Recent advances in small-animal cardiovascular imaging

Abstract

Because of the development of gene knockout and transgenic technologies, small animals, such as mice and rats, have become the most widely used animals for cardiovascular imaging studies. Imaging can provide a method to serially evaluate the effect of a particular genetic mutation or pharmacologic therapy (1). In addition, imaging can be used as a noninvasive screening tool for particular cardiovascular phenotypes. Outcome measures of therapeutic efficacy, such as ejection fraction, left ventricular mass, and ventricular volume, can be determined noninvasively as well. Furthermore, small-animal imaging can be used to develop and test new molecular imaging probes (2,3). However, the small size of the heart and rapid heart rate of murine models create special challenges for cardiovascular imaging.

FIGURE 1

Representative short-axis end-diastolic (left) and end-systolic (right) images from 16–cardiac phase cine, black-blood imaging sequence in mouse using 7-T MRI scanner (spatial resolution of 0.1 × 0.1 × 1 mm) with a clinical user interface acquired in 4 min. Notice high contrast from ventricular cavity and myocardium that enables highly accurate measurement of left ventricular global function. Courtesy of Dr. Fred Epstein.

FIGURE 2

BLI after intramuscular injection in medial thigh of rabbit model of peripheral arterial disease provides ability to assess cell viability in vivo in radiography-visible encapsulated MSCs similar to that in nonencapsulated MSCs. Bioluminescence image was acquired in 60 s and overlaid on light image for anatomic delineation. MSCs = mesenchymal stem cells.

FIGURE 3

SPECT/CT rendering of ¹¹¹In-oxine radiolabeled MSCs (∼2,886 kBq [∼78 mCi] total activity) delivered intravenously to rat with doxyrubicine cardiotoxicity demonstrates initial high lung uptake (blue green on SPECT) immediately after injection (left), followed by redistribution to other organs at 24 h (right). MSCs = mesenchymal stem cells.

FIGURE 4

Sample ultra-high-resolution ^99mTc-tetrofosmin SPECT images of heart of mouse in end-diastole (ED) and end-systole (ES), showing myocardial perfusion in minute detail in papillary muscles and right ventricular wall. Male C57BL/6 mouse (30 g) was injected intravenously with 190 MBq of ^99mTc-tetrofosmin and anesthetized using ketamine, medetomidine, and atropine. At 45 min after injection, mouse was imaged for 1 h using U-SPECT-II system with 0.6-mm-diameter pinhole inserts. During image acquisition, an ECG trigger signal was acquired (BioVet; m2m Imaging) and incorporated in list-mode data. A 16-gate reconstruction was performed. Image data courtesy of Freek J. Beekman.

FIGURE 5

Same single whole-body transaxial section from ¹⁸F-FDG mouse study (26-g mouse, ∼11.1 MBq [0.3 mCi] injected). Data were acquired using commercial small-animal PET system over 30 min, about 1 h after injection, and reconstructed with 3 different methods: Fourier rebinning (FORE)/filtered backprojection, FORE/2D ordered-subset expectation maximization (OS-EM), and 3D OS-EM. RV myocardium and intensely labeled LV myocardium are seen in all 3 ¹⁸F-FDG reconstructions. FBP = filtered backprojection.