A system and method for generating at least one optimized functional images of a lesion region of a subject is provided. The system includes a diffuse optical tomography (DOT) device, and a computing device. The DOT device is configured to acquire lesion functional data of an imaging volume including the lesion region of the breast and reference functional data from a corresponding imaging volume including healthy tissue within a contralateral breast. The computing device is programmed to generate at least one functional image of the breast by reconstructing the functional data at the plurality of regions including the lesion region and the surrounding adjacent background region. The functional images may be reconstructed by an optimization method regularized a preliminary estimate generated by applying a truncated pseudoinverse matrix of a weight matrix to the functional data. The optimized functional images relate to levels of hemoglobin at the voxels.
