TY - JOUR
T1 - Experimental and Mouse-Specific Computational Models of the Fbln4 SMKO Mouse to Identify Potential Biomarkers for Ascending Thoracic Aortic Aneurysm
AU - Bazzi, Marisa S.
AU - Balouchzadeh, Ramin
AU - Pavey, Shawn N.
AU - Quirk, James D.
AU - Yanagisawa, Hiromi
AU - Vedula, Vijay
AU - Wagenseil, Jessica E.
AU - Barocas, Victor H.
N1 - Publisher Copyright:
© 2021, Biomedical Engineering Society.
PY - 2022/8
Y1 - 2022/8
N2 - Purpose: To use computational methods to explore geometric, mechanical, and fluidic biomarkers that could correlate with mouse lifespan in the Fbln4SMKO 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 Fbln4SMKO 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 (TAWSSmin) at six months showed the largest correlation with lifespan (r2 = 0.70, 0.56), with both correlations being positive (i.e., mice with high OSImean and high TAWSSmin tended to live longer). When change between two and six months was considered, the change in TAWSSmin showed a much stronger correlation than OSImean (r2 = 0.75 vs. 0.24), and the correlation was negative (i.e., mice with increasing TAWSSmin 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.
AB - Purpose: To use computational methods to explore geometric, mechanical, and fluidic biomarkers that could correlate with mouse lifespan in the Fbln4SMKO 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 Fbln4SMKO 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 (TAWSSmin) at six months showed the largest correlation with lifespan (r2 = 0.70, 0.56), with both correlations being positive (i.e., mice with high OSImean and high TAWSSmin tended to live longer). When change between two and six months was considered, the change in TAWSSmin showed a much stronger correlation than OSImean (r2 = 0.75 vs. 0.24), and the correlation was negative (i.e., mice with increasing TAWSSmin 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.
KW - Aneurysm
KW - Biomarker
KW - Biomechanics
KW - Fluid–structure interaction
UR - http://www.scopus.com/inward/record.url?scp=85123245777&partnerID=8YFLogxK
U2 - 10.1007/s13239-021-00600-4
DO - 10.1007/s13239-021-00600-4
M3 - Article
C2 - 35064559
AN - SCOPUS:85123245777
SN - 1869-408X
VL - 13
SP - 558
EP - 572
JO - Cardiovascular Engineering and Technology
JF - Cardiovascular Engineering and Technology
IS - 4
ER -