Methodological framework and unified metrics for thrombus resolution analysis in the mouse inferior vena cava...

The inferior vena cava (IVC) stenosis model in mice is widely used in venous thrombosis research. However, high variability in thrombus size, reliance on discrete evaluation time points that vary across studies, and the absence of a unified measure of thrombus resolution dynamics hinder the preclinical assessment of candidate treatments designed to accelerate thrombus resolution.

To develop a methodological framework for assessing thrombus resolution dynamics in the IVC stenosis model.

Wild-type mice, neutrophil-specific integrin α9-deficient mice (α9^fl/flMrp8Cre⁺), and littermate control (α9^fl/fl) mice were subjected to IVC stenosis. Thrombus resolution was monitored using magnetic resonance angiography on days 2, 7, 14, and 21 postsurgery in the same mouse cohorts. Linear and nonlinear (exponential decay) mixed-effects models were fitted to analyze thrombus resolution.

Ligation of the IVC back branches improved the consistency of thrombus formation in wild-type mice by reducing length variance, independently of surgeon variability. The proportional thrombus resolution rate in wild-type mice was 10.5% per day, with a time to half-maximum thrombus volume of 6.3 days (from day 2 postsurgery). Although neutrophil-specific integrin α9-deficient mice exhibited smaller initial thrombus volumes compared with controls, no difference in thrombus resolution dynamics was observed between the 2 mouse cohorts.

Integrating the IVC stenosis model enhanced by back-branch ligation with serial imaging and statistical modeling to derive unified thrombus resolution metrics-proportional resolution rate and time to half-maximum thrombus volume-provides a robust methodological framework. This framework may facilitate the design of preclinical trials using these metrics as standardized outcome measures.