Abstract 131: Methods Behind Thrombus Size Variability in Murine IVC Ligation Model Revealed: Insights From MRI

Abstract

Objectives: Animal models are key tools for studying deep vein thrombosis (VT). Variation in thrombus size is a current concern that limits the ability to detect small differences between experimental groups. Our objective is to understand the mechanism of this variation. We hypothesized that thrombus size variability results from altered flow dynamics involving venous branches. Using MRI, we investigated the path of blood flow in the murine IVC ligation model. Methods: VT was induced in 11-15 week-old C57BL/6 mice (n=9) via IVC ligation with either interruption of all venous branches (IB), or all branches left open (OB). Mice were imaged by MRI 2 days post ligation to examine IVC patency and/or presence of thrombus. Venous flow was saturated to determine venous branching phenotype and flow direction, which was compared to pre-surgical MRI. Then, axial slices were acquired from the renal to iliac vessels to quantify thrombus volume. Finally, thrombus weight (TW) was quantified at harvest. Results: MRI: Thrombus volumes were larger in IB mice compared to OB mice (38.0 ± 4.6 mm 3 IB vs. 11.3 ± 8.3 mm 3 OB), with greater variability in OB mice (variation coefficient 12% IB vs. 73% OB). Open branches had great impact on reducing TW due to reversed flow direction, increasing thrombus size variability. IB mice showed flow compensation through the vertebral veins and collateral vessels. At harvest: TWs confirmed MRI findings (34.5 ± 3.8 mg IB vs. 15.7 ± 9.8 mg OB; variation coefficient 11% IB vs. 62% OB). The pattern of 2 back branches was observed in all mice, and 1 right branch was the most common phenotype. The OB mouse with the highest TW had 2 side branches, whereas the other OB mice had 1 right branch only. Conclusion: Thrombus size variability increased when branches were not interrupted. Blood flow dynamics detected by MRI were critical for understanding the “flow escape phenomenon” from the IVC that occurs through branches when they are left open. This study supports that the anatomical branching pattern affects blood flow in the IVC. Non-invasive MRI brings to light the important role of venous branches inducing thrombus variability in VT models.