Ultrasound upgrade improves drug delivery

Microbubbles can function as small, noninvasive drug carriers, but standard optical methods for tracking them can’t see far into biological tissue, which leaves doctors flying blind. Researchers have considered following the microbubbles’ progress by using ultrasound to image the drug’s destination. Typically, they transmit a focused beam of sound pulses that sequentially scans small slivers of space. The slow frame rate, however, isn’t fast enough to adequately monitor microbubbles or manipulate them for in vivo applications.

To speed things up, Qifa Zhou of the University of Southern California and his colleagues employed ultrafast plane-wave imaging with an ultrasound probe. It images the entire area of interest at once by using unfocused acoustic waves. To improve the picture quality of the ultrafast technique, the researchers coherently added images taken from five transmission angles. The kilohertz frame rate can provide sufficient resolution to track and harness the microbubbles. The new method also enables the researchers to filter out background noise, which improves the sensitivity by two orders of magnitude above conventional ultrasound imaging techniques.

The researchers generated plane waves, which propagated through a 10 mm slice of pig tissue and around a sample tube. As a syringe steadily injected deionized water with microbubbles directly into the tube, the 18 MHz imaging probe snapped pictures of the microbubbles’ progress in real time. Once they traveled partially across the tube, the experimenters turned on a transducer that used focused ultrasound at a 2.5 MHz frequency to trap the microbubbles in place. A video of the trapping is shown below.

To get a handle on the forces underlying the microbubbles’ manipulation, Zhou and his colleagues simulated the dynamics in a three-dimensional finite-element model. That analysis revealed that the microbubbles become trapped when the acoustic radiation force is balanced by both the drag force of the laminar flow and the supporting force of the tube walls. (H. Peng et al., Appl. Phys. Lett. 115, 203701, 2019.)