A system and method for non-invasively estimating an absolute blood flow of a vascular region in a subject using optical data are provided. In some aspects, the method includes acquiring optical data from the vascular region using one or more optical sensors placed about the subject, and determining, using the optical data, an index of blood flow and. a blood volume associated with the vascular region. The method also includes computing a blood inflow and a blood outflow using the index of blood flow and the blood volume, and estimating an absolute blood flow using the blood inflow and blood outflow. The method further includes generating a report indicative of the absolute blood flow of the vascular region.
