Published Online
on September 3, 2002

A more recent version of this article appeared on September 24, 2002

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Submitted on May 6, 2002
Revised on July 1, 2002
Accepted on July 2, 2002

Repeated Three-Dimensional Magnetic Resonance Imaging of Atherosclerosis Development in Innominate Arteries of Low-Density Lipoprotein Receptor-Knockout Mice

Paul D. Hockings PhD^*, Toby Roberts BSc Hons, Graham J. Galloway PhD, David G. Reid PhD, Dorothy A. Harris , Martin Vidgeon-Hart AIBMS, Pieter H.E. Groot PhD, Keith E. Suckling PhD, and G. Martin Benson PhD

From the Imaging Group (P.D.H., T.R., D.G.R., M.V.-H.), GlaxoSmithKline, The Frythe, Welwyn, UK; the Centre for Magnetic Resonance (G.J.G.), University of Queensland, St Lucia, Australia; and the Department of Atherosclerosis (D.A.H., P.H.E.G., K.E.S., G.M.B.), GlaxoSmithKline Medicines Research Centre, Stevenage, UK.

^* To whom correspondence should be addressed. E-mail: paul.d.hockings{at}gsk.com.

Background—In vivo methods to evaluate the size and composition of atherosclerotic lesions in animal models of atherosclerosis would assist in the testing of antiatherosclerotic drugs. We have developed an MRI method of detecting atherosclerotic plaque in the major vessels at the base of the heart in low-density lipoprotein (LDL) receptor-knockout (LDLR^-/-) mice on a high-fat diet.

Methods and Results—Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with 140-µm isotropic resolution, over 30 minutes. Comparison of normal and fat-suppressed images from female LDLR^-/- mice 1 week before and 8 and 12 weeks after the transfer to a high-fat diet allowed visualization and quantification of plaque development in the innominate artery in vivo. Plaque mean cross-sectional area was significantly greater at week 12 in the LDLR^-/- mice (0.14±0.086 mm² [mean±SD]) than in wild-type control mice on a normal diet (0.017±0.031 mm², P<0.01). In the LDLR^-/- mice, but not control mice, increase in plaque burden at week 12 relative to week 1 was also highly significant (P=0.001). Lumen cross section was not significantly different between time points or groups. MRI and histological assessments of plaque size were closely correlated (R=0.8). The lumen of proximal coronary arteries could also be visualized.

Conclusions—This is the first report of in vivo detection of aortic arch atherosclerosis in any animal model. The method could significantly assist rapid evaluation of experimental antiatherosclerotic therapies.

Key words: magnetic resonance imaging • atherosclerosis • receptors • mice • arteries

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