The disclosed embodiments relate to determining an amount of a contrast agent in an image. For example, a computer-implemented method of image processing includes generating, from a first polychromatic contrast-enhanced X-ray image obtained at a first energy and a second polychromatic contrast-enhanced X-ray image obtained at a second energy, a simulated first monochromatic contrast-enhanced X-ray image and a simulated second monochromatic contrast-enhanced X-ray image. The simulated first monochromatic contrast-enhanced X-ray image includes first regions of enhanced contrast and the simulated second monochromatic contrast-enhanced includes second regions of enhanced contrast. The method also includes isolating the first and second regions of enhanced contrast from other regions of the image, and determining an amount of the contrast agent within the first and second regions of enhanced contrast based at least on a derived partial signal attributable to the contrast agent.