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Developing metrics of medical image quality requires an understanding of how anatomic backgrounds reduce human visual detection performance. Visual psychophysics has shown that there are two distinct ways in which a complex background can degrade performance: (1) the presence of a deterministic high-contrast background, (2) variability in the background from location to location. The authors investigated how these two sources of performance degradation reduce human visual performance locating a lesion in anatomic backgrounds.Human performance localizing a disk-shaped lesion in one of four locations (four alternative forced choice) was measured for three background conditions. In the first condition the background was a uniform gray. In the second condition (the repeated background condition) an anatomic background was sampled on each trial and used as a background for the four possible lesion locations. In the third condition (the different background condition) four different anatomic backgrounds were sampled on each trial and used for the four possible lesion locations. Test images consisted of computer simulated lesions mathematically projected on digital x-ray coronary angiograms.For five levels of lesion contrast, visual detection performance for two observers decreased significantly from the uniform background condition to the repeated background condition, and decreased even further for the different background condition.Study results show that both the presence of a deterministic high-contrast background and the background variations contribute to performance degradation of human visual detection of signals in anatomic backgrounds.