This study presents in vivo diffuse optical tomography (DOT) of the human breast after indocyanine green (ICG) enhancement, performed concurrently with magnetic resonance imaging (MRI). The goal was to coregister ICG-enhanced optical images with Gadolinium (Gd)-enhanced MRI images to validate the ability of DOT to image breast tissue. The study involved three cases: a ductal carcinoma, a fibroadenoma, and a control case with no suspicious enhancement. The ICG-enhanced optical images showed good congruence with Gd-enhanced MRI images, demonstrating the potential of ICG to differentiate disease based on quantified enhancement of suspicious lesions. DOT is an emerging imaging modality with potential applications in radiology. It can produce quantitative images of intrinsic and extrinsic absorption and scattering in diffuse media such as tissue. These quantities can be used to derive tissue oxy- and deoxyhemoglobin concentrations, blood oxygen saturation, contrast agent uptake, and organelle concentration. DOT has the advantage of using non-ionizing radiation and relatively low cost instrumentation, but its main disadvantage is low spatial resolution due to the highly scattering nature of tissue in the near-infrared (NIR) region. The study used a NIR imager with a time-domain system and a laser diode at 830 nm. The DOT system used a 3x8 grid of source fibers and a 2x4 grid of detector fibers. The reconstruction process involved solving the forward problem using a perturbation approach and the inverse problem using matrix inversion. The study used five frequencies (80, 160, 240, 320, and 400 MHz) and an algebraic reconstruction technique with a relaxation parameter of 0.1 and 500 iterations. The MRI study used a 1.5 T imager with a body coil as the transmitter and a custom-built multicoil as the receiver. The examination protocol involved simultaneous MRI and DOT studies with informed consent. The study involved patients scheduled for excisional biopsy or surgery, with a previous suspicious mammogram or palpable lesion. The results showed that DOT could localize and quantify enhancing lesions in vivo. The ICG-enhanced images showed good congruence with Gd-enhanced MRI images, with the carcinoma showing a marked absorption increase. The fibroadenoma showed a moderate ICG enhancement, while the control case showed no suspicious enhancement. The study demonstrated the potential of ICG in diffuse optical mammography and the possibility of using DOT with engineered contrast agents to probe specific functionality in vivo. The study also showed that the use of quantified information is important for DOT diagnosis, as it produces quantitative images of the absorption coefficient. The study concluded that DOT has the potential to be used for clinical applications in breast imaging, with the ability to differentiate between disease and other structures based on quantified enhancement.This study presents in vivo diffuse optical tomography (DOT) of the human breast after indocyanine green (ICG) enhancement, performed concurrently with magnetic resonance imaging (MRI). The goal was to coregister ICG-enhanced optical images with Gadolinium (Gd)-enhanced MRI images to validate the ability of DOT to image breast tissue. The study involved three cases: a ductal carcinoma, a fibroadenoma, and a control case with no suspicious enhancement. The ICG-enhanced optical images showed good congruence with Gd-enhanced MRI images, demonstrating the potential of ICG to differentiate disease based on quantified enhancement of suspicious lesions. DOT is an emerging imaging modality with potential applications in radiology. It can produce quantitative images of intrinsic and extrinsic absorption and scattering in diffuse media such as tissue. These quantities can be used to derive tissue oxy- and deoxyhemoglobin concentrations, blood oxygen saturation, contrast agent uptake, and organelle concentration. DOT has the advantage of using non-ionizing radiation and relatively low cost instrumentation, but its main disadvantage is low spatial resolution due to the highly scattering nature of tissue in the near-infrared (NIR) region. The study used a NIR imager with a time-domain system and a laser diode at 830 nm. The DOT system used a 3x8 grid of source fibers and a 2x4 grid of detector fibers. The reconstruction process involved solving the forward problem using a perturbation approach and the inverse problem using matrix inversion. The study used five frequencies (80, 160, 240, 320, and 400 MHz) and an algebraic reconstruction technique with a relaxation parameter of 0.1 and 500 iterations. The MRI study used a 1.5 T imager with a body coil as the transmitter and a custom-built multicoil as the receiver. The examination protocol involved simultaneous MRI and DOT studies with informed consent. The study involved patients scheduled for excisional biopsy or surgery, with a previous suspicious mammogram or palpable lesion. The results showed that DOT could localize and quantify enhancing lesions in vivo. The ICG-enhanced images showed good congruence with Gd-enhanced MRI images, with the carcinoma showing a marked absorption increase. The fibroadenoma showed a moderate ICG enhancement, while the control case showed no suspicious enhancement. The study demonstrated the potential of ICG in diffuse optical mammography and the possibility of using DOT with engineered contrast agents to probe specific functionality in vivo. The study also showed that the use of quantified information is important for DOT diagnosis, as it produces quantitative images of the absorption coefficient. The study concluded that DOT has the potential to be used for clinical applications in breast imaging, with the ability to differentiate between disease and other structures based on quantified enhancement.