Murine Fetal Echocardiography

Summary

Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development. High-frequency ultrasound imaging has improved 2-D resolution and can provide excellent information on early cardiac development and is an ideal method to detect the impact on cardiac structure and function prior to death.

Abstract

Transgenic mice displaying abnormalities in cardiac development and function represent a powerful tool for the understanding the molecular mechanisms underlying both normal cardiovascular function and the pathophysiological basis of human cardiovascular disease. Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development ^1-3. In order to study the role of genetic or pharmacologic alterations in the early development of cardiac function, ultrasound imaging of the live fetus has become an important tool for early recognition of abnormalities and longitudinal follow-up. Noninvasive ultrasound imaging is an ideal method for detecting and studying congenital malformations and the impact on cardiac function prior to death ⁴. It allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies ^5,6. Until recently, imaging of fetal mouse hearts frequently involved invasive methods. The fetus had to be sacrificed to perform magnetic resonance microscopy and electron microscopy or surgically delivered for transillumination microscopy. An application of high-frequency probes with conventional 2-D and pulsed-wave Doppler imaging has been shown to provide measurements of cardiac contraction and heart rates during embryonic development with databases of normal developmental changes now available ^6-10. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. High-frequency ultrasound imaging of the fetus has improved 2-D resolution and can provide excellent information on the early development of cardiac structures ¹¹.

Protocol

1. Preparing Mice for Imaging

1. Prior to the imaging study, anesthetize the dam (2-3% isoflurane) in the induction chamber. Remove the animal from the induction chamber and immediately place the snout within a nose cone connected to the anesthesia system. Remove fur from the mid chest level to lower limbs (See Figure 1) with hair clippers. Remove the remaining body hair with depilatory cream. Depilatory cream may also be used without hair clippers, and should be thoroughly rinsed off of the skin after use to prevent irritation.
2. Place the anesthetized mouse in a supine position on a heating pad with embedded ECG leads in order to ma....

Discussion

The ability to perform serial measurements and to detect mutant fetuses with cardiac defects highlights the usefulness of echocardiography for investigating normal and abnormal cardiovascular development. Analysis of cardiac structure and function in vivo has become an integral part in the description of genetic and non-genetic modifications to normal fetal development. The availability of 2D-guided Doppler makes it possible to monitor heart rate and blood flow patterns while obtaining real-time images. De.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Vevo 770 Imaging System (Toronto, Canada)	VisualSonics
MHz transducer		RMV707B15-45
Isoflurane Vaporizer	Tec 3
Isoflurane			2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane