Simulations of spinal cord recruitment to optimize bioelectronic interventions for lower urinary tract control

Investigators
Dr. Robert Gaunt, Dr. Marco Capogrosso, Dr. Elvira Pirondini, Dr. Lee Fisher
Contact info (email)
rag53@pitt.edu
1. Define context(s)
identify/explore new therapies
reveal new biological insights
Current Conformance Level / Target Conformance Level
Partial
Primary goal of the model/tool/database

The primary goal of this model is to simulate the recruitment of different axon populations in a feline sacral spinal cord, dorsal rootlets and caudal equina in response to epidural electrical stimulation for the purpose of studying effects on the lower urinary tract. An accurate anatomical model will be created from high-resolution magnetic resonance images. Finally, axon recruitment will be coupled to spiking network models of sacral spinal reflexes.

Biological domain of the model
Spinal cord electrical stimulation, bladder function
Structure(s) of interest in the model
Feline sacral spinal cord and cauda equina
Spatial scales included in the model
25 microns to 10 cm
Time scales included in the model
0.1 ms to 30 s
Additional comments about the model’s context (optional)

This model does not currently exist. As a result some of the conformance assessments reflect expectations based on the tools, systems, methods and data that will be used to construct this model. Some conformance levels are described as "Insufficient" because it is currently unknown what the likely level of conformance will be with the rule.

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) No No Multiple scans from multiple animals Adequate
in vivo pre-clinical (lower-level organism or small animal)
in vivo pre-clinical (large animal) No No Repeated stimulation events in multiple animals 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) No No Repeated stimulation events in multiple animals 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 Developers During software design Adequate
Validation Developers After initial model has been completed, during refinement, and during new scenarios Model performance is checked agains experimentally recorded electrophysiological data using the same stimulation parameters in the model as were used in the experiment. Experimental nerve recruitment is qualitatively and qualitatively compared to the population of axons activated in the model. Adequate
Uncertainty quantification Developers and users During simulations Adequate
Sensitivity analysis Developers and users During simulations 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
Spinal cord anatomical images are taken from different specimens than the electophysiological data used to validate the model. Model users This will be stated in model documentation. Adequate
Axon population distributions in the dorsal rootlets are estimated from literature, and are not based on measurements in the specimens Model users This will be stated in model documentation. Adequate
5. Version control
Current Conformance Level / Target Conformance Level
Extensive
Naming Conventions? Repository? Code Review?
individual modeler Yes Git No
within the lab Yes Git No
collaborators ? Git/o2S2PARC No
6. Documentation
Current Conformance Level / Target Conformance Level
Code commented? Adequate: All code will be documented according to good practices.
Scope and intended use described? Adequate:grant and other documents describe intended purpose. Future publications will improve.
User’s guide? Adequate: available in o2S2PARC
Developer’s guide? Extensive: part of o2S2PARC
7. Dissemination
Current Conformance Level / Target Conformance Level
Expected to be Extensive. Results will be published, and all models will be made available on o2S2PARC.
Target Audience(s): “Inner circle” Scientific community Public
Simulations will be available
Models will be available
Software will be available
Results will be available
Implications of results will be available
8. Independent reviews
Current Conformance Level / Target Conformance Level
Insufficient: no review has been done.
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
Insufficient: no alternatives are known.
Yes or No (briefly summarize)
Were competing implementations tested? No: none known
Did this lead to model refinement or improvement?
10. Conform to standards
Current Conformance Level / Target Conformance Level
Insufficient
Yes or No (briefly summarize)
Are there operating procedures, guidelines, or standards for this type of multiscale modeling? No. No standards are known.
How do your modeling efforts conform?
11. (optional) Additional information to support items 1-10

This model has yet to be developed. Therefore, portions of this assessment reflect either assumptions about future implementations or expectations on the how much will be able to be accomplished as the model is developed.

This assessment will be updated as more information becomes available.