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Initial clinical results indicate that multislice spiral computed tomography (MDCT) might be useful for the noninvasive characterization of human coronary plaque morphology by determining tissue density within the lesions. This seems to be of clinical relevance, because coronary artery disease might be detected at an early stage before calcifications occur and noncalcified plaques that may be more likely to rupture could also be visualized noninvasively. The aim of the present study was to evaluate the reliability of contrast-enhanced MDCT in differentiating human atherosclerotic coronary plaque morphology by comparing it with the histopathologic gold standard.Twelve human hearts were scanned postmortem using an MDCT (Somatom Volume Zoom; Siemens, Forchheim, Germany) high-resolution computed tomography scanner to detect atherosclerotic coronary plaques. Density measurements were performed within detected plaque areas. The exact location of each plaque was marked at the surface of the heart to assure accurate histopathologic sectioning of these lesions. The plaques were classified according to a modified Stary classification. Seventeen plaques were identified by MDCT. Six plaques were histopathologically classified as lipid rich (Stary III/IV), 6 plaques as intermediate (Stary V), and 5 plaques as calcific (Stary VII). Lipid-rich plaques had a mean density on MDCT of 42 ± 22 Hounsfield units (HU), intermediate plaques had a mean density of 70 ± 21 HU, and calcific plaques had a mean density of 715 ± 328 HU. ANOVA analysis revealed a significant difference in plaque density between the 3 groups (P < 0.0001).The comparison with histopathology confirms that tissue density as determined by contrast-enhanced MDCT might be used to differentiate atherosclerotic plaque morphology.