A device for performing energy calibration of a nuclear imaging instrument, comprising: at least one electronic processor programmed to: construct a background radiation spectrum from event data acquired by the nuclear imaging instrument with no radioactive source loaded; construct a calibration source radiation spectrum from event data acquired by the nuclear imaging instrument with a radioactive source loaded that emits radiation particles with a known energy; calculate a difference spectrum as a difference between the calibration source radiation spectrum and the background radiation spectrum; identify a peak energy of a peak in the difference spectrum; and compute an energy correction factor that shifts the identified peak energy to the known energy; wherein the nuclear imaging instrument includes a detector array comprising radiation detector pixels; and the at least one electronic processor is programmed to construct the background and calibration source radiation spectra, calculate the difference spectrum, identify the peak energy, and compute the energy correction factor on a per-pixel basis to compute pixel-specific energy correction factors; and characterized in that the at least one electronic processor is further programmed to: multiply the calibration source radiation spectrum by the pixel-specific energy correction factor to produce a calibration source cluster event-energy spectrum; multiply the background radiation spectrum by the pixel-specific energy correction factor to produce a background cluster event-energy spectrum; and calculate a cluster energy difference spectrum (130, 356) by subtracting the background cluster event-energy spectrum from the calibration source cluster event-energy spectrum; identify a cluster peak energy of a lower-energy peak in the cluster energy difference spectrum (130, 356) wherein the identified cluster peak energy is lower than the identified peak energy; and compute a cluster energy correction factor that shifts the identified cluster peak energy to a known cluster energy corresponding to the known energy. construct a background radiation spectrum from event data acquired by the nuclear imaging instrument with no radioactive source loaded; construct a calibration source radiation spectrum from event data acquired by the nuclear imaging instrument with a radioactive source loaded that emits radiation particles with a known energy; calculate a difference spectrum as a difference between the calibration source radiation spectrum and the background radiation spectrum; identify a peak energy of a peak in the difference spectrum; and compute an energy correction factor that shifts the identified peak energy to the known energy; wherein the nuclear imaging instrument includes a detector array comprising radiation detector pixels; and the at least one electronic processor is programmed to construct the background and calibration source radiation spectra, calculate the difference spectrum, identify the peak energy, and compute the energy correction factor on a per-pixel basis to compute pixel-specific energy correction factors; and characterized in that the at least one electronic processor is further programmed to: multiply the calibration source radiation spectrum by the pixel-specific energy correction factor to produce a calibration source cluster event-energy spectrum; multiply the background radiation spectrum by the pixel-specific energy correction factor to produce a background cluster event-energy spectrum; and calculate a cluster energy difference spectrum (130, 356) by subtracting the background cluster event-energy spectrum from the calibration source cluster event-energy spectrum; identify a cluster peak energy of a lower-energy peak in the cluster energy difference spectrum (130, 356) wherein the identified cluster peak energy is lower than the identified peak energy; and compute a cluster energy correction factor that shifts the identified cluster peak energy to a known cluster energy corresponding to the known energy. multiply the calibration source radiation spectrum by the pixel-specific energy correction factor to produce a calibration source cluster event-energy spectrum; multiply the background radiation spectrum by the pixel-specific energy correction factor to produce a background cluster event-energy spectrum; and calculate a cluster energy difference spectrum (130, 356) by subtracting the background cluster event-energy spectrum from the calibration source cluster event-energy spectrum; identify a cluster peak energy of a lower-energy peak in the cluster energy difference spectrum (130, 356) wherein the identified cluster peak energy is lower than the identified peak energy; and compute a cluster energy correction factor that shifts the identified cluster peak energy to a known cluster energy corresponding to the known energy.