Choon Hwai Yap1, Xiaoqin Liu2, Kerem Pekkan3. 1. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore. 2. Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America. 3. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
Abstract
INTRODUCTION: Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5). METHODS: Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics. RESULTS: In normal mouse fetuses between E14.5-18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here. CONCLUSION: Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels.
INTRODUCTION: Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5). METHODS: Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics. RESULTS: In normal mouse fetuses between E14.5-18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here. CONCLUSION: Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels.
Authors: Jay R Hove; Reinhard W Köster; Arian S Forouhar; Gabriel Acevedo-Bolton; Scott E Fraser; Morteza Gharib Journal: Nature Date: 2003-01-09 Impact factor: 49.962
Authors: R Torii; J Keegan; N B Wood; A W Dowsey; A D Hughes; G-Z Yang; D N Firmin; S A Mcg Thom; X Y Xu Journal: Br J Radiol Date: 2009-01 Impact factor: 3.039
Authors: John S Lee; Qing Yu; Jordan T Shin; Eric Sebzda; Cara Bertozzi; Mei Chen; Patti Mericko; Matthias Stadtfeld; Diane Zhou; Lan Cheng; Thomas Graf; Calum A MacRae; John J Lepore; Cecilia W Lo; Mark L Kahn Journal: Dev Cell Date: 2006-12 Impact factor: 12.270
Authors: Sarah Al-Roubaie; Espen D Jahnsen; Masud Mohammed; Caitlin Henderson-Toth; Elizabeth A V Jones Journal: Am J Physiol Heart Circ Physiol Date: 2011-09-30 Impact factor: 4.733
Authors: Julie Rosenthal; Vipul Mangal; Diana Walker; Michael Bennett; Tim J Mohun; Cecilia W Lo Journal: Birth Defects Res C Embryo Today Date: 2004-09
Authors: Dhananjay Radhakrishnan Subramaniam; William A Stoddard; Kristian H Mortensen; Steffen Ringgaard; Christian Trolle; Claus H Gravholt; Ephraim J Gutmark; Goutham Mylavarapu; Philippe F Backeljauw; Iris Gutmark-Little Journal: J Cardiovasc Magn Reson Date: 2017-02-24 Impact factor: 5.364