Methodological framework and unified metrics for thrombus resolution analysis in the mouse IVC stenosis model

Ivan Budnik; Mariia Kumskova; Daniel Thedens; Anil K. Chauhan

doi:10.1016/j.rpth.2025.103009

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Methodological framework and unified metrics for thrombus resolution analysis in the mouse IVC stenosis model

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Methodological framework and unified metrics for thrombus resolution analysis in the mouse IVC stenosis model

Ivan Budnik, Mariia Kumskova, Daniel Thedens and Anil K. Chauhan

Research and practice in thrombosis and haemostasis, Vol.9(6), 103009

08/2025

DOI: 10.1016/j.rpth.2025.103009

PMCID: PMC12570168

PMID: 41169535

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Abstract

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, neutrophil-specific integrin α9-deficient (α9fl/flMrp8Cre+), and littermate control (α9fl/fl) mice were subjected to IVC stenosis. Thrombus resolution was monitored using magnetic resonance angiography on Days 2, 7, 14, and 21 post-surgery 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 %/day, with a time to half-maximum thrombus volume of 6.3 days (from Day 2). Although α9fl/flMrp8Cre+ mice exhibited smaller initial thrombus volumes compared to controls, no difference in thrombus resolution dynamics was observed when compared to α9fl/fl mice. 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.

Deep vein thrombosis

exponential decay mixed-effects model

inferior vena cava stenosis model

magnetic resonance angiography

thrombus resolution rate

time to half-maximum thrombus volume

Details

Title: Subtitle: Methodological framework and unified metrics for thrombus resolution analysis in the mouse IVC stenosis model
Creators: Ivan Budnik - University of Iowa
Mariia Kumskova - University of Iowa
Daniel Thedens - University of Iowa
Anil K. Chauhan - Department of Internal Medicine, Division of Hematology/Oncology, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Research and practice in thrombosis and haemostasis, Vol.9(6), 103009
DOI: 10.1016/j.rpth.2025.103009
PMID: 41169535
PMCID: PMC12570168
NLM abbreviation: Res Pract Thromb Haemost
ISSN: 2475-0379
eISSN: 2475-0379
Publisher: Elsevier Inc
Grant note: National Institutes of Health, the National Heart, Lung, and Blood Institute: HL139926, HL174460
The A.K.C. laboratory is supported by grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute (HL139926 and HL174460).
Language: English
Electronic publication date: 08/2025
Date published: 08/2025
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984948003302771

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