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)-, T(2)-, 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. Serial in vivo MRI of mouse arterial plaque after correction of dyslipidemia revealed a monotonic decrease in lesion size (regression) and changes in lesion composition consistent with a stable plaque phenotype. Serial in vivo MRI will enhance studies of plaque regression in animal models in response to therapeutic interventions.