BioMedical Research.

Wearable Vitals Tracker..................

In order to better care for patients, infants, and the elderly, research teams worldwide are investigating novel ways to continuously monitor people's health by tracking key life signs such as heart rate and body temperature. Such applications require sensors that are flexible and wireless for maximum comfort, self-powered to avoid replacement of batteries, and cheap enough to permit disposable use to ensure proper hygiene.
A new wearable electronic device that is the brainchild of scientists at the University of Tokyo might fit those criteria. It’s an armband that combines a temperature sensor to measure body heat under the arm, a piezoelectric speaker to provide audible feedback, amorphous silicon solar cells for power, and circuits made of organic ink printed onto a plastic film. The same researchers previously developed flexible electronic skins with an eye toward covering prosthetic limbs and humanoid robots.
The team said the medical armband contains the first organic circuit able to produce sound, and is first device to incorporate an organic power supply circuit. These organic circuits increase the range of illumination at which the armband can operate by 7.3 times; this allows it to be used indoors.
The armband can emit an audible buzz when the body temperature it detects exceeds a preset limit. That temperature can be anywhere between 36.5 and 38.5 degrees Celsius. The scientists do not plan on incorporating a video display onto the armband. “We think sending information wirelessly is more important," said the study’s lead author, Hiroshi Fuketa.
The researchers noted the armband could incorporate other sensors to monitor heart rate, blood pressure, or moisture, as well as a flexible battery to store energy from the solar cells so the device can continue working after dark. The scientists will present the armband at the 2015 IEEE International Solid State Circuits Conference (ISSCC) in San Francisco on 24 February.

Blasts of Ultrasound Could Get Needed Drugs Into the Brain

New focused ultrasound arrays can temporarily breach the blood-brain barrier:
There’s a barrier in your brain.
Composed of very densely packed cells in the capillary walls, it restricts the passage of substances of the wrong size or chemistry from the bloodstream. Like a locked fence around your home, the blood-brain barrier prevents intruders—such as infective bacteria—from entering.
But a locked fence can also keep out rescuers in an emergency, and the blood-brain barrier keeps out potentially helpful drugs that might be able to ease the suffering of the tens of millions of people with Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and other diseases of the central nervous system. Less than 5 percent of the roughly 7000 available drugs can get through. Basically, none of the large-molecule drugs can, severely limiting the options for new therapies.
But there’s hope. Blasts of ultrasound can temporarily open the barrier in tightly focused spots of the brain that are just millimeters in diameter. And engineers at Chang Gung University, in Taiwan, have recently come up with a much improved way of delivering that energy.
The prototype device they developed is a 256-channel ultrasound phased array. According to electrical engineering professor Hao-Li Liu, his team has developed a unique circuit design involving multiple microcontrollers and power-sensing feedback circuits that enable the system to deliver two frequencies at once instead of the single frequency that biomedical researchers have been working with. By altering the phase of individual channels, the array produces millimeters-wide spots of ultrasound energy that can be electronically steered to any point in the brain.
It’s been known for a while that ultrasound reversibly opens the blood-brain barrier, even if the exact workings haven’t quite been nailed down. The process relies on the acoustic cavitation effect, which is the growth and collapse of microbubbles in a liquid under the influence of an ultrasonic field. (Microbubbles are injected as a contrast agent to enhance ultrasound imaging.) This effect generates an acoustic shock wave, which causes the cells in the blood vessel walls—called endothelial cells—to deform.
“Like mimosa leaves, endothelial cells contract after being shocked, thereby generating gaps. The result increases the possibility of drug delivery,” Liu says, adding that other cells outside the ultrasound’s focal point are undisturbed. Doctors can deliver drugs for about 1 to 2 hours, after which the gaps close.
Therapeutic ultrasound machines available on the market today destroy benign tumors of the uterus and other tissue mostly using a single frequency to generate heat at the ultrasound array’s focal point.
Using two frequencies simultaneously instead can boost the power of these machines three- to fivefold, according to Liu. Greater cavitation “significantly enhances the blood-brain barrier opening,” he says.
In tests using pigs—which have a similar skull thickness to that of humans—the portion of the brain the researchers were aiming for took up 10 times as much of a test dye under the influence of ultrasound as it would have otherwise. They operated the array to produce either 400 kilohertz energy, 600 kHz (an “ultraharmonic” of 400 kHz), or both at once. The dual frequency produced the best results—nearly double what the single frequency delivered without causing damage. “Of course, the performance of different drugs vary,” Liu says.
Elisa Konofagou, associate professor of biomedical engineering and radiology at Columbia University, in New York City, who studies the mechanics of focused ultrasound’s effects, is concerned that the Chang Gung group might not be able to improve further on the results of their system. “The frequency range seems to be on the low end,” she says. “The frequencies would activate larger microbubbles—greater than 2 micrometers—when most microbubbles used are around 1 micrometer. So I’m not sure how they would enhance it.”
Liu counters that using multiple frequencies theoretically has a greater chance of exciting more bubbles. A bubble’s resonance frequency is primarily determined by its size, so more frequencies means more bubbles of different sizes are affected.
Liu hopes that a clinical trial involving the 256-channel ultrasound system could be launched within three years after gaining the support of neurologists. What might help to achieve that goal is a solution to the problem of real-time feedback. “After focused ultrasound energy is delivered to the target position, we can’t make sure if the blood-brain barrier is open. We can only have an answer postoperationally by using contrast-enhanced magnetic resonance imaging technology,” Liu says. His team and others have been looking for possible solutions to the problem.
According to research led by Kullervo Hynynen, senior scientist at Sunnybrook Health Sciences Centre, in Toronto, one way to determine if the blood-brain barrier has been breached is to listen for ultraharmonic frequencies emitted by the bubbles. “This signal can be used in a feedback system to control the exposures,” he says.
If researchers can prove that ultrasound can safely open a window into the brain, better drug therapies will likely step through it.
This article originally appeared in print as “Breaching the Blood-Brain Barrier.”

Electromagnetic Depression Treatment Nears Approval...............

Deep transcranial magnetic stimulation adds to psychiatry’s arsenal of electronicremedies.
A new type of brain stimulation device for combating difficult-to-treat cases of major depressive disorder is likely to break into the large American market soon. Its maker, Jerusalem-based Brainsway, plans to apply to the U.S. Food and Drug Administration for permission to market the device this month. The move follows initial results from a large-scale trial of the system, in which 30.4 percent of treated patients went into remission and 36.7 percent showed significant improvement. Research into device-based treatments for psychiatric problems has grown rapidly, and if the FDA gives its go-ahead, Brainsway’s system will become the fourth device-based therapy to go on the market since 2005.
Deep transcranial magnetic stimulation (TMS), as its name suggests, uses magnetic fields to stimulate activity in structures deep in the brain. The patient wears a helmet in which powerful, specially designed electromagnets have been carefully positioned. When a pulse of electricity flows through the magnets’ coils, the resulting magnetic field induces current to flow through a portion of the brain.
There are subtle differences between deep TMS and repetitive transcranial magnetic stimulation (rTMS), a brain stimulation tool widely used in research and also marketed as a treatment for depression. The electromagnetic elements in deep TMS are designed to produce a magnetic field that reaches its greatest strength deep within the brain. Ordinarily, magnetic fields fall away quickly inside the brain, but the orientation and structure of the coils in deep TMS lessens that effect. “The concept was to reduce the rate of reduction of the magnetic field as a function of distance,” says Abraham Zangen, coinventor of the technology. In contrast, rTMS typically uses a single coil that produces a tightly focused field just a few centimeters below the brain’s surface.
“The Brainsway coil is more like a shotgun than a rifle,” says Mark S. George, a pioneer of TMS and director of the brain stimulation laboratory at the Medical University of South Carolina, in Charleston. It’s unclear which weapon will be better at fighting depression. A tightly focused stimulation might be best if researchers knew exactly where to target that stimulation, he says, but they don’t.
The 30.4 percent remission rate Brainsway is claiming may not seem like much, especially when 14.5 percent of patients who underwent a sham procedure also recovered, but in the context of antidepressants it is quite good, according to experts. The patients enrolled in the trial had already been failed by at least one drug treatment, and studies have shown that the odds of success with subsequent drugs decrease. What’s more, as a group the treated patients on average showed a three-point improvement on the Hamilton depression rating scale, which doctors use to evaluate the severity of depression. “If you compared the three points to some antidepressant studies, it’s above average—quite a lot above average,” says U*i Sofer, Brainsway’s CEO. “Some medications are approved and marketed with a 1.5- or 2-point difference in the Hamilton.”
Brainsway executives expect their device to have an easier time with regulators than previous devices did, particularly Neuronetics’ rTMS system, NeuroStar. Although it was ultimately approved, NeuroStar’s initial results were a bit ambiguous, and as the first of its kind, the device suffered from a procedural problem that meant it had to be compared to electroconvulsive therapy. ECT is an inconvenient treatment and can have side effects that scare many patients, but it’s amazingly effective and was a high bar for Neuronetics to hurdle. However, with NeuroStar already on the market, the FDA lowered the bar for Brainsway, and the company is expected to surmount it.
“If these data hold up under peer review, if they are as they seem, then they are unambiguous,” says George.