A time-of-flight positron emission tomography (TOF PET) imaging system comprising: a TOF PET scanner comprising radiation detector elements; and an electronic data processing device programmed to: operate the TOF PET scanner to acquire calibration data based on annihilation event data acquired for positron-electron annihilation events occurring in a point source located at an isocenter of the TOF PET scanner wherein each annihilation event datum includes an identification of the radiation detector elements detecting two oppositely directed 511 keV gamma rays emitted by the annihilation event and a time difference between detection of the two oppositely directed 511 keV gamma rays emitted by the annihilation event, generate TOF corrections (92, 102, 112, 122) for the radiation detector elements by solving an over-determined set of equations defined by the calibration data, operate the TOF PET scanner to acquire list mode imaging data comprising 511 keV gamma ray detection events acquired from an imaging subject, generate corrected list mode imaging data by applying the TOF corrections to the list mode imaging data, and reconstruct the corrected list mode imaging data to generate a reconstructed image of at least a portion of the imaging subject. a TOF PET scanner comprising radiation detector elements; and an electronic data processing device programmed to: operate the TOF PET scanner to acquire calibration data based on annihilation event data acquired for positron-electron annihilation events occurring in a point source located at an isocenter of the TOF PET scanner wherein each annihilation event datum includes an identification of the radiation detector elements detecting two oppositely directed 511 keV gamma rays emitted by the annihilation event and a time difference between detection of the two oppositely directed 511 keV gamma rays emitted by the annihilation event, generate TOF corrections (92, 102, 112, 122) for the radiation detector elements by solving an over-determined set of equations defined by the calibration data, operate the TOF PET scanner to acquire list mode imaging data comprising 511 keV gamma ray detection events acquired from an imaging subject, generate corrected list mode imaging data by applying the TOF corrections to the list mode imaging data, and reconstruct the corrected list mode imaging data to generate a reconstructed image of at least a portion of the imaging subject. operate the TOF PET scanner to acquire calibration data based on annihilation event data acquired for positron-electron annihilation events occurring in a point source located at an isocenter of the TOF PET scanner wherein each annihilation event datum includes an identification of the radiation detector elements detecting two oppositely directed 511 keV gamma rays emitted by the annihilation event and a time difference between detection of the two oppositely directed 511 keV gamma rays emitted by the annihilation event, generate TOF corrections (92, 102, 112, 122) for the radiation detector elements by solving an over-determined set of equations defined by the calibration data, operate the TOF PET scanner to acquire list mode imaging data comprising 511 keV gamma ray detection events acquired from an imaging subject, generate corrected list mode imaging data by applying the TOF corrections to the list mode imaging data, and reconstruct the corrected list mode imaging data to generate a reconstructed image of at least a portion of the imaging subject.