Repeated three-dimensional magnetic resonance imaging of atherosclerosis development in innominate arteries of low-density lipoprotein receptor-knockout mice.
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.


RESULTS
Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with approximately 140- micro m 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.
Hockings
Paul D
PD
Imaging Group, GlaxoSmithKline, The Frythe, Welwyn, UK. paul.d.hockings@gsk.com
Roberts
Toby
T
Galloway
Graham J
GJ
Reid
David G
DG
Harris
Dorothy A
DA
Vidgeon-Hart
Martin
M
Groot
Pieter H E
PH
Suckling
Keith E
KE
Benson
G Martin
GM
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000175:diagnosis* / Q000473:pathology; D016122:Brachiocephalic Trunk / Q000473:pathology*; D004041:Dietary Fats; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D011237:Predictive Value of Tests; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics
D004041:Dietary Fats; D011973:Receptors, LDL