Small animal models, such as mice, are playing an increasingly important role in cardiovascular research. However, characterization of the cardiac phenotype in these models has a proven to be a quite challenging, and has thus provided the MRI community with a unique set of opportunities. Cardiac MRI in mice is, however, fairly challenging in its own right. The heart of a mouse is smaller than a peanut and beats at approximately 600 beats per minute. Nevertheless, with the appropriate physiological monitoring and pulse sequence design, high-resolution images of the beating mouse heart can be obtained in-vivo.
The 9.4 Tesla small animal scanner in our center lies at the core of our small-animal imaging program. This scanner (Bruker Biospec) is a horizontal bore system, which allows cardiac physiology in the mouse to be monitored with relative ease during a scan. We have two dedicated small animal monitoring systems in our center from SA Intruments Inc., which allow us to follow both the heart rate (ECG) and respiration of a mouse while in the bore of the scanner, and to trigger the MR acquisition to one or both of these physiological signals. In addition, we have built a dedicated surface coil for cardiovascular imaging at 9.4 Tesla, which provides a significant improvement in SNR.
Many of our studies involve the acquisition of bright blood cine MR images in live mice to evaluate cardiac function and physiology. We have modified and optimized the FLASH sequence on our scanner for cardiac imaging, and routinely obtain images with in-plane resolutions of 100-150 mm. The frame rate of these cines can likewise be defined by the user, with values as high as 240 frames per second possible.
Figure 1: End diastolic frames from cine acquisitions in live mice. The image on the left has been acquired in the short axis at the mid-ventricular level, while the image on the right provides a long axis view of the ventricles and the aortic root.
Tagged cines can also be obtained with a similar spatial and temporal resolution to that of regular cines. We are using these cines to study cardiac mechanics in mice with both normal and abnormal myocardial function.
|Figure 2: Systolic frame from tagged cine in a normal mouse.
In addition to a highly active mouse-imaging program, we also regularly perform cardiac studies on rats on the 4.7 Tesla (Bruker Biospec) system in our center. A 14 Tesla, 89 mm, vertical bore scanner (Bruker Avance) has recently been installed in our center and has been used for ultra-high resolution MR microscopy studies on ex-vivo specimens. Isotropic resolutions of 40 mm can be routinely achieved with this system. In-vivo studies on this system are being planned as well.
The small animal imaging initiative in our center is a collaborative effort between physicists, software and hardware engineers, cardiologists, physiologists and molecular biologists. The Bruker platform is extremely flexible and ideal for the development of new techniques for cardiac imaging. Mouse models suited to the validation of virtually any new imaging technique are available to us and highly convenient to use. For the biologist and translational researcher, MRI provides unique insights into cardiac pathophysiology, and allows serial studies to be performed. Our small-animal imaging group has thus developed into a highly stimulating environment where cutting-edge MRI technology and world-class molecular biology combine to address cardiovascular disease in novel and pioneering ways.