Submicron ultrasound contrast agents are gas-filled, double-walled microspheres with a diameter smaller than 1 μm that rupture when exposed to ultrasound energy at megahertz frequencies. These agents differ from traditional ultrasound contrast microbubbles in that the submicron bubbles may serve as extravascular agents. They are small enough to travel through the lymphatic system and to be extravasated from tumor neovasculature. The detection of these agents is limited by their hard shell, which requires high-pressure ultrasound insonation for shell rupture and excitation of the gas bubble. After shell rupture, the gas diffuses rapidly from submicron sized agents. The optimal processing of each echo is important.