Spatial velocity profile in mouse embryonic aorta and Doppler-derived volumetric flow: a preliminary model

Abstract

Phoon, Colin K. L., Orlando Aristizá bal, and Daniel H. Turnbull. Spatial velocity profile in mouse embryonic aorta and Doppler-derived volumetric flow: a preliminary model. Am J Physiol Heart Circ Physiol 283: H908-H916, 2002. First published May 16, 2002 10.1152/ajpheart.00869.2001.-Characterizing embryonic circulatory physiology requires accurate cardiac output and flow data. Despite recent applications of high-frequency ultrasound Doppler to the study of embryonic circulation, current Doppler analysis of volumetric flow is relatively crude. To improve Doppler derivation of volumetric flow, we sought a preliminary model of the spatial velocity profile in the mouse embryonic dorsal aorta using ultrasound biomicroscopy (UBM)-Doppler data. Embryonic hematocrit is 0.05-0.10 so rheologic properties must be insignificant. Low Reynolds numbers (Ͻ500) and Womersley parameters (Ͻ0.76) suggest laminar flow. UBM demonstrated a circular dorsal aortic cross section with no significant tapering. Low Dean numbers (Ͻ100) suggest the presence of minimal skewing of the spatial velocity profile. The inlet length allows for fully developed flow. There is no apparent aortic wall pulsatility. Extrapolation of prior studies to these vessel diameters (300-350 m) and flow velocities (ϳ50-200 mm/s) suggests parabolic spatial velocity profiles. Therefore, mouse embryonic dorsal aortic blood flow may correspond to Poiseuille flow in a straight rigid tube with parabolic spatial velocity profiles. As a first approximation, these results are an important step toward precise in utero ultrasound characterization of blood flow within the developing mammalian circulation. cardiac development; embryonic blood flow; physiology; ultrasound THE PHYSIOLOGICAL STUDY OF developing circulation remains technically challenging (for a review, see Ref. 37). The mouse is the primary model of mammalian development, but the assessment of developmental cardiovascular physiology, critical to the study of functional genomics, has lagged behind the recent advances in molecular cardiology. We recently (1, 36, 40) demonstrated that quantitative in utero study of mouse embryonic cardiovascular physiology is feasible using 40-to 50-MHz ultrasound biomicroscopy (UBM) and 43-MHz spectral pulsed-wave (PW) Doppler. UBM image-guided PW Doppler, in particular, is a powerful tool for the quantitative and noninvasive investigation of early mouse circulatory development, allowing for more physiologically relevant data than previously obtained (36).Precise characterization of developing embryonic circulatory physiology requires information on cardiac output and volumetric blood flow, allowing for insights into blood flow distribution and oxygen delivery. Volumetric blood flow (Q) in a given blood vessel may be calculated as Q ϭ vessel cross-sectional area ϫ time-averaged mean velocity Overall, current analysis of Doppler signals to provide volumetric blood flow information is very poorly developed (13). In Doppler assessment of cardiovascular physiology, several assumptions...

Imaging Tools for the Developmental Biologist: Ultrasound Biomicroscopy of Mouse Embryonic Development

“…In studies of ENUinduced mutagenesis, investigators have really only diagnosed cardiac malformations (excluding hypertrophy, ectopia cordis, and outflow tract regurgitation) at postnatal necropsy, not by ultrasound-in other words, not in the living embryo or fetus (35,36). The poor performance of even 15 MHz systems is due to axial resolution of 440 m, with lateral resolution of 630 m (37); to provide an idea of scale, the diameter of the embryonic mouse dorsal aorta is in the range of 300 m (38). Despite the inadequate spatial resolution, however, clinical ultrasound systems possess color Doppler flow mapping, not currently available on UBM imaging systems, that may aid in screening for major cardiac malformations (36).…”

“…Our laboratory's innovative multi-parameter in utero approach has yielded insights into integrative cardiovascular physiology, accounting not only for heart function but also the interactions of the heart with different intra-and extra-embryonic vascular beds (24,38,39). The developing embryo is exquisitely sensitive to environmental perturbations such as hypothermia, such that even non-physiological heart rates will change many hemodynamic parameters, such as contractile ability, relaxation, and regional blood flow (10,52).…”

“…The excellent spatial resolution of UBM, coupled with precise Doppler sample volume placement, permits non-invasive characterization of blood flow parameters in the in utero mouse embryo not possible with clinical ultrasound systems ( Fig. 1) (25,38); various functional UBM-Doppler parameters have recently been reviewed in detail elsewhere (39). This integrated approach to cardiovascular physiology, when combined with cellular and molecular techniques, is uniquely suited to answering many fundamental questions posed in developmental biology.…”

Multimodal imaging of mouse development: Tools for the postgenomic era

“…Since the initial study of mouse embryos in utero (Turnbull et al, 1995a), ultrasonography has been used for imaging and staging early postimplantation embryos in utero (Turnbull, 1999;Chang et al, 2003), and both transcutaneous and transuterine UBM has become a standard method for assessing normal and defective cardiovascular development in mice (Srinivasan et al, 1998;Fatkin et al, 1999;Phoon et al, 2000Phoon et al, , 2002Phoon et al, , 2004Ji et al, 2003;Phoon and Turnbull, 2003;Lickert et al, 2004;Mai et al, 2004;Ji and Phoon, 2005). Many of these studies have also used Doppler echocardiography, a highly sensitive method for measuring the direction and velocity of blood flow (see Phoon and Turnbull, 2003, for review).…”

Contrast Imaging in Mouse Embryos Using High-frequency Ultrasound

“…As a model of mammalian development, introduction of microbubbles into the embryonic vasculature enhances physiological study of the developing circulatory system (e.g., blood flow, cardiac output) and in cases of transgenic and targeted mutant mouse models of cardiac disease 6,7 , may yield insights into how genetic factors alter cardiovascular function. In fact, quantitative and qualitative 2D analyses of embryonic brain vasculature have already been achieved 8 .…”