Posts tagged ultrasound
Articles and news from the latest research reports.
New Method Could Improve Ultrasound Imaging
One day while casually reading a review article, Caltech chemical engineer Mikhail Shapiro came across a mention of gas vesicles—tiny gas-filled structures used by some photosynthetic microorganisms to control buoyancy. It was a light-bulb moment. Shapiro is always on the lookout for new ways to enhance imaging techniques such as ultrasound or MRI, and the natural nanostructures seemed to be just the ticket to improve ultrasound imaging agents.
Now Shapiro and his colleagues from UC Berkeley and the University of Toronto have shown that these gas vesicles, isolated from bacteria and from archaea (a separate lineage of single-celled organisms), can indeed be used for ultrasound imaging. The vesicles could one day help track and reveal the growth, migration, and activity of a variety of cell types—from neurons to tumor cells—using noninvasive ultrasound, one of the most widely used imaging modalities in biomedicine.
A paper describing the work appears as an advance online publication in the journal Nature Nanotechnology.
"People have struggled to make synthetic nanoscale imaging agents for ultrasound for many years," says Shapiro. "To me, it’s quite amazing that we can borrow something that nature has evolved for a completely different purpose and use it for in vivo ultrasound imaging. It shows just how much nature has to offer us as engineers."
Ultrasound directed to the human brain can boost sensory performance
Whales, bats, and even praying mantises use ultrasound as a sensory guidance system – and now a new study has found that ultrasound can modulate brain activity to heighten sensory perception in humans.
Virginia Tech Carilion Research Institute scientists have demonstrated that ultrasound directed to a specific region of the brain can boost performance in sensory discrimination. The study, published online Jan. 12 in Nature Neuroscience, provides the first demonstration that low-intensity, transcranial-focused ultrasound can modulate human brain activity to enhance perception.
“Ultrasound has great potential for bringing unprecedented resolution to the growing trend of mapping the human brain’s connectivity,” said William “Jamie” Tyler, an assistant professor at the Virginia Tech Carilion Research Institute, who led the study. “So we decided to look at the effects of ultrasound on the region of the brain responsible for processing tactile sensory inputs.”
The scientists delivered focused ultrasound to an area of the cerebral cortex that corresponds to processing sensory information received from the hand. To stimulate the median nerve – a major nerve that runs down the arm and the only one that passes through the carpal tunnel – they placed a small electrode on the wrist of human volunteers and recorded their brain responses using electroencephalography, or EEG. Then, just before stimulating the nerve, they began delivering ultrasound to the targeted brain region.
The scientists found that the ultrasound both decreased the EEG signal and weakened the brain waves responsible for encoding tactile stimulation.
The scientists then administered two classic neurological tests: the two-point discrimination test, which measures a subject’s ability to distinguish whether two nearby objects touching the skin are truly two distinct points, rather than one; and the frequency discrimination task, a test that measures sensitivity to the frequency of a chain of air puffs.
What the scientists found was unexpected.
The subjects receiving ultrasound showed significant improvements in their ability to distinguish pins at closer distances and to discriminate small frequency differences between successive air puffs.
“Our observations surprised us,” said Tyler. “Even though the brain waves associated with the tactile stimulation had weakened, people actually got better at detecting differences in sensations.”
Why would suppression of brain responses to sensory stimulation heighten perception? Tyler speculates that the ultrasound affected an important neurological balance.
“It seems paradoxical, but we suspect that the particular ultrasound waveform we used in the study alters the balance of synaptic inhibition and excitation between neighboring neurons within the cerebral cortex,” Tyler said. “We believe focused ultrasound changed the balance of ongoing excitation and inhibition processing sensory stimuli in the brain region targeted and that this shift prevented the spatial spread of excitation in response to stimuli resulting in a functional improvement in perception.”
To understand how well they could pinpoint the effect, the research team moved the acoustic beam one centimeter in either direction of the original site of brain stimulation – and the effect disappeared.
“That means we can use ultrasound to target an area of the brain as small as the size of an M&M,” Tyler said. “This finding represents a new way of noninvasively modulating human brain activity with a better spatial resolution than anything currently available.”
Based on the findings of the current study and an earlier one, the researchers concluded that ultrasound has a greater spatial resolution than two other leading noninvasive brain stimulation technologies – transcranial magnetic stimulation, which uses magnets to activate the brain, and transcranial direct current stimulation, which uses weak electrical currents delivered directly to the brain through electrodes placed on the head.
“Gaining a better understanding of how pulsed ultrasound affects the balance of synaptic inhibition and excitation in targeted brain regions – as well as how it influences the activity of local circuits versus long-range connections – will help us make more precise maps of the richly interconnected synaptic circuits in the human brain,” said Wynn Legon, the study’s first author and a postdoctoral scholar at the Virginia Tech Carilion Research Institute. “We hope to continue to extend the capabilities of ultrasound for noninvasively tweaking brain circuits to help us understand how the human brain works.”
“The work by Jamie Tyler and his colleagues is at the forefront of the coming tsunami of developing new safe yet effective noninvasive ways to modulate the flow of information in cellular circuits within the living human brain,” said Michael Friedlander, executive director of the Virginia Tech Carilion Research Institute and a neuroscientist who specializes in brain plasticity. “This approach is providing the technology and proof of principle for precise activation of neural circuits for a range of important uses, including potential treatments for neurodegenerative disorders, psychiatric diseases, and behavioral disorders. Moreover, it arms the neuroscientific community with a powerful new tool to explore the function of the healthy human brain, helping us understand cognition, decision-making, and thought. This is just the type of breakthrough called for in President Obama’s BRAIN Initiative to enable dramatic new approaches for exploring the functional circuitry of the living human brain and for treating Alzheimer’s disease and other disorders.”
A team of Virginia Tech Carilion Research Institute scientists – including Tomokazu Sato, Alexander Opitz, Aaron Barbour, and Amanda Williams, along with Virginia Tech graduate student Jerel Mueller of Raleigh, N.C. – joined Tyler and Legon in conducting the research. In addition to his position at the institute, Tyler is an assistant professor of biomedical engineering and sciences at the Virginia Tech–Wake Forest University School of Biomedical Engineering and Sciences. In 2012, he shared a Technological Innovation Award from the McKnight Endowment for Neuroscience to work on developing ultrasound as a noninvasive tool for modulating brain activity.
“In neuroscience, it’s easy to disrupt things,” said Tyler. “We can distract you, make you feel numb, trick you with optical illusions. It’s easy to make things worse, but it’s hard to make them better. These findings make us believe we’re on the right path.”
How Ultrasound Became the Newest Weapon Against Stroke
Ischemic strokes, caused by blood clots that can develop in the brain and cut off blood flow, make up more than 80 percent of strokes suffered in the U.S. annually. To date, the most effective treatment is the clot-dissolving thrombolysis drug tissue plasminogen activator, tPA. But tPA is a far-from-perfect solution, says Andrew Barreto, a neurologist at the University of Texas Health Science Center in Houston. “IV-tPA will help about 30 of 100 patients who receive it within the first 4.5 hours after stroke symptom onset,” Barreto says. “But, many patients are still disabled, so we need better treatments.”
Barreto and some of his colleagues think that ultrasound could be one of those treatments. Ultrasound has been a valuable tool for diagnosing and tracking strokes in the brain for years. Now, a wide variety of new technologies are making it possible for neurosurgeons to use ultrasound waves, which travel at frequencies too high for the human ear to pick up, to not only identify the signs of stroke such as blood clots in the brain but also to help treat them.
Barreto was a principal researcher in the recent study of the Clotbust device, a headband-like piece of equipment placed on a patient’s head that aims to use ultrasound directed to increase tPA’s effectiveness in breaking up clots in the brain. A preliminary test of the device, which fires 2-MHz pulses of ultrasound from a series of 18 transducers at 5-second intervals, found that it was safe to use in stroke patients. Now, the device is in the midst of effectiveness testing on a group of 830 stroke patients worldwide.
One of the sites involved in testing the device is Swedish Neuroscience Center in Seattle, where chief of neuroscience David Newell notes that preliminary results from the trial were promising. In safety trials, the Clotbust device combined with the thrombolysis drug tPA cleared 40 percent of clots in ischemic strokes in the first two hours after being used. That’s twice as effective as the 20 percent clearance rate usually achieved by tPA alone.
Clotbust isn’t the only tool of its kind being tested at Swedish. Newell and his colleagues are involved in testing three different types of ultrasound technologies for a variety of neurological ailments. Those include one technique devised by. Newell in collaboration with EKOS corporation, a Seattle-area company specializing in ultrasound-emitting catheters, which are designed to travel up a blood vessel and transmit ultrasound from an emitter at its tip, to help loosen blood clots. Newell and his colleagues have been testing a modified version of the EkoSonic catheter, which can more easily be placed directly in the brain and used to detect a different type of stroke known as intracerebral hemorrhage (ICH).
Caused by bleeding from ruptured blood vessels deep in the brain, ICH strokes are much harder to treat because of their location. They are also particularly deadly, with a mortality rate north of 50 percent. Even those who survive are likely to be left disabled or with long roads to recovery. The tPA may be effective in treating these strokes as well, breaking up the clots in the brain that form around the bleed and allowing fluid to be drained off before it can do lasting harm.
While the effectiveness of tPA in treating ICH is still being studied, Newell and his team used the repurposed EkoSonic catheter to improve delivery of clot-busting drugs to bleed sites deep in the brain, and their early results are promising. In an introductory round of tests on nine patients at Swedish, Newell and his colleagues found that clots accompanying hemorrhagic strokes were cleared three times faster by a combination of ultrasound and tPA than they were by drugs alone. By combining the two techniques, Newell said, he and his team could clear clots from most patients in the first day of treatment. He’s now working with the company that developed the technology on creating a new type of catheter, designed specifically for use within the brain, that combines drug delivery, ultrasound emission, and drainage in one tool.
Neither Clotbust nor the EkoSonic catheter uses ultrasound to physically destroy clots. Instead, the blasts of high-frequency sound produce “a micromechnical action that makes the lytic effect of tPA a lot more effective,” by improving the efficiency with which it is delivered. “Injecting tPA is like putting an ice cube in a drink and waiting for it to melt,” says Newell. “With ultrasound, it’s more akin to creating a snow flurry. The drug binds to more binding sites, and it does so a lot faster.”
That’s not the case in the third ultrasound device being tested at Swedish. The ExAblate Neuro device developed by Israeli company InsighTec uses thousands of beams of ultrasound focused on one spot to create intense heat at a targeted point in the brain. The ExAblate Neuro mimics the effects of a tool used in neurosurgery for years, the gamma knife, which uses highly focused radiation energy to cut out material like tumors or to create lesions that can lessen the effects of diseases like Parkinson’s or epilepsy. In the case of stroke, the Neuro could potentially superheat solidified clots, turning them to more easily cleared liquid.
Since it uses focused ultrasound rather than the dangerous radiation associated with the gamma knife, says Newell, ExAblate has the potential to perform similar surgeries that are more easily repeatable. Current gamma knife surgeries have to get it right the first time, as exposing patients to powerful radiation over and over again can be dangerous. Since ultrasound energy doesn’t carry the same exposure dangers, doctors could potentially do the same sort of treatments in smaller steps without raising concerns over patient health.
All three of these new methods are still in their experimental phases, but each one has the potential to transform—and improve—the way strokes and other ailments in the brain are treated. And that may be only the beginning of the potential for the techniques. “Ultrasound technology represents almost a whole new field in neurosurgery,” said Newell.
(Source: popularmechanics.com)
‘Good Vibrations’! Brain Ultrasound Improves Mood
Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) stimulation (tDCS), shown to improve memory. Transcranial ultrasound stimulation (TUS) has also shown promise.
Ultrasound consists of mechanical vibrations, like sound, but with frequencies far greater than the upper limit of human hearing, around 20 thousand to 20 million cycles per second (20 kilohertz to 20 megahertz). Ultrasound vibrations penetrate bodily tissue including bone, and are widely used to image anatomical structures via echo effects, e.g. visualizing unborn babies in mothers’ wombs, and organs, blood vessels, nerves and other structures in medical procedures. Virtually every part of the body, including the brain, has been safely imaged with low to moderate intensity ultrasound.
High intensity, focused ultrasound can damage tissue by heating and cavitation, and has been used to ablate tumors and other lesions. ‘Sub-thermal’ ultrasound can safely stimulate neural tissue. In 2002 a UCLA group led by Alexander Bystritsky noticed beneficial side effects in psychiatric patients whose brains were imaged by TUS. A team led by Virginia Tech’s W. Jamie Tyler has shown TUS-induced behavioral and electrophysiological changes in animals. A Harvard group led by S-S Yoo has used focused ultrasound aimed at mouse motor cortex to wag the mouse’s tail. But clinical trials of TUS aimed at human mental states have been lacking.
Now, in an article in the journal Brain Stimulation, a group from the Departments of Anesthesiology and Radiology at the University of Arizona Medical Center in Tucson, Arizona has investigated TUS for modulating mental states in a pilot study in human volunteers suffering from chronic pain. A clinical ultrasound imaging device (General Electric LOGIQe) was used, with the ultrasound probe applied at the scalp overlying the brain’s temporal and frontal cortex (visible on the imaging screen). In random order, each subject received two 15 second exposures: sham/placebo, and 8 megahertz ultrasound (undetectable to subjects). Following exposure, subjects reported (by visual analog scales) significant improvement in mood both 10 minutes and 40 minutes after TUS, but not after sham/placebo. In a followup study (led by University of Arizona psychologists Jay Sanguineti and John JB Allen) preliminary results suggest 2 megahertz TUS (which traverses skull more readily) may be more effective in mood enhancement than 8 megahertz TUS.
The mechanism by which TUS can affect mental states is unknown (as is the mechanism by which the brain produces mental states). Tyler proposed TUS acts by vibrational stretching of neuronal membranes and/or extracellular matrix, but two recent papers from the group of Anirban Bandyopadhyay at National Institute of Material Sciences (NIMS) in Tsukuba, Japan (Sahu et al. [2013] Appl. Phys. Letts.; Sahu et al [2013] Biosensors and Bioelectronics) have suggested another possibility. The NIMS group used nanotechnology to study conductive properties of individual microtubules, protein polymers of tubulin (the brain’s most prevalent protein). Major components of the neuronal cytoskeleton, microtubules grow and extend neurons, form and regulate synapses, are disrupted in Alzheimer’s disease, and theoretically linked to information processing, memory encoding and mental states. Bandyopadhyay’s NIMS group found that microtubules have remarkable electronic conductive properties when excited at certain specific resonant frequencies, e.g. in the low megahertz, precisely the range of TUS.
Dr. Stuart Hameroff, lead author on the new TUS study, said: “This suggests TUS may stimulate natural megahertz resonances in brain microtubules, enhancing not only mood and conscious mental states, but perhaps also microtubule functions in synaptic plasticity, nerve growth and repair. We plan further studies of TUS on traumatic brain injury, Alzheimer’s disease and post-traumatic stress disorders. ‘Tuning the tubules’ may help a variety of mental states and cognitive disorders.”
(Source: newswise.com)
Ultrasound reveals autism risk at birth
Low-birth-weight babies with a particular brain abnormality are at greater risk for autism, according to a new study that could provide doctors a signpost for early detection of the still poorly understood disorder.
Led by Michigan State University, the study found that low-birth-weight newborns were seven times more likely to be diagnosed with autism later in life if an ultrasound taken just after birth showed they had enlarged ventricles, cavities in the brain that store spinal fluid. The results appear in the Journal of Pediatrics.
“For many years there’s been a lot of controversy about whether vaccinations or environmental factors influence the development of autism, and there’s always the question of at what age a child begins to develop the disorder,” said lead author Tammy Movsas, clinical assistant professor of pediatrics at MSU and medical director of the Midland County Department of Public Health.
“What this study shows us is that an ultrasound scan within the first few days of life may already be able to detect brain abnormalities that indicate a higher risk of developing autism.”
Movsas and colleagues reached that conclusion by analyzing data from a cohort of 1,105 low-birth-weight infants born in the mid-1980s. The babies had cranial ultrasounds just after birth so the researchers could look for relationships between brain abnormalities in infancy and health disorders that showed up later. Participants also were screened for autism when they were 16 years old, and a subset of them had a more rigorous test at 21, which turned up 14 positive diagnoses.
Ventricular enlargement is found more often in premature babies and may indicate loss of a type of brain tissue called white matter.
“This study suggests further research is needed to better understand what it is about loss of white matter that interferes with the neurological processes that determine autism,” said co-author Nigel Paneth, an MSU epidemiologist who helped organize the cohort. “This is an important clue to the underlying brain issues in autism.”
Prior studies have shown an increased rate of autism in low-birth-weight and premature babies, and earlier research by Movsas and Paneth found a modest increase in symptoms among autistic children born early or late.
Propping Open the Door to the Blood Brain Barrier
The treatment of central nervous system (CNS) diseases can be particularly challenging because many of the therapeutic agents such as recombinant proteins and gene medicines are not easily transported across the blood-brain barrier (BBB). Focused ultrasound can be used to “open the door” of the blood brain barrier. However, finding a way to “prop the door open” to allow therapeutics to reach diseased tissue without damaging normal brain tissue is the focus of a new study by a team of researchers at the Institute of Biomedical Engineering at National Taiwan University presenting at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa.
The group is investigating the feasibility of using heparin, a common anticoagulant, to enhance the delivery of therapeutic macromolecules using ultrasound into the brain. Heparin could be employed to increase treatment efficacy in patients with different types of CNS diseases under the guidance of medical imaging system providing new hope in these challenging cases. Initial results show that heparin does have the potential to optimize therapeutic delivery with ultrasound, acting as a “doorstop,” allowing drugs to better permeate the BBB and enhancing treatment success.
“A higher acoustic pressure and longer sonication, and/or a higher dose of microbubbles may increase the delivery of drugs or tracers into the sonicated brain tissue,” explains Kuo-Wei Lu, a member of the research team, “but side-effects, such as microhemorrhage, can also increase dramatically. The results of this study indicate that heparin may offer a safer way can to enhance the delivery of therapeutics to patients with CNS diseases.”
With these encouraging results, the next step for the team is to develop a focused ultrasound system with Magnetic Resonance Imaging (MRI) guidance to establish suitable parameters needed for patient clinical trials. “Focused ultrasound sonication is a noninvasive technology capable of localized and transient BBB opening for the delivery of CNS therapeutics,” Lu states. “We hope by developing suitable parameters and using chemical enhancers like heparin, this can be a valuable tool in the treatment of patients with CNS diseases, opening the door to better patient outcomes.”
(Image: Ben Brahim Mohammed)
Ultrasound Can Be Tweaked to Stimulate Different Sensations
A century after the world’s first ultrasonic detection device – invented in response to the sinking of the Titanic – Virginia Tech Carilion Research Institute scientists have provided the first neurophysiological evidence for something that researchers have long suspected: ultrasound applied to the periphery, such as the fingertips, can stimulate different sensory pathways leading to the brain.
And that’s just the tip of the iceberg. The discovery carries implications for diagnosing and treating neuropathy, which affects millions of people around the world.
“Ideally, neurologists should be able to tailor treatments to the specific sensations their patients are feeling,” said William “Jamie” Tyler, an assistant professor at the Virginia Tech Carilion Research Institute, who led the study published this week in PLOS ONE.
“Unfortunately, even with today’s technologies, it’s difficult to stimulate certain types of sensations without evoking others. Pulsed ultrasound allows us to selectively activate functional subsets of nerve fibers so we can study what happens when you stimulate, for example, only the peripheral fibers and central nervous system pathways that convey the sensation of fast, sharp pain or only those that convey the sensation of slow, dull, throbbing pain.”
Scientists report a potential new treatment to prevent strokes
Scientists may have discovered a new way to prevent strokes in high risk patients, according to research from the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW).
Work by a new research group, led by Professor Donald Singer, Professor of Therapeutics at Warwick Medical School and Professor Chris Imray from UHCW, has now been published in US journal Stroke.
The group is using ultrasound scanning to look at patients with carotid artery disease, one of the major causes of stroke. Clots can form on diseased carotid arteries in the neck. Small parts of these clots can released to form microemboli, which can travel to block key brain arteries and lead to weakness, disturbed speech, loss of vision and other serious stroke syndromes. Standard anti-platelet drugs such as aspirin may not prevent the formation of harmful microemboli.
The scanning process can be used to find patients at very high risk of stroke because microemboli have formed despite prior anti-platelet drugs. Using scanning, the team has found that tirofiban, another anti-platelet drug designed to inhibit the formation of blood clots, can suppress microemboli where previous treatment such as aspirin has been ineffective. In their study, tirofiban was more effective than other ‘rescue’ treatment.
Professor Singer said: “These findings show that the choice of rescue medicine is very important when carotid patients develop microemboli despite previous treatment with powerful anti-platelet drugs such as aspirin. We now need to go on to further studies of anti-microemboli rescue treatments, to aim for the right balance between protection and risk for our patients.”
Professor Imray said: “These findings show the importance of ultrasound testing for micro-emboli in carotid disease patients. These biomarkers of high stroke risk cannot be predicted just from assessing the severity of risk factors such as smoking history, cholesterol and blood pressure.”
Hand-held 3D scanner could simplify medical imaging
Although there are various efforts under way to create a working Star Trek-like medical tricorder, such a device isn’t available for general use just yet. In the meantime, however, doctor’s offices may soon be equipped a piece of equipment that wouldn’t look at all out of place in the sick bay of the Enterprise. Developed by engineers from the University of Illinois at Urbana-Champaign, it’s a hand-held scanning device that provides real-time three-dimensional images of the insides of patients’ bodies.
The scanner utilizes optical coherence tomography (OCT), which has been described as “optical ultrasound,” in that it uses reflected light – as opposed to reflected sound – to image internal structures. Along with an OCT system, the device also incorporates a near-infrared light source, a video camera for obtaining images of surface features at the scan location, and a microelectromechanical systems (MEMS)-based scanner for directing the light.
Tomoko Sakai and colleagues from Kyoto University in Japan subjected a pregnant chimp to a 3D ultrasound to gather images of the fetus between 14 and 34 weeks of development. The volume of its growing brain was then compared to that of an unborn human.
The team found that brain size increases in both chimps and humans until about 22 weeks, but after then only the growth of human brains continues to accelerate. This suggests that as the brain of modern humans rapidly evolved, differences between the two species emerged before birth as well as afterwards.
The researchers now plan to examine how different parts of the brain develop in the womb, particularly the forebrain, which is responsible for decision-making, self-awareness and creativity.
(Source: newscientist.com)