An apparatus for multi-energy tissue quantification includes an x-ray imaging system comprises an x-ray source configured to emit a beam of x-rays toward an object to be imaged, a detector configured to receive the x-rays attenuated by the object, and a data acquisition system (DAS) operably coupled to the detector. A computer operably connected to the x-ray source and the DAS is programmed to cause the x-ray source to emit x-rays at each of a first kVp and a second kVp toward the detector, acquire x-ray data from x-rays emitted at the first and second kVp through a region of interest (ROI), and perform a first multi-material decomposition based on the acquired x-ray data. The computer is also programmed to quantify a volume fraction of a first material in the ROI based on the first multi-material decomposition and display the volume fraction of the first material to a user.