Provided herein are compositions comprising a microbubble contrast agent, wherein at least 20% by volume of the microbubbles in the contrast agent has a size of less than 1 micron, wherein the contrast agent produces non-linear scattering when contacted by ultrasound at a frequency above 20 MHz. Provided herein are compositions comprising a microbubble contrast agent, wherein at least 10% by volume of the microbubbles in the contrast agent has a size of less than 500 nanometers, wherein the contrast agent produces non-linear scattering when contacted by ultrasound at a frequency above 20 MHz. Provided herein are compositions comprising a microbubble contrast agent, wherein at least 5% by volume of the microbubbles in the contrast agent has a size of less than 200 nanometers, wherein the contrast agent produces non-linear scattering when contacted by ultrasound at a frequency above 20 MHz. The disclosed contrast agents can be targeted contrast agents. Further provided are methods of using the compositions disclosed herein. Specifically provided are methods for producing an ultrasound image comprising: administering contrast agent to a laboratory animal generating ultrasound at a frequency of at least 20 MHz transmitting ultrasound at a frequency of at least 20 MHz into the subject receiving non-linear ultrasound from the contrast agent in the subject processing the received ultrasound to provide an image.
