From The Cardiovascular Institute, Mount Sinai School of Medicine, New
York, NY (Z.A.F., J.T.F., M.S., M.P., J.J.B., E.A.F., V.F.); the Division of
Biochemical Development and Molecular Diseases, Children's Hospital of
Philadelphia, Philadelphia, Pa (S.W.); and the Laboratory of Biochemical
Genetics and Metabolism, Rockefeller University, New York, NY (H.M.D., S.A.C.,
J.L.B.).
Correspondence to Zahi A. Fayad, PhD, Mount Sinai School of Medicine, The Cardiovascular Institute and Department of Radiology, Box 1234, One Gustave L. Levy Place, New York, NY 10029-6574. E-mail fayadz01{at}doc.mssm.edu
Background—The pathogenesis of
atherosclerosis is currently being investigated in
genetically engineered small animals. Methods to follow the time course
of the developing pathology and/or the responses to therapy in vivo
are limited.
Methods and Results—To address this problem, we developed a
noninvasive MR microscopy technique to study in vivo atherosclerotic
lesions (without a priori knowledge of the lesion location or
lesion type) in live apolipoprotein E–knockout (apoE-KO) mice. The
spatial resolution was 0.0012 to 0.005 mm3. The lumen
and wall of the abdominal aorta and iliac arteries were identified on
all images in apoE-KO (n=8) and wild-type (n=5) mice on chow diet.
Images obtained with MR were compared with corresponding
cross-sectional histopathology (n=58). MR accurately determined wall
area in comparison to histopathology (slope=1.0,
r=0.86). In addition, atherosclerotic lesions were
characterized in terms of lesion shape and type. Lesion type was graded
by MR according to morphological appearance/severity and by
histopathology according to the AHA classification. There was excellent
agreement between MR and histopathology in grading of lesion shape and
type (slope=0.97, r=0.91 for lesion shape; slope=0.64,
r=0.90 for lesion type).
Conclusions—The combination of high-resolution MR microscopy and
genetically engineered animals is a powerful tool to investigate
serially and noninvasively the progression and regression of
atherosclerotic lesions in an intact animal model and should greatly
enhance basic studies of atherosclerotic disease.
© 1998 American Heart Association, Inc.
Basic Science Reports
Noninvasive In Vivo High-Resolution Magnetic Resonance Imaging of Atherosclerotic Lesions in Genetically Engineered Mice
Key Words: atherosclerosis • magnetic resonance imaging • genes
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