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Project Title:  Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 04/01/2016  
End Date: 07/05/2021  
Task Last Updated: 07/05/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Hu, Xiao  Ph.D. University of California, San Francisco 
Key Personnel Changes / Previous PI: NOTE: This project has been combined with "Invasive and Noninvasive ICP Monitoring and SANS (previously VIIP) Biomarker Identification" (PI Dr. Michael Williams). The 2021 report constitutes a final report for this task. Dr Zanello now supports the Human Research Program (HRP) Chief Scientist Office and is no longer able to act as Principal Investigator (PI). Transfer of this role has been done to Dr Michael Williams. [November 2019: Xiao Hu, Ph.D. is only CoInvestigator per HRP. February 2017 report: Dr. James Fiedler (previous CoInvestigator) and Dr Jessica Scott moved to other positions and are no longer working on the project.]
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX16AH78G 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Unique ID: 10966 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-ILSRA. International Life Sciences Research Announcement 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX16AH78G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)
Human Research Program Gaps: (1) SANS-101:Determine the relationship between fluid shifts (intravascular, interstitial, CSF) and ocular manifestations in astronauts during spaceflight.
(2) SANS-102:Determine the relationship between the fluid shifts-induced ocular changes and fluid shifts in the CNS, including whether elevated intracranial pressure or brain edema play a role.
Flight Assignment/Project Notes: NOTE: End date changed to 7/5/2021 per R. Schulte/HRP HHC element, due to PI move to KBR/NASA JSC management (Ed., 12/15/21)

NOTE: End date changed to 9/02/2025 per NSSC and R. Schulte/HRP (Ed., 7/14/2020)

NOTE: End date changed to 1/1/2026; note also with PI move to imec USA-Florida, PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2025 per HRP (Ed., 11/19/18)

Task Description: There is a clear need to investigate whether there is an association between intracranial pressure (ICP) increase and the Visual Impairment and Intracranial Pressure (VIIP) syndrome [Ed. note July 2020: now referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS)]. The Non-Invasive ICP Framework (NICF) is a general approach for inferring ICP using noninvasive signals that are related to ICP. Leveraging multimodal noninvasive data from crew members to be collected in planned longitudinal experiments in flight will significantly improve the accuracy of this noninvasive ICP measurement tool. In addition, we will evaluate biomarkers in blood and urine of crew members, with the aim of investigating the molecular bases and genetic predisposition of developing VIIP syndrome. Overall, this study proposes the use of noninvasive measures plus biomarker discovery and validation as input to build a predictive model that will inform the likelihood of a given crew member of developing vision/neurological complications post flight.

Research Impact/Earth Benefits: Investigating the propensity and molecular mechanisms associated with ICP increase in microgravity will yield valuable information applicable to similar conditions on Earth, contributing to the knowledge of why conditions such as idiopathic intracranial hypertension develop, and how to manage elevated ICP. Moreover, the improvement of the non-invasive algorithm for ICP estimation will be of utmost importance for the diagnosis and management of neurologic conditions with high ICP and traumatic brain injury.

Task Progress & Bibliography Information FY2021 
Task Progress: Since the start of the project, efforts have been dedicated towards the integration of this task with its companion study (PI Dr. Michael Williams, "Zero G and ICP"). The resulting study is named "Direct ICP" (Williams/Zanello). The team has since carried through processes of feasibility assessment, flight selection, Institutional Review Board (IRB) protocol approval and TRR. With regards to this specific task, activities completed two pilot phase studies: a) optimization of protocols for exosome and RNA isolation and RNA sequencing of all biofluids (cerebrospinal fluid-CSF, plasma, and urine) and b) a study of the compatibility of flight-certified tubes for urine collection with the established bioanalytical methods. Both pilot mini-studies were successful.

NOTE: Due to Dr Zanello’s recent transition to the Human Research Program (HRP) Office of the Chief Scientist, she is no longer able to continue the role of PI for her study; however, she will remain as a participant in an advisory role. Her study and Dr. Williams’ study have been combined into a single study with a single budget, for which Dr. Williams is the sole PI. We have recruited Dr. David Furman from the Buck Institute in California to assume the co-investigator role for the biomarkers portion of the Direct ICP study. Dr. Furman’s unique expertise in human immunology and data science brings a great deal of knowledge in predictive modeling, biomarker discovery, and identification of interventions aimed at normalizing immune dysregulation associated with clinically relevant phenotypes. As part of the transition, we have been able to retain the original biomarker methods and aims from Dr. Zanello’s study, and to expand upon them with the addition of new hypotheses and analyses under the direction of Dr. Furman, using the same biofluids and fluid volumes as originally approved. Subsequent progress on this aspect will be reported with Dr. Williams’s study.

Bibliography: Description: (Last Updated: 09/04/2023) 

Show Cumulative Bibliography
 
 None in FY 2021
Project Title:  Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 04/01/2016  
End Date: 07/05/2021  
Task Last Updated: 07/13/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Hu, Xiao  Ph.D. University of California, San Francisco 
Key Personnel Changes / Previous PI: NOTE: This project has been combined with "Invasive and Noninvasive ICP Monitoring and SANS (previously VIIP) Biomarker Identification" (PI Dr. Michael Williams). November 2019: Xiao Hu, Ph.D. is only CoInvestigator per HRP. February 2017 report: Dr. James Fiedler (previous CoInvestigator) moved to another position and is no longer working on the project.
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX16AH78G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Unique ID: 10966 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-ILSRA. International Life Sciences Research Announcement 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX16AH78G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)
Human Research Program Gaps: (1) SANS-101:Determine the relationship between fluid shifts (intravascular, interstitial, CSF) and ocular manifestations in astronauts during spaceflight.
(2) SANS-102:Determine the relationship between the fluid shifts-induced ocular changes and fluid shifts in the CNS, including whether elevated intracranial pressure or brain edema play a role.
Flight Assignment/Project Notes: NOTE: End date changed to 7/5/2021 per R. Schulte/HRP HHC element, due to PI move to KBR/NASA JSC management (Ed., 12/15/21)

NOTE: End date changed to 9/02/2025 per NSSC and R. Schulte/HRP (Ed., 7/14/2020)

NOTE: End date changed to 1/1/2026; note also with PI move to imec USA-Florida, PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2025 per HRP (Ed., 11/19/18)

Task Description: There is a clear need to investigate whether there is an association between intracranial pressure (ICP) increase and the Visual Impairment and Intracranial Pressure (VIIP) syndrome [Ed. note July 2020: now referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS)]. The Non-Invasive ICP Framework (NICF) is a general approach for inferring ICP using noninvasive signals that are related to ICP. Leveraging multimodal noninvasive data from crew members to be collected in planned longitudinal experiments in flight will significantly improve the accuracy of this noninvasive ICP measurement tool. In addition, we will evaluate biomarkers in blood and urine of crew members, with the aim of investigating the molecular bases and genetic predisposition of developing VIIP syndrome. Overall, this study proposes the use of noninvasive measures plus biomarker discovery and validation as input to build a predictive model that will inform the likelihood of a given crew member of developing vision/neurological complications post flight.

Research Impact/Earth Benefits: Investigating the propensity and molecular mechanisms associated with ICP increase in microgravity will yield valuable information applicable to similar conditions on Earth, contributing to the knowledge of why conditions such as idiopathic intracranial hypertension develop, and how to manage elevated ICP. Moreover, the improvement of the non-invasive algorithm for ICP estimation will be of utmost importance for the diagnosis and management of neurologic conditions with high ICP and traumatic brain injury.

Task Progress & Bibliography Information FY2020 
Task Progress: During this reporting period, we have continued the optimization of protocols in this study. In particular, we have completed an evaluation of the current flight-certified tubes used for urine collection on the International Space Station (ISS). We have demonstrated that the flight-certified urine collection tubes perform no differently from the standard urine collection tubes used in the regular research and clinical settings, and are compatible with the methods for exosome isolation, library construction, and RNA sequencing planned to be applied in this project.

Bibliography: Description: (Last Updated: 09/04/2023) 

Show Cumulative Bibliography
 
 None in FY 2020
Project Title:  Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome Reduce
Images: icon  Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 04/01/2016  
End Date: 07/05/2021  
Task Last Updated: 02/24/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Scott, Jessica  Ph.D. Universities Space Research Association 
Hu, Xiao  Ph.D. University of California, San Francisco 
Key Personnel Changes / Previous PI: NOTE: This project has been combined with "Invasive and Noninvasive ICP Monitoring and VIIP Biomarker Identification" (PI Dr Michael Williams). February 2017 report: Dr. James Fiedler (previous CoInvestigator) moved to another position and is no longer is working on the project.
Project Information: Grant/Contract No. NNX16AH78G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Unique ID: 10966 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-ILSRA. International Life Sciences Research Announcement 
Grant/Contract No.: NNX16AH78G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)
Human Research Program Gaps: (1) SANS-101:Determine the relationship between fluid shifts (intravascular, interstitial, CSF) and ocular manifestations in astronauts during spaceflight.
(2) SANS-102:Determine the relationship between the fluid shifts-induced ocular changes and fluid shifts in the CNS, including whether elevated intracranial pressure or brain edema play a role.
Flight Assignment/Project Notes: NOTE: End date changed to 7/5/2021 per R. Schulte/HRP HHC element, due to PI move to KBR/NASA JSC management (Ed., 12/15/21)

NOTE: End date changed to 1/1/2026; note also with PI move to imec USA-Florida, PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2025 per HRP (Ed., 11/19/18)

Task Description: There is a clear need to investigate whether there is an association between intracranial pressure (ICP) increase and the Visual Impairment and Intracranial Pressure (VIIP) syndrome. The Non-Invasive ICP Framework (NICF) is a general approach for inferring ICP using noninvasive signals that are related to ICP. Leveraging multimodal noninvasive data from crew members to be collected in planned longitudinal experiments in flight will significantly improve the accuracy of this noninvasive ICP measurement tool. In addition, we will evaluate biomarkers in blood and urine of crew members, with the aim of investigating the molecular bases and genetic predisposition of developing VIIP syndrome. Overall, this study proposes the use of noninvasive measures plus biomarker discovery and validation as input to build a predictive model that will inform the likelihood of a given crew member of developing vision/neurological complications post flight.

Research Impact/Earth Benefits: Investigating the propensity and molecular mechanisms associated with ICP increase in microgravity will yield valuable information applicable to similar conditions on Earth, contributing to the knowledge of why conditions such as idiopathic intracranial hypertension develop, and how to manage elevated ICP. Moreover, the improvement of the non-invasive algorithm for ICP estimation will be of utmost importance for the diagnosis and management of neurologic conditions with high ICP and traumatic brain injury.

Task Progress & Bibliography Information FY2017 
Task Progress: The activities within the first year of this project have been centered on its integration with a complementary study that aims to measure ICP directly in crew members in order to test the involvement of ICP increase in the pathophysiology of VIIP (Refer to “ZERO G AND ICP: INVASIVE AND NONINVASIVE ICP MONITORING OF ASTRONAUTS ON THE ISS”, PI: Michael Williams (University of Washington)). This included discussions among investigators as well as consultation with an expert bioinformatics team. In addition, we have completed the design of a small study for the biomarker discovery portion by coordinating a pilot investigation in patients with idiopathic intracranial hypertension, which will validate the sample collection logistics and genomic methodological approaches to be used in the main stage of the project.

Bibliography: Description: (Last Updated: 09/04/2023) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals Theriot CA, Westby CM, Morgan JLL, Zwart SR, Zanello SB. "High dietary iron increases oxidative stress and radiosensitivity in the rat retina and vasculature after exposure to fractionated gamma radiation." npj Microgravity. 2016 May 5;2:16014. http://dx.doi.org/10.1038/npjmgrav.2016.14 , May-2016
Articles in Peer-reviewed Journals Taibbi G, Cromwell R, Zanello S, Yarbough P, Ploutz-Snyder R, Godley B, Vizzeri G. "Ocular outcomes comparison between 14- and 70-day head-down-tilt bed rest." Invest Ophthalmol Vis Sci. 2016 Feb;57(2):495-501. http://dx.doi.org/10.1167/iovs.15-18530 ; PubMed PMID: 26868753; PubMed Central PMCID: PMC4758300 , Feb-2016
Articles in Peer-reviewed Journals Chakrabortty SK, Khodor YL, Kitchen RR, Miller DL, Babcock KM, Manning KS, Lang SP, Tadigotla V, Yu W, Bershad E, Skog J, Zanello S. "Exosome based analysis for Space Associated Neuro-Ocular Syndrome and health risks in space exploration." npjMicrogravity. 2022 Sep 14;8:40. https://pubmed.ncbi.nlm.nih.gov/36104352 ; PMID: 36104352; PMCID: PMC9474550 , Sep-2022
Project Title:  Multimodal Modeling towards Noninvasive Assessment of Intracranial Pressure in Weightlessness and Biomarker Identification of Predisposition to VIIP Syndrome Reduce
Images: icon  Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 04/01/2016  
End Date: 07/05/2021  
Task Last Updated: 08/22/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Fiedler, James  Ph.D. Universities Space Research Association 
Scott, Jessica  Ph.D. Universities Space Research Association 
Hu, Xiao  Ph.D. University of California, San Francisco 
Key Personnel Changes / Previous PI: NOTE: Co-Principal Investigator is Dr. Michael Williams, University of Washington, with project entitled, "Invasive and Noninvasive ICP Monitoring and VIIP Biomarker Identification."
Project Information: Grant/Contract No. NNX16AH78G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Unique ID: 10966 
Solicitation / Funding Source: 2013-14 HERO NNJ13ZSA002N-ILSRA. International Life Sciences Research Announcement 
Grant/Contract No.: NNX16AH78G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)
Human Research Program Gaps: (1) SANS-101:Determine the relationship between fluid shifts (intravascular, interstitial, CSF) and ocular manifestations in astronauts during spaceflight.
(2) SANS-102:Determine the relationship between the fluid shifts-induced ocular changes and fluid shifts in the CNS, including whether elevated intracranial pressure or brain edema play a role.
Flight Assignment/Project Notes: NOTE: End date changed to 7/5/2021 per R. Schulte/HRP HHC element, due to PI move to KBR/NASA JSC management (Ed., 12/15/21)

Task Description: There is a clear need to investigate whether there is an association between intracranial pressure (ICP) increase and the Visual Impairment and Intracranial Pressure (VIIP) syndrome. The Non-Invasive ICP Framework (NICF) is a general approach for inferring ICP using noninvasive signals that are related to ICP. Leveraging multimodal noninvasive data from crew members to be collected in planned longitudinal experiments in flight will significantly improve the accuracy of this noninvasive ICP measurement tool. In addition, we will evaluate biomarkers in blood and urine of crew members, with the aim of investigating the molecular bases and genetic predisposition of developing VIIP syndrome. Overall, this study proposes the use of noninvasive measures plus biomarker discovery and validation as input to build a predictive model that will inform the likelihood of a given crew member of developing vision/neurological complications post flight.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2016 
Task Progress: New project for FY2016.

Bibliography: Description: (Last Updated: 09/04/2023) 

Show Cumulative Bibliography
 
 None in FY 2016