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. 2016 Mar 1;6(1):15-38.
doi: 10.1002/9780470942390.mo150122.

Cardiovascular Imaging in Mice

Colin K L Phoon  1 , Daniel H Turnbull  2   3
Affiliations

Cardiovascular Imaging in Mice

Colin K L Phoon et al. Curr Protoc Mouse Biol. .

Abstract

The mouse is the mammalian model of choice for investigating cardiovascular biology, given our ability to manipulate it by genetic, pharmacologic, mechanical, and environmental means. Imaging is an important approach to phenotyping both function and structure of cardiac and vascular components. This review details commonly used imaging approaches, with a focus on echocardiography and magnetic resonance imaging and brief overviews of other imaging modalities. We also briefly outline emerging imaging approaches but caution that reliability and validity data may be lacking.

Keywords: Doppler; echocardiography; magnetic resonance imaging; mouse models; ultrasound biomicroscopy.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

Drs. Phoon and Turnbull have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Transducer placement and echocardiographic imaging planes. (A) Parasternal long axis view. The transducer (blue rectangle) is oriented along the long axis of the heart, typically with the long edge of the probe aimed towards the right shoulder of the mouse. The imager must move up or down the chest to obtain an appropriately angled image (see Fig. 2). (B) Parasternal short axis view. If the heart is orthogonal to the transducer, all that needs to be done is to rotate the transducer 90° clockwise. The mid-LV level is good for determination of cardiac function (level of the mitral valve papillary muscles); while at the base of the heart, the aortic valve and pulmonary arteries can be seen. (C) Apical 4-chamber view. A true apical view that displays all four chambers cannot be obtained most of the time in the mouse, but one can usually obtain a foreshortened left ventricle with mitral inflow and aortic outflow. (D) Aortic arch view. The transducer must be positioned high into the neck, slightly off-vertical as shown, and aimed slightly downward. The imager must be careful not to exert any pressure since this will often lead to profound bradycardia and possible airway compression. (E) Abdominal aorta. The transducer is placed just below the xiphoid process, and the abdominal aorta may be imaged in either the longitudinal plane (as shown) or the cross-sectional plane (rotate the transducer 90°).
Figure 2
Figure 2
Heart images from different planes. (A) Parasternal long axis view. The left ventricular apex is to our left, with the mitral valve, aortic valve, and aortic root shown. Note how the heart lies “flat” and is orthogonal to the transducer, and the normal left ventricle is shaped like a prolate ellipsoid (“bullet shaped”). (B) Parasternal long axis view, with superimposed color Doppler flow map, showing mitral inflow and aortic outflow. (C) Parasternal short axis view. The normal left ventricle is round, and systolic function is normally determined at the level of the papillary muscles. The right ventricle is often poorly seen. (D) Apical 4-chamber view, with superimposed color Doppler flow map showing mitral inflow (red jet). (E) Apical 4-chamber view, with superimposed color Doppler flow map showing aortic outflow (blue jet). (F) Pulsed-wave Doppler signal of mitral inflow plus off-angle aortic outflow.
Figure 3
Figure 3
Parasternal short axis imaging of the left ventricle through the ages. (A) Adult heart. (B) Corresponding M-mode echocardiogram. (C) Juvenile (few weeks old, post-weaning). (D) Newborn pup. Note the far grainier image. (E) Newborn pup being imaged. The pup is held very gently with the thumb and forefinger, and ultrasound gel is applied all over the chest, taking care not to cover the snout. Parasternal long and short axis imaging can be accomplished in this manner. Scale bars (A, C, D): 2 mm.
Figure 4
Figure 4
Pulmonary and right ventricular imaging. (A) From the parasternal long axis view, tilting the transducer leftwards will open up the pulmonary artery, and this image shows a superimposed color Doppler map showing normal pulmonary arterial flow (blue jet). (B) Pulsed-wave Doppler signal in the main pulmonary artery. (C) Typical parasternal short axis imaging of the left ventricle will not yield good images of the right ventricle, but sliding the transducer towards the right parasternal edge may yield limited images of the right ventricle (D,E).
Figure 5
Figure 5
Strain imaging on the Vevo 2100 system. (A) Normal heart, with nearly ideal data. (B) Time-to-peak analysis. (C and D) Examples of poor strain data and pitfalls of strain imaging (highlighted areas). In C, the speckle tracking is poor, even though the heart is normal, resulting in wide variations in strain during systole. D shows our typical experience with newborn pup hearts, which do not appear to track well at all, despite reasonable B-mode images.
Figure 6
Figure 6
Noninvasive (transabdominal) embryonic/fetal heart imaging. (A) 4-chamber view of the E13.5 embryonic heart. Note how the intraluminal blood is echogenic. (B) Short axis view of the fetal E18.5 ventricles. Note how the intraluminal blood at this later stage is now relatively echolucent. (C and D) Method for measuring systolic ventricular function. The combined left and right ventricular areas are traced at end-diastole (C) and end-systole (D) to yield the fractional area shortening.
Figure 7
Figure 7
Examples of arterial flow in the prenatal mouse. (A) Sagittal view of an E12.5 mouse embryo, with superimposed color Doppler flow map showing the dorsal aorta. (B) Color Doppler flow map of the umbilical vessels (red-blue “stripes” to the right of center; placenta is the homogeneous gray region below the embryo). (C) Pulsed-wave Doppler signal in the dorsal aorta (not the same embryo as in A). (D) Pulsed-wave Doppler signal in the umbilical cord (not the same embryo as in B). The pulsatile positive deflection is the umbilical artery, while the more continuous negative deflection is the umbilical vein. In C and D, the maternal EKG and respiratory waveforms are shown at the bottom, which help monitor the pregnant mouse during embryonic/fetal imaging.
Figure 8
Figure 8
Imaging of the aorta (may require multiple imaging planes) and its branches. (A) Ascending aorta and very proximal aortic arch. (B) Aortic arch and very proximal thoracic descending aorta. (C) Color Doppler flow map of aortic arch (inset: pulsed-wave Doppler signal of the distal aortic arch). (D) Thoracic descending aorta, behind the heart. (E) Abdominal aorta, near the level of the kidneys. (F) Abdominal aorta with superimposed color Doppler flow map. The brachiocephalic branches off the aortic arch may also be imaged. (G) Distal ascending aorta, with innominate artery takeoff. (H) Same as (G), but the superimposed color Doppler flow map showing normal flow into the innominate artery. (I) Pulsed-wave Doppler signal of the proximal innominate artery. (J) Right common carotid artery, further up into the neck.
Figure 9
Figure 9
In utero MRI of an E17.5 fetal mouse heart. After motion correction and cardiac gating, color coded volumetric renderings of the four chambers in a beating fetal mouse heart shows differences between diastole (A) and systole (B). Right ventricle, RV (purple); left ventricle, LV (red); right atrium, RA (blue); left atrium, LA (yellow).
Figure 10
Figure 10
Ex vivo MRI of perfusion-fixed, gadolinium (Gd)-enhanced E17.5 mouse embryonic vasculature. (A) Following perfusion-fixation with the BSA-DTPA-Gd-gelatin solution, a maximum intensity projection (MIP) through the 3D, T1-weighted MRI data set, viewed from the side, shows the heart and vasculature in the brain, liver, and other regions of the embryo. (B) MIPs of wild-type (WT; left) and Gli2−/− mutant (right) embryos, viewed from the back, show the missing basilar artery (BA) in the mutant, a vascular phenotype that was discovered using MRI. Other vessels labeled are the carotid (CA) and vertebral (VA) arteries.
Figure 11
Figure 11
Molecular imaging of E11.5 mouse embryonic vasculature. The Biotag transgene was expressed from the Tie2 promoter-enhancer elements in Ts-Biotag vascular reporter mice. (A) Time-averaged cine ultrasound biomicroscopy images were acquired 20 min after intravascular injection of avidinated microbubbles (Av-MB). Av-MB binding and enhancement in Ts-Biotag embryos compared to wild-type (WT) littermates allowed visualization of embryonic vasculature and quantitation of vascular maps after threshold segmentation (bottom panels). (B) Similar experiments using MRI after injection of avidin-conjugated to DTPA-Gd (Av-DTPA-Gd) showed vascular labeling in maximum intensity projection (MIP) images and quantitative vascular maps. Cerebral blood vessels, CBV; dorsal aorta, DA; heart, H; intersomitic vessels, ISV; placenta, Pl.
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