Measurement of Pulse Propagation Velocity, Distensibility and Strain in an Abdominal Aortic Aneurysm Mouse Model
February 23rd, 2020
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This manuscript describes a detailed protocol for using high frequency ultrasound imaging to measure luminal diameter, pulse propagation velocity, distensibility and radial strain on a mouse model of abdominal aortic aneurysm.
Overview
This manuscript describes a detailed protocol for using high frequency ultrasound imaging to measure luminal diameter, pulse propagation velocity, distensibility and radial strain on a mouse model of abdominal aortic aneurysm. This non-invasive technique allows for monitoring subtle changes in aortic functions.
Key Study Components
Area of Science
- Neuroscience
- Cardiovascular Imaging
- Preclinical Trials
Background
- Ultrasound imaging is a powerful technique for assessing abdominal aortic aneurysms.
- Aortic stiffness is an important indicator of aneurysm progression.
- Velocity and strain measurements correlate with vascular changes in cardiovascular diseases.
- This study utilizes a mouse model for imaging procedures.
Purpose of Study
- To measure key parameters related to abdominal aortic aneurysms.
- To assess the effects of therapeutic agents in preclinical trials.
- To provide a detailed protocol for high frequency ultrasound imaging.
Methods Used
- High frequency ultrasound imaging technique.
- Measurement of luminal diameter and pulse wave velocity.
- Assessment of aortic distensibility and radial strain.
- Preparation of mouse model for imaging.
Main Results
- Successful measurement of aortic parameters using ultrasound.
- Correlation of aortic stiffness with aneurysm stability.
- Insights into the effects of various therapeutic agents.
- Demonstration of the imaging procedure by Dr. Sun.
Conclusions
- High frequency ultrasound is effective for monitoring aortic aneurysms.
- The protocol can aid in preclinical research and therapeutic assessments.
- Further studies may enhance understanding of cardiovascular diseases.
Frequently Asked Questions
What is the significance of measuring aortic stiffness?
Aortic stiffness is an important indicator of abdominal aortic aneurysm progression and stability.
How does ultrasound imaging compare to traditional methods?
Ultrasound imaging provides a non-invasive way to assess aortic function beyond just size and diameter.
Who demonstrates the imaging procedure?
Dr. Sun, a research assistant professor from the Imaging Core facility, demonstrates the procedure.
What parameters are measured using this technique?
Luminal diameter, pulse propagation velocity, distensibility, and radial strain are measured.
What is the purpose of the mouse model in this study?
The mouse model is used to simulate abdominal aortic aneurysms for imaging and analysis.
Can this technique be used for other cardiovascular diseases?
Yes, velocity and strain measurements can be correlated to various cardiovascular diseases.
Executive Industry Relevance
Assessing aortic stiffness through pulse propagation velocity, distensibility, and strain measurements provides predictive value for aneurysm stability beyond luminal diameter alone. This ultrasound-based approach enables early detection of vascular wall changes in preclinical models, supporting mechanistic de-risking of therapeutic candidates targeting vascular remodeling pathways. The method offers translational continuity by correlating functional readouts with structural disease progression in abdominal aortic aneurysm models.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of vascular wall integrity hypotheses by quantifying functional changes in aortic stiffness.
- Operational Value: Provides quantitative, ultrasound-derived endpoints for target engagement and pathway modulation studies.
Screening & Assay Development
- Scientific Value: Generates reproducible, biomechanical readouts (PPV, distensibility, strain) suitable for assay standardization across treatment groups.
- Operational Value: Supports high-frequency ultrasound platform readiness for longitudinal monitoring of vascular phenotypes in mouse models.
Translational & Preclinical Research
- Scientific Value: Links pharmacological interventions (e.g., angiotensin II, notch inhibitor) to measurable changes in aortic biomechanics and extracellular matrix remodeling.
- Operational Value: Facilitates risk-adjusted advancement decisions by correlating stiffness metrics with aneurysm progression and stability.
Pipeline & Workflow Integration
The method integrates into discovery workflows by providing functional vascular assessments that complement anatomical measurements, enabling earlier identification of mechanistically active compounds.
- Discovery Biology: Supports hypothesis testing of vascular stiffening mechanisms and target-mediated effects on aortic wall properties.
- Screening: Delivers standardized, quantitative ultrasound outputs for compound screening in preclinical aneurysm models.
- Analytics: Yields PPV, distensibility, and strain measurements that enable comparative analysis of vascular function across experimental conditions.
- Translational Research: Connects functional aortic changes to preclinical continuity and biomarker alignment in vascular disease models.
- Enterprise Reuse: Establishes a reusable ultrasound capability for multi-disease cardiovascular assessment beyond aneurysm studies.
Operational & Enterprise Impact
- Scientific Value: Predictive confidence in target validation through direct measurement of vascular stiffening as a disease-relevant functional endpoint.
- Operational Value: Standardization and reproducibility via protocolized ultrasound acquisition and analysis at consistent anatomical locations.
- Strategic Value: Improved go/no-go decisions by reducing mechanistic ambiguity in vascular therapeutic development.
- Portfolio Impact: Risk-adjusted prioritization based on biomechanical de-risking of aortic wall-targeting interventions.
Implementation Considerations
- Expertise in high-frequency ultrasound imaging and vascular anatomy identification (e.g., super renal aorta via renal and mesenteric artery landmarks).
- Instrumentation requirements including ultrasound system with M-mode, EKV mode, ECG gating, and respiratory gating capabilities.
- Cross-team standardization needs for consistent image acquisition, gate settings, and analysis by the same operator to ensure reproducibility.
- Adaptation considerations for different disease models where vascular stiffness correlates with hypertension, diabetes, obesity, or atherosclerosis.
- Practical limitations include the critical dependence on proper animal preparation, probe positioning, and gel application to avoid artifacts in velocity and strain measurements.
Biopharma FAQs
Why does pulse propagation velocity measurement matter for target validation in aneurysm models?
PPV serves as a quantitative indicator of aortic stiffness, reflecting vascular wall functional changes that correlate with aneurysm progression and stability, enabling mechanistic assessment of therapeutic effects beyond diameter alone.
How does isolation of independent variables like angiotensin II dose support discovery pipeline decisions?
Controlled infusion of angiotensin II allows isolation of its effect on aortic stiffening, enabling clear attribution of PPV, distensibility, and strain changes to specific pharmacological interventions in preclinical studies.
What quantitative dependent variable measurements enable assessment of vascular wall stability?
Distensibility and radial strain provide quantitative, ultrasound-derived measures of aortic wall deformation capacity, with decreases indicating increased stiffness and reduced compliance in aneurysm models.
Why do replication requirements matter for cross-functional collaboration in vascular stiffness studies?
Analyzing images by the same person at the same anatomical location ensures consistency in PPV, distensibility, and strain measurements, supporting reliable data sharing across discovery and preclinical teams.
What statistical analysis capabilities are required before implementing PPV and strain measurements in therapeutic studies?
Correlation analysis between PPV and maximal intraluminal diameter (MILD) is needed to assess stiffness-diameter relationship strength at different disease stages, as demonstrated by strong correlation at day 28 weakening at day 56.
Chapters in this video
0:04
Introduction
1:11
Mouse Preparation
2:07
Abdominal Aorta Imaging
4:47
Abdominal Aortic Image Analysis
5:13
Pulse Propagation Velocity (PPV) Analysis
5:48
Distensibility and Radial Strain Analysis
6:47
Results: Representative PPV and Aortic Structural Analyses in an Established Abdominal Aortic Aneurysm (AAA) Model
8:31
Conclusion
