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NASA Technical Reports Server (NTRS) 20170000927: Analysis by NASA's VESGEN Software of Retinal Blood Vessels in Human Subjects Undergoing Head-Down Tilt During 70-Day Bed Rest PDF

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Preview NASA Technical Reports Server (NTRS) 20170000927: Analysis by NASA's VESGEN Software of Retinal Blood Vessels in Human Subjects Undergoing Head-Down Tilt During 70-Day Bed Rest

NASA Investigator’s Workshop, Human Research Program January 23-26, 2017 Galveston, TX National Aeronautics and Space Administration Poster Session A: VISUAL IMPAIRMENT AND INTRACRANIAL PRESSURE Abstract 17351 ANALYSIS BY NASA’S VESGEN SOFTWARE OF RETINAL BLOOD VESSELS IN HUMAN SUBJECTS UNDERGOING HEAD-DOWN TILT DURING 70-DAY BED REST Ruchi J. Vyas1,2, Matthew C. Murray1,3, Marina Predovic1,3, Shiyin Lim1,3, Kayleigh N. Askin1,4, Gianmarco Vizzeri5, Giovanni Taibbi5, Sara Stroble Mason6,7, Susana B. Zanello8, Millenia Young6,9 and Patricia Parsons-Wingerter1 1Space BioSciences Research Branch, NASA Ames Research Center, Mountain View CA, 2SGT, Inc/MORi Associates, Inc, 3Blue Marble Space Institute of Science, 4National Space Biomedical Research Institute, 5Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston TX, 6NASA Johnson Space Center, Houston TX, 7MEI Technologies, 8Universities Space Research Association and 9Human Health and Countermeasures INTRODUCTION AND BACKGROUND Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions [1]. We hypothesize that microgravity-induced fluid shifts result in pathological changes within blood vessels of the retina that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated for two studies in 30° infrared (IR) Heidelberg Spectralis® images with NASA’s innovative VESsel GENeration Analysis (VESGEN) software [2,3]. The retrospective studies include: (1) before, during and after (pre, mid and post) 6º head-down tilt (HDT) in human subjects during 70 days of bed rest, and (2) before and after missions to the International Space Station (ISS) by U.S. crew members. Results for both studies are almost complete. A preliminary example for HDT is described below. METHODS The mature (beta-level), automated VESGEN software was developed as a translational and basic vascular research discovery tool to map and quantify branching Figure 2 Arterial and venous branching generations within 2 images of an HDT vascular patterns, particularly for retinal vascular disease [2-4]. IR Spectralis® images of retina currently blinded as to pre and post status retinal blood vessels from the retinas of six healthy human subjects undergoing HDT (A–D) Image 1 arterial generations, arterial generations grouped, venous generations and venous were collected by NASA previously [5]. For our 2013 NASA NRA award, VESGEN generations grouped. (E–H) Image 2 arterial and venous generations. (B,F,D,H) Vessels were grouped into generations of G and G . analysis of the IR images was approved by NASA’s Institutional Review Board (Pro1384) 1-4 ≥5 according to previously published methods for progressive, visually impairing vascular RESULTS AND DISCUSSION disease in the human retina [2,3]. In brief, binary vascular patterns are extracted from The VESGEN analysis of HDT images (Phase 1) is complete. However, because the grayscale images, and automatically analyzed by VESGEN according to weighted Phase 1 VESGEN analysis of Crew Members is not yet finished, the pre, mid and post physiological branching rules. For Phase 1, the initial portion of our study, the pre, mid status of HDT images remains blinded. Two images of the same HDT retina are therefore and post bed rest status of retinal images was blinded to the VESGEN analysts. presented as an example of the VESGEN analysis (Figure 2). For the grouped Images 1 Longitudinal status of the images will be revealed during Phase 2, when final VESGEN and 2, the number of large and small vessels (N and N ) are 34 and 83 compared to results will be correlated with other ophthalmic and medical findings such as visual 1-4 ≥5 33 and 83 for arteries (C,F), and 37 and 92 compared to 33 and 102 for veins (D,H). acuity, changes in retinal thickness and optic nerve, and cardiovascular parameters such Space-filling capacities of the arterial and venous branching trees were quite consistent as blood pressure. by space-filling measures such as vessel length density (L ) and the fractal dimension v (D ). For arteries (C,F), L and D were 1.41E-3 and 1.45E-3 µm/µm2, and 1.37 and 1.38, f v f compared to 1.40E-3 and 1.44E-3 µm/µm2, and 1.33 and 1.33, for veins (D,H). Arterial and venous diameters of grouped large and small vessels were quite equivalent. CONCLUSIONS The study is scheduled to conclude in mid April 2017. Preliminary inspection of the Spectralis® images, supported by VESGEN analysis, suggest that the IR images lack sufficient resolution to definitively test our hypothesis, which proposes that small blood vessels within the retina remodel to accommodate and mediate prolonged cephalad fluid shifts. Newer ophthalmic imaging such as OCT angiography (OCT-A) and adaptive optics scanning laser ophthalmoscopy (AOSLO) offer significant advances in retinal Figure 1 Comparison of two images of an HDT retina using a masking transformation by Matlab® algorithm vascular resolution that, combined with VESGEN analysis, would provide the necessary (A) Pink vessels correspond to vessels from Image 1 (reference), Green vessels imaging technology to conclusively test the hypothesis. correspond to Image 2 (transformed to fit reference). Both interpretations are in agreement REFERENCES where the vessels appear black, whereas, the pink and green vessels show vessel differences. (B,C) Grayscale Images 1 and 2. 1. Mader T.H., Gibson C.R., Pass A.F., Kramer L.A., Lee A.G., Fogarty J., Tarver W.J., Dervay J.P., Hamilton D.R., Sargsyan A., Phillips J.L., Tran D., Lipsky W., Choi J., Stern C., Kuyumjian R. and Polk J.D. (2011) Ophthalmology 118:2058-2069. 2. Parsons-Wingerter P.A.,* Radhakrishnan K.,* Vickerman M.B. and Kaiser P.K. (2010) Inv Ophthal Vis Sci 51(1):498-507. The smaller blood vessels, which in general remodel most actively during progression of *Co-authors contributed equally. vascular-dependent diseases, are not easily resolved from image background by the low- 3. Vickerman M.B., Keith P.A., McKay T.L., Gedeon D.J., Watanabe M., Montano M., Karunamuni G., Kaiser P.K., Sears J.E., resolution (low contrast) IR Spectralis® imaging modality (average resolution for HDT Ebrahem Q., Ribita D., Hylton A.G. and Parsons-Wingerter P.A. (2009) Anat Rec 292:320-332. 4. Chen X., Yang G., Song J.H., Xu H., Li D., Yang X., Zeng H., Parsons-Wingerter P.A., Reinecker H.C. and Kelly C.P. (2013) PLOS images, 11.4 micron/pixel). Therefore a novel tool was developed with Matlab® ONE 8(5):e64227. (Mathworks) for aligning vessels in pre, mid and post images (Figure 1) to compare 5. Taibbi G, Cromwell R.L., Zanello S.B., Yarbough P.O., Ploutz-Snyder R.J., Godley B.F., Vizzeri G. (2016) Inv Ophthal Vis Sci (query) differences in image capture of critically important small vessels. 57(2):495-501.

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