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A novel two-step reconstruction scheme using a combined near-infrared and ultrasound technique and its utility in imaging distributions of optical absorption and hemoglobin concentration of breast lesions are demonstrated. In the first-step image reconstruction, the entire tissue volume is segmented based on initial coregistered ultrasound measurements into lesion and background regions. Reconstruction is performed by use of a finer grid for lesion region and a coarse grid for the background tissue. As a result, the total number of voxels with unknown absorption can be maintained on the same order of total measurements, and the matrix with unknown total absorption distribution is appropriately scaled for inversion. In the second step, image reconstruction is refined by optimization of lesion parameters measured from ultrasound images. It is shown that detailed distributions of wavelength-dependent absorption …