Experimental and Mouse-Specific Computational Models of the Fbln4SMKO 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 (OSImin) and minimum time-averaged wall shear stress (TAWSS(min)) at six months showed the largest correlation with lifespan (r(2) = 0.70, 0.56), with both correlations being positive (i.e., mice with high OSImean 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 OSImean (r(2) = 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.