Sharpening the view of hidden heart risks

Heart disease is the leading cause of death for most individuals in the United States. To optimize treatment and improve diagnosis, one University of Pittsburgh researcher is advancing ultrasound technology to peer into the tiny vessels that surround our arteries. 

Kang Kim, professor of bioengineering and medicine at the Swanson School of Engineering and School of Medicine, Vascular Medicine Institute, and UPMC’s Heart and Vascular Institute, has been awarded a four-year, $2.8M NIH R01 grant for his project “Dual frequency intravascular ultrasound for super-resolution imaging of vasa vasorum and thin fibrous cap of vulnerable atherosclerotic plaques.” 

In collaboration with Qifa Zhou, professor of biomedical engineering and ophthalmology at the University of Southern California, and Xiaoning Jiang, distinguished professor of mechanical and aerospace engineering at NC State University, the trio will develop super-resolution intravascular ultrasound (IVUS) technology to improve diagnosis of vulnerable atherosclerotic plaques – which create a high risk of heart attack or stroke.

"We are integrating super-resolution technology into miniature ultrasound sensors to precisely visualize coronary plaques, which will provide crucial guidance to interventional cardiologists for patient treatment.” Kim said. "Our goal is to fundamentally enhance clinicians' ability to assess and predict risk of rupture.”

Vasa vasorum are microvessels that penetrate the outer layers of larger blood vessels and supply them with nutrients and oxygen. When plaque builds up in the arteries, the vasa vasorum grows inside of the plaque, which increases the risk for heart attack, according to John Pacella, the project’s clinical expert co-investigator, interventional cardiologist, and professor at both Pitt’s School of Medicine and the Department of Bioengineering.  

"The vessels of the vasa vasorum leak blood into the plaque, filling it with broken down red blood cell membranes.” Pacella said. “As this occurs, the plaque becomes more cholesterol laden, more likely to rupture, and more likely to cause a heart attack.” 

To examine plaque buildup, clinicians like Pacella often use intravascular ultrasound (IVUS), an imaging technique that works by inserting a tube equipped with an ultrasound probe into the body’s arteries. The probe emits high-frequency sound waves that reflect off the vessel walls, producing echoes that are converted into real-time visual images by a computer. IVUS, however, lacks sufficient resolution and contrast to clearly visualize the vasa vasorum, so accurately evaluating plaque vulnerability is challenging. 

“Imaging modalities are typically limited by the diffraction limit, where we cannot see anything smaller than the wavelengths that we’re using.” Kim said. “But with super-resolution imaging, we can create unprecedented spatial resolution beyond the diffraction limit and improve IVUS by developing new signal processing algorithms and sensors to see into the microvasculature.” 

Ultrasound techniques often use microbubbles: tiny bubbles composed of a gas core and a stabilizing shell used as contrast agents. When exposed to ultrasound, they oscillate, scattering sound waves and creating a bright, detailed image. In super resolution imaging, Kim’s team takes the microbubble technique a step further by localizing the center of the microbubbles to track their flow in the blood stream.

“This technique was inspired by optical super resolution microscopy, and we found that microbubbles randomly oscillate when these clinically approved bubbles were injected into the bloodstream and exposed to ultrasound.” Kim said. “Localizing the center of the bubbles allows us to pull together the different oscillations and visualize tiny vessels we’ve never been able to see before.” 

Kim, who has been working on developing super resolution imaging for the past seven years, hopes the team can transition into human studies after this project. Pacella is also hopeful and believes that this technique could ultimately usher in a new age of interventional cardiology. 

“When someone comes into the hospital already clutching their chest during a heart attack, we know what we have to do, but we need to get to them before that happens.” Pacella said. “The idea of identifying a vulnerable plaque and preventing heart attacks with advanced imaging technology is incredibly important— this is the holy grail of interventional cardiology.”