Oscillating Microbubbles Could Revolutionize Ultrasound

“There are a number of therapeutic approaches that we are pursuing for clinical use with microbubbles,” said Flemming Forsberg, PhD, professor of radiology at Thomas Jefferson University in Philadelphia. Dr. Forsberg and his colleagues are leading clinical trials focusing on adding microbubbles to existing cancer therapies and the use of targeted microbubbles for molecular US imaging and drug or gene delivery.

The U.S. Food and Drug Administration (FDA) first approved microbubbles — gas-filled bubbles about the size of a human red blood cell — for use with US in the early 2000s. These injectable bubbles were initially used in cardiology, but the number of applications has increased in recent years as researchers have begun to exploit their ability to oscillate, or grow and collapse. This oscillation, under the precise control of acoustic pressure from the transducer, has opened new venues in both diagnosis and therapy for cancer and other diseases.

For example, microbubbles, when paired with subharmonic imaging technology, can be used as pressure sensors, a discovery that led the way to the development of a noninvasive pressure measurement technique known as subharmonic-aided pressure estimation (SHAPE), explained Dr. Forsberg, who delivered the 2018 RSNA New Horizons lecture on this topic.

“These pressure estimates represent something that is fundamentally different and that no other imaging mode can do right now,” Dr. Forsberg said.

SHAPE measurements are a potential noninvasive alternative to catheter-based measurements of pressure in the heart — measurements that provide important information for heart transplant patients and those with cardiovascular disease. Costs and use of ionizing radiation are the chief drawbacks of the invasive approach.

A 2017 proof-of-concept study on 15 patients led by Dr. Forsberg’s Thomas Jefferson University colleague Jaydev Dave, PhD, showed that pressure errors between the subharmonic technique and the catheter were very low (<3.5 mmHg), lending support to SHAPE’s viability for noninvasive pressure measurements.

“These numbers are so good that even cardiologists are paying attention,” said Dr. Forsberg. “We are now running a larger clinical trial of about 130 patients. We think if we continue achieving this level of success we will be able to do something you can’t do with any other imaging modality.”

Potential in Hypertension, Breast Cancer