A Systemic embolization model in a rat with real-time micro-fluoroscopy for direct quantification of thrombolysis

Area of Science:

• Biomedical Engineering
• Pharmacology
• Vascular Biology

Background:

• Intravenous thrombolysis for stroke often yields incomplete recanalization.
• Standardized preclinical models are crucial for evaluating new thrombolytic therapies.

Purpose of the Study:

• To develop and validate a rat systemic embolization model for real-time, in vivo assessment of thrombolysis.
• To quantitatively evaluate the efficacy of alteplase (rtPA) using this novel model.

Main Methods:

• A rat model with human fibrin-based clots labeled with BaSO₄ was established in the abdominal aorta.
• High-resolution micro-fluoroscopy was employed for direct, real-time visualization and quantitative assessment of clot dissolution.
• Micro-CT imaging was used as a reference modality to validate the micro-fluoroscopy findings.

Main Results:

• Micro-fluoroscopy enabled continuous visualization and detection of clot dissolution in vivo.
• Alteplase (rtPA) demonstrated a dose-dependent reduction in clot area, with significant differences observed between doses and controls.
• The model exhibited high measurement reliability (ICC=0.89) and concordance with micro-CT, supporting its validity.

Conclusions:

• The developed rat model with micro-fluoroscopy provides a standardized, reproducible, and technically feasible platform for pharmacodynamic evaluation of thrombolytic agents.
• Utilizing multiple clots per animal reduces the number of animals needed, enhancing ethical considerations in preclinical research.
• This model offers translational relevance for assessing thrombolytic therapies in stroke treatment.