Different stages of testing drugs in humans for example ultrasound contrast agents, from first application in humans through limited and broad clinical tests, to postmarketing studies. Preclinical trials are the testing in animals.

See also Drug Development and Approval Process USA, Food and Drug Administration, and European Medicines Agency.

Standard scanners allow visualizing microbubbles on conventional gray scale imaging in large vascular spaces. In the periphery, more sensitive techniques such as Doppler or non-linear gray scale modes must be used because of the dilution of the microbubbles in the blood pool. Harmonic power Doppler (HPD) is one of the most sensitive techniques for detecting ultrasound contrast agents.
Commonly microbubbles are encapsulated or otherwise stabilized to prolong their lifetime after injection. These bubbles can be altered by exposure to ultrasound pulses. Depending on the contrast agent and the insonating pulse, the changes include deformation or breakage of the encapsulating or stabilizing material, generation of free gas bubbles, reshaping or resizing of gas volumes.
High acoustic pressure amplitudes and long pulses increase the changes. However, safety considerations limit the pressure amplitude and long pulses decrease spatial resolution. In addition, lowering the pulse frequency increases destruction of contrast bubbles. However, at low insonation power levels, contrast agent particles resist insonation without detectable changes. Newer agents are more reflective and will usually allow gray scale imaging to be used with the advantages of better spatial resolution, fewer artifacts and faster frame rates.

Feasible imaging methods with advantages in specific acoustic microbubble properties:
Resonating microbubbles emit harmonic signals at double their resonance frequency. If a scanner is modified to select only these harmonic signals, this non-linear mode produces a clear image or trace. The effect depends on the fact that it is easier to expand a bubble than to compress it so that it responds asymmetrically to a symmetrical ultrasound wave. A special array design allows to perform third or fourth harmonic imaging. This probe type is called a dual frequency phased array transducer.

See also Bubble Specific Imaging.

The main advantage of ultrasound is that certain structures can be observed without using radiation. However, ultrasound is energy and there are ultrasound safety regulations, because two bioeffects of ultrasound are heat and cavitation. Ultrasound is a mechanical energy in which a pressure wave travels through tissue. Reflection and scattering back to the transducer are used to form the image. As sound energy is transmitted through the tissue, some energy is reflected and some power is absorbed.
Possible physical effects with ultrasound:
The ultrasound safety is based on two indices, the mechanical index (MI) and the thermal index (TI). The WFUMB guidelines state that ultrasound that produces temperature rises of less than 1.5°C may be used without reservation. They also state that ultrasonic exposure causing temperature rises of greater than 4°C for over 5 min should be considered potentially hazardous. This leaves a wide range of temperature increases which are within the capability of diagnostic ultrasound equipment to produce and for which no time limits are recommended. However, it has not been determined that medical ultrasound causes any adverse reaction or deleterious effect.
The American Institute of Ultrasound in Medicine states that as of 1982, no independently confirmed significant biologic effects had been observed in mammalian tissue below (medical usage) 100mW/cm2.

See also Ultrasound Regulations and Ultrasound Radiation Force.