Magnetic resonance imaging and spectroscopy of the murine cardiovascular system

Abstract

Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to noninvasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Furthermore, magnetic resonance spectroscopy (MRS) has allowed the nondestructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiological insights from the application of MRI/MRS technology to murine models of cardiovascular disease.

Fig. 1.

A: vector maps acquired by phase-contrast magnetic resonance imaging (MRI), displaying both direction (arrowhead) and amplitude (length of arrow) of myocardial motion. Systolic short-axis image in wild-type control mouse displays normal systolic contraction. Magnitude of myocardial contraction velocity is significantly reduced in creatine kinase (CK)-deficient mouse. B: graphical depiction of maximum contraction velocities in all groups. *P < 0.05 vs. wild-type control. Reproduced with permission from Nahrendorf et al. (94).

Fig. 2.

Tagged images obtained before myocardial infarction demonstrating baseline cardiac function: end-systolic image with left-right myocardial tags (A), end-systolic image with up-down myocardial tags (B), and percent circumferential shortening map (C). Tagged images obtained post-myocardial infarction: end-systolic image with left-right myocardial tags (D), end-systolic image with up-down myocardial tags (E), and percent circumferential shortening map (F). The area of severe dysfunction is shown in red. Reproduced with permission from Epstein et al. 2002 (31).

Fig. 3.

Ex vivo ³¹P magnetic resonance (MR) spectra of perfused mouse heart obtained at 11.75 T. P_i, inorganic phosphate; PCr, phosphocreatine, and and 3 phosphates of ATP are shown (α, β, and γ). ppm, Parts/million.

Fig. 4.

MR image of a mouse thorax (top, left) and 2 spatially localized ³¹P MR spectra acquired with one-dimensional chemical shift imaging from outside the chest and intersecting a spherical phantom containing a ³¹P standard (B) and another from the heart (A). An ECG tracing (C) is also shown, indicating the heart rate of ∼530/min. Reproduced with permission from Chacko et al. (15).

Fig. 5.

In vivo murine cardiac MRI (A), saturation (Sat) transfer ³¹P MR spectra (B–D) used to measure PCr/ATP (E), high-energy phosphate concentrations (F and G), and ATP kinetics (H) including the rate of ATP synthesis through CK (I). Note that overexpression of muscle-specific isoenzyme of CK (CK-M) improves metabolism in failing thoracic aortic constriction (TAC) hearts (E, F, and I) and improves contractile function at 4 and 12 wk post-TAC (J and K), although the latter is reversible and dependent on persistent CK-M overexpression (K). MRS, magnetic resonance spectroscopy; EF, ejection fraction; SV, stroke volume; CO, cardiac output. *P < 0.05; **P < 0.01; ***P < 0.001; ΔP < 0.01; #P = 0.07. Reproduced with permission from Gupta et al. (46).

Fig. 6.

Top: representative stacked ¹³C NMR spectra acquired in the first 60 s following [2-¹³C]pyruvate infusion into a perfused rat heart. [2-¹³C]Pyruvate was observed at 207.8 ppm. Peaks 1, 2, and 3 represent the metabolic products [5-₁₃C]glutamate (183.7 ppm), [1-¹³C]citrate (181.0 ppm), and [1-¹³C]acetylcarnitine (175.2 ppm); peak 4 represents natural abundance [1-¹³C]pyruvate (172.8 ppm, left inset); peak 5 represents [2-¹³C]pyruvate hydrate; and peaks 7 and 8 represent [2-¹³C]lactate and [2-¹³C]alanine. Bottom: summary of the metabolic fate of infused [2-¹³C]pyruvate along with the measured parameters of the observed metabolites in normal and ischemic isolated hearts. See Schroeder et al. (121) for definitions of symbols. Reproduced with permission from Schroeder et al. (121).