Cardiac MR Imaging to Assess Heart Disease in Mice

Over the past decade, the field of cardiovascular MR (CMR) has rapidly evolved and introduced innovative applications across a wide range of research areas.

Cardiac MR research consists of:

  • evaluation of myocardial injury and myocardial infarction
  • characterization of pressure overload induced myocardial hypertrophy
  • investigations into pharmacologically or genetically induced hypertension
  • identification of sex specific or hormonal effects of cardiac (dys)function and cardiac damage

In CMR of mice, a wide range of imaging methods is available. Applications of CMR comprise evaluation of cardiac anatomy, myocardial perfusion, regional wall motion, myocardial viability, cardiac function assessment, and cardiac chamber quantification. This study focuses on the evaluation of morphometric and cardiac function.

Cardiac Hardware/Software

Since mice have a small build and have heart rates ranging from 400 to 600 beats per minute, dedicated cardiac hardware/software and customized imaging protocols are necessary to obtain appropriate spatial and temporal resolution for CMR in mice.

A field strength ≥7 Tesla is generally preferred. Images in this report were obtained with the help of a Bruker Biospec 9.4/20) and radio-frequency (RF) coils with improved dimensions, such as a Bruker four-element cardiac coil array (for signal reception) along with a Bruker linear volume resonator (for signal transmission).

Dynamic (Cine) Cardiac MR Imaging

Dynamic imaging of the heart for evaluation of myocardial contractile function, cardiac morphology, and wall motion demands high temporal resolution, full coverage of the cardiac cycle, and high muscle/blood contrast.

In order to balance these constraints, spoiled gradient echo based cine imaging methods are employed. Multiple frames are obtained during the cardiac cycle and the image acquisition is proliferated across a series of heart beats, which need synchronization with the cardiac cycle. For this reason, ECG is generally used for cardiac gating.

Experimental Protocol

1.5% Isoflurane in an oxygen/air mixture (2:1) with a flow rate of 750 ml/min is used for anesthesia. Body temperature, heart rate, and respiration rate through pulse oximeter are monitored utilizing an MR compatible small animal monitoring and gating system. Animals are placed in a prone fashion on the heart array coil. A warm water heating is used to maintain a stable body temperature.

MR Protocols

The following methods are used for MR protocols:

  • Single-slice FLASH cine: ScanMode ‘RetrospectiveGating', TR 5 ms, TE 2.9 ms, FOV 35 mm, matrix size 128 zero-filled to 256, 0.7 mm slice thickness, 30 repetitions, 10 cardiac movie frames.
  • Multi-slice tri-pilot: ScanMode'PilotScan',TR85ms,TE 1,5 ms, FOV 35 mm, 3x7 slices of 0.7 mm thickness, 10 repetitions.
  • Multi-slice FLASH cine: TR 72 ms, TE 2.1 ms, FOV 30 mm, matrix size 192x128 zero-filled to 256, spatial resolution 156 x 234 µm2, 8 slices of 0.8 mm thickness, 70 repetitions, 20 cardiac movie frames (cardiac phases), acquisition time 10 min 51 sec.

Standard Cardiac Views

The shape of the heart defines the standard views in cardiac MRI: the long axis four chamber view (4CV) and the short axis view (SAX).

Because of the double oblique direction of the heart, these views have to be obtained in a number of steps, starting with a multi-slice tri-pilot.

Depending on the coronal pilot images, a single-slice cine image is obtained such that the slice joins the apex and the center of the left atrio-ventricular valve, as shown in figure 1.

Similarly, another single-slice cine is placed in the same manner but perpendicular to the earlier image slice. Finally, the SAX slice package is placed perpendicular to this image and also perpendicular to the long heart axis, as indicated in figure 1.

For quantification and quantitative function assessment of cardiac chamber, the entire left ventricle needs to be covered from the base to apex with multiple adjacent slices and for all cardiac phases. The first slice is placed beneath the mitral valve in end diastole, and the last slice is positioned low enough to prevent lumen penetration.

Contrast between Bright and Black-Blood

The contrast of cine images is normally dominated by bright inflowing blood that includes unsaturated spins, against the darker stationary tissues inside the image slice (bright-blood contrast). On the other hand, blood suppression (black-blood contrast) can help prevent flow artifacts and improve blood/endocardium contrast.

Blood suppression can be attained by positioning a saturation band over the atria parallel to the imaging slice package with a gap of about one slice thickness. The thickness of the saturation slice must be sufficiently broad to cover the atria and afferent vessels.

Analysis of Contractile Function and Cardiac Morphology

Although gross effects of myocardial infarction, like those illustrated in figures 4 and 5, can easily be evaluated by visual inspection of the SAX and 4CV views, quantitative data is important in most studies. In visual assessments, slight pathologies may not be identified.

Evaluation of cardiac mass and contractile function involves the division of the myocardium on multiple SAX images, covering the heart from base to apex. Accurate data analysis is critical for assessing left ventricular function to ensure that the mean inter-observer variability is less than 5%.

Therefore, meticulous separation of epi- and endocardial borders is needed for cardiac phases obtained from end diastole and end systole. To achieve this objective, the CMR42 or Mass4Mice software is recommended.

Advantages of a Cryogenic RF coil

Signal-to-noise ratio (SNR) constraints tend to restrict blood myocardium delineation and image quality that critically depend on high spatial resolution. A cryogenic RF coil (CryoProbe, Bruker Biospin) offers SNR gains of 3.0 to 5.0 against the traditional mouse heart coil array and therefore allows an improved spatial resolution. This dramatically enhances the image quality and promotes improved and precise cardiac chamber quantification, owing to reduced inter- and intra-observer variability.

Conclusion

Cardiac MR imaging is increasingly being used for animal research. This should help in advancing the capabilities of MRI for assessment of heart diseases.

Acknowledgement

Produced from articles authored by Andreas Pohlmann, Babette Dieringer, Philipp Boyé, Jeanette Schulz-Menger and Thoralf Niendorf.

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Last updated: May 2, 2019 at 8:15 AM

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