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Abstract #0030

In Vivo Volumetric MRI in Drug Discovery: A Preclinical Study of the Ezetimibe Therapeutic Efficacy on Atherosclerotic Plaque Burden in the Thoracic Ascending Arterial Tree in ApoE-/- Mice

Haiying Tang1, Ching H. Chang2, Donna Suresch1, Lesley A. Mcnamara2, Christopher Tong3, Bernd Misselwitz4, Dan Zhou1, Brett M. Connolly1, Jing Xu5, Xun Chen2, Xiaolan Shen6, Chunlian Zhang1, Eric L. Rickes2, Michelle Mariano6, Karim Azer5, Jun Wang2, Cyrille Sur1, Donald S. Williams1, Michael Klimas1, Andrew S. Plump1, Richard Hargreaves1, Haiying Liu1

1Imaging, Merck Research Laboratories, Rahway, NJ, USA; 2Cadiovascular Disease, Merck Research Laboratories, Rahway, NJ, USA; 3Biometrics, Merck Research Laboratories, Rahway, NJ, USA; 4TRG Diagnostic Imaging, Bayer Schering Pharma AG., Berlin, Germany; 5Applied Computer Science & Math, Merck Research Laboratories, Rahway, NJ, USA; 6LAR, Merck Research Laboratories, Rahway, NJ, USA

Volumetric MRI of atherosclerotic plaque in the thoracic ascending arterial tree may provide valuable insight into disease progression and therapeutic responses. In this study, in vivo MRI was validated to demonstrate the effectiveness of a potent cholesterol absorption inhibitor, ezetimibe, on the inhibition of the progression of atherosclerosis. Atherosclerotic plaque burden changes in apoE-/- mouse were monitored by longitudinal MRI using a plaque targeting contrast agent Gadofluorine-M. MRI plaque burden quantitation and therapeutic responses were validated by biological approaches. The volumetric data were evaluated to determine the most sensitive biomarker through univariate analysis of plaque volume, area, and thickness measurements.