Cardiovascular Biomechanics and Ultrasound Laboratory

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National University of Singapore, Department of Bioengineering

 

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High Frequency Ultrasound Imaging of Embryonic Cardiovascular System for Computational Fluid Dynamics

We seek to understand the role of mechanical environments in normal development and congenital malformation. For such studies, the chick embryo is a very good animal model. Micro-surgery can be performed to create chick embryos with clinically relevant structural malformations, thus creating a disease model which is based on purely mechanics alterations, without any genetic alterations.

To enable studies of the small animal embryonic cardiovascular fluid mechanics, an imaging technique is important. To date, most imaging techniques that provided sufficient resolution in 3D to enable subsequent computational fluid mechanics studies are invasive, and/or require the sacrifice of the embryo, making it difficult to perform longitudinal, repeated studies of the same subject. We developed techniques to use high frequency ultrasound (40MHz) to perform 4D scans of chick embryos, which included image processing to digitally distinguish between blood volumes and tissue volumes in the scans. Image processing also included phase averaging, temporal and spatial correlations.

The images obtained could then be used for computational fluid dynamics to understand how mechanics affects development of the embryonic heart

 

(Left) raw ultrasound images of a 4.0 days chick embryo.

(right) the same image after image processing to distinguish blood and tissue pixels.

 

(Left) raw ultrasound images of a 4.5 days chick embryo.

(right) the same image after image processing to distinguish blood and tissue pixels.

 

 

3D reconstruction of the carotid arteries and the dorsal aortas of the chick embryo at various stages, reconstructed from high frequency ultrasound scans of live embryos.

 

Computational Fluid Dynamics Simulations of the chick embryo primitive arteries,

Based on high frequency ultrasound scans of live chick embryos.

 

Reconstruction of the Dynamic Motion of the 4.5 days chick embryonic heart,

obtained using phase averaging of ultrasound images, and spatial and temporal correlation.

 

 

 

Human Fetus Ventricular Fluid Dynamics

 

We strive to characterize the fluid mechanical force environment in the human fetus, and to understand the role of fluid mechanical force environment in congenital heart malformations (such as such as Hypoplastic Left Heart Syndrome, Tetralogy of Fallot, and Aortic Coarctation). To achieve this, we use ultrasound-image-based computational fluid dynamics (CFD) and study both normal fetuses and fetuses with congenital malformations.

We have established methodology for ultrasound-based CFD. In collaboration with the Maternal Fetal Medicine Division of the National University Hospital Systems, 4D STIC images of human fetuses were obtained. Images were segmented with a combination of lazy snapping algorithm and level set segmentation. Dynamic Mesh CFD was performed

 

 

 

4D ultrasound images of a normal fetus at 22 weeks of gestation

 

 

 

Vorticity iso-surface plot from the CFD simulations of

the Left Ventricle of a 22nd week human fetus

 

Velocity and 2D Vorticity on a Cut-plane of the Left Ventricle CFD in the 22nd week human fetus.

Complex Vorticity Dynamics is observed, including vortex shedding from both E and A wave, and the outflow of entire vortices through the outflow tract.

 

 

 

 

 

Placenta Biomechanics in normal and Growth Restricted Pregnancies

 

 

Intrauterine Growth Restriction is a disease of the placenta where not enough nutrients and oxygen can be transferred from the mother to the fetus, leading to 5-10x higher mortality rate, and life-long morbidities such as nuero-maldevelopment, hypertension, diabetes and cardiovascular diseases. Even in developed world, its prevalence is high, at 3%. Currently, there are no proven method to prevent or treat IUGR. However, successful detection can allow management strategies such as timing of delivery, which can improve outcome.

We are interested in studying the mechanics of the placenta in normal and IUGR pregnancies, such that improved understanding can inspire new detection and treatment. Mechanical testing of post-delivery human placenta samples have shown that have different mechanical properties from normal placenta, indicating that technique such as elastography may be useful in detecting IUGR.

We also employ ultrasound-image based computational fluid dynamics, and vascular casting to understand umbilical-placenta circulation.

 

Results of Cyclic Uniaxial mechanical testing of post-delivery human placenta (both normal and with IUGR disease), demonstrating that IUGR samples have different mechanical properties.

* p<0.05; ** p<0.10

 

 

3D reconstruction of the umbilical arteries and vein of a human fetus at 32 weeks of gestation

 

 

Vascular casting of human placenta to understand vascular branching geometry and fluid dynamics

 

 

 

Pre-natal Cardiovascular Fluid Mechanics and Its Effects on Cardiovascular Development

 

On top of using the ultrasound, we seek to employ serial histology and Optical Coherence Tomography to obtain accurate geometry of chick embryonic cardiovascular system for Computational Fluid Dynamics analysis. Our techniques are applicable to other small animal embryos and fetuses as well.

 

Investigation of Fluid Mechanical Environment of the Foetal Mouse Great Vessels

Presentation1

 

Computation of Vascular Wall Shear Stresses in

the Embryonic Mouse Pharyngeal Aortic Arches

 

Double Helical Flow Pattern in the Newborn Mouse Aorta

 

 

 

 

Fluid Mechanics of Heart Valve Regurgitation

We seek to develop novel techniques for quantifying heart valve regurgitation, which is needed by clinicians to evaluate severity of valve diseases. Our approach is to improve our understanding of the fluid mechanics of the regurgitation heart valve. Using a combination of 3D ultrasound imaging and computational fluid dynamics, we create computer simulations of regurgitation heart valves, to identify quantifiable fluid mechanics parameters that can be used to develop new methods for regurgitation quantification.

 

Reconstruction of 3D Mitral Valve Anatomy from Clinical 3D Ultrasound ScansSlide1

Computational Fluid Dynamics Simulations of Mitral Valve RegurgitationSlide3

 

The Use of Ultrasound in Mechanical Testing:

Concurrent Quantification of Mechanical Property

and Fiber Orientation

Traditional mechanical testing (Uniaxial, Biaxial, pressure-diameter, etc) of biological samples uses optical cameras and markers on the surface of samples to make strain measurements. However, this limits strain deformation quantification to the surface of samples, and limits strain quantification to 2D. By using 3D ultrasound speckle tracking instead of optical cameras in mechanical testing, however, we can quantify strains in 3D, anywhere within the sample. We find that with this technique, additional information can be obtained, such as the spatially-varying fiber orientation of the biological sample being tested.

We endeavor to develop further in vitro and in vivo methods to test material strength and fiber orientations of biological samples including native tissues and tissue engineering implants.

Experimental setup combining biaxial mechanical testing and 3D ultrasound

 

3 of 9 Green Strain components quantifiable with 3D Ultrasound Speckle Tracking

 

Spatially-varying fiber orientation of rat myocardium quantified with our technique

figure12_v2

 

Our fiber orientation measured using the ultrasound-biaxial technique are validated with histology. (left) fiber orientaiton measurements using ultrasound-biaxial technique at 4 planes within a rat myocardium, compared with fiber orientation quantified using histology using the same sample.fiberorientationplot3 ImageOrientation154b

 

Translational Research Medical Device Design

We are interested in developing translational medical devices, such as ultrasound-guided robotic intravascular guide-wires, implantable blood pumps using dielectric elastomers, and extracorporeal blood pumps.