Intra-plaque hemorrhage (IPH) and lipid core, characteristics of rupture prone carotid plaques, are often visualized in vivo with MRI using T1 weighted gradient and spin echo, respectively. Increasing magnetic field strength may help to identify IPH and lipid core better. As a proof of concept, automatic segmentation of plaque components was performed with the Mahalanobis distance (MD) measure derived from image contrast from multicontrast MR images including inversion recovery spin echo and T1 weighted gradient echo with fat suppression. After MRI of nine formaldehyde-fixated autopsy specimens, the MDs and Euclidean Distances between plaque component intensities were calculated for each MR weighting. The distances from the carotid bifurcation and the size and shape of calcification spots were used as landmarks for coregistration of MRI and histology. MD between collagen/ cell-rich area and IPH was largest with inversion recovery spin echo (4.2/9.3, respectively), between collagen/cell-rich area/foam cells and lipid core with T1 weighted gradient echo with fat suppression (26.9/38.2/4.6, respectively). The accuracy of detection of IPH, cell-rich area, and collagen increased when the MD classifier was used compared with the Euclidean Distance classifier. The enhanced conspicuity of lipid core and IPH in human carotid artery plaque, using ex vivo T1 weighted gradient echo with fat suppression and inversion recovery spin echo MRI and MD classifiers, demands further in vivo evaluation in patients. Magn Reson Med 67:1764-1775, 2012. V C 2011 Wiley Periodicals, Inc.Key words: MRI; rupture prone plaque; intra-plaque hemorrhage; lipid core Clinically, the degree of stenosis, which is generally identified by angiography, is often used as a marker for plaques that may give rise to clinical symptoms. However, lumenography is regarded to be insufficient for identification of vulnerable plaques for two reasons. Outward remodeling with preservation of lumen size is a characteristic of vulnerable plaques but cannot be identified with lumenography (1). Second, plaque composition rather than lumen size appears to determine plaque vulnerability. For identification of high-risk carotid artery plaque not only the classical markers of plaque vulnerabilitylarge lipid core (LC), a thin fibrous cap (2), and abundance of macrophages (3) but also intra-plaque hemorrhage (IPH) has been recognized as an important predictor of major clinical events, e.g., transient ischemic attack or stroke (4-6). MRI is the most promising technique for visualization of these plaque markers, because each plaque component generates unique MR contrast in various MR acquisitions, the technique is noninvasive and depicts the anatomy of the vessel. A substantial number of studies have been reported on carotid artery plaque MRI both ex vivo (7-11) and in vivo (4,5,(12)(13)(14)(15). In most studies, multicontrast weighted MRI is used for characterization of carotid atherosclerotic plaque. In particular, reports have stressed the importance of T2 weighted (T2w) spi...