Lasers and Ultrasound Combine to Pulverize Arterial Plaque

Lasers are one of the tools physicians can lean on to tackle plaque buildup on arterial walls, but current approaches carry a risk of complications and can be limited in their effectiveness. By bringing ultrasound into the mix, scientists at the University of Kansas have demonstrated a new take on this treatment that relies on exploding microbubbles to destroy plaque with greater safety and efficiency, while hinting at some unique long-term advantages.

Scientists have demonstrated a new technique to take out arterial plaque, using low-power lasers and ultrasound to break it apart with tiny bubbles

The novel ultrasound-assisted laser technique builds off what’s known as laser angioplasty, an existing treatment designed to improve blood flow in patients suffering from plaque buildup that narrows the arteries. Where more conventional treatments such as stents and balloon angioplasty expand the artery and compress the plaque, laser angioplasty destroys it to eliminate the blockage.

The laser is inserted into the artery with a catheter, and the thermal energy it generates turns water in the artery into a vapor bubble that expands, collapses and breaks up the plaque. Because this technique calls for high-power lasers, it has the potential to perforate or dissect the artery, something the scientists are looking to avoid by using low-power lasers instead.

They were able to do so in pork belly samples and ex vivo samples of artery plaque with the help of ultrasound. The method uses a low-power nanosecond pulsed laser to generate microbubbles, and applying ultrasound to the artery then causes these microbubbles to expand, collapse and disrupt the plaque.

In conventional laser angioplasty, a high laser power is required for the entire cavitation process, whereas in our technology, a lower laser power is only required for initiating the cavitation process,” said team member Rohit Singh. “Overall, the combination of ultrasound and laser reduces the need for laser power and improves the efficiency of atherosclerotic plaque removal.

The mix of lasers and ultrasound has shown potential in other areas of medicine, with Singh and his colleagues pursuing similar therapies to tackle abnormal microvessels in the eye that cause blindness and blood clots in the veins. We’ve also seen ultrasound used to explode tiny bubbles in cancer research, providing a way of wiping out cancerous cells within a tumor.

Source: https://newatlas.com/

Ultrasound to Command Bacteria to Nuke Tumors

Scientists at Caltech have genetically engineered, sound-controlled bacteria that seek and destroy cancer cells. In a new paper appearing in the journal Nature Communications, researchers from the lab of Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute investigator, show how they have developed a specialized strain of the bacteria Escherichia coli (E. coli) that seeks out and infiltrates cancerous tumors when injected into a patient’s body. Once the bacteria have arrived at their destination, they can be triggered to produce anti-cancer drugs with pulses of ultrasound.

The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” Shapiro says.

The starting point for their work was a strain of E. coli called Nissle 1917, which is approved for medical uses in humans. After being injected into the bloodstream, these bacteria spread throughout the body. The patient’s immune system then destroys them—except for those bacteria that have colonized cancerous tumors, which offer an immunosuppressed environment.

To turn the bacteria into a useful tool for treating cancer, the team engineered them to contain two new sets of genes. One set of genes is for producing nanobodies, which are therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. The presence of these nanobodies allow the immune system to attack the tumor. The other set of genes act like a thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.

By inserting the temperature-dependent and nanobody genes, the team was able to create strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42–43 degrees Celsius. Since normal human body temperature is 37 degrees Celsius, these strains do not begin producing their anti-tumor nanobodies when injected into a person. Instead, they quietly grow inside the tumors until an outside source heats them to their trigger temperature.

But how do you heat bacteria that are located in one specific location, potentially deep inside the body where a tumor is growing? For this, the team used focused ultrasound (FUS). FUS is similar to the ultrasound used for imaging internal organs, or a fetus growing in the womb, but has higher intensity and is focused into a tight point. Focusing the ultrasound on one spot causes the tissue in that location to heat up, but not the tissue surrounding it; by controlling the intensity of the ultrasound, the researchers were able to raise the temperature of that tissue to a specific degree.

Source: https://www.caltech.edu/

How to Control Neurons in the Brain

Researchers out of San Diego’s Salk Institute have gotten mice to move their limbs by stimulating brain cells using ultrasound. When mice were engineered to have their brain cells produce a special protein, the researchers found that hitting them with ultrasoundturned on” the cells, causing small, but perceptible, movements in their limbs. The technique, called “sonogenetics,” is the latest in a line of methods that look to stimulate and alter neurons directly, without using drugs.

We’ve spent so much time over the last few decades focusing on pharmacologic therapies,” said Colleen Hanlon, a biologist at Wake Forest not involved with the study. “This paper is another really important piece to this puzzle of developing neural circuit-based therapeutics for disease.”

 Sonogenetics is just one of the ways researchers have begun controlling neurons in the brain, turning them off or on at will. Perhaps the most well-known method is using electrical stimulation. In deep brain stimulation, researchers surgically implant electrodes into specific areas of the brain. When these electrodes fire off at the right time and with the right frequency, they can make tremors disappear, improve memory, and even treat depression.

Taking a step up on the wildness scale, scientists can also activate, or turn off, neurons using light, a technique called optogenetics. Optogenetics works by genetically engineering brain cells to produce light-sensitive proteins, which can be hit with a laser, causing the neuron to fire or not. A similar mechanism is behind sonogenetics, except the protein reacts to ultrasound. Ultrasound is appealing because of its well-understood safety profile and the fact that it is already used to target locations deep within the body. “Ultrasound is safe, noninvasive, and can be easily focused through thin bone and tissue to volumes of a few cubic millimeters,” the researchers wrote in their study, published in Nature Communications.

In optogenetics, by contrast, because skin and bone are opaque, even powerful lights will have a hard time reaching neurons deeper than the outer layer of the brain. Salk neuroscientist Sreekanth Chalasani and his colleagues pioneered sonogenetics several years ago in a tiny worm called a nematode. In the worms, they used an ultrasound-reacting protein called TRP-4. But when they put it into mammalian cells, well … nada. And thus began a six-year quest to find an ultrasound-reactive protein that works in mammals. They found it — a protein called TRPA1. The researchers first tested the protein in mouse neurons in the lab. When those cells reacted to ultrasound by producing electrical signals, they engineered it into living mice. When the TRPA1-producing mice were exposed to ultrasound, electrical signals coursed through their limbs — and a little bit of movement, too.

It’s a very exciting contribution and an important step,” adds Caltech sonogenetics researcher Mikhail Shapiro, who was uninvolved with the work.  “This is one of the papers that’s come out over the last several years that shows that it’s a real possibility that you can use ultrasound to directly modulate the activity of specific neurons.”

Source: https://www.freethink.com/

Could Sound Replace Pacemakers and Insulin Pumps?

Imagine a future in which crippling epileptic seizures, faltering hearts and diabetes could all be treated not with scalpels, stitches and syringes, but with sound. Though it may seem the stuff of science fiction, a new study shows that this has solid real-world potential.

Sonogenetics – the use of ultrasound to non-invasively manipulate neurons and other cells – is a nascent field of study that remains obscure amongst non-specialists, but if it proves successful it could herald a new era in medicine.

In the new study published in Nature Communications, researchers from the Salk Institute for Biological Studies in California, US, describe a significant leap forward for the field, documenting their success in engineering mammalian cells to be activated using ultrasound. The team say their method, which they used to activate human cells in a dish and brain cells inside living mice, paves the way toward non-invasive versions of deep brain stimulation, pacemakers and insulin pumps.

Going wireless is the future for just about everything,” says senior author Dr Sreekanth Chalasani, an associate professor in Salk’s Molecular Neurobiology Laboratory. “We already know that ultrasound is safe, and that it can go through bone, muscle and other tissues, making it the ultimate tool for manipulating cells deep in the body.

Chalasani is the mastermind who first established the field of sonogenetics a decade ago. He discovered that ultrasound sound waves beyond the range of human hearing — can be harnessed to control cells. Since sound is a form of mechanical energy, he surmised that if brain cells could be made mechanically sensitive, then they could be modified with ultrasound.

In 2015 his research group provided the first successful demonstration of the theory, adding a protein to cells of a roundworm, Caenorhabditis elegans, that made them sensitive to low-frequency ultrasound and thus enabled them to be activated at the behest of researchers.

Chalasani and his colleagues set out to search for a new protein that would work in mammals. Although a few proteins were already known to be ultrasound sensitive, no existing candidates were sensitive at the clinically safe frequency of 7MHz – so this was where the team set their sights. To test whether TRPA1 protein could activate cell types of clinical interest in response to ultrasound, the team used a gene therapy approach to add the genes for human TRPA1 to a specific group of neurons in the brains of living mice. When they then administered ultrasound to the mice, only the neurons with the TRPA1 genes were activated.

Clinicians treating conditions including Parkinson’s disease and epilepsy currently use deep brain stimulation, which involves surgically implanting electrodes in the brain, to activate certain subsets of neurons. Chalasani says that sonogenetics could one day replace this approach—the next step would be developing a gene therapy delivery method that can cross the blood-brain barrier, something that is already being studied. Perhaps sooner, he says, sonogenetics could be used to activate cells in the heart, as a kind of pacemaker that requires no implantation.

Source: https://www.salk.edu/
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https://cosmosmagazine.com/

Ultrasound guides supercharged immune cells to only attack cancer

Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.

The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors. CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient’s T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface.

This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity.

CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang’s lab.

The problem with standard CAR T cells is that they are always on—they are always expressing the CAR protein, so you cannot control their activation,” explained Wu.

To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on.

We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What’s exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body.

The team’s approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that’s on top of the tumor to activate the CAR T cells. The transducer uses what’s called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied.

The research was published in the journal Nature Biomedical Engineering.

Ultrasound Therapy for Alzheimer’s

One promising possibility when it comes to treating Alzheimer’s is the idea of using non-invasive ultrasound to take out toxic brain plaques, and a group of researchers in Australia have been at the cutting edge of this technology for a number of years. The scientists’ latest investigations have uncovered some surprising new ways this technique can improve cognition in mouse models of the disease, which they believe could have wider implications for restoring cognition in the elderly.

Led by Professor Jürgen Götz at the University of Queensland, the researchers behind this promising ultrasound therapy published some exciting early results in 2015. Initially, the idea was to use ultrasound in combination with gas-filled microbubbles to temporarily open the blood-brain barrier to allow in drugs that take out toxic amyloid and tau brain plaques that destroy synapses and are seen as key drivers of Alzheimer’s disease.

As it turned out, this technique proved an effective way to clear away the brain plaques without the need for any drugs, with the ultrasound activating microglial cells that could digest the plaques all on their own. The scientists then published a study in 2018 demonstrating how this technique could safely clear the toxic brain plaques and restore memory function in mouse models resembling human brains of 80 to 90 years old, and set their sights on human trials.

As they’ve continued to study this technique in mice, the scientists have continued to uncover new information about its effects on the brain, and how it might boost cognition. In newly published research, the team carried out new experiments on mouse models of brains with age-related deterioration, and found that it brought about yet further unexpected changes.

One of the physiological hallmarks of age-related cognitive decline is a deterioration in a type of signaling between neurons called long-term potentiation (LTP), which is associated with memory. The scientists were able to show that combining ultrasound with the microbubbles fully restored LTP in one region of the hippocampus. More interesting still, the ultrasound proved even more effective without the help of the microbubbles, not only restoring LTP but also improving the spatial learning deficits of the elderly mice by improving synaptic signaling and neurogenesis, among other physiological alterations.

Ultrasound may be a way to not just tackle brain plaques associated with Alzheimer’s, but also age-related cognitive decline in the broader population

The team’s ultrasound technique could serve as a two-pronged attack on Alzheimer’s, combining with microbubbles and plaque-busting agents to tackle the condition while simultaneously improving cognition via a separate pathway. And promisingly, the scientists believe the technique may one day prove a viable way to address age-related cognitive decline in the broader population.

Historically, we have been using ultrasound together with small gas-filled bubbles to open the almost-impenetrable blood-brain barrier and get therapeutics from the bloodstream into the brain,” Professor Götz says. “The entire research team was surprised by the remarkable restoration in cognition. We conclude therapeutic ultrasound is a non-invasive way to enhance cognition in the elderly.”

Source: https://qbi.uq.edu.au/

Ultrasound Can Selectively Kill Cancer Cells

A new technique could offer a targeted approach to fighting cancer: low-intensity pulses of ultrasound have been shown to selectively kill cancer cells while leaving normal cells unharmed.

Ultrasound wavessound waves with frequencies higher than humans can hear—have been used as a cancer treatment before, albeit in a broad-brush approach: high-intensity bursts of ultrasound can heat up tissue, killing cancer and normal cells in a target area. Now, scientists and engineers are exploring the use of low-intensity pulsed ultrasound (LIPUS) in an effort to create a more selective treatment.

A study describing the effectiveness of the new approach in cell models was published in Applied Physics Letters. The researchers behind the work caution that it is still preliminary—it still has not been tested in a live animal let alone in a human, and there remain several key challenges to address—but the results so far are promising.

The research began five years ago when Caltech‘s Michael Ortiz, Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering, found himself pondering whether the physical differences between cancer cells and healthy cells—things like size, cell-wall thickness, and size of the organelles within them—might affect how they vibrate when bombarded with sound waves and how the vibrations might trigger cancer cell death.

I have my moments of inspiration,” Ortiz says wryly.

And so Ortiz built a mathematical model to see how cells would react to different frequencies and pulses of sound waves. Together with then-graduate student Stefanie Heyden (PhD ’14), who is now at ETH Zurich, Ortiz published a paper in 2016 in the Journal of the Mechanics and Physics of Solids showing that there was a gap in the so-called resonant growth rates of cancerous and healthy cells. That gap meant that a carefully tuned sound wave could, in theory, cause the cell membranes of cancerous cells to vibrate to the point that they ruptured while leaving healthy cells unharmed. Ortiz dubbed the process “oncotripsy” from the Greek oncos (for tumor) and tripsy (for breaking).

Source: https://www.caltech.edu/

Microwave Stimulated Nanoparticles To Fight Efficiently Cancer

A physicist at The University of Texas at Arlington (UTA) has proposed a new concept for treating cancer cells. In a recently published paper in the journal Nanomedicine: Nanotechnology, Biology and Medicine, UTA physics Professor Wei Chen and a team of international collaborators advanced the idea of using titanium dioxide (TiO2) nanoparticles stimulated by microwaves to trigger the death of cancer cells without damaging the normal cells around them.

The method is called microwave-induced radical therapy, which the team refers to as microdynamic therapy, or MDT. The use of TiO2 nanoparticles activated by light and ultrasound in cancer treatments has been studied extensively, but this marks the first time researchers have shown that the nanoparticles can be effectively activated by microwaves for cancer cell destruction—potentially opening new doors to treatment for patients fighting the disease. Chen said the new therapy centers on reactive oxygen species, or ROS, which are a natural byproduct of the body’s metabolism of oxygen. ROS help kill toxins in the body, but can also be damaging to cells if they reach a critical level. TiO2 enters cells and produces ROS, which are able to damage plasma membranes, mitochondria and DNA, causing cell death.

Cancer cells are characterized by a higher steady-state saturation of ROS than normal, healthy cells,” Chen said. “This new therapy allows us to exploit that by raising the saturation of ROS in cancer cells to a critical level that triggers cell death without pushing the normal cells to that same threshold.

The pilot study for this new treatment concept builds upon Chen’s expertise in the use of nanoparticles to combat cancer.

Chen’s collaborators hail from the Guangdong Academy of Medical Sciences and Beihang University. The team conducted experiments that demonstrate the nanoparticles can significantly suppress the growth of osteosarcomas under microwave irradiation.

While TiO2 and low-power microwave irradiation alone did not effectively kill cancer cells, the combination of the two proved successful in creating a toxic effect for the tumor cells. Microwave ablation therapy has already proven to be an effective treatment against bone cancer, obtaining better results than MDT. However, MDT has applications for combatting other types of cancer, not just the osteosarcomas used for this pilot case.

Using light to activate ROS—as is seen in photodynamic therapy—can be challenging for the treatment of tumors deeply located within the body; in contrast, microwaves lend the ability to create deeper penetration that propagates through all types of tissues and non-metallic materials.

This new discovery is exciting because it potentially creates new avenues for treating cancer patients without causing debilitating side effects,” Chen said. “This targeted, localized method allows us to keep healthy cells intact so patients are better equipped to battle the disease.

Source: https://www.uta.edu/

Soldiers To Control Machines With Their Minds

The Department of Defense’s research and development wing, DARPA, is working on technology to read and write to the human brain. The focus isn’t on mind control but rather machine control, allowing the human brain to directly send instructions to machines. The goal of the process is to streamline thought control of machines to the point where humans could control them with a simple helmet or head-mounted device, making operating such systems easier.

The brain makes physical events happen by turning thoughts into action, sending instructions through the nervous system to organs, limbs, and other parts of the body. It effortlessly sends out a constant stream of commands to do everything from drive a car to make breakfast. To operate today’s machines, humans being need a middleman of sorts, a physical control system manipulated by hands, fingers, and feet.

What if human beings could cut out the middleman, operating a machine simply by thinking at it? So DARPA is funding the (Next Generation Nonsurgical Neurotechnology  (N3) initiative. N3’s goal is to create a control system for machines—including weapons—that can directly interact with the human brain. According to IEEE Spectrum, DARPA is experimenting with “magnetic fields, electric fields, acoustic fields (ultrasound) and light” as a means of controlling machines.

The implications of such a technology are huge. Instead of designing complicated controls and control systems for every machine or weapon devised, engineers could instead just create a thought-operated control system. Wearable technology becomes easier to operate as it doesn’t require a separate control system. This could also apply to notifications and data: as IEEE Spectrum points out, network administrators could feel intrusions into computer networks. DAPRA is, of course, an arm of the Pentagon, and a neurotechnological interface would almost certainly find its way into weapons.

DARPA has awarded development contracts to six groups for amounts of up to $19.48 million each. Each group has one year to prove their ability to read and write to brain tissue with an 18-month animal testing period to follow.

Source: https://www.popularmechanics.com/

Ultrasonic Comb Kills Lice

The Israeli company ParaSonic is developing a revolutionary home-use ultrasonic device that kills lice and their eggs in a single 5-minute combing treatmentHead lice infestations are a global problem, with 12 million infestations in children and adults every year in the United States alone. It can be very difficult to completely eradicate head lice, and re-infection occurs easily.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

ParaSonic’s revolutionary home-use comb, XlicerTM kills lice and their eggs in a single combing treatment that takes about 5 minutes. Ultrasound waves generated by the teeth of the wide-toothed comb destroy lice and lice eggs after exposure of about one second. XlicerTM simultaneously sprays a natural solution onto the hair, to augment the efficacy of the the ultrasound and significantly increase the lice and eggs’ mortality. Because there is no use of pesticides, there is no possibility of the lice developing resistance. The comb’s wide-tooth design means no discomfort to the person being treated.

Source: http://para-sonic.com/