Scientists at the Massachusetts Institute of Technology (MIT), and at the University of Southern California (USC), have developed a small ultrasound sticker that can be worn on the skin to monitor the stiffness of organs deep inside the body as a sign of disease, such as liver and kidney failure, or the progression of solid tumors. Known as wearable bioadhesive ultrasound elastography, BAUS-E, the sticker is about the size of a postage stamp, comprising a thin transducer array that sends sound waves through the skin into the body, where the waves reflect off internal organs and back out to the sensors. The pattern of the reflected waves can be read as a signature of organ rigidity, which the sticker can measure and track.
In a study reported in Science Advances “Wearable bioadhesive ultrasound shear wave elastography,” the team demonstrated that BAUS-E sticker could continuously monitor the stiffness of organs over 48 hours and detect subtle changes that could signal the progression of disease. In preliminary experiments, the researchers found that the sticky sensor can detect early signs of induced acute liver failure (ALF) in rats.
“When some organs undergo disease, they can stiffen over time,” said senior author Xuanhe Zhao, PhD, professor of mechanical engineering at MIT. “With this wearable sticker, we can continuously monitor changes in rigidity over long periods of time, which is crucially important for early diagnosis of internal organ failure.”
Lead author Hsiao-Chuan Liu, PhD, an assistant professor at the University of Southern California, who was a visiting scientist at MIT at the time of the study, added, “We imagine that, just after a liver or kidney transplant, we could adhere this sticker to a patient and observe how the rigidity of the organ changes over days. If there is any early diagnosis of acute liver failure, doctors can immediately take action instead of waiting until the condition becomes severe.”
The engineers are working to adapt the design for use in humans. They envision that the sticker could be used in intensive care units (ICUs) where the low-profile sensors could continuously monitor patients who are recovering from organ transplants. In their paper, Zhao, Liu and colleagues concluded, “BAUS- E holds promise for clinical applications, particularly in patients after organ transplantation or postoperative care in the intensive care unit …”
Like our muscles, the tissues and organs in our body stiffen as we age. With certain diseases, stiffening organs can become more pronounced, signaling a potentially precipitous health decline. Clinicians currently have ways to measure the stiffness of organs, such as the kidneys and liver, using ultrasound shear wave elastography (SWE)— a fast and noninvasive technique similar to ultrasound imaging. Existing ultrasound elastography probes measure shear waves, or an organ’s vibration in response to sonic impulses. The faster a shear wave travels in the organ, the stiffer the organ is interpreted to be. (Think of the bounce-back of a water balloon compared to a soccer ball.)
The technique is typically used in the ICU to monitor patients who have recently undergone an organ transplant. A technician manipulates a handheld probe or wand over the skin. The probe sends sound waves through the body, which cause internal organs to vibrate slightly and send waves out in return. The probe senses an organ’s induced vibrations, and the pattern of the vibrations can be translated into how wobbly or stiff the organ must be.
Technicians will use the technique periodically to check in on a patient after surgery to quickly probe the new organ and look for signs of stiffening and potential acute failure or rejection. “Previous studies have reported that liver stiffness, measured using conventional ultrasound SWE, is a reliable biomarker that significantly increases in critically ill patients with ALF compared to healthy controls,” the investigators pointed out. However, they continued, “… an intrinsic limitation of conventional ultrasound elastography is that it requires clinicians to handhold ultrasound probes on patients during examination, making it unable to continuously monitor changes in liver stiffness over the course of rapidly changing diseases …To the best of our knowledge, there is no ultrasound elastography technology that can provide continuous measurements of internal organ stiffness over a few hours.”
Added co-senior author Qifa Zhou, PhD, a professor at USC: “After organ transplantation, the first 72 hours is most crucial in the ICU. With traditional ultrasound, you need to hold a probe to the body. But you can’t do this continuously over the long term. Doctors might miss a crucial moment and realize too late that the organ is failing.”
The researchers’ realized that they might be able to provide a more continuous, wearable alternative to handheld devices. The new technology expands on an ultrasound sticker they previously developed to image deep tissues and organs. “Our imaging sticker picked up on longitudinal waves, whereas this time we wanted to pick up shear waves, which will tell you the rigidity of the organ,” Zhao explained.
The team looked to miniaturize ultrasound elastography to fit on a stamp-sized sticker. They also aimed to retain the same sensitivity as that of commercial handheld probes, which typically incorporate about 128 piezoelectric transducers, each of which transforms an incoming electric field into outgoing sound waves.
To create the BAUS-E technology the researchers precisely fabricated 128 miniature transducers that they incorporated onto a 25-millimeter-square chip. “The thin transducer array can generate acoustic radiation force impulse (ARFI) as the excitation source to produce shear waves for elastography measurement,” they noted. The chip’s underside was then lined with an adhesive made from a hydrogel—a sticky and stretchy material that is a mixture of water and polymer—which allows sound waves to travel into and out of the device almost without loss. “We used advanced fabrication techniques to cut small transducers from high-quality piezoelectric materials that allowed us to design miniaturized ultrasound stickers,” Zhou said.
In preliminary experiments, the team tested the stiffness-sensing sticker in rats. They found that the stickers were able to take continuous measurements of liver stiffness over 48 hours. “BAUS- E was used to continuously monitor the stiffness changes of rat livers with ALF over 48-hour period with measurements taken at six-hour intervals,” they wrote. From the sticker’s collected data, the researchers observed clear and early signs of pharmacologically induced acute liver failure in the animals, which they later confirmed with tissue samples. “We demonstrated that the wearable BAUS- E can provide continuous measurements of live moduli over time and effectively differentiate stiffness changes in different stages of ALF progression compared to normal livers,” the team continued. “This has the potential for early prognosis prediction of ALF and could assist in evaluation of the graft condition after liver transplantation in ICU.
“Once liver goes into failure, the organ will increase in rigidity by multiple times,” Liu noted. “You can go from a healthy liver as wobbly as a soft-boiled egg, to a diseased liver that is more like a hard-boiled egg,” Zhao added. “And this sticker can pick up on those differences deep inside the body and provide an alert when organ failure occurs.”
The team is working with clinicians to adapt the sticker for use in patients recovering from organ transplants in the ICU. In that scenario, they don’t anticipate much change to the sticker’s current design, as it can be stuck to a patient’s skin, and any sound waves that it sends and receives can be delivered and collected by electronics that connect to the sticker, similar to electrodes and EKG machines in a doctor’s office.
The researchers are also hoping to work the sticker into a more portable, self-enclosed version, where all its accompanying electronics and processing is miniaturized to fit into a slightly larger patch. “In the near future, we plan to integrate the external power source and data processing into chips for portable style, creating an all-in-one BAUSE-E for clinical use,” they stated. The researchers also envision that the sticker could be worn by patients at home, to continuously monitor conditions over longer periods, such as the progression of solid tumors, which are known to harden with severity.
“We believe this is a life-saving technology platform,” Zhao says. “In the future, we think that people can adhere a few stickers to their body to measure many vital signals, and image and track the health of major organs in the body.”
As the authors concluded in their paper, “BAUS- E holds great potential for expanding substantial applications of ultrasound wearable devices such as in patients undergoing organ transplantation in ICU, cancer research, and acute decompensated heart failure in clinical settings …”
