Functional and morphologic imaging of coronary atherosclerosis in living mice using high-resolution color Doppler echocardiography and ultrasound biomicroscopy.

OBJECTIVES: This study aimed to establish non-invasive methods of assessing coronary artery morphology in normal and atherosclerotic mice in vivo.
BACKGROUND: Coronary flow velocity reserve (CFVR) has been shown to correlate with coronary minimal lumen diameter (MLD) in patients with coronary artery stenosis. In mice, there are no existing non-invasive imaging techniques allowing quantitative measurement of the coronary artery morphology and function.
METHODS: Systemic hemodynamic effects of adenosine were studied in seven C57BL/6 mice. In 17 C57BL/6 mice, CFVR was measured in the mid left coronary artery (LCA) using either hypoxia- or adenosine-induced coronary hyperemia. Further, in another 10 atherosclerotic low-density lipoprotein receptor (LDLR)-/- mice, the hypoxia-induced CFVR was performed and proximal LCA MLD was measured using ultrasound biomicroscopy (UBM). Histologic sections of the LCA were collected.
RESULTS: The adenosine dose of 160 microg/kg/min induced maximal coronary hyperemia without any systemic hemodynamic effects. Adenosine and hypoxia-induced CFVR values averaged at 2.0 +/- 0.1 and 1.9 +/- 0.3, respectively, in C57BL/6 mice (p = NS). In LDLR-/- mice, CFVR and MLD ranged between 1.4 to 2.9 microm and 190 to 370 microm, respectively. Histology revealed proximal lumen-narrowing plaques in the LCA. Significant correlation was found between hypoxia-induced CFVR and the MLD (p < 0.005, R2 = 0.8707).
CONCLUSIONS: The CDE and UBM technique can be used to measure atherosclerosis-related lumen narrowing of the LCA in living mice. These non-invasive techniques may provide us with novel tools for following up disease status in mouse coronary arteries in a quantitative manner.