Delineating the Impact of Weightlessness on Human Physiology Using - PowerPoint PPT Presentation

https://ntrs.nasa.gov/search.jsp?R=20160010063 2018-08-09T20:56:33+00:00Z 31 st Annual Meeting of ASGSR, Alexandria, VA President’s Plenary Symposium Delineating the Impact of Weightlessness on Human Physiology Using Computational Models Mohammad Kassemi National Center for Space Exploration Research (NCSER) NASA Glenn Research Center Case Western Reserve University Cleveland, Ohio Mohammad.Kassemi@nasa.gov Nov 10, 2015 National Aeronautics and Space Administration Glenn Research Center

Outline  PBE & CFD models for prediction of renal calculi development in microgravity .  Fluid-Structural-Interaction (FSI) models to assess vestibular response.  Multi-scale FE Heart model to investigate cardiac restructuring in weightlessness.  Modeling overview  Computational model to assess impact of AG. (1)

System & Multiphase CFD Models for Renal Stone Development & Transport in 1G and Microgravity RSFM was developed to address important NASA questions/needs:  Evaluate the risk of developing a critical renal stone incident during long duration microgravity missions based on available astronaut biochemical data  Assess efficacy of countermeasures such as • Increase Hydration • Potassium Citrate & Magnesium  Perform " what if " parametric studies to understand and assess risk of developing renal stone upon entry into a 1g or a remote partial gravitational field such as Mars or Moon where relevant astronaut biochemical data is unavailable (1)

Renal Stone Population Balance System Model: Nucleation, Growth & Agglomeration Population Balance Equation: 𝐸 2 ∞ 𝑜 𝐸 𝜖𝑜 𝐸 𝜸𝑜 𝐸 − 𝐸 ′ 𝑜 𝐸 ′ 𝑒𝐸 ′ − 𝑜(𝐸) 𝜸𝑜 𝐸 ′ 𝑒𝐸 ′ + 𝐻 𝐸 = 𝜐 𝜖𝐸 0 0 Agglomeration-Death Agglomeration-Birth Growth Nucleation BC: 𝐶 𝑝 𝑜 𝐸 = 0 = 𝑜 𝑝 = Physical Flow CV (Nephron) 𝐻 𝐸 Q V Kidney: Mixed Suspension D L Mixed Product Imaginary Growth CV Removal G Crystallizer D D Population Density Relative Supersaturation: Inhibition: Citrate, Pyrophosphare, 1 2 Hydration 2 𝐷 𝑑𝑏,∞ 𝐷 𝑝𝑦,∞ 𝑔 2 𝑺𝑻 = Direct : K B , K D , b , t • 𝐿 𝑡𝑝 Stone Size • Indirect : RS (2)

Prediction for 4 Subject Test Cases Kassemi & Thompson (JAP-Renal, 2015a) (b) (a)  1G Normal: 24 urine sample Mineral Metabolism Laboratory at University of Texas Southwestern Medical Center UTSW 34 .  1G Recurrent Stone-former: 24 Urine Sample (Robertson et al. 26 , Laube et al. 13 )  Microgravity Astronaut: Average of 24-urine excretion rates obtained from 86 astronauts on the day of landing. (Whitson et al. 36 )  Microgravity Stone Former: Hypothetical worst case scenario constructed using the long duration 24-urine data R+2 (Whitson et al. 38 .) (3)

Effect of Dietary Countermeasures for Microgravity Astronaut Subject Kassemi & Thompson (JAP-Renal, 2015b) (4)

G Effect: Coupling Stone PBE to Urinary Flow & Ca and Ox Transport in the Nephron Population Balance Equation Coupled to Urinary Flow & Species Transport Population Density ANSYS/FLUENT CFD Code • Momentum Equation Stone Size G v = dV/dt • Species Transport Equation (5)

Realistic 3D Nephron Geometry Ducts Tubules (1,200,000) IMCD DoB OMCD 8 Paplia (320) (200,000) (5,120) (6)

Effect of Gravity on Stone Transit through Nephron ( Kassemi, Griffin & Iskovitz, ICES 2014) m g 0g 1g 1 g g (7)

Effect of Gravity on Stone Size Distribution in 3D Nephron Simulations G – y-dir G – x-dir 0G G – x-dir G – y-dir CFD results are confirmed by recent CT scans indicating CaOx Randal plaque formation: Cludin et al, 2012; Williams & McAteer, 2012 ; Kim et al, 2005 . (8)

Effect of Gravity & Flow on Stone Transport and Size Distributions in 3D CFD Nephron Simulations Preliminary 3D CFD results indicate preferential sedimentation of crystals in the vicinity of tubule/duct walls due to intricate coupling effect of flow and gravity resulting in increased propensity for nucleation and/or adherence on certain sections of the nephron tubule/duct wall and development towards critical stone condition in accordance to the Randall plaque hypotheses presented by Evan et al G – x-dir (2010). G – y-dir G – y-dir 0G G – x-dir (8)

Fluid-Structural-Interactions in the Vestibular System Caloric Stimulation Test • Space Motion Sickness (SMS): Head movements Rotational Chair Test result in conflicting signals from the Otolith Organs (OO) and the Semicircular Canals (SSC) • Centrifuge Induced Sickness (CIS): Caused by transition between different gravity levels • Coriolis Motion Sickness (CMS): caused by head movement/velocity out of the PoR • Cross-Coupled Angular Acceleration Sickness: caused by head rotations around an axis other than centrifuge axis of rotation • End organ physics (cause) is partially masked by a neurological overhead (adaptation). • Adaptation effects have to be isolated from end organ effects (9)

The Microgravity Caloric Irrigation Test (CIT) Slow phase eye velocity indicative of the direction and magnitude of Cupula deflection g Ampulla Utricle Cupula Heated Section g Horizontal Semicircular Canal • Barany won the 1906 Noble prize for his natural convection theory explaining CIT • Skylab microgravity experiment negated Barany’ s theory by recording nystagmus in microgravity • Parabolic flight experiments have shown negative nystagmus attributed to adaptation or heating of the nerves.(Oostervald, 1985; Stahle, 1990) (10)

Simulation of 1G & Microgravity Caloric Test in Supine Position ( Kassemi & Oas , JVR 2005) 1G: Sustained Natural Convection g Endol. Streamline 0 30 80 Cupula Stress Microgravity: Dissipating Expansive Convection EndoVelocity Endo Streamline Endolymph Cupula Displac Cupula Stress Pressure Evolving Temperature through Tymphanic Bone 0-G 1G T Evolution The dynamics of microgravity and 1g cupular displacements are entirely different in both magnitudes and trends. Microgravity case produces reverse nystagmus (11)

Rotational Chair Test (RCT) – Determining Angular Velocity Treshholds for Cupulae Displacements -80 Pendulum Model Results c1=0.05 c1=0.1 c1=0.5 c1=1.0 Bode Diagram -90 -50 Magnitude(dB) -100 -110 -55 -120 Magnitude (dB) -60 -130 -140 -65 -150 -70 0.01 0.1 1 10 100 1000 Frequency(Rad/sec) -75 90 45 Phase (deg) 0 -45 -90 -2 -1 0 1 2 3 10 10 10 10 10 10 Frequency (rad/sec) 1 rad/s 50 rad/s 7.5cm (12)

FSI Simulation Rotational Chair Test – Reverse Nystagmus (Axis of rotation at the center of horizontal SCC) Baloh : “ Clinical Neurophysiology of Impulse Vestibular System ” Sinusoidal Ramp (13)

Multi-scale Cardiovascular Analysis TCa TCa T xb Ca T xb Ca h b h b Ca Ca Ca Ca Ca Ca K d: > K' d K d: > K' d F F PreF PreF h f h f T xb T xb T T g app g app (ratio set by SL and PreF/F) (ratio set by SL and PreF/F) g XB g XB f app f app Apparent Ca binding Apparent Ca binding P P T xb Ca T xb Ca TCa TCa Ca Ca Ca k np (TCa Tot ) 15 k np (TCa Tot ) 15 k pn k pn K d: > K' d K d: > K' d T xb T xb T T N N (ratio set by SL alone) (ratio set by SL alone) Regulatory Ca binding Regulatory Ca binding NASA’s Space Cardiovascular Risks: Atrophy, Arrhythmia, Orthostatic Intolerance Gravity  Blood Flow & Shape Change  Spatial Distribution of Stress on the Muscle  Spatial Distribution of Strain in the Tissue  Spatial Nature of Atrophy & Arrhythmia  Heart Performance/Failure (15)

The Components of Multi-scale Heart Model  Realistic 3D heart geometry  Precise 3D fiber/sheet orientation  Nonlinear orthotropic material model for passive behavior  Cell level Cross-Bridging Calcium Kinetics models for active contraction  An eight compartment lumped model TCa TCa T xb Ca T xb Ca h b h b Ca Ca Ca Ca Ca Ca K d: > K' d K d: > K' d of the cardiovascular system based on F F PreF PreF T xb T xb h f h f T T g app g app (ratio set by SL and PreF/F) (ratio set by SL and PreF/F) g XB g XB f app f app a earlier CCF version (Jim Thomas) Apparent Ca binding Apparent Ca binding P P T xb Ca T xb Ca TCa TCa Ca Ca Ca k np (TCa Tot ) 15 k np (TCa Tot ) 15 k pn k pn K d: > K' d K d: > K' d  Couple the lumped cardiovascular and T xb T xb T T N N (ratio set by SL alone) (ratio set by SL alone) Heart FSI/FE models Regulatory Ca binding Regulatory Ca binding  Validate & Verify the integrated heart model at local and global levels  Describe blood flow using continuum- based non-Newtonian Navier-Stokes analysis  Already Developed  Future Development (16)

Change in Sphericity of the Heart in Reduced Gravity Summers et al. (2011) Apical 4-Chamber View of LV • End diastolic LV dimensions captured with echocardiography • Six parabolic flights at each gravitational level: • Microgravity (20-25s) H  R • Moon (30s) i W i • Mars (40s) • Subjects in upright positions • Ventricular pressures predicted using QSP a physiological simulator Benchmark Validation Experiments Intact Heart Uniaxial Test Pressure vs. Volume (Demer et. al, 1983) McCulloch et. al, 1992, Hunter et. al, 2000 Shear Tests (Dokos et. al, 2002) (17)