint effort between HRP and Medical Operations, with SD focusing primarily on ocular measures and HRP focusing on ICP. While there has been recent progress in upgrading in-flight hardware to monitor ocular structure and function, several noninvasive tools are being evaluated for suitability for in-flight measurement of intracranial pressure (ICP). Elevated ICP (resulting from microgravity-induced cephalad fluid shifts) is speculated to be the main contributor to the development of the VIIP syndrome, so HRP considers the identification of tools and/or methodologies to accurately measure in-flight ICP to be the project’s highest priority within this gap.

Target for Closure

No Target for Closure Available.

Tasks (21)

Non-invasive ICP device purchase & evaluation [VITTAMED ICP DEVICE EVALUATION/BERSHAD/COMPLETED]

Task Book: Entry Unavailable
Principal Investigator: Bershad, Eric

Short Title: Vittamed ICP Device Evaluation

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
Evaluation and validation of the Vittamed non-invasive, absolute intracranial pressure measurement device.

Resources (None Listed)

Deliverables (1)

Non-Invasive Monitoring of Intracranial Pressure (ICP) with Volumetric Ophthalmic Ultrasound [ULTRASOUND ICP/DENTINGER/ACTIVE]

Task Book: Entry
Principal Investigator: Dentinger, Aaron

Short Title: Ultrasound ICP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Exploration Medical Capability (ExMC) Element

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:
1. Develop a volumetric ultrasound ophthalmic imaging system with improved image quality providing user independent, 3D imaging of the full ocular anatomy for pre-flight scans, postflight scans, and in-flight scans with minimal crew time and ground guidance during image capture.

2. Enable multimodality volume registration of in-flight ultrasound and pre-flight magnetic resonance (MR) ophthalmic scans enabling the ability to longitudinally track structural alterations in response to microgravity and correlate these ocular structural changes with elevated ICP and visual acuity changes.

3. Non-invasively monitor the ICP based on reliable measurements of the optic nerve sheath diameter and posterior globe flattening determined from volumetric ultrasound scan scans performed by non-expert operators with minimal image capture time required.

4. Non-invasively observe intracranial dynamics through measurement of the pulsation in the retinal blood flow and the optic nerve sheath from ultrasound image sequences and demonstrate the interaction between ICP and cerebral hemodynamics as they relate to cerebrospinal compensatory reserve.

Resources (None Listed)

Deliverables (1)

Comparison of Continuous Non-Invasive and Invasive Intracranial Pressure Measurement [NON-INVASIVE ICP GROUND COMPARISON/WILLIAMS/COMPLETED]

Task Book: Entry
Principal Investigator: Williams, Michael

Short Title: Non-invasive ICP Ground Comparison

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

This is a prospective, blinded, human subject research study comparing two noninvasive ICP methods (listed below) to a reference standard of invasive ICP monitoring.

The tympanic membrane displacement (TMD)/cerebral and cochlear fluid displacement (CCFP) method
Distortion product otoacoustic emissions (DPOAE) method

In separate subprotocols, we will compare the accuracy of the noninvasive methods to two

established reference methods of invasive ICP measurement:

1. Continuous ICP monitoring with a fluid-coupled external transducer via temporary

spinal catheter or via a 25 gauge needle inserted into an existing shunt reservoir

2. CSF infusion testing using the Likvor Celda System

Resources (None Listed)

Deliverables (1)

Mapping by VESGEN of Blood Vessels in the Human Retina for Improved Understanding of Visual Impairments and Increased Intracranial Pressure [RETINAL VASCULAR REMODELING/PARSONS/ACTIVE]

Task Book: Entry
Principal Investigator: Parsons-Wingerter, Patricia

Short Title: Retinal Vascular Remodeling

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Alterations in vascular patterning of the human retina responding to fluid shifts incurred by spaceflight will be mapped and quantified by analyzing existing pre- and postflight Optical Coherence Tomography (OCT) images. A complementary analysis of retrospective bedrest images will also be performed.

Resources (Ground Analog)

Deliverables (1)

SD/Upgrade Visual Acuity Software and In-flight Tonometer

Task Book: Entry Unavailable
Principal Investigator: N/A

Short Title: Tonometer

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:
Space Medicine is currently upgrading the visual acuity software and in-flight tonometry equipment. The new software and equipment are expected to be ready for flight operations in early 2013.

Resources (None Listed)

Deliverables (1)

ICP Tech Search (Innocentive, Yet To Come) COMPLETED

Task Book: Entry Unavailable
Principal Investigator: Villarreal, Jennifer

Short Title: ICP Tech Search

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:
A public solicitation using innovative tools to determine the current intracranial pressure measuring devices in the research and clinical environments.

Resources (None Listed)

Deliverables (1)

SD/Diagnostic OCT Trade Study

Task Book: Entry Unavailable
Principal Investigator: N/A

Short Title: OCT Trade Study

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:
The NASA Space Medicine group is performing a trade study to identify the optimal optical coherence tomography (OCT) device for both clinical and research use during flight.

Resources (None Listed)

Deliverables (1)

SD/Development of in-flight diagnostic OCT

Task Book: Entry Unavailable
Principal Investigator: N/A

Short Title: In-flight OCT

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:
To develop the identified OCT hardware for use during flight.

Resources (None Listed)

Deliverables (1)

SD/Fundoscopy Trade Study

Task Book: Entry Unavailable
Principal Investigator: N/A

Short Title: Flight Fundoscopy Trade Study

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:
The NASA Space Medicine group is performing a trade study to identify the optimal fundoscopy device for both clinical and research use during flight.

Resources (None Listed)

Deliverables (1)

SD/Development of in-flight fundoscopy

Task Book: Entry Unavailable
Principal Investigator: N/A

Short Title: Flight Fundoscope Upgrade

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Aims:
To develop and flight certify the fundoscope identified during the market survey. This work is funded by the ISS Program Office and performed by Space Medicine.

Resources (None Listed)

Deliverables (1)

Analysis of a Clinical Database as a Means to Validate Non-invasive Assessment of Intracranial Pressure Using the Cerebral and Cochlear Fluid Pressure (CCFP) Analyzer [CCFP DATA MINING/EBERT/COMPLETED]

Task Book: Entry Unavailable
Principal Investigator: Ebert, Doug

Short Title: CCFP Data Mining

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Space Medicine Medical Operations (SMMO)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
1. Correlate tympanic membrane displacement (TMD) analysis with lumbar puncture (LP) data in a retrospective blinded cohort analysis of clinical cerebral and cochlear fluid pressure (CCFP) device data points obtained in approximately 60 patients; evaluate its potential as a surrogate measure to the clinical gold standard (LP).
2. Determine the age-dependent distribution of cochlear aqueduct patency in this patient population.

Resources (None Listed)

Deliverables (1)

Preventing Secondary Brain Injury by Early Detection of Cerebral Bleeding and Edema [CEREBROTECH/LEVINSON/COMPLETED]

Task Book: Entry
Principal Investigator: Levinson, Mitchell

Short Title: Cerebrotech

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

Study will provide proof of concept in patients for intracranial fluid correlation (ICF) with intracranial pressure (ICP) and technology enhancements to remove motion artifacts for use in ambulatory subjects. The technology has demonstrated the ability to detect very small changes to brain fluids in animal models and is now the subject of an IRB- controlled clinical study.

Resources (None Listed)

Deliverables (1)

Clinical Evaluation of the Newest Generation of a Non-Invasive ICP Meter (Vittamed) in Subjects Undergoing Invasive ICP Measurement [VITTAMED 2/BERSHAD/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Eric Bershad

Short Title: Vittamed 2

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
1. Assess the accuracy of the newest generation of the non-invasive intracranial pressure (ICP) meter (Vittamed) compared to simultaneous ICP measurement in subjects with an Ommaya reservoir or undergoing lumbar CSF pressure measurements.

2. Assess the accuracy (sensitivity and specificity) of the non-invasive ICP meter to detect acute changes in ICP induced by body tilt in Ommaya reservoir undergoing invasive ICP measurements, or in patients undergoing lumbar CSF drainage.

Resources (None Listed)

Deliverables (1)

Optical System for Monitoring Net Ocular Blood Flow (OCULAR BLOOD FLOW SBIR/ACTIVE)

Task Book: Entry Unavailable
Principal Investigator: Mircea Mujat

Short Title: Ocular Blood Flow SBIR

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Program Science Management Office (PSMO)

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
There is currently no device that performs both structural and hemodynamic analysis of the retina and choroid. The PI proposes an integrated device that can do both, and moreover include both spatial and temporal resolution.

Resources (None Listed)

Deliverables (1)

Identification of functional metabolomic alterations during the simulated spaceflight environment. (Rana)

Task Book: Entry Unavailable
Principal Investigator: Rana, Brinda

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

Resources (Ground Analog)

Deliverables (1)

Eye Vein Pressure Device

Task Book: Entry Unavailable
Principal Investigator: Sit, Arthur

Short Title: Eye Vein Pressure Device

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Technology Development

Resources (Other)

Deliverables (1)

A gene expression and histological approach to the study of cerebrospinal fluid production and outflow in rats [RODENT CSF/ZANELLO/ACTIVE]

Task Book: Entry
Principal Investigator: Zanello, Susana

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:

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

*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

Resources (Other)

Deliverables (1)

VIIP Simulations of CSF, Hemodynamics and Ocular Risk (OPHTHALMIC MODELING CHANGES 2)

Task Book: Entry Unavailable
Principal Investigator: Ethier, Christopher

Short Title: Ophthalmic Modeling Changes 2

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

the NASA-funded MONSTR Sim project. Four specific aims were proposed:

SA1: Measure key physiologic parameters needed for modeling, including effects of intracranial pressure on optic nerve sheath

diameter, optic nerve tortuosity, craniospinal volume and cerebral blood flow.

SA2: Incorporate “quasi-1D” effects into existing compartment models, allowing us to evaluate the effects of microgravity and

countermeasures on CSF and blood flows/pressures.

SA3: Extend finite element models of ocular biomechanics, specifically modeling: (i) optic nerve kinking, and (ii) compression of optic

nerve fiber bundles in the lamina cribrosa; and relate kinking/compression to an index of axoplasmic insult/stasis.

SA4: Carry out parametric studies integrating the above models to identify individual-specific factors that: (i) predispose for the

development of VIIP syndrome, and (ii) influence the efficacy of proposed countermeasures, both useful for risk profiling

Resources (None Listed)

Deliverables (1)

CO2 Dose Response Study

Task Book: Entry Unavailable
Principal Investigator: TBD

Short Title: CO2 Dose Response

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.

Resources (Ground Analog)

Deliverables (1)

SPACE-CENT: Studying the Physiological and Anatomical Cerebral Effects of CENTrifugation and Head Down Tilt Bed Rest

Task Book: Entry Unavailable
Principal Investigator: Bershad, Eric

Short Title: Intermittent Rotation AGBRESA - Bershad

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
In this proposal, the effects of a 60-day exposure to simulated microgravity (6° head down tilt

bedrest, HDBR) on the cerebral, ocular and vestibular systems with and without the intervention

of intermittent artificial gravity (AG, short-arm centrifugation) will be evaluated. Our

overarching objective is to reveal the effects of HDBR-induced headward fluid shifts as well as

the reversal of these hydrostatic pressure gradients with AG using innovative, integrated

techniques to provide novel insights into the physiological adaptations during simulated

microgravity.

Aims:

To determine the between-group effects of 60 days HDBR alone versus HDBR with AG (2 different regimens) on the cerebral, ocular, and sensorimotor systems.
To determine the within-group effects of the experimental conditions (60 days HDBR +/- AG) on the cerebral, ocular and sensorimotor systems compared to pre HDBR baseline.
Assess the within and between group transient effects of AG (intervention groups) on cerebral and ocular systems using non-invasive technologies in the peri-centrifuge period.

Additional measures and data collections are also being performed on the subjects to create a non-CO2 control group for comparison to the Thirty-day CO2 Bedrest (VAPER) study (PI: S. Laurie).

Resources (Ground Analog)

Deliverables (1)

Changes of the optic nerve dura mater in astronauts and SANS (OPTIMA)

Task Book: Entry Unavailable
Principal Investigator: Ethier, Christopher

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:

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

Aims:

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

Resources (Flight)

Deliverables (1)

SANS 12: We do not know whether ground-based analogs and/or models can simulate Space Associated Neuro-ocular Syndrom.

Responsible Element: Human Health Countermeasures (HHC)

Status: Open

Description

Initial State:

Ocular standard measures data from the Flight Analog Project’s 14-day and 70-day studies indicated that six degree head-down tilt did not produce signs and symptoms analogous with SANS. Animal studies were recently awarded to determine whether hind-limb suspended rodents are an appropriate analog. Additional analog validation studies and modeling efforts are required to determine whether SANS can be simulated terrestrially. The research group is collaborating with the Digital Astronaut project, which will generate a computer model simulating the physiological changes seen in spaceflight and SANS.

Target for closure:

Identify an environment (e.g. bed rest, high altitude chamber, animal model, etc.) and/or disease model (e.g. idiopathic intracranial hypertension) for ground-based testing that can be used to simulate the signs and symptoms of the VIIP syndrome.

Interim steps:

Determine whether a rodent hindlimb suspension model can simulate the signs and symptoms of SANS. (30%)
Evaluate various bed rest tilt angles to determine which, if any, most closely reproduce the cephalad fluid shift that results from microgravity exposure. (30%)
Evaluate combinations of a high sodium diet, elevated CO2 exposure, and/or resistive exercise in the most relevant analogs to converge upon the highest fidelity ground analog for modeling SANS. (40%)

Research Approach:

Analogs and/or models that reproduce SANS can be used to 1) test etiology and risk factor hypotheses and 2) test the efficacy of as-yet-to-be-determined countermeasures.The research group is amenable to exploring various environmental models, but current efforts are focused on head-down tilt (HDT) human bed rest analogs and hindlimb suspended rodent models.

Target for Closure

No Target for Closure Available.

Tasks (19)

Head-down tilt as a model for intracranial and intraocular pressures, and retinal changes during spaceflight [RAT MODEL FOR VIIP/FULLER/ACTIVE]

Task Book: Entry
Principal Investigator: Fuller, Charles

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.

Resources (Other)

Deliverables (1)

Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure [HINDLIMB SUSPENSION MODEL ICP/ZANELLO/ACTIVE]

Task Book: Entry
Principal Investigator: Zanello, Susana

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.

Resources (Other)

Deliverables (1)

Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes [CRANIAL VENOUS CIRCULATION/BUCKEY/ACTIVE]

Task Book: Entry
Principal Investigator: Buckey, Jay

Short Title: Cranial Venous Circulation

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

1. Develop a numerical model to estimate changes in intracranial venous

flow, volume, compliance and pressure in response to a fluid shift and changes in

hydrostatic gradients. Include tissue compressive forces in the model.

2. Determine the cranial venous changes produced by fluid shifts and

altered hydrostatic gradients. Use interventions that can produce fluid shifts

(lower body negative pressure and lower body positive pressure) and alter

hydrostatic gradients (supine and prone postures). These experiments are

designed to provide data for validating and verifying the model developed as a

part of Aim #1.

3. Identify individuals with common intracranial venous variants, and study

them using the protocol outlined in Aim #2.

By building and validating a numerical model, we will be able to use the model to: (a)

develop hypotheses about spaceflight visual changes, (b) provide estimates of likely

changes in intracranial pressure and venous pressure in space, and (c) offer predictions

about future visual changes in an individual. This could provide unique insights into the

etiology of microgravity-induced vision changes, as well as serve as a diagnostic tool.

Resources (Other)

Deliverables (1)

Microgravity-driven Optic Nerve/Sheath Remodeling Simulator [OPHTHALMIC CHANGES MODELING/ETHIER/ACTIVE]

Task Book: Entry
Principal Investigator: Ethier, Christopher

Short Title: Ophthalmic Changes Modeling

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

1. Develop validated tools for computing IOP and ICP in microgravity. These tools will be based on modeling of fluid shifts between the eye and various compartments in the cardiovascular, cerebrospinal and lymphatic systems.

2. Develop validated finite element-based tools for computing the biomechanical environment and subsequent connective tissue remodeling in the optic nerve head, optic nerve sheath and posterior globe. These tools will be complemented by a model of the eye's optical performance.

3. Integrate the models from Aims 1 and 2 to produce a unified, open and extensible software package that can predict ocular biomechanics and ocular connective tissue remodeling under microgravity conditions.

4. Use the integrated model of Aim 3 to study clinically observable attributes and determine the role they may play in the development of VIIP.

Resources (None Listed)

Deliverables (1)

Effects of short term hypercapnia during head-down tilt on ocular structures, cerebral blood flow, and visual acuity in healthy human subjects [CO2 TILT/LAURIE/ACTIVE]

Task Book: Entry
Principal Investigator: Vizzeri, Gianmarco

Short Title: CO2 Tilt

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Resources (Ground Analog)

Deliverables (1)

Integrative physiology of VIIP: cardiopulmonary, sleep, and cognitive function assessment during hypercapnic bed rest [Thirty-day CO2 Bedrest/LAURIE/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Steven Laurie

Short Title: Thirty-day CO2 Bedrest - Laurie

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Behavioral Health & Performance (BHP) Element

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Specific Aim I

Specific Aim II

Specific Aim III

Determine if 30 days of BR combined with 0.5% CO₂ causes sleep disruption, alters circadian and ultradian rhythms, and if these changes correlate with the development of VIIP symptoms.

Resources (Ground Analog)

Deliverables (1)

Hindlimb suspension (HS) as an analog model of ocular alterations associated with cephalad fluid shifts: resveratrol as a countermeasure

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: Microgravity-HS-Retina

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Resources (None Listed)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Spaceflight effects on the mouse retina: Histological, gene expression and epigenetic changes after flight on STS-135

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: Spaceflight - Retina

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Resources (None Listed)

Deliverables (1)

Combined effects of gamma radiation and high dietary iron on oxidative damage and antioxidant status in rat eyes

Task Book: Entry Unavailable
Principal Investigator: Zanello, Susana

Short Title: Iron-radiation-eye

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Resources (None Listed)

Deliverables (1)

Digital Astronaut: VIIP Modeling [ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Mulugeta, Lealem

Short Title: DA VIIP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

NASA Glenn Research Center (GRC)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
VIIP modeling activities. This is a collaborative effort between Glenn Research Center, Johnson Space Center, and external scientists.

Resources (None Listed)

Deliverables (1)

SPACECOT: Studying Physiological and Anatomical Cerebral Effects of CO2 and Tilt [SPACECOT/BERSHAD/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Bershad, Eric

Short Title: SPACECOT

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:

Specific Aim 1 – Determine the qualitative and quantitative changes in CBF, ICV, ICP, cognitive function and ocular structure from 1% CO2 /-12 degree HDT condition compared to ambient air/-12 degree HDT and ambient air/upright conditions using non-invasive brain/ocular monitoring devices and MRI.

Specific Aim 2 – Determine the acute (2 hours) effects of 3% CO2 /-12 HDT on CBF, ICV and cognitive function and ocular structure compared to 1% CO2 /-12 HDT, ambient/-12 HDT or ambient air/upright conditions using non-invasive brain/ocular monitoring devices and MRI.

Specific Aim 3 – Evaluate the suitability of Envihab-DLR to successful implement multiple measures in 3 simultaneous subjects in bed-rest position, and perform NASA standard measures for ground-based analogs of spaceflight.

Resources (Ground Analog)

Deliverables (1)

Comparing Globe Distortions Following Head-Down Bed Rest to those Measured in Astronauts in Short and Long-Duration Spaceflights [Thirty-day CO2 Bedrest/ALPERIN/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Alperin, Noam

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

Resources (Ground Analog)

Deliverables (1)

Optical System for Monitoring Net Ocular Blood Flow (OCULAR BLOOD FLOW SBIR/ACTIVE)

Task Book: Entry Unavailable
Principal Investigator: Mircea Mujat

Short Title: Ocular Blood Flow SBIR

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Program Science Management Office (PSMO)

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Resources (None Listed)

Deliverables (1)

Eye Vein Pressure Device

Task Book: Entry Unavailable
Principal Investigator: Sit, Arthur

Short Title: Eye Vein Pressure Device

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Technology Development

Resources (Other)

Deliverables (1)

A gene expression and histological approach to the study of cerebrospinal fluid production and outflow in rats [RODENT CSF/ZANELLO/ACTIVE]

Task Book: Entry
Principal Investigator: Zanello, Susana

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:

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

*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

Resources (Other)

Deliverables (1)

VIIP Simulations of CSF, Hemodynamics and Ocular Risk (OPHTHALMIC MODELING CHANGES 2)

Task Book: Entry Unavailable
Principal Investigator: Ethier, Christopher

Short Title: Ophthalmic Modeling Changes 2

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

the NASA-funded MONSTR Sim project. Four specific aims were proposed:

SA1: Measure key physiologic parameters needed for modeling, including effects of intracranial pressure on optic nerve sheath

diameter, optic nerve tortuosity, craniospinal volume and cerebral blood flow.

SA2: Incorporate “quasi-1D” effects into existing compartment models, allowing us to evaluate the effects of microgravity and

countermeasures on CSF and blood flows/pressures.

SA3: Extend finite element models of ocular biomechanics, specifically modeling: (i) optic nerve kinking, and (ii) compression of optic

nerve fiber bundles in the lamina cribrosa; and relate kinking/compression to an index of axoplasmic insult/stasis.

SA4: Carry out parametric studies integrating the above models to identify individual-specific factors that: (i) predispose for the

development of VIIP syndrome, and (ii) influence the efficacy of proposed countermeasures, both useful for risk profiling

Resources (None Listed)

Deliverables (1)

CO2 Dose Response Study

Task Book: Entry Unavailable
Principal Investigator: TBD

Short Title: CO2 Dose Response

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

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

Procurement Mechanism(s):

TBD

Resources (Ground Analog)

Deliverables (1)

Investigating Structure and Function of the Eye (Flight)

Task Book: Entry Unavailable
Principal Investigator: Macias, Brandon

Short Title: iSAFE

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Aims:

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
Determine if ocular vascular structure and function is altered to a greater degree during 1YMs, and if recovery is more prolonged
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
Determine if the vascular adaptations correlate with alterations in ocular structure and function.

Resources (Flight)

Deliverables (1)

SPACE-CENT: Studying the Physiological and Anatomical Cerebral Effects of CENTrifugation and Head Down Tilt Bed Rest

Task Book: Entry Unavailable
Principal Investigator: Bershad, Eric

Short Title: Intermittent Rotation AGBRESA - Bershad

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
In this proposal, the effects of a 60-day exposure to simulated microgravity (6° head down tilt

bedrest, HDBR) on the cerebral, ocular and vestibular systems with and without the intervention

of intermittent artificial gravity (AG, short-arm centrifugation) will be evaluated. Our

overarching objective is to reveal the effects of HDBR-induced headward fluid shifts as well as

the reversal of these hydrostatic pressure gradients with AG using innovative, integrated

techniques to provide novel insights into the physiological adaptations during simulated

microgravity.

Aims:

To determine the between-group effects of 60 days HDBR alone versus HDBR with AG (2 different regimens) on the cerebral, ocular, and sensorimotor systems.
To determine the within-group effects of the experimental conditions (60 days HDBR +/- AG) on the cerebral, ocular and sensorimotor systems compared to pre HDBR baseline.
Assess the within and between group transient effects of AG (intervention groups) on cerebral and ocular systems using non-invasive technologies in the peri-centrifuge period.

Additional measures and data collections are also being performed on the subjects to create a non-CO2 control group for comparison to the Thirty-day CO2 Bedrest (VAPER) study (PI: S. Laurie).

Resources (Ground Analog)

Deliverables (1)

SANS 13: We need to identify preventative and treatment countermeasures (CMs) to mitigate changes in ocular structure and function and intracranial pressure during spaceflight.

Responsible Element: Human Health Countermeasures (HHC)

Status: Open

Description

Initial State:

Current options to mitigate SANS-related changes are limited to preflight screening, corrective lenses (in-flight and postflight), aerobic exercise in-flight, reduced sodium diet in-flight (currently in-work through SD), on-orbit assessments, reduction of in-flight CO2 levels, and return to Earth. Potential countermeasures include pharmaceutical and mechanical (i.e. Lower Body Negative Pressure, Braslet) interventions. The research group must reach a higher percentage of closure toward SANS 1 (etiology and risk factors) and SANS 12 (analogs and models) before this countermeasure gap can be adequately informed.

Target for closure:

Validated preventative and treatment countermeasures for SANS-related signs and symptoms.

Interim steps:

Transfer susceptibility findings from SANS 1 to Medical Operations. (10%)
Evaluate mechanical countermeasures to counteract spaceflight-induced fluid shifts. (20%)
Identify pharmaceutical countermeasures to mitigate SANS-related signs and symptoms. (20%)
Evaluate the contribution of aerobic exercise in mitigating SANS-related signs and symptoms. (20%)
If CO2 is identified as a highly correlated risk factor (SANS 1), investigate the utility and benefit of additional reductions in CO2 levels. (20%)
Complete the Transfer to Operations process for an HSRB-vetted, integrated suite of potentially mechanical and/or pharmaceutical countermeasures. (10%)

Research Approach:

Efforts toward closing this gap will eventually focus on terrestrial and in-flight countermeasure investigations, but SANS 13 is currently the least mature of the research gaps. Its closure is predicated on completion of a number of SANS 1 and SANS 12 tasks.

Target for Closure

No Target for Closure Available.

Tasks (14)

Distribution of Body Fluids during Long Duration Space Flight and Subsequent Effects on Intraocular Pressure and Vision Disturbance [FLUID SHIFTS / STENGER / ACTIVE]

Task Book: Entry
Principal Investigator: Stenger, Michael

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:

Resources (Flight)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Fluid Distribution before, during and after Prolonged Space Flight-NNX13AJ12G [FLUID SHIFTS / HARGENS / ACTIVE]

Task Book: Entry
Principal Investigator: Hargens, Alan

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

Resources (Flight)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Microgravity Associated Compartmental Equilibration (MACE) [FLUID SHIFTS / DULCHAVSKY / ACTIVE]

Task Book: Entry
Principal Investigator: Dulchavsky, Scott

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

Resources (Flight)

Deliverables (1)

Category: Risk Characterization, Quantification
Subcategory: Evidence or Risk Characterization

Internal Customers:
Human Health Countermeasures
External Customers:
None Is a Customer-Supplier Agreement (CSA) Required? No

Influence of Exercise Modality on Cerebral-Ocular Hemodynamics and Pressures [EXERCISE MODALITY/SCOTT/ACTIVE]

Task Book: Entry
Principal Investigator: Scott, Jessica

Short Title: Exercise Modality

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

Resources (None Listed)

Deliverables (1)

Testing Mechanical Countermeasures for Cephalad Fluid Shifts [MECHANICAL COUNTERMEAURES - MARKETED DEVICES/STRANGMAN/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Strangman, Gary

Short Title: Mechanical Countermeasures - Marketed Devices

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Human Health Countermeasures (HHC) Element

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

The objective is to test two qualitatively distinct countermeasures (CMs) for VIIP, based on the

assumption that VIIP is caused—or influenced—by cephalad fluid shifts. Studies will be

conducted at MGH as well as at Baylor College of Medicine/NSBRI Center for Space Medicine.

Aim 1: Identify and characterize cerebrovascular and/or ophthalmological parameters altered

by cephalad fluid shifts that are mitigated by mechanical countermeasures.

Aim 2: Identify and characterize any rebound effects or other adverse occurrences when use of

the mechanical countermeasure device is discontinued.

Aim 3: Quantify the effect of two mechanical countermeasures on their ability to reduce

invasively-measured continuous ICP.

Aim 4: Determine if gradual CM discontinuation is safer than abrupt discontinuation.

Aim 5: Quantify the relationship between CM exposure time vs. ICP reduction (and rebound).

Resources (Other)

Deliverables (1)

Venous Congestion Countermeasure Study

Task Book: Entry Unavailable
Principal Investigator: Stenger, Michael

Short Title: SANS CMs

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Directed

Aims:

Specific Aims:

Determine if a single or combination of mechanical countermeasures, including lower body negative pressure (LBNP), veno-constrictive thigh cuffs (VTC), and breathing through an impedance threshold device (ITD), will acutely reverse a seated-to-supine posture headward fluid shift and sustain it for up to 30 min. Outcomes will include noninvasive measures of intracranial pressure (ICP), internal jugular vein cross sectional area (IJVA), internal jugular vein cross sectional pressure (IJVP), choroid thickness, and intraocular pressure.
Determine if the most effective combination of CMs to reverse vascular outcomes in specific aim #1 also reverses the cerebral spinal fluid (CSF) shift by quantifying intraventricular volumes using magnetic resonance imaging (MRI).
Determine if up to 8 hours of daily LBNP during sleep can prevent the headward fluid shift-induced changes during 3 days of head-down tilt bedrest.

Resources (Other)

Deliverables (1)

Evaluation of an Impedance Threshold Device as a Vision Impairment and Intracranial Pressure (VIIP) Countermeasure [IMPEDANCE THRESHOLD COUNTERMEASURE/EBERT/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Ebert, Doug

Short Title: Impedance Threshold Countermeasure

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

Using a supine and head-down tilt model, this investigation will:

1. Determine if an impedance threshold device can reduce venous sinus congestion in the head and neck.

*Primary outcome measures are the IJV cross sectional area, TCD, tissue thickness, and IJV, carotid artery, and SOV Doppler.

2. Determine if an impedance threshold device can reduce indicators of elevated intracranial pressure

*Primary outcome measures are ONSD, OCT, CCFP, IOP

This task might also inform SANS3 (tools) and SANS12 (ground based countermeasures).

Resources (Other)

Deliverables (1)

Validation of a Cephalad Fluid Shift Countermeasures [FLUID SHIFT COUNTERMEASURE/MACIAS/ACTIVE]

Task Book: Entry Unavailable
Principal Investigator: Macias, Brandon

Short Title: Fluid Shift Countermeasure

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

1) Determine the efficacy of a novel thigh cuff device to mitigate cephalad fluid shifts.

2) Determine the dose-response curve for thigh cuff application during simulated spaceflight (where dose equals time).

3) Maximize mobility, comfort, and fluid sequestration during simulated crew tasks.

4) Deliver an optimized Lower Body Negative Pressure Design for long duration spaceflight.

Resources (Other)

Deliverables (1)

STOP VIIP Study: Safe and Effective Countermeasures to Reduce Intracranial Pressure and Ameliorate VIIP in Astronauts [STOP VIIP/Levine/Active]

Task Book: Entry Unavailable
Principal Investigator: Levine, Ben

Short Title: STOP VIIP

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

National Space Biomedical Research Institute (NSBRI)

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Directed

Aims:
Specific Aim 1: Using direct invasive recording of ICP, we will determine the optimal level of LBNP required to cause a sustained reduction in ICP towards that observed in the upright position, while avoiding hypotension and maintaining cerebral perfusion.

Specific Aim 2: We will examine the long-term efficacy of nightly LBNP (6-8 hours) to simulate the upright position and ICP circadian variability and prevent structural changes in the eye during multiple (4) days of HDT bedrest. We will use comprehensive, non-invasive state-of-the-art imaging to examine the structure of the visual apparatus, the intra- and extra-cranial veins, cerebral spinal fluid production and localized intracranial fluid shifts using high-resolution physiological, optical and magnetic resonance techniques, combined with invasive direct measurement of ICP.

Resources (None Listed)

Deliverables (1)

Gravitational dose and multi-system physiologic response

Task Book: Entry Unavailable
Principal Investigator: Ploutz-Snyder, Lori

Short Title: AG dose

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Characterize the relationship between gravitational dose and acute physiologic responses of the cardiovascular, cerebrovascular, ocular, muscular, and sensorimotor systems.

Resources (Ground Analog)

Deliverables (1)

VIIP Simulations of CSF, Hemodynamics and Ocular Risk (OPHTHALMIC MODELING CHANGES 2)

Task Book: Entry Unavailable
Principal Investigator: Ethier, Christopher

Short Title: Ophthalmic Modeling Changes 2

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

the NASA-funded MONSTR Sim project. Four specific aims were proposed:

SA1: Measure key physiologic parameters needed for modeling, including effects of intracranial pressure on optic nerve sheath

diameter, optic nerve tortuosity, craniospinal volume and cerebral blood flow.

SA2: Incorporate “quasi-1D” effects into existing compartment models, allowing us to evaluate the effects of microgravity and

countermeasures on CSF and blood flows/pressures.

SA3: Extend finite element models of ocular biomechanics, specifically modeling: (i) optic nerve kinking, and (ii) compression of optic

nerve fiber bundles in the lamina cribrosa; and relate kinking/compression to an index of axoplasmic insult/stasis.

SA4: Carry out parametric studies integrating the above models to identify individual-specific factors that: (i) predispose for the

development of VIIP syndrome, and (ii) influence the efficacy of proposed countermeasures, both useful for risk profiling

Resources (None Listed)

Deliverables (1)

SANS Integrated Flight Countermeasure Studies

Task Book: Entry Unavailable
Principal Investigator: TBD

Short Title: SANS Integrated Flight CM

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

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

Procurement Mechanism(s):

Solicited

Aims:

This is a planned flight study to be solicited or directed after completion of the ground based SANS Ground Analog Countermeasure Study.

Resources (Flight)

Deliverables (1)

Countermeasures for Mitigation of Spaceflight Associated Neuro-ocular Syndrome, Ground Study

Task Book: Entry Unavailable
Principal Investigator: TBD

Short Title: SANS Ground Analog CM

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

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

Procurement Mechanism(s):

Directed

Solicited

Aims:

This Task is a placeholder for a study in response to the HERO NRA 18 Appendix C solicitation topic:

Mechanisms and Evaluation of Countermeasures for Mitigation of Spaceflight Associated Neuro-ocular Syndrome (SANS) in a Novel Ground-Based Head-Down Tilt Bed Rest Analog

This solicitation topic is seeking proposals for ground-based evaluation of countermeasures that prevent or mitigate the signs and symptoms associated with Spaceflight Associated Neuro-ocular Syndrome (SANS) and SANS-related behavioral outcomes including cognition, sleep, and mood, as well as investigation of potential mechanisms by which SANS occurs in this ground-based analog.

The bed rest campaign for which proposals are being sought will consist of at least four arms, depending on the selected proposals, each lasting 30 days:

A “posture-control”-arm, where for the 30-day duration the subjects will be seated during the daytime and supine when sleeping (16 hrs. seated vs. 8 hrs. supine). This is a unique approach that has not been used before in bed rest research, but which is considered necessary to explore further:
1. The mechanistic aspects of the fluid shift induced manifestations of SANS.
2. Whether the behavioral/cognitive changes as well as the objective and subjective aspects of mood and sleep (which as noted above were correlated with the degree of thickening of retinal tissues) are associated with the fluid shifts and whether they are related to any degree of edema formation in the brain.
3. A better insight into the mechanisms of the tested countermeasures in the other bed rest arms.
A 6° head-down tilt "no countermeasure"-control arm. For this arm of the study, NASA will consider proposals that will evaluate the mechanisms of the SANS ocular changes. Both fluid-shift based as well as other potential mechanisms are of interest.
A 6° head-down tilt “Mechanical countermeasures”-arm to test a specific mechanical countermeasure developed by NASA (protocol will be shared with the selected investigators once available). The mechanical countermeasure will likely consist of a combination of LBNP, VTC, and ITD (all of these are under investigation at present, with the optimized combined mechanical countermeasure to be determined at the conclusion of the study that is currently underway).
A 6° head-down tilt bed rest arm, where other types of countermeasure interventions (i.e., that do not duplicate the mechanical countermeasure used in the “mechanical countermeasures”-arm) can be tested and for example, compared to outcomes of the two control and the mechanical countermeasure arm, respectively.

Resources (Ground Analog)

Deliverables (1)

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	24

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	15

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	12

Ground-Based Flight Analogs	Bedrest [e.g., envihab, other bedrest facilities]
Number of Subjects	12

Ground-Based Flight Analogs	Reduced Gravity Flight
Number of Subjects	15