Polystyrene (PS) hollow beads with holes on the surfaces are employed as containers for quick loading and encapsulation of a variety of contrast enhancement agents: saline solutions for thermoacoustic tomography, iodinated organic compounds for micro-computed tomography, and perfluorooctane for magnetic resonance. Because of the hole on the surface of the PS hollow bead, the contrast agent to be encapsulated could quickly enter the hollow interior via direct flow rather than slow diffusion through the wall. After loading, the hole on the surface is conveniently sealed by annealing the sample at a temperature (e.g., 95?C) slightly above the glass-transition temperature of PS. In vitro methods are also used to investigate the effectiveness of encapsulation by quantifying the contrast enhancement enabled by the contrast agents. A facile method based on hollow beads with holes on the surfaces for quick encapsulation of various types of contrast agents is described. The potential uses of these encapsulated contrast agents for biomedical imaging is also demonstrated. Copyright ? 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.