Comprehensive cardiovascular magnetic resonance of myocardial mechanics in mice using three-dimensional cine DENSE

Abstract

Background: Quantitative noninvasive imaging of myocardial mechanics in mice enables studies of the roles of individual genes in cardiac function. We sought to develop comprehensive three-dimensional methods for imaging myocardial mechanics in mice.

Methods: A 3D cine DENSE pulse sequence was implemented on a 7T small-bore scanner. The sequence used three-point phase cycling for artifact suppression and a stack-of-spirals k-space trajectory for efficient data acquisition. A semi-automatic 2D method was adapted for 3D image segmentation, and automated 3D methods to calculate strain, twist, and torsion were employed. A scan protocol that covered the majority of the left ventricle in a scan time of less than 25 minutes was developed, and seven healthy C57Bl/6 mice were studied.

Results: Using these methods, multiphase normal and shear strains were measured, as were myocardial twist and torsion. Peak end-systolic values for the normal strains at the mid-ventricular level were 0.29 ± 0.17, -0.13 ± 0.03, and -0.18 ± 0.14 for E(rr), E(cc), and E(ll), respectively. Peak end-systolic values for the shear strains were 0.00 ± 0.08, 0.04 ± 0.12, and 0.03 ± 0.07 for E(rc), E(rl), and E(cl), respectively. The peak end-systolic normalized torsion was 5.6 ± 0.9°.

Conclusions: Using a 3D cine DENSE sequence tailored for cardiac imaging in mice at 7 T, a comprehensive assessment of 3D myocardial mechanics can be achieved with a scan time of less than 25 minutes and an image analysis time of approximately 1 hour.

Figure 1

Timing diagram for the 3D cine DENSE pulse sequence. Timing diagram for the 3D cine DENSE pulse sequence. Upon detection of an ECG trigger, a displacement-encoding module is played out. Phase cycling of the second radiofrequency pulse is used for artifact suppression. The displacement-encoding module is followed by successive multiphase applications of a readout module, which includes a displacement unencoding gradient. A stack-of-spirals k-space trajectory is used to achieve efficient data sampling. For mouse heart imaging at 7T, a relatively short spiral readout is used to reduce off-resonance-induced blurring.

Figure 2

Diagram of left-ventricular strain and twist. Diagram of left-ventricular strain and twist. A 3D view is shown in (A), a 2D short-axis view as observed from the LV base is shown in (B), and a 2D long-axis view is displayed in (C). Strain measures the lengthening or shortening of muscle tissue in a given direction. During contraction, normal tissue lengthens radially (RR), shortens both circumferentially (CC) and longitudinally (LL), and shears slightly (RC, RL, CL). Twist (θ) measures the angular displacement of muscle tissue around the left ventricular centerline. During contraction, normal tissue undergoes a clockwise twist from p(0) to p(t).

Figure 3

Example end-systolic images from one mid-ventricular short-axis partition. Example end-systolic images from one mid-ventricular short-axis partition from a 3D cine DENSE dataset of a mouse heart. A magnitude-reconstructed image is shown in (A), and phase-reconstructed images are shown in (B-D), where the image in (B) is encoded for displacement in the y-direction, the image in (C) is encoded for displacement in the x-direction, and the image in (D) is encoded for displacement in the z-direction. Phase wrapping within the myocardium occurred in (B) and (C), and is accounted for by phase unwrapping during image analysis.

Figure 4

Example end-systolic short-axis E_rr, E_cc, and E_ll strain maps. Example end-systolic short-axis E_rr, E_cc, and E_ll strain maps at basal, mid-ventricular, and apical locations measured using 3D cine DENSE in a normal mouse. Fairly uniform shortening is observed for the circumferential and longitudinal strains, while fairly uniform lengthening is observed for radial strain.

Figure 5

Bar chart of the average end-systolic normal and shear strains. Bar chart of the average end-systolic normal (A) and shear strains (B) at the basal, mid-ventricular, and apical levels for the 7 healthy mice measured by 3D cine DENSE in this study. Data are plotted as mean ± standard error.

Figure 6

Normal strain-time curves for healthy mice measured by 3D cine DENSE. Normal strain-time curves for healthy mice measured by 3D cine DENSE. The average E_rr, E_cc, and E_ll values for the 7 mice studied are plotted as a function of cardiac phase. Furthermore, separate curves are shown for the subendocardial and subepicardial layers. A statistically significant difference in E_cc between the two layers was detected (B). No significant differences between layers were found for E_rr and E_ll, although both of these strains showed consistent trends towards larger absolute values in the subendo- vs. subepicardium. Data are plotted as mean ± standard error.

Figure 7

Shear strain-time curves for healthy mice measured by 3D cine DENSE. Shear strain-time curves for healthy mice measured by 3D cine DENSE. The average E_rc, E_rl, and E_cl for the 7 mice are plotted as a function of cardiac phase. Data are plotted as mean ± standard error.

Figure 8

Myocardial twist and torsion as a function of cardiac phase measured by 3D cine DENSE in seven mice. Myocardial twist and torsion as a function of cardiac phase measured by 3D cine DENSE in seven mice. In (A), twist angle as a function of cardiac phase is shown for basal, mid-ventricular, and apical locations. In (B), LV torsion, which is the normalized gradient of twist in the longitudinal direction, is plotted. Data are plotted as mean ± standard error.