Quantifying Inferior Vena Cava Compliance and Distensibility in an In Vivo Ovine Model Using 3D Angiography
April 26th, 2024
This protocol allows for the in vivo quantification of venous compliance and distensibility using catheterization and 3D angiography as a survival procedure allowing for a variety of potential applications.
We aim to improve long-term outcomes for congenital-heart-disease patients using a regenerative medicine approach. Our tissue-engineered vascular graft develops into a neo vessel comprised of the patient's own cells. Our goal is to make comparisons between our graft, the native vein, and the clinical standard polytetrafluoroethylene or PTFE.
We have established that our neo vessel displays growth capacity and that it approaches native vessel functionality. Using this method, we've also recently demonstrated that the neo vessel retains compliance and distensibility at a long-term time point, and is resistant to the formation of dystrophic calcification. Using 3D angiography allows us to image the entire path of the thoracic inferior vena cava in our ovine large-animal model.
In addition to allowing us to view the morphology of the vessel, it also allows for post-capture orientation adjustments to ensure we're obtaining measurements from a true cross-section. Our in-vivo method allows us to determine the capacity for vessel compliance and distensibility in its native context. Additionally, it allows us to take longitudinal measurements of the same study animal, which is necessary to track changes in neo-vessel development and remodeling.
Overview
This protocol allows for the in vivo quantification of venous compliance and distensibility using catheterization and 3D angiography. This survival procedure has a variety of potential applications in improving outcomes for congenital-heart-disease patients.
Key Study Components
Area of Science
- Regenerative medicine
- Cardiovascular research
- 3D imaging techniques
Background
- Congenital heart disease presents significant challenges in patient management.
- Tissue-engineered vascular grafts can potentially improve patient outcomes.
- Understanding venous compliance and distensibility is crucial for graft functionality.
- 3D angiography provides detailed imaging of vascular structures.
Purpose of Study
- To develop a tissue-engineered vascular graft that mimics native vessel functionality.
- To compare the performance of the graft with native veins and standard materials.
- To assess long-term compliance and distensibility of the neo vessel.
Methods Used
- Catheterization for in vivo measurements.
- 3D angiography for imaging the thoracic inferior vena cava.
- Comparative analysis of graft and native vessel properties.
- Long-term follow-up to evaluate graft performance.
Main Results
- The neo vessel shows growth capacity similar to native vessels.
- Compliance and distensibility are retained over time.
- The graft is resistant to dystrophic calcification.
- 3D imaging effectively captures the vascular anatomy.
Conclusions
- Tissue-engineered grafts can approach the functionality of native vessels.
- Long-term compliance and distensibility are critical for graft success.
- 3D angiography is a valuable tool for vascular research.
Frequently Asked Questions
Executive Industry Relevance
Quantitative in vivo assessment of venous compliance and distensibility addresses a critical gap in vascular graft development, enabling direct comparison of engineered constructs to native vessels under physiological conditions. This capability enhances predictive confidence in graft performance, supporting risk-adjusted decisions at the interface of regenerative medicine and cardiovascular device pipelines. Longitudinal measurement in large-animal models positions this method as a strategic asset for translational continuity and portfolio triage.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables direct interrogation of graft biomechanical properties in a disease-relevant system.
- Supports mechanistic de-risking by quantifying compliance and distensibility in vivo.
- Facilitates functional target validation for next-generation vascular constructs.
Screening & Assay Development
- Provides standardized, quantitative outputs for compliance and distensibility across graft types.
- Enables reproducible, longitudinal assessment within the same animal, reducing biological variability.
- Supports assay readiness for comparative evaluation of novel biomaterials and tissue-engineered vessels.
Translational & Preclinical Research
- Aligns preclinical model outputs with clinical endpoints relevant to graft integration and function.
- Enables tracking of neo-vessel remodeling and growth over time in a large-animal context.
- Supports risk-adjusted advancement of candidates with superior physiological performance.
Pipeline & Workflow Integration
This method integrates into the discovery-to-preclinical continuum for vascular grafts, bridging early mechanistic studies and translational validation in large-animal models.
- Discovery Biology: Quantifies biomechanical properties critical for hypothesis testing and pathway clarification in graft development.
- Screening: Delivers reproducible, quantitative compliance and distensibility metrics for candidate prioritization.
- Analytics: Provides cross-sectional area and pressure-derived outputs to enable robust statistical comparison between grafts and native vessels.
- Translational Research: Supports longitudinal tracking of graft remodeling and functional integration in vivo.
- Enterprise Reuse: Establishes a reusable platform for evaluating diverse vascular constructs and biomaterials.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in graft performance and reduces mechanistic ambiguity.
- Operational Value: Standardizes biomechanical assessment and enables longitudinal, within-animal comparisons.
- Strategic Value: Informs go/no-go decisions and enhances capital efficiency by de-risking candidates early.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of regenerative and synthetic vascular technologies.
Implementation Considerations
- Requires expertise in large-animal surgery, vascular imaging, and pressure measurement.
- Demands access to 3D angiography and intravascular pressure monitoring infrastructure.
- Necessitates cross-team standardization of imaging and measurement protocols.
- Adaptation may be needed for different vessel types or animal models.
- Longitudinal study design must account for animal welfare and procedural repeatability.
