Abstract: The present approach generally relates to systems and methods for implementing energy modulated tomographic imaging of nanoparticles. In certain embodiments, a first energy is used to activate probe particles labeling an anatomy or tissue of interest. The probe particles, once activated, emit photons at a different rate and/or spectrum in response to an underlying physiological event, such as action potentials propagating in the labeled anatomy or tissue. The emitted photons may then be detected and used to map or image the occurrence of the physiological event.