Assessment of global and regional myocardial function in the mouse using cine and tagged MRI

Abstract

Mouse models are expected to play an important role in future investigations of human cardiac diseases. In the present report, MRI methods for determining global and regional cardiac function in the mouse are demonstrated. ECG-gated cine images were acquired in five C57BL/6 mice at physiological temperatures (37°C) and heart rates of 500 ؎ 50 beats per minute. Left ventricular mass, ejection fraction, and cardiac output were estimated from the resulting images. Regional myocardial function was also determined in three animals by application of 2D SPAtial Modulation of Magnetization (SPAMM) in combination with the cine protocol. The quality of the tagged images was sufficient to allow mapping of myocardial strains and displacements. The results of the regional strain analysis were consistent with similar studies in larger animals. Recent advances in molecular genetics and the description of the mouse genome have made the mouse a key model for understanding and characterizing human diseases. Of the many disorders for which murine models are suitable, heart failure is known to contribute to more fatalities in developed countries than any other disease (1). These facts have been the driving force in the development of numerous genetically engineered murine models for studying a broad spectrum of heart disease. Targeted ablation (knockout) or overexpression (knockin) of genes responsible for various aspects of cardiac development, differentiation, and function have yielded mouse models of cardiac hypertrophy (2), dilated cardiomyopathy (3), and hypertrophic cardiomyopathy (4). More sophisticated models that allow controlled activation of a specific gene have been demonstrated and continue to be developed (5). The study of these models would benefit significantly from a nondestructive and noninvasive method for the detailed assessment of heart function.Two-dimensional and M-mode echocardiography are frequently used tools for evaluating global and regional cardiac function in mouse models (6). The method is inexpensive, portable, and well-suited for repeated studies. However, quantitative echocardiography makes use of geometric assumptions and is subject to variability, especially for deformed ventricles.MRI methods for determining cardiac function utilize tomographic acquisition techniques and as such are free from these complications. MRI has been shown to yield accurate and reliable quantification of murine global myocardium function, left ventricular (LV) mass, and right ventricular size (7-9). A particularly useful and unique capability of MR is the ability to noninvasively generate fiducial markers. Spatial modulation of magnetization (SPAMM) uses gradient and RF pulses to generate a grid of dark bands within an image (10,11). These bands track the deformation of the myocardium during the heart cycle and can be used to extract regional measures of the strain within the tissues. Myocardial strain parameters measured by this method have been validated by comparison to sonomicrometry (12) and databases of normal val...

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Magnetic resonance imaging of regional cardiac function in the mouse

“…Regional tissue viability can be assessed with perfusion MR, e.g., using arterial spin labeling techniques [8], or from the delayed enhancement effect following gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) injection [9]. Phase velocity [10] and tagging techniques [11][12][13][14] are able to measure local wall motion and muscle fiber shortening, which provide important insights into local tissue function. The metabolic state of the heart tissue can be determined using 31 P-, 13 C-, or 23 Na magnetic resonance spectroscopy (MRS) [15][16][17], or by MRI measurements of the local influx of Mn 2+ , which acts as an MRI contrast agent and can be considered a calcium analogue [18].…”