The present invention provides a method of calibrating gamma-ray and photon counting detectors, including, but not limited to, monolithic crystal detectors. The method of the present invention is based on the observation that measurement of fan beam datasets allows the synthesis of collimated beam data to derive MDRFs by use of an algorithm that finds the common or intersecting data subsets of two or more orthogonal calibration datasets. This makes the calibration process very efficient while still allowing the full benefits of maximum-likelihood event-parameter estimation that incorporates the statistical nature of the light sensor measurements.