An ultrasound imaging technique called passive cavitation imaging was able to create an image and estimate the amount of a drug that crossed the blood-brain barrier to reach a specific location in the brain, according to a study by NIBIB-funded bioengineers at Washington University. The technique monitors the activity of microbubbles, microscopic bubbles that help create clearer ultrasound images using detectors to estimate the effects they have on the different biological structures – in this case, the brain.

The brain is responsible for a person’s most vital functions; therefore, the brain protects itself with a tough-to-penetrate boundary called the blood-brain barrier (BBB). However, there are times when disease treatments need to get beyond the BBB to treat an illness that has invaded the brain.

“Researchers are developing non-invasive approaches using microbubbles and focused ultrasound waves to disrupt the blood-brain barrier (FUS-BBBD) briefly,” explains Randy King, Ph.D., director of the program in ultrasound at the National Institute of Biomedical Imaging and Bioengineering (NIBIB). “As new techniques are established to permeate the BBB, we need complementary methods to monitor the delivery of treatments to ensure they are safely delivered to the site(s) of brain disease.”
Hong Chen, Ph.D., assistant professor of biomedical engineering and radiation oncology at Washington University in St. Louis, explained that FUS-BBBD is achieved by concentrating or focusing, sound waves emitted from a device called a transducer, to a specific location. Chen compared the concept to focused sunlight passing through a magnifying glass to a localized spot. In FUS, the ultrasound waves are concentrated with specially designed ultrasound generators and help focus the BBB opening at a specific brain location.

Microbubbles can be injected into the bloodstream to amplify the effects of the ultrasound waves on the blood vessels, thereby opening the BBB in a localized spot. Researchers can store drugs for treatments inside the microbubbles. The pressure generated by ultrasound pulses can cause the microbubbles in the bloodstream to expand, contract, and eventually burst. When the microbubbles break in BBB blood vessels, the pressure created gently massages the blood vessels and makes them permeable to drugs injected into the bloodstream or carried by the microbubbles.

PCI images compared to PET/CT images showing location and dose of drug in a mouse brainPCI imaging is comparable to PET/CT imaging for showing a drug’s dose and location, as indicated by these maps of drug-treated mouse brains. The images on the far left were acquired using an ultrasound imaging technique named PCI, and the center images with PET/CT imaging. On each image, the yellow color indicates a higher concentration of drug in the brain. The right pane is an overlay of the two individual scans illustrating their overlap. Credit: Chen lab, Washington University

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