Using sound to treat disease
Image from http://www.trust-biosonics.com/technology/1
Getting cancer therapies to their target is hard. And there are a lot of side effects. The drugs that are effective at killing cancer cells are also really effective at killing healthy cells, especially those in the gastrointestinal lining, blood, and hair follicles. Because of this, there is a huge effort in the scientific community to develop new drug delivery systems, which are systems that are designed to increase drug accumulation in the places they need to go while sparing healthy areas where they should not go. One of these techniques is to use ultrasound – but don’t worry, no babies are involved.
While ultrasound is most often used for pregnancy imaging, there’s a special kind of ultrasound, called contrast-enhanced ultrasound that relies on tiny particles that are injected to provide an extra boost of signal. These are called “contrast agents” and most imaging methods have them. Ultrasound contrast agents are gas-filled spheres called microbubbles – small enough to fit into tiny blood vessels but big enough not to leak out of them. Under an ultrasound beam, the waves of sound pressure from the ultrasound transducer cause the microbubbles to expand and contract. This oscillation gets picked up by the ultrasound transducer. Because the echo from oscillating bubbles is different from normal ultrasound echoes that bounce off of other tissue surfaces, the bubble signal can be easily isolated. This makes them a great tool to see blood flow in the microcirculation, and they have numerous diagnostic applications ranging from oncology to cardiology. See below an example of a liver contrast ultrasound exam, with the contrast side on the left and the standard imaging mode on the right.
But how does that translate to better drug delivery systems? Think about those oscillating bubbles again. The way that microbubbles respond to ultrasound pressure is dependent on the amount of pressure that is applied. So, if you use a small ultrasound pressure, then the bubbles will undergo small oscillations – this is what is generally used for imaging. But if you crank up the ultrasound pressure, the bubbles will oscillate with much more energy and will expand to much larger sizes. This rapid expansion can eventually cause the bubbles to burst. When that happens next to a blood vessel, it can temporarily make that vessel “leakier”. If this happens when drugs are nearby, the drug is more likely to escape the vasculature and get to the cells they need to go to. And the best part is that this can all be controlled and focused from outside of the body and is often done with standard ultrasound transducers.
One of the most exciting applications of this technology is in the brain. It is notoriously difficult to get anything past the blood vessels of the brain. This is usually a really good thing – our brain is an important organ that should be safeguarded from toxins or other things that could potentially harm it. However, getting drugs past these barriers is equally difficult. That’s where ultrasound comes in handy; the oscillation of microbubbles causes the vessels to temporarily allow larger things through, such as chemotherapy drugs, genes, and even cells! It is so effective that clinical trials have begun in Canada for Alzheimer’s Disease treatment. Outside of the brain, this therapy was also performed on a patient with liver cancer this past December.
Treating cancer and other diseases is getting one step easier – all with the help of a little sound and a lot of bubbles!
Sara Keller is a fourth-year PhD student in Bioengineering working in the lab of Dr. Mike Averkiou. She studies the use of contrast-enhanced ultrasound for cancer diagnostics and therapy.