Abstract: A system for calibrating a pixelated detector includes a detector assembly comprising an array of pixels, an energy source positioned to direct energy toward the array of pixels, a collimating device positioned to pass energy from the energy source to illuminate one pixel, and a data acquisition system (DAS). The DAS is configured to measure a signal in the illuminated one pixel, and measure signals in pixels neighboring the pixel. The system includes a computer programmed to calculate an amount of crosstalk from the illuminated pixel of the pixels neighboring the illuminated pixel based on the measured signals in the DAS, and calculate a crosstalk correction vector for the illuminated pixel based on the measured signal in the illuminated pixel, the measured signals in the pixels neighboring the illuminated pixel, and the calculated amount of crosstalk from the illuminated pixel to each of the pixels neighboring the illuminated pixel.