Investigators
Dr. Raj Prabhu, Dr. Greg Burgreen, Dr. Youssef Hammi, Dr. Like Li
Contact info (email)
rprabhu@abe.msstate.edu
1. Define context(s)
reveal new biological insights
other
Current Conformance Level / Target Conformance Level
Adequate
Primary goal of the model/tool/database
Due to the paucity in the scientific knowledge of the biomechanics of ventilation-related lung injury (VLRI), we propose to develop a coupled multi-physics multiscale computational fluid dynamics (CFD)- phase-field method (PFM)- finite element analysis (FEA) model that would quantify the lungs' airflow dynamics, including alveolar O2, and CO2 gas exchange, and alveoli inflammatory response, during mechanical ventilation (MV)-based breathing cycles in severe Covid-19 distressed lungs. The model can be made patient-specific across all genders and age groups with the availability of appropriate lungs scans to generate 3-dimensional (3D) meshes for CFD, PFM, and FEA in silico calculations.
Biological domain of the model
Lungs' injury
Structure(s) of interest in the model
Respiratory system, lungs, bronchioli, alveoli
Spatial scales included in the model
10^-3 to 10^1 meters
Time scales included in the model
10^-4 to 10^2 seconds
Other uses for the model (optional)
The model can also be extended for use in the design and optimization of a patient or demographic-specific MV device.
2. Data for building and validating the model
| Data for building the model | Published? | Private? | How is credibility checked? | Current Conformance Level / Target Conformance Level |
|---|---|---|---|---|
| in vitro (primary cells cell, lines, etc.) | ||||
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | ||||
| in vivo pre-clinical (large animal) | ||||
| Human subjects/clinical | Yes | Patient-specific data is private. Non-patient specific data is available through digital libraries and previously published literature | Individual have been scanned extensively for the development of a detailed model | Extensive |
| Other: ________________________ |
| Data for validating the model | Published? | Private? | How is credibility checked? | Current Conformance Level / Target Conformance Level |
|---|---|---|---|---|
| in vitro (primary cells cell, lines, etc.) | ||||
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | ||||
| in vivo pre-clinical (large animal) | ||||
| Human subjects/clinical | Yes | No, previously published data is available | Patients are continuously monitored for PEEP and O2 and CO2 pulse oximetry data for several breathing cycles | adequate |
| Other: ________________________ |
3. Validate within context(s)
| Who does it? | When does it happen? | How is it done? | Current Conformance Level / Target Conformance Level | |
|---|---|---|---|---|
| Verification | Model developers will perform individual verification for each multi-physics method | Each model developer will perform verification prior to release of the model for further coupling with other modeling techniques | Verification is assessed through a mesh and time-step convergence study, and review of model output's correlation to available for human subjects/clinical data | Extensive |
| Validation | Model developers and users will perform the validation for the final coupled CFD-PFM-FEA simulations | Model validation will occur at two stages- 1. At the completion of each multi-physics model and simulation, and 2. At the completion of the coupled CFD-PFM-FEA model and simulation | The models will be validated to previously published data on PEEP, and O2 and CO2 pulse oximetry and expiratory data | Adequate |
| Uncertainty quantification | We can perform uncertainty qualification based on grid and time-step convergence following grid convergence Index (GCI) method derived from Richardson extrapolation. | It can be performed along with the verification study. | The numerical certainties are estimated by monitoring the convergence of results with grid and time step refinement. Ref. ASME 2008, Procedure for Estimation and Reporting of Uncertainty Due to Discretization in CFD Applications, J. Fluids Eng. Jul 2008, 130(7): 078001 (4 pages). | Adequate |
| Sensitivity analysis | ||||
| Other:__________ | ||||
| Additional Comments |
4. Limitations
| Disclaimer statement (explain key limitations) | Who needs to know about this disclaimer? | How is this disclaimer shared with that audience? | Current Conformance Level / Target Conformance Level |
|---|---|---|---|
| For the CFD calculations, specific alveolar pressure and airflow dynamics data is lacking, and hence, the model is applicable for airflow and pressure dynamics at the expiratory end | Modelers, clinicians, and MV device designers | A list of limitations will be provided with each report and publication for CFD simulations | Extensive |
| For the PFM-based O2 and CO2 gas exchange, we assumed that PO2 and PCO2 data at the expiratory end and through pulse oximetry represents the alveolar gas exchange | Modelers, clinicians, and MV device designers | A list of limitations will be provided with each report and publication for PFM simulations | Extensive |
| For the CFD-PFM-FEA calculations, it is assumed that expiratory and pulse oximetry data represents alveolar VLRI pathophysiological progression | Modelers, clinicians, and MV device designers | A list of limitations will be provided with each report and publication for CFD-PFM-FEA simulations | Extensive |
| For the PFM-based simulations of alveolar inflammation, it is assumed that the inflammatory thickness changes that leads to changes in the boundaries CFD and coupled CFD-PFM-FEA simulations can be validated using expiratory airflow dynamics data | Modelers, clinicians, and MV device designers | A list of limitations will be provided with each report and publication for CFD-PFM-FEA simulations | Partial |
5. Version control
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Naming Conventions? | Repository? | Code Review? | |
|---|---|---|---|
| individual modeler | Yes | Subversion (off site) | Yes |
| within the lab | N/A | ||
| collaborators | Yes | Subversion (off site) | Yes |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | To be filled |
| Scope and intended use described? | Extensive |
| User’s guide? | To be filled |
| Developer’s guide? | To be filled |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | MSU cyberinfrastructure | MSU cyberinfrastructure | MSU cyberinfrastructure |
| Models | MSU cyberinfrastructure | MSU cyberinfrastructure | MSU cyberinfrastructure |
| Software | |||
| Results | MSU cyberinfrastructure | publication | publication |
| Implications of results | MSU cyberinfrastructure | publication | publication |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| To be filled |
| Reviewer(s) name & affiliation: | To be filled |
|---|---|
| When was review performed? | To be filled |
| How was review performed and outcomes of the review? | To be filled |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| To be filled |
| Yes or No (briefly summarize) | |
|---|---|
| Were competing implementations tested? | To be filled |
| Did this lead to model refinement or improvement? | To be filled |
10. Conform to standards
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Yes or No (briefly summarize) | |
|---|---|
| Are there operating procedures, guidelines, or standards for this type of multiscale modeling? | No |
| How do your modeling efforts conform? | To be filled |
The model context is primarily targetted for severe Covid-19 patients who are undergoing acute respiratory distress syndrome (ARDS), and hence, the physiological aspects of the model would be catered to this patient demographic.