Measuring Tissue Stiffness and Elasticity
As a PhD student in Trahey’s lab, Kathy Nightingale studied the potential uses of acoustic radiation force, or ARF, in diagnostic imaging. This technique allows researchers to send an ultrasonic impulse into tissue, which pushes on and momentarily displaces the tissue. At the time, Nightingale was using the technique to investigate how researchers could improve ultrasound techniques to better differentiate fluid-filled cysts from solid lesions in breast tissue.
“Generally, if you could determine that a breast mass was fluid-filled, it was a much less concerning finding than if a mass was hard and immovable,” explains Nightingale. “For my thesis, I demonstrated that you could use ARF to push on the fluid in a cyst and make the fluid swirl around. This movement could then be detected with ultrasound, making it easier to tell the difference between potentially benign and malignant masses.”
The success of this project prompted Nightingale and Trahey to explore if they could similarly use ARF to gather information about a tissue’s material properties and use it to create images. They theorized that they could use ARF to remotely palpate a target area, and then use ultrasound to image the resulting tissue motion to learn about the tissue’s stiffness.
To test this hypothesis, Nightingale and Trahey recruited the help of Mark Palmeri, who at the time was an undergraduate student at Duke.
“I became Kathy and Gregg’s research fellow, and my summer project was to simulate how ARF could deform different types of soft tissues.” says Palmeri, now a professor of the practice in Duke BME. “We published a paper in 1999 that laid out the foundation of this approach, and it was so successful that it actually led to the formation of this entirely new subfield of study in ultrasound.”
The new research avenues available with ARF led to the development of ARFI imaging, or acoustic radiation force impulse imaging, which uses the ultrasound images of tissue displacement to create a 2D map that shows relative tissue stiffness.
Nightingale, Trahey and Palmeri also began to investigate how ARF could be used to excite tissues to create shear waves, which are ripples that travel perpendicular to the acoustic disturbance. Nightingale theorized that they could use ultrasound to measure the speed of the waves as they moved across the tissue. This data could then help to specifically calculate the tissue’s stiffness. This measurement of stiffness could be used as a biomarker and help with disease diagnostics.
The approach, called SWEI, or shear wave elasticity imaging, could be paired with ARFI imaging to help researchers target and then specifically examine the elasticity of areas of tissue. Initially, Nightingale studied how the approach could be used to better characterize breast lesions as benign or malignant, but she soon recognized that breast tissue wasn’t the most optimal target if the team wanted to make an impact on diagnostic procedures.
“Breast tissue is fairly accessible, so it’s easier to do tissue biopsies without significant side effects, but the cost of a false negative is quite high,” explains Nightingale. “Unless we were almost perfect in our sensitivity with ARFI and specificity with SWEI, we were not really going to change clinical practice significantly.”
But that wasn’t true when it came to diagnosing disease in the liver.
“Liver biopsies are very painful, and they aren’t well tolerated. Physicians will therefore not perform liver biopsies frequently, so they aren’t used to monitor disease progression for things like liver fibrosis or cirrhosis, which causes scarring across the liver,” Palmeri says. “We found that we could use SWEI to numerically define the stiffness of different liver regions. This helped us identify when the tissue was diseased and scarred, allowing us to track progression in a very non-invasive way."
This liver research was particularly exciting to Siemens Healthineers, a large manufacturer of ultrasound machines. The company, which had numerous longstanding collaborations with Trahey and Nightingale, pushed to commercially translate SWEI. The technique is now a feature on most commercial ultrasound scanners.
“Over a period of eight years, this went from an idea on paper, to a simulated demonstration, to feasibility experiments, to experimental implementation, to commercial translation,” says Palmeri. “That’s the storybook fairy tale for an engineer, to have your ideas become commercially translated in a reasonable timeline."