Investigators
Dr. Julius Guccione, Dr. Ghassan Kassab, Dr. Daniel Ennis, Dr. Lik Chuan Lee, Dr. Jeffrey Ardell, Dr. Colleen Clancy
Contact info (email)
julius.guccione@ucsf.edu
1. Define context(s)
aid in FDA decision making
aid in clinical decision making
aid in clinical trial design
identify/explore new therapies
reveal new biological insights
Current Conformance Level / Target Conformance Level
Extensive
Primary goal of the model/tool/database
The primary goals of this project are to optimize vagus nerve stimulation (VNS) in swine with ischemic heart failure with reduced ejection fraction (HFrEF) and to translate these findings to the clinic within the next 1-4 years.
Biological domain of the model
ischemic heart failure with reduced ejection fraction
Structure(s) of interest in the model
right and left ventricles, right and left cervical vagus nerves
Spatial scales included in the model
0.01 to 10 cm
Time scales included in the model
10^-1 to 10^7 seconds
Other uses for the model (optional)
We expect users of o2S2PARC to find the regional biventricular wall stress distributions in normal swine-specific finite element models useful as targets for computational studies of ventricular stress normalization. We have similar expectations for the utility of the corresponding model simulations of coronary blood flow and electrical activation.
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) | Yes (doi: 10.1016/j.actbio.2020.04.033) | No (swine data) | Overnight high-resolution (0.3 x 0.3 x 0.8 mm) ex-vivo diffusion tensor MRI | Adequate |
| in vivo pre-clinical (lower-level organism or small animal) | ||||
| in vivo pre-clinical (large animal) | Yes (doi: 10.1016/j.actbio.2020.04.033) | No (swine data) | Multiple cardiac cycle transesophageal 3D echocardiography and speckle-tracking | Adequate |
| Human subjects/clinical | ||||
| 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) | Yes (doi: 10.1016/j.actbio.2020.04.033) | No (swine data) | Multiple cardiac cycle transesophageal 3D echocardiography and speckle-tracking | Adequate |
| Human subjects/clinical | ||||
| Other: ________________________ |
3. Validate within context(s)
| Who does it? | When does it happen? | How is it done? | Current Conformance Level / Target Conformance Level | |
|---|---|---|---|---|
| Verification | Dassault Systemes | After converting existing swine models from commercial grade (Abaqus) software to free and open-source (FEniCS) software | Abaqus software used to verify accuracy of FEniCS-based finite element models run on o2S2PARC | Extensive |
| Validation | Developers and users have done independent validations | Throughout development and prior to peer review of manuscripts | Model is used to reproduce experimental scenarios, primarily myocardial deformation at specific locations, then population predictions are quantitatively and qualitatively compared to observed heart failure device efficacy in analog populations | Extensive |
| Uncertainty quantification | The model is designed to propagate uncertainty, so this requirement is met by virtue of the model | Every time the model is run for a new scenario | Using polynomial chaos expansion with our existing geometric data calibrating the probability distribution | Extensive |
| Sensitivity analysis | User performs sensitivity analysis on influential parameters | At each new scenario | A post-processing tool that implements Partial Rank Correlation Coefficient algorithm to address sensitivity of model parameters | Adequate |
| 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 |
|---|---|---|---|
| Normal swine VNS models are validated using chronic VNS data from normal dogs | Users of o2S2PARC | A list of limitations is provided with each report from each model run and stated in the accompanying documentation. | Extensive |
| Infarcted swine VNS models have not been validated using any chronic VNS data | Users of o2S2PARC | A list of limitations is provided with each report from each model run and stated in the accompanying documentation. | Extensive |
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 | NA | ||
| collaborators | NA | Yes |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | Extensive: Code will be extensively commented, which together with the documentation, will enable interested users to follow the algorithm |
| Scope and intended use described? | Extensive: Yes - in both internal documentation and supporting material in publications |
| User’s guide? | Adequate |
| Developer’s guide? | Partial: No, there is a concept document and a software design document |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | doi: 10.1016/j.actbio.2020.04.033 | ||
| Models | doi: 10.1016/j.actbio.2020.04.033 | ||
| Software | |||
| Results | doi: 10.1016/j.actbio.2020.04.033 | ||
| Implications of results | doi: 10.1016/j.actbio.2020.04.033 |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| to be filled |
| Reviewer(s) name & affiliation: | |
|---|---|
| When was review performed? | |
| How was review performed and outcomes of the review? |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Yes or No (briefly summarize) | |
|---|---|
| Were competing implementations tested? | Yes - predictive capability tested against FEM analysis and analog populations, included recreation of code by independent researchers. |
| Did this lead to model refinement or improvement? | Yes - improvements on data passing and model performance. No changes to the underlying concepts or overall results. |
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? | Yes - every component of the FEniCS Project is distributed under a license approved by the Open Source Initiative (https://opensource.org/). |
| How do your modeling efforts conform? | We meet all documentation, programming and credibility standards as confirmed by independent assessment by users and management customers. |
Moreover, we have shown that these swine-specific biventricular finite element models can be translated to humans using patient-specific in-vivo MRI data to realistically simulate the efficacy of devices for treating heart failure.