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Fiscal Year: FY 2017  Task Last Updated:  01/24/2018 
PI Name: Buckey, Jay C. M.D. 
Project Title: Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Cardiovascular Alterations Team 
 
Joint Agency Name:   TechPort:  No 
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) SANS12:We do not know whether ground-based analogs and/or models can simulate Space Associated Neuro-ocular Syndrome (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: jay.buckey@dartmouth.edu  Fax:  603-650-6013 
PI Organization Type: UNIVERSITY  Phone: 603-650-6012  
Organization Name: Dartmouth College 
PI Address 1: Department of Medicine 
PI Address 2: 1 Medical Center Drive 
PI Web Page:  
City: Lebanon  State: NH 
Zip Code: 03756-0001  Congressional District: 
Comments: Address updated 9/2008 
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 08/01/2013  End Date:  05/31/2017 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: End date changed to 5/31/2017 per NSBRI (Ed., 3/1/16)

NOTE: Title change to "Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes" (original proposal title was "Ocular Venous Contributions to Spaceflight Visual Impairment")--Ed., 2/6/14

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Weaver, John  Ph.D. ( Dartmouth College )
Knaus, Darin  Ph.D. ( Creare, Inc. )
Deserranno, Dimitri  Ph.D. ( Creare, Inc. )
Belden, Clifford  M.D. ( Dartmouth College )
Kattamis, Nicholas  Ph.D. ( Creare, Inc. )
Phillips, Scott  Ph.D. ( Creare, Inc. )
Davis, Brynmor  Ph.D. ( Creare, Inc. )
Zegans, Michael  M.D. ( Dartmouth College ) 
Grant/Contract No.: NCC 9-58-CA03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: We developed a numerical model of the cerebral venous circulation that describes how this circulation responds to both fluid shifts and changes in gravitational forces. We validated this model using physiologic studies to measure the responses of the cranial vascular and cerebrospinal fluid (CSF) systems to fluid shifts in both the supine and prone positions. This model and supporting data will provide a means to develop hypotheses about how microgravity produces visual changes over time and may allow predictions about which subjects may be at risk for the visual deficits associated with microgravity.

Aim #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. We developed a numerical model that predicts alterations in the hemodynamics of the cranial venous system produced by changes in hydrostatic gradients and fluid shifts. While models describing the cranial venous system exist in the literature, incorporation of hydrostatic gradient and fluid shift effects is novel. Our computer model consists of two parts—a system model and a structural model. The system model describes flow and pressure in the circulatory system, the cerebral spinal fluid regulatory system, and the eye's aqueous humor regulatory system. The structural model uses a separate decoupled finite element model to describe the eye globe and structures contained within. The structural model was developed on a separate parallel effort funded by the NASA EPSCoR (Established Program to Stimulate Competitive Research) program. Both the system level model and the structural model account for changes in tissue properties that may be induced in microgravity, as well as effects of microgravity exposure duration. We validated the computer model with magnetic resonance imaging (MRI) measurements of venous flow, venous volume, venous pressure, intracranial compliance, CSF volume, and flow pulsatility during cephalad fluid shifts both supine and prone. We also used measurements of intraocular pressure (IOP) and other ocular parameters obtained outside of the MRI magnet. This model and supporting data will provide a means to develop hypotheses about how microgravity produces visual changes over time and may allow predictions about which subjects may be at risk for visual deficits associated with microgravity.

Aim #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. During this reporting period, we published the results on the effects of posture on eye parameters in the prone and supine postures over 60 minutes. These data are essential for understanding the effects of changes in the gravitational vector on the eye. We completed studies on 14 individuals both inside and outside of the MR device in both the supine and prone postures. MR Imaging was also done with and without lower body negative pressure (LBNP) and lower body positive pressure (LBPP). These data have been incorporated into the model and are being prepared for publication.

Aim #3: Identify individuals with common intracranial venous variants, and study them using the protocol outlined in Aim #2. Our cohort of subjects included subjects with a range of venous anatomy, which was adequate for our purposes.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: The model and experimental results will give a better understanding of cranial venous insufficiency. Cranial venous insufficiency results when venous outflow from the head is reduced or obstructed. This can be due to an increase in venous resistance from anatomical variations. The increased resistance to flow can produce headaches or vision changes. Venous insufficiency has been proposed as a possible etiology for symptoms in acute mountain sickness, obstructive sleep apnea, jugular outflow obstruction syndrome, multiple sclerosis, and idiopathic intracranial hypertension (IIH). Bilateral transverse sinus stenosis is found in 90% of IIH sufferers, and internal jugular vein stenosis occurs in 80% of IIH patients. Although numerical models of the circulatory system, cerebral venous system, and cerebral spinal fluid system exist (as do fluid models of the aqueous humor regulatory system and structural finite element models of the eye) the model developed on this project is the first comprehensive model that links the effects of all systems together. It could be used in the future to predict how surgical interventions, such as sagittal stenting, can improve an individual's symptoms. The model is also useful for understanding the visual problems that occur during prolonged surgical procedures in unusual postures (i.e., robotic prostatectomy, spinal surgery).

 

Task Progress: Aim #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.

1. Built a comprehensive model of the cerebrovascular circulation that includes a circulatory sub-model, an aqueous humor submodel, and a cerebrospinal fluid submodel.

2. Model includes effects of hydrostatic gradients and tissue weight, making it well suited for predicting microgravity effects.

3. Model validated using physiologic data from the lab studies that examined the effects of posture (prone vs. supine) and fluid shifts (LBNP) on the cerebrovascular circulation using detailed measurements of the eye and cerebrovascular circulation using various ocular measures (optical coherence tomography, optical biometry) and MRI measures of arterial, venous, and CSF flow.

4. Overall model description and outputs for sample microgravity conditions being prepared for publication.

Aim #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.

1. Completed a study on the short-term effects of posture and microgravity (using parabolic flight) on the eye and published the results.

2. Completed a study on the longer-term (60 minutes) effects of posture (changes in direction of hydrostatic gradients going from supine to prone) and fluid shifts on the eye and published the results.

3. Completed a study on the effects of posture/changes in the direction of hydrostatic gradients and fluid shifts on the cerebrovascular circulation and CSF using MR imaging. Results are being prepared for publication.

Aim #3: Identify individuals with common intracranial venous variants, and study them using the protocol outlined in Aim #2.

1. Subjects studied for this project had a range of venous anatomy that is suitable for further analysis.

 

Bibliography Type: Description: (Last Updated: 04/16/2019) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Masterova KS, Nelson E, Buckey JC. "Accounting for Gravity in Ocular Hemodynamics and Intraocular Pressure Modeling." 88th Aerospace Medical Association Annual Meeting, Denver, CO, April 30-May 4, 2017.

Aerospace Medicine and Human Performance. 2017;88(3):261. , Mar-2017

Abstracts for Journals and Proceedings Phillips SD, Chepko AB, Archambault-Leger V, Kattamis NT, Knaus DA, Anderson AP, Masterova KS, Zegans ME, Buckey JC. "Numerical modeling of eye structure and the cerebrovascular/cerebrospinal circulation." 2017 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 23-26, 2017.

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

Articles in Peer-reviewed Journals Anderson AP, Swan JG, Phillips SD, Knaus DA, Kattamis NT, Toutain-Kidd CM, Zegans ME, Fellows AM, Buckey JC. "Acute effects of changes to the gravitational vector on the eye." J Appl Physiol (1985). 2016 Apr 15;120(8):939-46. Epub 2015 Dec 10. https://doi.org/10.1152/japplphysiol.00730.2015 ; PubMed PMID: 26662052 , Apr-2016
Articles in Peer-reviewed Journals Anderson AP, Babu G, Swan JG, Phillips SD, Knaus DA, Toutain-Kidd CM, Zegans ME, Fellows AM, Gui J, Buckey JC. "Ocular changes over 60 min in supine and prone postures." J Appl Physiol (1985). 2017 Aug 1;123(2):415-23. Epub 2017 May 25. https://doi.org/10.1152/japplphysiol.00687.2016 ; PubMed PMID: 28546470 , Aug-2017
Articles in Peer-reviewed Journals Buckey JC, Phillips SD, Anderson AP, Chepko AB, Archambault-Leger V, Gui J, Fellows AM. "Microgravity-induced ocular changes are related to body weight." Am J Physiol Regul Integr Comp Physiol. 2018 Sep 1;315(3):R496-R499. Epub 2018 May 16. https://doi.org/10.1152/ajpregu.00086.2018 ; PubMed PMID: 29768035 , Sep-2018
Download in PDF pdf     
Fiscal Year: FY 2015  Task Last Updated:  10/19/2015 
PI Name: Buckey, Jay C. M.D. 
Project Title: Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Cardiovascular Alterations Team 
 
Joint Agency Name:   TechPort:  No 
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) SANS12:We do not know whether ground-based analogs and/or models can simulate Space Associated Neuro-ocular Syndrome (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: jay.buckey@dartmouth.edu  Fax:  603-650-6013 
PI Organization Type: UNIVERSITY  Phone: 603-650-6012  
Organization Name: Dartmouth College 
PI Address 1: Department of Medicine 
PI Address 2: 1 Medical Center Drive 
PI Web Page:  
City: Lebanon  State: NH 
Zip Code: 03756-0001  Congressional District: 
Comments: Address updated 9/2008 
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 08/01/2013  End Date:  05/31/2017 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: End date changed to 5/31/2017 per NSBRI (Ed., 3/1/16)

NOTE: Title change to "Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes" (original proposal title was "Ocular Venous Contributions to Spaceflight Visual Impairment")--Ed., 2/6/14

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Weaver, John   ( Dartmouth College )
Knaus, Darin   ( Creare, Inc. )
Deserranno, Dimitri   ( Creare, Inc. )
Belden, Clifford   ( Dartmouth College )
Kattamis, Nicholas   ( Creare, Inc. )
Phillips, Scott   ( Creare, Inc. )
Davis, Brynmor   ( Creare, Inc. )
Zegans, Michael   ( Dartmouth College ) 
Grant/Contract No.: NCC 9-58-CA03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: We are developing a numerical model of the cerebral venous circulation and how it responds to both fluid shifts and changes in gravitational forces. We are validating this model using magnetic resonance imaging (MRI) to measure the responses of the cranial vascular and cerebrospinal fluid systems to fluid shifts in both the supine and prone positions. A companion set of ocular measures are also being taken using these same interventions outside of the MRI magnet. The likely anatomic differences that could alter the responses to a fluid shift will be identified. This model and supporting data will provide a means to develop hypotheses about how microgravity produces visual changes over time and may allow predictions about which subjects may be at risk for the visual deficits associated with microgravity.

Aim #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. During this reporting period, we advanced and expanded the numerical model. Specifically, we introduced collapsible vessels, which allows behavior such as body-orientation-dependent flow shunting in the jugular veins (i.e., jugular vein collapse in the upright position) to be modeled. We also used transmural pressure across the boundaries of model components (e.g., vessels and fluid cavities) to capture the effects of tissue weights and the resulting gravity dependent impact on the circulatory and cerebrospinal fluid (CSF) systems. Finally, we targeted integration of the circulatory and CSF sub-models, providing mass and pressure communications between the two sub-models.

Aim #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. During this reporting period, we developed the protocol to collect the data for this experiment. We conducted an experiment with 10 subjects and determined that ocular measures plateau after an average of 12 minutes upon entering the posture. This will be used to ensure consistent data for all subjects. We designed and built a MRI-compatible chamber to provide lower body positive and negative pressures, aimed at creating cephalad fluid shift similar to that experienced in space flight. The apparatus will be used in the MRI studies. We plan to finalize the apparatus and employ it in the test campaign during the next reporting period. The imaging protocol needed to collect our parameters for the model was established through an iterative process to establish the optimum trade-off between scan accuracy, data needed for the model, and subject acceptability. The analysis techniques for the MRI data were also established. We developed tools to aid hypothesis development of the etiology behind visual changes in long duration space flight. We developed graphical descriptions of the potential mechanisms for the microgravity-induced ocular and visual changes. We have acquired several devices to measure key parameters needed in the studies, such as an anterior segment module, episcleral venous pressure device, and a BIOPAC continuous, noninvasive blood pressure system. The data collected from these devices will be use to provide additional information for the model.

Aim #3: Identify individuals with common intracranial venous variants, and study them using the protocol outlined in Aim #2. Aim 3 is an objective for our third year. The data collection methods have been established in this reporting period through our Aim 2 objectives. In our initial cohort of pilot subjects, we have identified subjects with anatomical variants--a primary interest of this experiment. Over the next reporting year, we will collect data from our experiments for Aims #2 and #3. These data will feed directly into the model. We provide tools to develop hypotheses about the etiology of microgravity induced visual changes. Our models will help predict which subjects may be at risk for the visual deficits associated with microgravity, and could help develop potential countermeasures in the future.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: The model and experimental results will give a better understanding of cranial venous insufficiency. Cranial venous insufficiency results when venous outflow from the head is reduced or obstructed. This can be due to an increase in venous resistance from anatomical variations. The increased resistance to flow can produce headaches or vision changes. Venous insufficiency has been proposed as a possible etiology for symptoms in acute mountain sickness, obstructive sleep apnea, jugular outflow obstruction syndrome, multiple sclerosis, and idiopathic intracranial hypertension (IIH). Bilateral transverse sinus stenosis is found in 90% of IIH sufferers, and internal jugular vein stenosis occurs in 80% of IIH patients. Although numerical models of the circulatory system, cerebral venous system, and cerebral spinal fluid system exist (as do fluid models of the aqueous humor regulatory system and structural finite element models of the eye) the model developed on this project is the first comprehensive model that links the effects of all systems together. It could be used in the future to predict how surgical interventions, such as sagittal stenting, can improve an individual's symptoms.

 

Task Progress: Aim #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. During this reporting period, we advanced and expanded the numerical model. We introduced collapsible vessels, which allow behavior such as body-orientation-dependent flow shunting in the jugular veins (i.e., jugular vein collapse in the upright position) to be modeled. We also used transmural pressure across the boundaries of model components (e.g., vessels and fluid cavities) to capture the effects of tissue weights and the resulting gravity dependent impact on the circulatory and CSF systems. Finally, we targeted integration of the circulatory and CSF sub-models, providing mass and pressure communications between the two sub-models.

Aim #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. The main efforts this reporting period were to design and test the MRI-compatible LBNP/LBPP (lower body negative pressure/lower body positive pressure) chamber, test the MRI imaging protocols, and develop the MRI data analysis tools needed for the studies. We also conducted a posture experiment with 10 subjects and determined that ocular measures plateau after an average of 12 minutes upon entering a new posture (e.g., seating, supine, prone). This will be used to ensure consistent data for all subjects in the MRI studies. The MRI-compatible LBNP/LBPP chamber will be employed it in the test campaign during the next reporting period. The optimal parameters for collecting and analyzing MRI data were established, which involved examine the trade off between scan accuracy, data needed for the model, and subject acceptability. We developed tools to aid hypothesis development of the etiology behind visual changes in long duration space flight. We developed graphical descriptions of the potential mechanisms for the microgravity-induced ocular and visual changes. We have acquired several devices to measure key parameters, such as an anterior segment module, episcleral venous pressure device, and a BIOPAC continuous, noninvasive blood pressure system. The data collected from these devices will be use to provide additional information for the model.

Aim #3: Identify individuals with common intracranial venous variants, and study them using the protocol outlined in Aim #2. Aim 3 is an objective for our third year. The data collection methods have been established in this reporting period through our Aim 2 objectives. In our initial cohort of pilot subjects, we have identified subjects with anatomical variants, the primary interest of this aim.

 

Bibliography Type: Description: (Last Updated: 04/16/2019) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Anderson A, Fellows A, Buckey J. "Feasibility of dpoae mapping as an in-flight measure of intracranial pressure in space." 2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015.

2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015. , Jan-2015

Abstracts for Journals and Proceedings Anderson A, Fellows A, Babu G, Swan J, Phillips S, Kattamis N, Knaus D, Zegans M, Buckey J. "Ocular and cerebrovascular changes in microgravity." 86th Scientific Meeting of the Aerospace Medical Association, Lake Buena Vista, Florida, May 10-14, 2015.

86th Scientific Meeting of the Aerospace Medical Association, Lake Buena Vista, Florida, May 10-14, 2015. , May-2015

Abstracts for Journals and Proceedings Swan JG, Phillips SD, Kattamis N, Knaus DA, Zegans ME, Fellows AM, Buckey JC. "Effect of posture and microgravity on the eye and cranial vascular system." 2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015.

2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015. , Jan-2015

Abstracts for Journals and Proceedings Phillips SD, Chepko A, Kattamis NT, Knaus DA, Swan JG, Zegans M, Buckey JC. "Modeling gravity dependence in the cranial venous circulatory system." 2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015.

2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015. , Jan-2015

Abstracts for Journals and Proceedings Phillips S, Kattamis N, Chepko AB, Knaus DA, Swan JG, Zegans ME, Buckey JC. "Modeling the ocular and cerebrovascular changes in microgravity." 86th Scientific Meeting of the Aerospace Medical Association, Lake Buena Vista, Florida, May 10-14, 2015.

86th Scientific Meeting of the Aerospace Medical Association, Lake Buena Vista, Florida, May 10-14, 2015. , May-2015

Awards Anderson A. "NSBRI First Award Fellowship, October 2015." Oct-2015
Download in PDF pdf     
Fiscal Year: FY 2014  Task Last Updated:  09/08/2014 
PI Name: Buckey, Jay C. M.D. 
Project Title: Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Cardiovascular Alterations Team 
 
Joint Agency Name:   TechPort:  No 
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) SANS12:We do not know whether ground-based analogs and/or models can simulate Space Associated Neuro-ocular Syndrome (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: jay.buckey@dartmouth.edu  Fax:  603-650-6013 
PI Organization Type: UNIVERSITY  Phone: 603-650-6012  
Organization Name: Dartmouth College 
PI Address 1: Department of Medicine 
PI Address 2: 1 Medical Center Drive 
PI Web Page:  
City: Lebanon  State: NH 
Zip Code: 03756-0001  Congressional District: 
Comments: Address updated 9/2008 
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 08/01/2013  End Date:  07/31/2016 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: Title change to Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes (original proposal title was "Ocular Venous Contributions to Spaceflight Visual Impairment")--Ed., 2/6/14

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Weaver, John   ( Dartmouth College )
Knaus, Darin   ( Creare, Inc. )
Deserranno, Dimitri   ( Creare, Inc. )
Belden, Clifford   ( Dartmouth College )
Kattamis, Nicholas   ( Creare, Inc. )
Phillips, Scott   ( Creare, Inc. )
Davis, Brynmor   ( Creare, Inc. )
Zegans, Michael   ( Dartmouth College ) 
Grant/Contract No.: NCC 9-58-CA03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: This report covers the 10-month period from project initiation in October 2013 to the end of June 2014. --Original project aims/objectives: Aim #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. Aim #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. Aim #3: Identify individuals with common intracranial venous variants, and study them using the protocol outlined in Aim #2.

--Key findings/developments: Work in the past year has focused on constructing the model (Aim #1), and developing the protocols, hardware and experimental designs needed for Aim #2. For Aim #1, the key developments since October have been to (a) evaluate and select the best software for the modeling needed in the project, and (b) use the software to design a numerical model for the circulatory system that includes gravitational forces and the effects of gravity on tissue weight/tissue compliance. We are using the Simscape modeling environment. The primary strengths of this environment are the ability to leverage (a) MATLAB's robust set of solvers for systems of differential equations, (b) Simscape's automatic construction of the overall set of differential equations based on the variable relationships defined in each component block, and (c) the existing fluid component models available in the Simscape and SimHydraulics libraries. A lumped parameter circulatory system has been developed. The system includes a gravity dependent pressure drop element to capture the effects of changing orientation within a gravitational field on flow systems with multiple flow loops and branch points (such as the circulatory system). The model also includes flexible tubes that change size according to external pressure differences (i.e. modeling the effects of collapsing veins such as the internal jugular veins). Work on the overall modeling design for the circulatory system is also applicable to the CSF circulation model. Data from the studies in Aim #2 and existing data from NASA will be used to test the model.

For Aim #2, several elements are under development to permit the MRI imaging studies planned for year 2. An MRI compatible LBNP device has been constructed, and is beginning initial trials within the MRI magnet. This device will be important for producing fluid shifts for the MRI imaging studies. MRI imaging protocols are being tested to optimize the tradeoff between measurement accuracy and test time. The current protocol will assess vascular anatomy, as well as venous, arterial, and CSF flows in and out of the head. Sequences are also included to provide information on eye flow, and sequences to measure regional brain tissue compliance will be assessed. The MRI studies will be complemented by ocular measurements made in different body positions, with and without fluid shifts, outside of the magnet. These posture studies have been advanced significantly by the acquisition of a Heidelberg Spectralis Optical Coherence Tomography device in the past year. This new device will greatly enhance the data collection for the postural studies beyond what had been proposed initially. A similar device is being used on the ISS to evaluate astronauts. An additional advance has been progress in obtaining existing data from NASA that can be used to help build the model. To date, we have received data from a bed rest study, and just recently received approval to receive deidentified OCT, MRI, and other astronaut data.

---Impact of key findings on hypotheses, technology requirements, objectives, and specific aims of the original proposal. The model development is a core objective of the project. The development of a model including gravitational and tissue compressive forces is novel, and will be essential for predicting microgravity effects. Work over the past 10 months has developed the major scaffolding for the circulatory system model. The primary subsystems are represented and the model includes both body orientation and gravitational effects. Further refinement of model parameters is needed to fine-tune the system to represent the circulatory flow system more accurately. From there, detail and complexity will be added to the model as needed to capture the effects of blood flow and pressures on the eye fluid system. To complete this work we developed custom units within Simscape to incorporate gravity dependence and custom compliance inputs. These custom units allow us to construct flow loops with branch points sensitive to body orientation. We plan to extend this work during the next reporting period by completing development of the shared pressure boundary unit and fluid exchange units to create model coupling between the CSF and circulatory system, the CSF and eye, and the circulatory system and aqueous humor regulatory system. The LBNP device and MRI protocols will be essential for completing the objectives planned for year 2 of the project.

--Proposed research plan for the coming year. In the remainder of the existing year and in the coming year, we will increase the complexity of the model and extend it to the CSF circulation. In the next year we will begin the MRI studies that include both changes in gravitational orientation (supine/prone) and fluid shifts (LBNP/LBPP).

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: While the numerical model we are developing in Aim #1 targets visual changes associated with microgravity, the model is also a tool for studying other instances where changes in intraocular, intracranial, or venous pressures affect vision. For example, the microgravity changes are similar in some aspects to changes seen on Earth in conditions such as idiopathic intracranial hypertension (IIH), psuedotumor, or prolonged prone positioning (i.e. during surgery). Our model has the potential to improve the understanding of how these conditions affect vision. The model is also applicable for studying intraocular pressure changes in glaucoma, and could be a useful tool for understanding this common disease. In Aims #2 and #3, we are developing novel MRI sequences for measuring cranial venous flow that may be useful for diagnosing cranial venous insufficiency. Cranial venous insufficiency has been proposed as a possible etiology (or associated factor) for symptoms seen in acute mountain sickness, obstructive sleep apnea, jugular outflow obstruction syndrome, multiple sclerosis, and IIH. The model and the MRI imaging sequences may be useful in studying these conditions.

 

Task Progress: 1. Evaluated software for performing the modeling needed in the project. Selected the Simscape modeling environment. 2. Developed a lumped parameter cardiovascular system model with custom modules for gravitational effects and tissue compliance. 3. Designed and built MRI-compatible LBNP/LBPP device 4. Tested MRI imaging protocols for angiography, CSF flow/volume, venous/arterial flow, and pressure. 5. Acquired a Heidelberg Spectralis Ocular Coherence Tomography device to enhance the data collection during the postural studies (a similar device is currently on the ISS). 6. Received NASA IRB approval to obtain astronaut data from long-duration missions.

 

Bibliography Type: Description: (Last Updated: 04/16/2019) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Phillips SD, Katamis NT, Knaus DA, Swan JG, Zegans ME, Buckey JC. "Biophysical Parameters Important for Structural Eye Modeling." 85th Annual Scientific Meeting, Aerospace Medical Association, San Diego, CA, May 10-15, 2014.

Aviation, Space, and Environmental Medicine. 2014 Mar;85(3):237. See http://www.ingentaconnect.com/content/asma/asem/2014/00000085/00000003 , Mar-2014

Abstracts for Journals and Proceedings Phillips SD, Kattamis NT, Knaus DA, Swan JG, Zegans ME, Buckey JC. "Predicting Microgravity Induced Vision Changes Using a Cranial Venous Circulatory Model." 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/3219.pdf , Feb-2014

Abstracts for Journals and Proceedings Swan JG, Phillips SD, Kattamis NT, Knaus DA, Jastrzembski B, Zegans ME, Fellows AM, Buckey JC. "Hydrostatic Pressure Changes May Provide Insight into Microgravity-Associated Vision Changes" 85th Annual Scientific Meeting, Aerospace Medical Association, San Diego, CA, May 10-15, 2014.

Aviation, Space, and Environmental Medicine. 2014 Mar;85(3):237-8. See http://www.ingentaconnect.com/content/asma/asem/2014/00000085/00000003 , Mar-2014

Abstracts for Journals and Proceedings Swan JG, Zegans ME, Jastrzembski BG, Fellows AM, Kattamis NE, Knaus DA, Phillips SD, Buckey JC. "Postural Effects on the Eye and Ear." 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/3270.pdf , Feb-2014

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Fiscal Year: FY 2013  Task Last Updated:  02/04/2014 
PI Name: Buckey, Jay C. M.D. 
Project Title: Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Cardiovascular Alterations Team 
 
Joint Agency Name:   TechPort:  No 
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) SANS12:We do not know whether ground-based analogs and/or models can simulate Space Associated Neuro-ocular Syndrome (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: jay.buckey@dartmouth.edu  Fax:  603-650-6013 
PI Organization Type: UNIVERSITY  Phone: 603-650-6012  
Organization Name: Dartmouth College 
PI Address 1: Department of Medicine 
PI Address 2: 1 Medical Center Drive 
PI Web Page:  
City: Lebanon  State: NH 
Zip Code: 03756-0001  Congressional District: 
Comments: Address updated 9/2008 
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 08/01/2013  End Date:  07/31/2016 
No. of Post Docs:   No. of PhD Degrees:   
No. of PhD Candidates:   No. of Master' Degrees:   
No. of Master's Candidates:   No. of Bachelor's Degrees:   
No. of Bachelor's Candidates:   Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: Title change to Role of the Cranial Venous Circulation in Microgravity-Associated Visual Changes (original proposal title was "Ocular Venous Contributions to Spaceflight Visual Impairment")--Ed., 2/6/14

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Davis, Brynmor   ( Creare Incorporated )
Deserranno, Dimitri   ( Creare Incorporated )
Kattamis, Nicholas   ( Creare Incorporated )
Knaus, Darrin   ( Creare Incorporated )
Zegans, Michael   ( Dartmouth College )
Phillips, Scott   ( Creare Incorporated ) 
Grant/Contract No.: NCC 9-58-CA03401 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: As has been seen with other systems and measurements in space (central venous pressure, pulmonary capillary blood volume), it’s likely that microgravity has unique effects on the eye that can’t be replicated easily on Earth. Microgravity may change how retinal venous pressure, choroidal venous pressure, intraocular pressure (IOP) and intracranial pressure (ICP) respond to a fluid shift compared to the responses when moving to the supine or head-down position on Earth. The visual changes in space may be the interplay between the different factors affecting the eye, rather than the alteration in one particular pressure (e.g., ICP, IOP, retroorbital pressure etc.) or volume (e.g. choroidal volume). For this proposal we will measure intraocular pressure (IOP), retinal vein diameter, axial length, and choroidal volume in different postures on Earth (seated, supine, and 6 degree head down tilt) and with acute microgravity exposure during parabolic flight. These data will establish comparison data for longer-term microgravity exposure, and will also be used as inputs to refine a mathematical model of the eye. The mathematical model will include the ability to alter hydrostatic and tissue pressure values so that microgravity effects can be simulated. We hypothesize that when hydrostatic and tissue pressures are altered in the model, this will produce acute changes in choroidal volume, retinal diameter, venous pressure, and other measurements unlike those that can be measured on Earth. Also, if the microgravity-induced headward fluid shift is the major factor producing visual changes in space, reversing this fluid shift with lower body negative pressure (LBNP) could provide an inflight countermeasure. We will evaluate the effects of LBNP exposure on the eye by making measurements of IOP, axial length, retinal vein diameter, and choroidal volume in supine subjects before, during, and after LBNP exposure. The effects of LBNP on parameters that cannot be easily measured (episcleral vein pressure, vortex vein pressure, and ICP) will be estimated using mathematical modeling. The effects of LBNP in microgravity will also be estimated using mathematical modeling. We hypothesize that LBNP can provide acute changes in ocular and venous pressures. This will provide a basis to study the effect of LBNP on the longer-term changes in ocular structure associated with spaceflight. Lastly, since not all individuals develop significant visual changes in response to microgravity exposure, it’s likely that some people are predisposed to develop visual changes in response to spaceflight. Microgravity may affect the physical characteristics of optic tissues, such as the viscoelastic properties of the sclera, and some individuals may be more likely to experience these changes than others. For example, Mader et al. postulated that inter-individual differences in the characteristics of the choroid could explain why some individuals are more susceptible to microgravity-induced vision changes. The model and data from this study will provide the ability to test hypotheses about which tissue and vascular parameters would have the greatest impact on vision. These data could then be used to guide spaceflight experiments.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: 0

 

Task Progress: New project for FY2013.

 

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