Serial studies of mouse atherosclerosis by in vivo magnetic resonance imaging detect lesion regression after correction of dyslipidemia

Abstract

Objective-We determined the effects of sustained normocholesterolemia on advanced mouse atherosclerosis and whether changes in plaque size and composition can be detected noninvasively by MRI. Methods and Results-Aortic arch segments containing advanced lesions from apolipoprotein E-deficient (apoE-/-) mice (total cholesterol 1281±97 mg/dL) were transplanted into syngeneic wild-type (WT; 111±11 mg/dL) or apoE-/- (702±74 mg/dL) recipient mice on chow diet. Mice underwent serial MRI at 3, 5, 7, and 9 weeks after transplantation. Compared with 3 weeks, correction of dyslipidemia in WT recipient mice resulted in a monotonic decrease (regression) in arterial wall volume, whereas in apoE-/- recipient mice, further plaque progression was noted (P<0.05). MRI and histological measurements were closely correlated (R=0.937). The lesional content of macrophages decreased >90% (P<0.001), and smooth muscle cells increased in the WT recipient mice. In vivo T 1-, T2-, and proton density-weighted images of the mouse thoracic aorta differentiated intraplaque lipid and collagen. Conclusions-Plaque changes can be noninvasively monitored by serial in vivo MRI of a mouse regression model. Our ability to image the thoracic aorta and perform in vivo plaque characterization will further enhance atherosclerosis studies.