Experimental and Mouse-Specific Computational Models of the Fbln4 ^SMKO Mouse to Identify Potential Biomarkers for Ascending Thoracic Aortic Aneurysm

Purpose: To use computational methods to explore geometric, mechanical, and fluidic biomarkers that could correlate with mouse lifespan in the Fbln4^SMKO mouse. Mouse lifespan was used as a surrogate for risk of a severe cardiovascular event in cases of ascending thoracic aortic aneurysm. Methods: Image-based, mouse-specific fluid-structure-interaction models were developed for Fbln4^SMKO mice (n = 10) at ages two and six months. The results of the simulations were used to quantify potential biofluidic biomarkers, complementing the geometrical biomarkers obtained directly from the images. Results: Comparing the different geometrical and biofluidic biomarkers to the mouse lifespan, it was found that mean oscillatory shear index (OSI_min) and minimum time-averaged wall shear stress (TAWSS_min) at six months showed the largest correlation with lifespan (r² = 0.70, 0.56), with both correlations being positive (i.e., mice with high OSI_mean and high TAWSS_min tended to live longer). When change between two and six months was considered, the change in TAWSS_min showed a much stronger correlation than OSI_mean (r² = 0.75 vs. 0.24), and the correlation was negative (i.e., mice with increasing TAWSS_min over this period tended to live less long). Conclusion: The results highlight potential biomarkers of ATAA outcomes that can be obtained through noninvasive imaging and computational simulations, and they illustrate the potential synergy between small-animal and computational models.