By Jennifer Chu MIT News
MIT engineers have developed a non-invasive pacemaker that stimulates the heart using ultrasound. The design may one day provide a surgery-free alternative to traditional cardiac implants.
The new device is designed as a small sticker that can be worn on the chest. Tiny transducers on the sticker send ultrasound pulses through the chest to stimulate the heart. Ultrasound waves trigger the opening of specific ion channels in heart cells, an effect researchers have amplified through genetic engineering. When the channels open, they release calcium, which signals the heart cells to squeeze and beat.
In lab experiments, researchers applied ultrasound waves to engineered human cardiac cells and found that the pulses effectively maintained healthy contraction of the cells. They tested the ultrasound sticker on mice and the device quickly, safely and non-invasively corrected arrhythmias and restored normal, regular heart contractions.
The team developed a prototype that includes an ultrasound sticker (about the size of a postage stamp) and a small, pocket-sized device with attached batteries and electronics. The same group previously demonstrated a sticker design that uses Deep organ and tissue imaging ultrasound. They now plan to combine the two approaches into an ultrasound sticker to simultaneously monitor and control heart activity.
“We believe that one day your body may have stickers that can do long-term imaging deep inside the body and also stimulate for therapeutic effects, in a non-invasive closed-loop way,” said Xuanhe Zhao, professor of mechanical engineering and civil and environmental engineering at MIT.
Zhao and his colleagues, along with colleagues from the group of University of Southern California (USC) professor Keefa Zhou published their results In a study appearing today in the journal Nature Biomedical Engineering. MIT co-authors of the study include first authors Chen Gong, Runze Li, Wan Jun Song, and former postdocs Gengxi Lu, Shukong Li, and Seo-Chuan Liu. Other collaborators include researchers from other groups at Harvard University, the University of California at Los Angeles, and USC.
sound gene
Currently, approximately 3 million adults in the United States live with a pacemaker. Small battery-operated devices are surgically implanted in a person’s chest and work to deliver electrical impulses to regulate heart rate. Implantable pacemakers are a well-established and generally safe treatment that nonetheless carry risks.
“Pacemakers are one of the most important and widely used human implants, and they have saved millions of lives,” said Gengxi Lu, co-corresponding author of the paper. “But they’re invasive, and they communicate directly with the beating heart. The dream for many years has been non-invasive heart stimulation with ultrasound.”
Ultrasound contains many sound waves that safely penetrate the body. Ultrasound waves reflect and resonate with structures in characteristic ways that allow technicians to resolve and image organs and tissues inside the body. Ultrasound can also be directed and focused to stimulate specific therapeutic effects, for example in the brain, where scientists are exploring the use of ultrasound to treat Parkinson’s disease, Alzheimer’s and other brain disorders.
Scientists have also found that ultrasound can benefit the heart. Previous studies in animals have shown that focused ultrasound can safely activate heart cells, although the effect is inconsistent and weak.
Zhao and his colleagues wanted to enhance the effect of ultrasound on the heart. In their new study, they applied sonogenetics, a relatively new approach that takes after optogenetics – a technique that genetically manipulates specific parts of a cell to respond to light. Similarly, sonogenetics involves genetically engineering cells to respond to sound, including ultrasound.
In developing an ultrasound pacemaker, the team first looked at increasing the sensitivity of heart cells to ultrasound through sonogenetics. In the lab, they used standard practices to derive heart cells from embryonic stem cells and then introduced a genetic change to the cells that increased their sensitivity to ultrasound. Specifically, the manipulation creates ion channels that open more readily in response to ultrasound.
“These channels can now ‘hear’ the ultrasound better, and open to let calcium in, which directly activates the cell and allows it to beat,” explained Chen Gong, first author of the paper.
Sticker health
In experiments with sonogenetically engineered heart cells, the researchers found that when they exposed the cells to ultrasound, the cells beat in sync with the waves, unlike cells that had not been genetically manipulated.
In any clinical application of an ultrasound pacemaker, the team envisions that a patient might first receive a one-time injection, like a vaccine, that would work to genetically increase the sensitivity of heart cells to the pacemaker’s ultrasound waves. The injection would be a form of gene therapy — a treatment currently approved by the FDA to treat certain inherited conditions such as sickle cell disease and spinal muscular dystrophy.
“We think this step will be clinically translatable as a form of gene therapy that can enable non-invasive pacemakers,” Gong said.
The team then designed the original ultrasound pacemaker, in the form of a postage stamp-sized sticker embedded with tiny ultrasound transducers. The adhesive portion of the device is made from a hydrogel material that Zhao’s group has refined over the years to adhere tightly to skin and a variety of materials, while allowing ultrasound waves to pass through without weakening. Transducers within the sticker can be tuned to generate ultrasound waves at specific frequencies.
In experiments with mice, the researchers first administered a sonogenetic, ultrasound-boosting solution through their tails. They then implanted a miniature version of the pacemaker into the mice’s chest. When they turned on the sticker, they found that the ultrasound quickly controlled the animals’ hearts. Some individuals with slow heartbeats were brought to a normal rate, while others with irregular heartbeats remained stationary in line with the “ticks” of the ultrasound.
“We can now use low-intensity ultrasound to open ion channels in cells for very effective heart pacing,” Gong said. “We’re now making these stickers in smaller form factors, and more compact, so they’re easier to wear over the long term, more stable and more accurate.”
“In this paper, we have demonstrated non-invasive pacemaking. However, we think this concept may also be useful outside the heart,” Zhao said. “We believe that one day you could have stickers on different parts of your body that could do long-term imaging, monitoring and closed-loop therapeutic stimulation.”
This work was supported in part by the National Institutes of Health, the National Science Foundation, the Department of Ophthalmology from Research to Prevent Blindness, and the US Department of War.
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Reprinted with permission MIT News
Image: splash
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