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Project Title:  Mapping by VESGEN of Blood Vessels in the Human Retina Undergoing Bed Rest for Improved Understanding of Visual Impairments and Increased Intracranial Pressure Reduce
Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2013  
End Date: 06/30/2018  
Task Last Updated: 12/12/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Parsons-Wingerter, Patricia  Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch (SCR) 
Mailstop N236-7 
Moffet Field , CA 94035-1000 
Email: patricia.a.parsons-wingerter@nasa.gov 
Phone: (650) 604-1729  
Congressional District: 18 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: NOTE: Formerly at NASA Glenn Research Center until summer 2014 
Co-Investigator(s)
Affiliation: 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch at Galveston 
Young, Millennia H. Ph.D. NASA Johnson Space Center 
Zanello, Susana B. Ph.D. KBRWyle 
Key Personnel Changes / Previous PI: August 2017 report: Co-Investigator Dr. Rob Ploutz-Snyder is no longer with the team.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT,GROUND 
Flight Program: Pre/Post Flight 
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 (IRP Rev I)
Human Research Program Gaps: (1) SANS03:We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function (IRP Rev I)
Flight Assignment/Project Notes: NOTE: End date changed to 6/30/2018 per discussion with PI (Ed., 3/26/18)

NOTE: End date changed to 10/01/2017 per A. Allcorn/JSC and PI (Ed., 7/31/17)

NOTE: End date changed to 4/08/2017 per PI (Ed., 1/30/17)

NOTE: End date changed to 1/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016 and 4/8/2017, which is actually supposed to be due date for final reporting), per PI (Ed., 5/17/16)

NOTE: End date changed to 4/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016), per PI (Ed., 10/20/15)

NOTE: End date changed to 10/01/2016 (originally 9/30/2014 and subsequently 9/22/2015), per PI (Ed., 10/20/15)

NOTE: End date changed to 9/22/2015 (originally 9/30/2014), per R. Brady/HRP (Ed., 7/17/14)

NOTE: Gap change per IRP Rev E (Ed., 3/19/14)

Task Description: The hypothesis proposed for our investigation of vascular contributions to Spaceflight Associated Neuro-ocular Syndrome (SANS) is that blood vessels within the retina, particularly the microvasculature, necessarily remodel to accommodate the cephalad fluid shifts and associated ocular changes incurred in microgravity and terrestrial head-down tilt (HDT) bed rest. Arterial and venous patterns were therefore analyzed in Heidelberg Spectralis 30° infrared (IR) images using NASA’s VESsel GENeration Analysis (VESGEN) software. Results for the trends in pre to post status of vascular patterning within the retinas of Crew Members and HDT subjects are opposite. By two confirming measures of vascular branching complexity, the fractal dimension and length density of small vessels, the space-filling capacity of arterial and venous trees decreased for a majority of Crew Members following six-month missions to the International Space Station (ISS). As predicted, the length density of larger vessels remained relatively constant. The assignment of vascular branching generations into large and small vessels by VESGEN further confirmed that vascular adaptations to microgravity occurred primarily at the level of the smaller arteries and veins. In contrast, vascular densities increased by these same parameters for a majority of subjects following 70 days of HDT. Differing trends of arterial and venous response to cephalad fluid shifts after HDT and the ISS may have resulted from a long-duration adaptation phenomenon (6 months compared to 70 days), or from the presence of a gravity vector in HDT compared to microgravity on the ISS. Results further suggest the importance of individual variability (susceptibility) of vascular adaptations in Crew Members.

Research Impact/Earth Benefits: Results on vascular decreases in the retinas of ISS Crew Members support further investigation of vascular patterning as a potential biomarker of early SANS susceptibility. The one clinically diagnosed case of SANS by optic disk edema displayed the greatest decrease in vascular density. Smaller vascular decreases in most of the other Crew Member retinas were identified that could precede subsequent secondary vascular effects such as cotton wool spots, choroidal folds, and edemas of the optic disc and retinal/choroidal layers. The role of VESGEN vascular mapping and quantification as a useful research and technology (R&T) discovery tool was therefore validated. Fractal-based vascular patterning could offer a new, insightful biomarker of progressive, vascular-dependent pathologies such as SANS that is sensitive to the detection of subtle, early-stage remodeling, especially of smaller vessels. Results on opposite trends in retinal vascular remodeling in Crew Members and Bed Rest Subjects may contribute to better understanding and countermeasures development for SANS.

The VESGEN vascular analysis is relevant to the study of other Human Research Program (HRP) risks such as cardiovascular response to radiation. The vascular analysis is being applied to another HRP study on rodent hindlimb unloading, an experimental model of cephalad fluid shifts resulting from microgravity. Increased knowledge and innovations from this investigation will benefit similar studies for terrestrial diseases such as diabetic retinopathy (DR), the major blinding retinal disease of working-aged adults, and other vascular-dependent diseases such as tumors.

Task Progress & Bibliography Information FY2018 
Task Progress: Two Specific Aims were proposed to support the microvascular hypothesis that addresses NASA solicitation requirements for an 'accelerated, new scientific approach to produce novel scientific knowledge and deliver initial proof-of-concept mappings.' The proposal further addressed HRP Risk ‘Microgravity-induced Visual Alterations and Intracranial Pressure’ by investigation of the HRP Gap ‘VIIP1 What is the etiology of visual acuity and ocular structural and functional changes in-flight and post-flight?’ ('VIIP' is now designated as Spaceflight Associated Neuro-ocular Syndrome (SANS)). The study further addressed the first objective of the NASA solicitation, quantification of crew health and performance risks. Below are the aims proposed for the study. The second aim was accepted by NASA, resulting in expansion of the original study design.

Aim 1—Alterations in vascular patterning of the human retina responding to fluid shifts incurred by long-duration head-down tilt bed rest will be mapped and quantified.

Aim 2—Alterations in the retinal vascular patterning of astronauts before and after spaceflight will be mapped and quantified, should NASA decide to provide additional resources to support this Aim.

Work proposed for the study is now complete, including insightful biostatistical and ophthalmic correlations. Arterial and venous branching were analyzed by VESGEN in the retinas of eight Crew Members before and after six-month flight to the ISS, and of six subjects before and after 70-day 6° HDT Bed Rest. Trends in pre to post status within the retinas of Crew Members and HDT subjects measured by the VESGEN analysis are opposite. By two confirming measures of vascular branching complexity, the fractal dimension (Df) and length density of small vessels (Lv=5), the space-filling capacity of arterial and venous trees, decreased for a majority of Crew Members. In contrast, vascular densities increased by these same parameters for a majority of HDT subjects. As predicted, the length density of larger vessels (Lv1-4) remained relatively constant. The assignment of vascular branching generations into large and small vessels by VESGEN further confirmed that vascular adaptations to microgravity and HDT occurred primarily at the level of the smaller arteries and veins.

One of 16 Crew Member retinas was found by NASA to display early SANS using a clinical optic disc edema (ODE) measure. A subclinical vascular pathology index (SVPI) was therefore calculated to compare the magnitude of vascular change measured by VESGEN in the SANS retina with the 15 other retinas assessed as clinically normal by clinical ocular measures that include ODE and total retinal and choroidal thicknesses. By the SVPI, twelve retinas displayed vascular decreases from 6% to 76%, compared to the SANS retina. Relationships of vascular change to other parameters such as globe flattening and total retinal and choroidal thickness were investigated as mixed effects. For example, vascular decreases were associated with increased total retinal and retinal nerve fiber layer thicknesses.

Results of this first proof-of-concept VESGEN study support further investigation of vascular patterning as a potential biomarker of early vascular changes related to SANS etiology and susceptibility.

Bibliography Type: Description: (Last Updated: 11/30/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Murray MC, Vizzeri GM, Taibbi G, Mason SS, Young M, Zanello SB, Parsons-Wingerter P. "Differences in Pre and Post Vascular Patterning within Retinas of ISS Crew Members and Head-Down Tilt Subjects by VESGEN Analysis." Oral presentation at Spaceflight-Associated Neuro-Ocular Syndrome (SANS/VIIP) – Flight Findings, Human Research Program Investigators’ Workshop (IWS), 'The Gateway to Mars,' 2018 Human Research Program Investigators' Workshop, Galveston, TX, January 22-25, 2018.

2018 Human Research Program Investigators' Workshop, Galveston, TX, January 22-25, 2018. https://ntrs.nasa.gov/search.jsp?R=20170009912 , Jan-2018

Abstracts for Journals and Proceedings Vyas RJ, Murray MC, Predovic M, Lim S, Askin KN, Vizzeri GM, Taibbi G, Mason SS, Zanello SB, Young M, Parsons-Wingerter P. "Analysis by NASA’s VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest." Human Research Program Investigators’ Workshop (IWS), 'A New Dawn: Enabling Human Space Exploration,' Galveston, TX, January 23-26, 2017.

2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017. , Jan-2017

Abstracts for Journals and Proceedings Parsons-Wingerter P, Vyas RJ, Murray MC, Predovic M, Lim S, Vizzeri GM, Taibbi G, Mason SS, Zanello SB, Young M. "Mapping by VESGEN of Blood Vessels in the Retina of Astronauts Pre- and Post-Flight to the ISS." Human Research Program Investigators’ Workshop (IWS), 'A New Dawn: Enabling Human Space Exploration,' Galveston Island Convention Center, TX, January 23-26, 2017.

2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017. https://ntrs.nasa.gov/search.jsp?R=20170009806&hterms=parsons-wingerter&qs=N%3D0%26Ntk%3DAll%26Ntt%3Dparsons-wingerter%26Ntx%3Dmode%2520matchallpartial , Jan-2017

Abstracts for Journals and Proceedings Parsons-Wingerter P, Kao D, Valizadegan H, Martin R, Murray M, Ramesh S, Sekaran S. "VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine." NASA Ames Research Center Research and Technology Showcase (ARTS), Moffett Field, CA, September 28, 2017.

NASA Ames Research Center Research and Technology Showcase (ARTS), Moffett Field, CA, September 28, 2017. https://ntrs.nasa.gov/search.jsp?R=20170012213&hterms=parsons-wingerter&qs=N%3D0%26Ntk%3DAll%26Ntt%3Dparsons-wingerter%26Ntx%3Dmode%2520matchallpartial , Sep-2017

Abstracts for Journals and Proceedings Parsons-Wingerter P, Vyas RJ, Raghunandan S, Vu AC, Zanello S, Ploutz-Snyder R, Taibbi G, Vizzeri GM. "Analysis by NASA’s VESGEN Software of Vascular Branching in the Human Retina with a Ground-Based Microgravity Analog." Session 223: Imaging Posterior Segment, Presentation 1671-CO127, Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting 'A Vision of Hope,' Seattle WA, May 1-5, 2016.

Invest Ophthalmol Vis Sci (ARVO Meeting Abstracts). 2016 Sep;57(12):1671. (Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting 'A Vision of Hope,' Seattle WA, May 1-5, 2016.) https://iovs.arvojournals.org/article.aspx?articleid=2560278&resultClick=1 ; https://ntrs.nasa.gov/search.jsp?R=20160006884 , Sep-2016

Abstracts for Journals and Proceedings Raghunandan S, Vyas RJ, Vu AC, Vizzeri G, Taibbi G, Zanello SB, Ploutz-Snyder R, Zanello SB, Parsons-Wingerter P. "Analysis by NASA’s VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest: A Retrospective Study." Poster Session A: Visual Impairment and Intracranial Pressure #0645-256, Human Research Program Investigators’ Workshop (IWS), 'Frontiers in Human Space Exploration Research,' Galveston Island Convention Center, TX, February 8-11, 2016.

2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016. https://ntrs.nasa.gov/search.jsp?R=20160002099 , Feb-2016

Abstracts for Journals and Proceedings Vu AC, Raghunandan S, Vyas RJ, Radhakrishnan K, Taibbi G, Vizzeri GM, Grant MB, Chalam KV, Parsons-Wingerter P. "Retinal Image Quality Assessment for Spaceflight-Induced Vision Impairment Study." Space Biomedical Research Session, 31st Annual Meeting, American Society for Gravitational & Space Research (ASGSR), Alexandria VA, November 11-14, 2015.

31st Annual Meeting of the American Society for Gravitational and Space Research, Alexandria, VA, November 11-14, 2015. https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20160001752.pdf , Nov-2015

Articles in Peer-reviewed Journals Vyas RJ, Young M, Murray MC, Predovic M, Lim S, Jacobs NM, Mason SS, Zanello SB, Taibbi G, Vizzeri G, Parsons-Wingerter P. "Decreased vascular patterning in the retinas of astronaut crew members as new measure of ocular damage in spaceflight-associated neuro-ocular syndrome." Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):34. https://doi.org/10.1167/iovs.61.14.34 ; PMID: 33372980; PMCID: PMC7774106 , Dec-2020
Articles in Peer-reviewed Journals Lagatuz M, Vyas RJ, Predovic M, Lim S, Jacobs N, Martinho M, Valizadegan H, Kao D, Oza N, Theriot CA, Zanello SB, Taibbi G, Vizzeri G, Dupont M, Grant MB, Lindner DJ, Reinecker HC, Pinhas A, Chui TY, Rosen RB, Moldovan N, Vickerman MB, Radhakrishnan K, Parsons-Wingerter P. "Vascular patterning as integrative readout of complex molecular and physiological signaling by VESsel GENeration Analysis." J Vasc Res. 2021 Jul;58(4):207-30. https://doi.org/10.1159/000514211 ; PMID: 33839725 , Jul-2021
Articles in Peer-reviewed Journals Taibbi G, Young M, Vyas RJ, Murray MC, Lim S, Predovic M, Jacobs NM, Askin KN, Mason SS, Zanello SB, Vizzeri G, Theriot CA, Parsons-Wingerter P. "Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity." npj Microgravity. 2021 Oct 14;7(1):38. https://doi.org/10.1038/s41526-021-00165-5 ; PMID: 34650071; PMCID: PMC8516890 , Oct-2021
Project Title:  Mapping by VESGEN of Blood Vessels in the Human Retina Undergoing Bed Rest for Improved Understanding of Visual Impairments and Increased Intracranial Pressure Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2013  
End Date: 06/30/2018  
Task Last Updated: 08/01/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Parsons-Wingerter, Patricia  Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch (SCR) 
Mailstop N236-7 
Moffet Field , CA 94035-1000 
Email: patricia.a.parsons-wingerter@nasa.gov 
Phone: (650) 604-1729  
Congressional District: 18 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: NOTE: Formerly at NASA Glenn Research Center until summer 2014 
Co-Investigator(s)
Affiliation: 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Zanello, Susana  Ph.D. Universities Space Research Association 
Key Personnel Changes / Previous PI: August 2017 report: Co-Investigator Dr. Rob Ploutz-Snyder is no longer with the team.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Allcorn, Aaron  
Center Contact: 281.244.8402 
aaron.j.allcorn@nasa.gov 
Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT,GROUND 
Flight Program: Pre/Post Flight 
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 (IRP Rev I)
Human Research Program Gaps: (1) SANS03:We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function (IRP Rev I)
Flight Assignment/Project Notes: NOTE: End date changed to 6/30/2018 per discussion with PI (Ed., 3/26/18)

NOTE: End date changed to 10/01/2017 per A. Allcorn/JSC and PI (Ed., 7/31/17)

NOTE: End date changed to 4/08/2017 per PI (Ed., 1/30/17)

NOTE: End date changed to 1/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016 and 4/8/2017, which is actually supposed to be due date for final reporting), per PI (Ed., 5/17/16)

NOTE: End date changed to 4/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016), per PI (Ed., 10/20/15)

NOTE: End date changed to 10/01/2016 (originally 9/30/2014 and subsequently 9/22/2015), per PI (Ed., 10/20/15)

NOTE: End date changed to 9/22/2015 (originally 9/30/2014), per R. Brady/HRP (Ed., 7/17/14)

NOTE: Gap change per IRP Rev E (Ed., 3/19/14)

Task Description: Hypothesis: We hypothesize that blood vessels in the retina necessarily remodel to accommodate cephalad fluid shifts incurred in microgravity, and that vascular remodeling occurs in advance of other ocular and visual changes associated with visual impairments and increased intracranial pressure (VIIP), such as choroidal folds, cotton wool spots, and visual impairments. In particular, we predict that smaller blood vessels are mostly likely to remodel in response to the fluid shifts.

Aims: Alterations of vascular patterning in the retinas of Astronaut Crew Members and Bed Rest Subjects will be mapped and quantified by NASA’s VESsel GENeration Analysis (VESGEN) software. For the two retrospective studies, vascular patterning will be analyzed in images acquired by Heidelberg 30 degree Spectralis infrared (IR) imaging before and after (pre and post) astronaut missions to the International Space Station (ISS), and before and after 70 days of bed rest at 6 degree head-down tilt. Results for retinal vascular patterning by VESGEN will be correlated with other ocular and cardiovascular parameters.

Methods: A preliminary feasibility study with the Human Research Program (HRP) of vascular images acquired by the same Heidelberg IR modality demonstrated that the sensitive VESGEN analysis can detect vascular patterns of arterial and venous branching that were highly similar in two retinas, but significantly different from arterial and venous branching in a third retina.

The design of the subsequent investigations of Crew Members (n=8) and Bed Rest Subjects (n=10) is essentially identical. During Phase 1, the pre and post status of the retinal vascular images is blinded (i.e., unknown) during the VESGEN analysis of retinal vascular pattern. During Phase 2, following communication of pre and post status to the VESGEN team, results for retinal vascular patterning are evaluated according to the pre and post status of the Crew Members and Bed Rest Subjects. Finally, results for the vascular patterning analysis are compared with other ocular and cardiovascular parameters.

Research Impact/Earth Benefits: Results of VESGEN research on retinal vascular remodeling in Crew Members and Bed Rest Subjects may contribute to better understanding and countermeasures development for the VIIP syndrome. The VESGEN vascular analysis is being applied to another HRP study on rodent hindlimb unloading, an experimental model of cephalad fluid shifts resulting from microgravity. The increased knowledge and innovations from our VESGEN project for astronaut health will benefit similar studies for vascular-based terrestrial diseases such as diabetic retinopathy (DR), the major blinding retinal disease of working-aged adults, and other vascular-dependent diseases.

Task Progress & Bibliography Information FY2017 
Task Progress: Phase 1, Complete: Mapping and quantification of the retinal arterial and venous branching patterns by VESGEN analysis is complete for both the Crew Members and Bed Rest Subjects. Preliminary observations during this phase of study suggested that vascular resolution in the Crew Member and Bed Rest images was less clear (more diffuse) than in images of the feasibility study. Concerns were discussed with HRP that any changes in vascular patterning detected by the VESGEN analysis could result from two causes: 1) actual pre and post changes in vascular patterning, and/or 2) differences in imaging quality between the pre and post images. A novel automated masking method for comparing the relative presence or absence of blood vessels in the two images of the same retina was developed as an analytical tool with Matlab.

Phase 2, In Progress: The pre and post status of the Spectralis images for Crew Members and Bed Rest Subjects has been communicated to the VESGEN team. As requested previously by HRP, assessment of vascular patterning determined by VESGEN analysis for the Bed Rest images will be completed first, and is in progress. Next other ocular and cardiovascular parameters will be compared with the VESGEN results. After completion of the Bed Rest Phase 2 analysis, the same analysis will be applied to the Crew Member images. The Final Report will follow in the near future.

Bibliography Type: Description: (Last Updated: 11/30/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2017
Project Title:  Mapping by VESGEN of Blood Vessels in the Human Retina Undergoing Bed Rest for Improved Understanding of Visual Impairments and Increased Intracranial Pressure Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2013  
End Date: 04/08/2017  
Task Last Updated: 05/18/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Parsons-Wingerter, Patricia  Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch (SCR) 
Mailstop N236-7 
Moffet Field , CA 94035-1000 
Email: patricia.a.parsons-wingerter@nasa.gov 
Phone: (650) 604-1729  
Congressional District: 18 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: NOTE: Formerly at NASA Glenn Research Center until summer 2014 
Co-Investigator(s)
Affiliation: 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Ploutz-Snyder, Robert  Universities Space Research Association 
Zanello, Susana  Universities Space Research Association 
Key Personnel Changes / Previous PI: No changes to research team personnel.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Allcorn, Aaron  
Center Contact: 281.244.8402 
aaron.j.allcorn@nasa.gov 
Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT,GROUND 
Flight Program: Pre/Post Flight 
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 (IRP Rev I)
Human Research Program Gaps: (1) SANS03:We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function (IRP Rev I)
Flight Assignment/Project Notes: NOTE: End date changed to 4/08/2017 per PI (Ed., 1/30/17)

NOTE: End date changed to 1/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016 and 4/8/2017, which is actually supposed to be due date for final reporting), per PI (Ed., 5/17/16)

NOTE: End date changed to 4/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016), per PI (Ed., 10/20/15)

NOTE: End date changed to 10/01/2016 (originally 9/30/2014 and subsequently 9/22/2015), per PI (Ed., 10/20/15)

NOTE: End date changed to 9/22/2015 (originally 9/30/2014), per R. Brady/HRP (Ed., 7/17/14)

NOTE: Gap change per IRP Rev E (Ed., 3/19/14)

Task Description: Accelerated, high-priority NASA studies have established that the adverse effects of cephalad fluid shifts incurred by microgravity spaceflight, especially by long-duration missions, are associated with significant risks for ocular and visual impairments and increased intracranial pressure (VIIP), including decreased near visual acuity, choroidal flattening, and optic disc edema (papilledema). However, much remains to be learned about the etiology of VIIP to support the development of effective countermeasures. Contributions of remodeling retinal blood vessels to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive remodeling of the vascular architecture. We hypothesize that the fluid shifts resulting in VIIP ocular and visual impairments are mediated in part by the retinal blood vessels, and that such vascular involvement requires the significant, progressive remodeling of retinal vascular architecture. To test our hypothesis, retinal blood vessels will be mapped and quantified using the innovative VESsel GENeration Analysis (VESGEN), a mature, beta-level software developed at NASA as a translational and basic research discovery tool for biomedical vascular applications, particularly for retinal vascular disease. Modified retinal vascular patterning may provide early prediction of future ocular damage and decreased visual acuity. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina are currently guiding other NIH- and NASA-supported research on retinal disease and the VIIP risk. Our VESGEN project addresses VIIP countermeasures development with two retrospective studies that utilize previous ophthalmic clinical imaging performed on International Space Station (ISS) US Crew Members before and after spaceflight, and NASA Subjects previously undergoing Bed Rest Head Down Tilt (HDT).

Research Impact/Earth Benefits: Results of VESGEN research on retinal vascular remodeling will contribute to better understanding and preventive treatments of the VIIP syndrome. Such innovations will help improve the health and well being of astronauts, and consequently their ability to successfully perform and complete future long-duration missions such as lunar and asteroid colonization and Mars explorations. Moreover, the increased medical knowledge and technical innovations required to successfully complete our VESGEN medical research project for astronaut health will benefit similar studies for vascular-based terrestrial diseases such as diabetic retinopathy (DR), the major blinding retinal disease of working-aged adults in industrialized countries, cancer, heart disease, and regenerative medicine. NASA’s VESGEN technology is simultaneously being developed to map and quantify vascular remodeling in major experimental organisms on the International Space Station (ISS) that also support future human space exploration and medicine. These ISS model organisms and tissues include the mouse, fruitfly (Drosophila melanogaster), and even leaf venation of the plant Arabidopsis thaliana.

Task Progress & Bibliography Information FY2016 
Task Progress: In consultation with NASA’s Human Research Program, our NASA National Research Award was re-designed as a retrospective study of US astronauts and NASA-approved subjects who underwent 70-day head-down tilt (HDT) bed rest. Specifically, Heidelberg Spectralis infrared (IR) images acquired during routine health monitoring of US Crew Members pre- and post- flight to the International Space Station (ISS) by Johnson Space Center (JSC) Medical Operations, and by ophthalmic imaging of NASA-approved subjects for 70-day head-down tilt (HDT) bed rest (FARU Campaign 11) will be analyzed by NASA’s VESGEN software using a masked protocol. The redesign of the study required extensive reviews and approvals by NASA’s Institutional Review Board (IRB) and Lifetime Surveillance of Astronaut Health (LSAH). The HDT images and the first data set of astronaut images were received for VESGEN analysis in later 2015. The second, final data set of astronaut images are expected to be sent to the VESGEN Laboratory in Summer 2016. The VESGEN analysis of the Crew Member and HDT images are currently in progress. The study is scheduled for completion by January 8, 2017.

Bibliography Type: Description: (Last Updated: 11/30/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Parsons-Wingerter P, Hosamani R, Vickerman MB, Bhattacharya S. "Mapping by VESGEN of wing vein phenotype in Drosophila for quantifying adaptations to space environments." Gravit Space Res. 2015 Dec;3(2):54-64. http://gravitationalandspacebiology.org/index.php/journal/article/view/693/731 , Dec-2015
Project Title:  Mapping by VESGEN of Blood Vessels in the Human Retina Undergoing Bed Rest for Improved Understanding of Visual Impairments and Increased Intracranial Pressure Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2013  
End Date: 01/08/2017  
Task Last Updated: 10/29/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Parsons-Wingerter, Patricia  Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch (SCR) 
Mailstop N236-7 
Moffet Field , CA 94035-1000 
Email: patricia.a.parsons-wingerter@nasa.gov 
Phone: (650) 604-1729  
Congressional District: 18 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: NOTE: Formerly at NASA Glenn Research Center until summer 2014 
Co-Investigator(s)
Affiliation: 
Vizzeri, Gianmarco  University of Texas Medical Branch 
Ploutz-Snyder, Robert  Universities Space Research Association 
Zanello, Susana  Universities Space Research Association 
Key Personnel Changes / Previous PI: No changes to research team personnel.
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: Internal Project 
Project Type: FLIGHT,GROUND 
Flight Program: Pre/Post Flight 
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 (IRP Rev I)
Human Research Program Gaps: (1) SANS03:We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function (IRP Rev I)
Flight Assignment/Project Notes: NOTE: End date changed to 1/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016 and 4/8/2017, which is actually supposed to be due date for final reporting), per PI (Ed., 5/17/16)

NOTE: End date changed to 4/08/2017 (originally 9/30/2014 and subsequently 9/22/2015 and 10/1/2016), per PI (Ed., 10/20/15)

NOTE: End date changed to 10/01/2016 (originally 9/30/2014 and subsequently 9/22/2015), per PI (Ed., 10/20/15)

NOTE: End date changed to 9/22/2015 (originally 9/30/2014), per R. Brady/HRP (Ed., 7/17/14)

NOTE: Gap change per IRP Rev E (Ed., 3/19/14)

Task Description: Accelerated, high-priority NASA studies recently established that the adverse effects of cephalad fluid shifts incurred by microgravity spaceflight, especially by long-duration missions, are associated with significant risks for ocular and visual impairments and increased intracranial pressure (VIIP), including decreased near visual acuity, choroidal flattening, and optic disc edema (papilledema). However, much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of remodeling retinal blood vessels to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive remodeling of the vascular architecture. We hypothesize that the fluid shifts resulting in VIIP ocular and visual impairments are mediated in part by the retinal blood vessels, and that such vascular involvement requires the significant, progressive remodeling of retinal vascular architecture. To test our hypothesis, retinal blood vessels will be mapped and quantified using the innovative VESsel GENeration Analysis (VESGEN), a mature, beta-level software developed at NASA as a translational and basic research discovery tool for biomedical vascular applications, particularly for retinal vascular disease. Modified retinal vascular patterning may provide early prediction of future decreased visual acuity. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina are currently guiding other NIH- and NASA-supported therapeutic development for retinal disease and modeling of the VIIP risk. Our new VESGEN project addressing the VIIP risk will be conducted as a straightforward add-on study that synergistically leverages ophthalmic clinical imaging currently scheduled for ongoing bed rest studies at NASA Johnson Space Center (JSC). The VESGEN analysis can also be applied to ophthalmic images of astronauts undergoing long-duration spaceflight, should such images become available.

Research Impact/Earth Benefits: Results of VESGEN research on retinal vascular remodeling will contribute to better understanding and preventive treatments of the (VIIP) syndrome. Such innovations will help improve the health and well being of astronauts, and consequently their ability to successfully perform and complete future long-duration missions such as lunar and asteroid colonization and Mars explorations. Moreover, the increased medical knowledge and technical innovations required to successfully complete our VESGEN medical research project for astronaut health will benefit similar studies for vascular-based terrestrial diseases such as diabetic retinopathy (DR), the major blinding retinal disease of working-aged adults in industrialized countries, cancer, heart disease, and regenerative medicine. NASA’s VESGEN technology is simultaneously being developed to map and quantify vascular remodeling in major experimental organisms on the International Space Station (ISS) that also support future human space exploration and medicine. These ISS model organisms and tissues include the mouse, fruitfly (Drosophila melanogaster), and even leaf venation of the plant Arabidopsis thaliana.

Task Progress & Bibliography Information FY2015 
Task Progress: Our VESGEN research project was re-designed during 2014 by the VIIP VESGEN project team and NASA to address the VIIP risk more quickly and effectively. Our study will be conducted as a straightforward add-on study that synergistically leverages state-of-the-art ophthalmic clinical imaging, the Heidelberg Spectralis imaging of retinal blood vessels, that was established by NASA during 2013 for routine crew health surveillance. A preliminary study during 2014 demonstrated that VESGEN can successfully analyze and discriminate among subtle differences in arterial and venous patterning in the Spectralis images. We therefore now will analyze retinal vascular images of astronauts acquired before and after spaceflight missions to the International Space Station (ISS). The Spectralis ophthalmic retinal vascular images of human volunteer subjects before and after bed rest accompanied by head-down tilt (HDT), a well-established model of microgravity fluid shifts, will also be analyzed. Because the VESGEN study of astronaut and HDT IR images uses the same ophthalmic imaging modality, our study will quickly and optimally assess the usefulness of VESGEN for monitoring crew health, and for developing improved countermeasures and diagnostics for the VIIP risks. Mapping and quantification by VESGEN of retinal vascular remodeling will therefore contribute to the increased understanding of VIIP, may provide early prediction of VIIP when the syndrome is still reversible, and may help to guide the successful development of future countermeasures and therapies.

Bibliography Type: Description: (Last Updated: 11/30/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Theriot CA, Parsons-Wingerter P, Vizzeri G, Zanello SB. "Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. http://www.hou.usra.edu/meetings/hrp2014/pdf/3104.pdf , Feb-2014

Abstracts for Journals and Proceedings Parsons-Wingerter P, Vizzeri G, Taibbi G, Zanello SB, Ploutz-Snyder R. "Mapping by VESGEN of Blood Vessels in the Human Retina Undergoing Bed Rest for Increased Understanding of VIIP." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. http://www.hou.usra.edu/meetings/hrp2014/pdf/3115.pdf , Feb-2014

Abstracts for Journals and Proceedings Parsons-Wingerter P, Pinhas A, Dubow M, Shah N, Gan A, Razeen M, Chui T, Dubra A, Rosen RB. "VESGEN analysis of human macular microvasculature in venous occlusive disease imaged in vivo using AOSLO FA." Program 5754, Session 517:A272, Vascular Mechanisms in Diabetic Retinopathy Session 382, Retinal and Choroidal Vascular Diseases, 2014 Vision and Ophthalmology (ARVO) Annual Meeting-- 'Leading Eye and Vision Research,' Orlando FL, May 4-8, 2014.

Invest Ophthalmol Vis Sci (ARVO Meeting Abstracts). 2014 Apr 30;55:3880. (2014 Vision and Ophthalmology (ARVO) Annual Meeting, Orlando FL, May 4-8, 2014. Presentation 3880-C0182.) http://iovs.arvojournals.org/article.aspx?articleid=2269344 ; accessed 11/16/15. , Apr-2014

Abstracts for Journals and Proceedings Radhakrishnan K, Parsons-Wingerter P, Chalam KV, Mames R, Kay C, Grant MB. "VESGEN Analysis of Fractal-Based Branching in Arterial and Venous Trees for Investigating Diabetic Retinopathy with Spectralis® Angiographic Imaging." Presentation 275-B0083, Session 109, Retinal Imaging, 2014 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting--'Leading Eye and Vision Research,' Orlando FL, May 4-8, 2014.

Invest Ophthalmol Vis Sci. (ARVO Meeting Abstracts) 2014 Apr;55: E-Abstract 275. (2014 Vision and Ophthalmology (ARVO) Annual Meeting, Orlando FL, May 4-8, 2014. Presentation 3880-C0182.) http://iovs.arvojournals.org/article.aspx?articleid=2268105 ; accessed 11/16/15. , Apr-2014

Project Title:  Mapping by VESGEN of Blood Vessels in the Human Retina Undergoing Bed Rest for Improved Understanding of Visual Impairments and Increased Intracranial Pressure Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2013  
End Date: 09/22/2015  
Task Last Updated: 08/26/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Parsons-Wingerter, Patricia  Ph.D. / NASA Ames Research Center 
Address:  Space Biosciences Research Branch (SCR) 
Mailstop N236-7 
Moffet Field , CA 94035-1000 
Email: patricia.a.parsons-wingerter@nasa.gov 
Phone: (650) 604-1729  
Congressional District: 18 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Ames Research Center 
Joint Agency:  
Comments: NOTE: Formerly at NASA Glenn Research Center until summer 2014 
Co-Investigator(s)
Affiliation: 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
Flight Program:  
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 (IRP Rev I)
Human Research Program Gaps: (1) SANS03:We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function (IRP Rev I)
Flight Assignment/Project Notes: NOTE: End date changed to 9/22/2015 (originally 9/30/2014), per R. Brady/HRP (Ed., 7/17/14)

NOTE: Gap change per IRP Rev E (Ed., 3/19/14)

Task Description: Accelerated, high-priority NASA studies recently established that the adverse effects of cephalad fluid shifts incurred by microgravity spaceflight, especially by long-duration missions, are associated with significant risks for ocular and visual impairments and increased intracranial pressure (VIIP), including decreased near visual acuity, choroidal flattening and optic disc edema (papilledema). However, much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of remodeling retinal blood vessels to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive remodeling of the vascular architecture. We hypothesize that the fluid shifts resulting in VIIP ocular and visual impairments are mediated in part by the retinal blood vessels, and that such vascular involvement requires the significant, progressive remodeling of retinal vascular architecture. To test our hypothesis, retinal blood vessels will be mapped and quantified using the innovative VESsel GENeration Analysis (VESGEN), a mature, beta-level software developed at NASA as a translational and basic research discovery tool for biomedical vascular applications, particularly for retinal vascular disease. Modified retinal vascular patterning may provide early prediction of future decreased visual acuity. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina are currently guiding other NIH- and NASA-supported therapeutic development for retinal disease and modeling of the VIIP risk. Our new VESGEN project addressing the VIIP risk will be conducted as a straightforward add-on study that synergistically leverages ophthalmic clinical imaging currently scheduled for ongoing bed rest studies at NASA Johnson Space Center (JSC). The VESGEN analysis can also be applied to ophthalmic images of astronauts undergoing long-duration spaceflight, should such images become available.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2014 
Task Progress: New project for FY2014.

Bibliography Type: Description: (Last Updated: 11/30/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2014