Experimental and mouse-specific computational models of the Fbln4(SMKO) mouse to identify potential biomarkers for ascending thoracic aortic aneurysm

The prediction of risk to the patient in ascending thoracic aortic aneurysm (ATAA) is a significant challenge and the subject of much active research. In the present work, a combination of mouse model experiments and computer simulations was used to explore potential biomarkers that correlate with mouse lifespan, used as a surrogate for risk of a catastrophic event. 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. Comparing the different geometrical and biofluidic biomarkers to the mouse lifespan, it was found that mean oscillatory shear index (OSI(mean)) 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 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) (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). The results highlight potential biomarkers of ATAA outcomes that can be obtained through noninvasive imaging and computational simulations.