Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions
March 8th, 2019
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Ultrasound imaging has become a common modality to determine the luminal dimensions of thoracic and abdominal aortic aneurysms in mice. This protocol describes the procedure to acquire reliable and reproducible two-dimensional ultrasound images of the ascending and abdominal aorta in mice.
Overview
This protocol outlines the use of ultrasound imaging to accurately measure the dimensions of thoracic and abdominal aortic aneurysms in mice. It provides a step-by-step guide for researchers to obtain reliable two-dimensional images of the aorta.
Key Study Components
Area of Science
- Neuroscience
- Imaging Techniques
- Cardiovascular Research
Background
- Ultrasound imaging is a non-invasive method for assessing aortic dimensions.
- High-resolution measurements are crucial for studying aortic aneurysms.
- The protocol is designed for use in murine models.
- Accurate imaging techniques are essential for reproducible results.
Purpose of Study
- To provide a practical guide for ultrasound imaging of the aorta in mice.
- To facilitate the acquisition of reproducible and accurate measurements.
- To demonstrate the procedure for researchers in the field.
Methods Used
- Application of dilatory cream and ultrasound gel to the imaging area.
- Use of color Doppler to confirm blood flow in the aorta.
- Adjustment of probe and stage settings for optimal imaging.
- Capture of images for both thoracic and abdominal aorta measurements.
Main Results
- Demonstrated the procedure for capturing aortic images in mice.
- Confirmed the accuracy of ultrasound measurements compared to ex vivo images.
- Showed no inter or intra observer variability in measurements.
- Highlighted the importance of probe adjustment for reliable imaging.
Conclusions
- This ultrasound technique allows for reproducible and accurate aortic measurements.
- Proper preparation and technique are critical for successful imaging.
- The protocol can be utilized for further studies on aortic aneurysms.
Frequently Asked Questions
What is the main purpose of this ultrasound protocol?
The protocol aims to provide a reliable method for measuring aortic dimensions in mice using ultrasound imaging.
Who are the researchers demonstrating the procedure?
Dr. Hasashi Sawada and Jessica Morrleghen from the University of Kentucky.
What are the key steps in preparing the mouse for imaging?
Apply dilatory cream, remove hair, and apply ultrasound gel before imaging.
How is blood flow confirmed during the imaging process?
Color Doppler is used to visualize and confirm blood flow in the aorta.
What factors are important for accurate aortic measurements?
Probe adjustment, stage settings, and consideration of the cardiac cycle are crucial.
What were the findings regarding observer variability?
No major differences in measurements were observed between independent observers.
Executive Industry Relevance
Accurate in vivo measurement of aortic dimensions in murine models is critical for evaluating aneurysm progression and therapeutic efficacy in cardiovascular drug development. This ultrasound protocol provides a standardized, reproducible approach to quantify thoracic and abdominal aortic diameters, supporting target validation and mechanistic de-risking in preclinical studies. By minimizing variability from probe positioning and cardiac cycle, the method enhances predictive confidence in aortic pathology models.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by quantifying aortic dilation as a functional readout of pathway modulation in aneurysm models.
- Operational Value: Supports biological de-risking through longitudinal, non-invasive monitoring of aortic dimensions in live mice.
Screening & Assay Development
- Scientific Value: Prepares validated biological systems for downstream compound screening by establishing baseline aortic measurements and tracking disease progression.
- Operational Value: Promotes assay standardization and reproducibility via consistent ultrasound parameter settings and image acquisition protocols.
Translational & Preclinical Research
- Scientific Value: Aligns with disease-relevant systems by enabling serial measurements that mirror clinical aneurysm monitoring practices.
- Operational Value: Facilitates translational continuity from discovery through preclinical validation by providing quantitative, imaging-based endpoints.
Pipeline & Workflow Integration
The method integrates into the discovery continuum from target validation through preclinical evaluation, offering a non-invasive imaging modality for assessing aortic pathology in murine models.
- Discovery Biology: Supports hypothesis testing and pathway clarification by enabling direct visualization and measurement of aortic structural changes in response to genetic or pharmacological interventions.
- Screening: Enhances assay readiness by providing reproducible, quantitative luminal diameter and area measurements that can be used to evaluate compound effects on aneurysm progression.
- Analytics: Delivers standardized readouts (aortic sinus, ascending aortic, and abdominal aortic diameters) that allow cross-condition comparison and effect size calculation.
- Translational Research: Connects to preclinical continuity by enabling longitudinal tracking that informs risk-adjusted advancement decisions based on aneurysm growth kinetics.
- Enterprise Reuse: Functions as a reusable imaging platform across cardiovascular studies, reducing need for terminal procedures and supporting longitudinal cohort designs.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence by reducing mechanistic ambiguity in aneurysm models through direct, serial imaging of aortic dimensions.
- Operational Value: Improves standardization and reproducibility via defined probe placement, gel application, and cardiac cycle considerations.
- Strategic Value: Supports better go/no-go decisions by providing objective, imaging-based endpoints that reduce reliance on terminal histology alone.
- Portfolio Impact: Enables risk-adjusted prioritization by quantifying aneurysm progression rates to inform resource allocation across therapeutic candidates.
Implementation Considerations
- Requires expertise in murine handling, anesthesia, and ultrasound imaging techniques.
- Depends on high-resolution ultrasound systems with color Doppler and adjustable focal depth capabilities.
- Necessitates standardization across users for probe angle, stage positioning, and image acquisition timing relative to the cardiac cycle.
- Involves adaptation considerations when applying to different mouse strains or aneurysm models with varying aortic geometries.
- Includes practical limitations such as the need for careful skin preparation to avoid artifacts and the influence of heart rate stability on image quality.
Biopharma FAQs
Why does cardiac cycle timing matter for aortic diameter measurement?
Aortic luminal dimensions vary between systole and diastole, so consistent timing relative to the cardiac cycle is essential for reproducible and comparable measurements across sessions and subjects.
How does probe positioning affect ultrasound image accuracy?
Probe angle and placement relative to anatomical landmarks (e.g., sternum, xyphoid process) directly influence visualization of the aortic lumen and must be optimized to avoid foreshortening or off-axis imaging that distorts diameter measurements.
What quantitative outputs enable aneurysm progression tracking?
The protocol provides luminal diameter measurements (aortic sinus, ascending aorta, abdominal aorta) and luminal area tracings, which serve as quantitative endpoints for assessing dilation over time in aneurysm models.
Why are replication requirements important for cross-functional collaboration?
Demonstrated lack of inter- and intra-observer variability supports reliable data sharing between discovery, preclinical, and translational teams, ensuring consistent interpretation of aortic measurements across sites and studies.
What statistical analysis capabilities are needed before implementation?
Teams require the ability to compare longitudinal diameter measurements, calculate effect sizes, and assess variability to determine significant changes in aneurysm progression between experimental conditions.
