Present embodiments relate to the calibration of detectors having one or more arrays of pixelated detectors. According to an embodiment, a method includes detecting optical outputs generated by a plurality of scintillation crystals of a detector with an array of pixelated detectors, generating, with the array of pixelated detectors, respective signals indicative of the optical outputs, generating, from the respective signals, a unique energy spectrum correlated to each of the plurality of scintillation crystals, grouping subsets of the plurality of scintillation crystals into macrocrystals, determining a representative energy spectrum peak for each macrocrystal based on the respective energy spectra of the scintillation crystals in the macrocrystal, comparing a value of the representative energy spectrum peak for each macrocrystal with a target peak value, and adjusting an operating parameter of at least one pixelated detector in the array of pixelated detectors as a result of the comparison.