MIT engineers have developed a tiny ultrasound sticker that can monitor the stiffness of organs inside the body. The postage stamp-sized sticker can be worn on the skin and is designed to capture signs of disease such as liver and kidney failure and solid tumor progression.
in one Open-access study appearing today In science advancementThe team reports that the sensor can send sound waves through the skin and into the body, where the waves reflect off internal organs and return to the sticker. The patterns of the reflected waves can be read as a signature of organ stiffness, which the sticker can measure and track.
“When certain organs undergo disease, they can become stiff over time,” says the paper’s senior author Xuanhe Zhao, a professor of mechanical engineering at MIT. “With this wearable sticker, we can continuously monitor changes in stiffness over a long period of time, which is extremely important for early diagnosis of internal organ failure.”
The team demonstrated that the sticker could continuously monitor limb stiffness for up to 48 hours and detect subtle changes that could indicate disease progression. In preliminary experiments, the researchers found that the sticky sensor could detect early signs of acute liver failure in mice.
Engineers are working on optimizing the design for use in humans. They envision that the stickers could be used in intensive care units (ICUs), where low-profile sensors could continuously monitor patients who are recovering from organ transplants.
“We envision that, right after a liver or kidney transplant, we could stick this sticker on a patient and watch how the stiffness of the organ changes over the days,” says lead author Hsiao-Chuan Liu. “If there is an early diagnosis of acute liver failure, doctors can take immediate action rather than waiting until the condition becomes severe.” At the time of the study Liu was a visiting scientist at MIT and is currently an assistant professor at the University of Southern California.
MIT co-authors of the study include Xiaoyu Chen and Chonghe Wang, along with colleagues from USC.
Like our muscles, the tissues and organs in our bodies become stiffer as we age. With some diseases, stiffness in the limbs may become more pronounced, potentially indicating rapid health decline. Physicians currently have ways to measure the stiffness of organs such as the kidneys and liver using ultrasound elastography – a technique similar to ultrasound imaging, in which a technician moves a handheld probe or hand over the skin. The probe sends sound waves through the body, causing internal organs to vibrate slightly and send out waves in return. The probe senses the induced vibration of a limb, and the pattern of vibration can be translated into how much the limb will wobble or stiffen.
Ultrasound elastography is commonly used in the ICU to monitor patients who have recently had an organ transplant. Technicians check the patient periodically immediately after surgery to check the new organ and look for stiffness and signs of possible acute failure or rejection.
“After an organ transplant, the first 72 hours in the ICU are the most critical,” says another senior author, Qifa Zhou, a professor at USC. “With traditional ultrasound, you need to place a probe in the body. But you cannot do this continuously for a long time. Doctors may miss a critical moment and realize too late that the organ is failing.
The team realized that they might be able to provide a more sustainable, wearable alternative. Their solution expands on an ultrasound sticker they previously developed to image deep tissues and organs.
“Our imaging sticker captures longitudinal waves, whereas this time we wanted to capture shear waves, which will tell you the stiffness of the organ,” explains Zhao.
Current ultrasound elastography probes measure shear waves, or vibrations of an organ in response to sound impulses. The faster the shear wave travels through the organ, the stiffer the organ is considered to be. (Think of the bounce-back of a water balloon compared to a soccer ball.)
The team considered miniaturizing ultrasound elastography to fit on a stamp-sized sticker. They are intended to maintain the same sensitivity of commercial hand-held probes, typically consisting of about 128 piezoelectric transducers, each of which converts an incoming electric field into outgoing sound waves.
“We used advanced manufacturing techniques to cut tiny transducers from high-quality piezoelectric materials, which allowed us to design miniature ultrasound stickers,” says Zhou.
The researchers created precisely 128 miniature transducers that they incorporated into a 25-millimeter-square chip. They covered the bottom of the chip with an adhesive made from hydrogel – a sticky and flexible substance that is a mixture of water and polymers, which allows sound waves to pass in and out of the device with almost no damage.
In preliminary experiments, the team tested the stiffness-sensing sticker in rats. They found that the stickers were able to continuously measure liver stiffness for up to 48 hours. From the data the stickers collected, the researchers observed clear and early signs of acute liver failure, which they later confirmed with tissue samples.
“Once the liver degenerates, the stiffness of the organ will increase several times,” says Liu.
“You can go from a healthy liver wobbly like a soft-boiled egg to a sick liver wobbly like a hard-boiled egg,” says Zhao. “And this sticker can capture those differences deep inside the body and provide a warning when organ failure occurs.”
The team is working with physicians to adapt the stickers for use in patients recovering from organ transplants in the ICU. In that scenario, they don’t expect much change in the sticker’s current design, since it can stick to the patient’s skin, and whatever sound waves it sends and receives are delivered by the electronics that connect to the sticker. and may be collected, such as for electrodes and EKG machines in a doctor’s office.
“The real beauty of this system is that because it is now wearable, it will allow for low weight, conformability, and continuous monitoring over time,” says Shrike Zhang, MD, associate professor of medicine at Harvard Medical School and associate bioengineer at the Brigham. Women’s Hospital, which was not involved in the study. “This will not only allow patients to suffer less while their disease progression is monitored over a longer period of time, in near real-time, but will also free up trained hospital personnel for other important tasks.”
The researchers are also hoping to make the sticker work in a more portable, self-attached version, where all the electronics and processing associated with it is miniaturized to fit into a slightly larger patch. Then, they envisioned that the stickers could be worn by patients at home to continuously monitor conditions over a long period of time, such as the progression of solid tumors, which are known to harden with severity.
“We believe this is a life-saving technology platform,” says Zhao. “In the future, we think people can stick a few stickers on their bodies to measure multiple vital signs and image and track the health of major organs in the body.”
This work was supported, in part, by the National Institutes of Health.
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