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

IF 3.4 3区 医学 Q2 HEMATOLOGY
Ivan Budnik , Mariia Kumskova , Daniel Thedens , Anil K. Chauhan
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引用次数: 0

Abstract

Background

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.

Objectives

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

Methods

Wild-type mice, neutrophil-specific integrin α9-deficient mice (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 postsurgery in the same mouse cohorts. Linear and nonlinear (exponential decay) mixed-effects models were fitted to analyze thrombus resolution.

Results

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.

Conclusion

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.
小鼠下腔静脉狭窄模型血栓溶解分析的方法学框架和统一指标
背景小鼠下腔静脉狭窄模型在静脉血栓形成研究中得到广泛应用。然而,血栓大小的高度可变性,依赖于不同研究的离散评估时间点,以及缺乏统一的血栓溶解动态测量,阻碍了旨在加速血栓溶解的候选治疗的临床前评估。目的建立一个评估下腔静脉狭窄模型中血栓溶解动力学的方法学框架。方法采用野生型小鼠、中性粒细胞特异性整合素α9缺失小鼠(α9fl/flMrp8Cre+)和同窝对照小鼠(α9fl/fl)进行下腔静脉狭窄实验。在相同的小鼠队列中,在术后第2、7、14和21天使用磁共振血管造影监测血栓溶解。拟合线性和非线性(指数衰减)混合效应模型来分析血栓分辨率。结果下腔静脉后支结扎通过减少长度变异而改善了野生型小鼠血栓形成的一致性,而不受外科医生变异的影响。野生型小鼠的比例血栓溶解率为10.5% /天,达到血栓体积一半的时间为6.3天(从术后第2天开始)。虽然中性粒细胞特异性整合素α9缺陷小鼠的初始血栓体积比对照组小,但两组小鼠的血栓溶解动力学没有差异。将后支结扎增强的IVC狭窄模型与序列成像和统计建模相结合,得出统一的血栓分辨率指标——比例分辨率和达到一半最大血栓体积的时间——提供了一个强大的方法框架。该框架可以促进临床前试验的设计,使用这些指标作为标准化的结果测量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.60
自引率
13.00%
发文量
212
审稿时长
7 weeks
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