This invention relates to bifunctional detection agents useful for providing high-resolution, in vivo imaging of biochemical activity in a living organism. Methods of using these bifunctional detection agents may comprise administering them into a living organism, and then estimating the localization of the detection agent using one modality (i.e., MRI), while concurrently estimating the level of biological activity using a second modality (i.e., optical imaging). One of the bifunctional detection agents comprises a magnetic resonance component and an optical imaging component. The magnetic resonance component comprises a contrast agent that is always activated or "on". The optical imaging component comprises an activatable contrast agent or dye that is activated or turned "on" only in the presence of a particular event. For example, the optical imaging component may be activated by a certain wavelength of light and (1) by the presence of a particular biochemical marker, (2) by enzyme cleavage, or (3) by a change in the temperature or pH of the surrounding medium. These bifunctional detection agents allow both anatomical and functional/metabolic information to be obtained simultaneously.