Restoring The Sense Of Touch In Amputees Using Natural Signals Of The Nervous System

Scientists at the University of Chicago and Case Western Reserve University have found a way to produce realistic sensations of touch in two human amputees by directly stimulating the nervous system.

The study, published Oct. 26 in Science Translational Medicine (STM), confirms earlier research on how the nervous system encodes the intensity, or magnitude, of sensations. It is the second of two groundbreaking publications this month by University of Chicago neuroscientist Sliman Bensmaia, PhD, using neuroprosthetic devices to recreate the sense of touch for amputee or quadriplegic patients with a “biomimetic” approach that approximates the natural, intact nervous system.

On Oct. 13, in a separate publication from STM, Bensmaia and a team led by Robert Gaunt, PhD, from the University of Pittsburgh, announced that for the first time, a paralyzed human patient was able to experience the sense of touch through a robotic arm that he controls with his brain. In that study, researchers interfaced directly with the patient’s brain, through an electrode array implanted in the areas of the brain responsible for hand movements and for touch, which allowed the man to both move the robotic arm and feel objects through it.

The new study takes a similar approach in amputees, working with two male subjects who each lost an arm after traumatic injuries. In this case, both subjects were implanted with neural interfaces, devices embedded with electrodes that were attached to the median, ulnar and radial nerves of the arm. Those are the same nerves that would carry signals from the hand were it still intact.

“If you want to create a dexterous hand for use in an amputee or a quadriplegic patient, you need to not only be able to move it, but have sensory feedback from it,” said Bensmaia, who is an associate professor of organismal biology and anatomy at the University of Chicago. “To do this, we first need to look at how the intact hand and the intact nervous system encodes this information, and then, to the extent that we can, try to mimic that in a neuroprosthesis.”

Recreating different sensations of intensity

The latest research is a joint effort by Bensmaia and Dustin Tyler, PhD, the Kent H. Smith Professor of Biomedical Engineering at Case Western Reserve University, who works with a large team trying to make bionic hands clinically viable. Tyler’s team, led by doctoral student Emily Graczyk, systematically tested the subjects’ ability to distinguish the magnitude of the sensations evoked when their nerves were stimulated through the interface. They varied aspects of the signals, such as frequency and intensity of each electrical pulse. The goal was to understand if there was a systematic way to manipulate the sensory magnitude.

Earlier research from Bensmaia’s lab predicted how the nervous system discerns intensity of touch, for example, how hard an object is pressing against the skin. That work suggested that the number of times certain nerve fibers fire in response to a given stimulus, known as the population spike rate, determines the perceived intensity of a given stimulus.

Results from the new study verify this hypothesis: A single feature of electrical stimulation—dubbed the activation charge rate—was found to determine the strength of the sensation. By changing the activation charge rate, the team could change sensory magnitude in a highly predictable way. The team then showed that the activation charge rate was also closely related to the evoked population spike rate.

Building neuroprosthetics that approximate the natural nervous system

While the new study furthers the development of neural interfaces for neuroprosthetics, artificial touch will only be as good as the devices providing input. In a separate paper published earlier this year in IEEE Transactions on Haptics, Bensmaia and his team tested the sensory abilities of a robotic fingertip equipped with touch sensors.

Using the same behavioral techniques that are used to test human sensory abilities, Bensmaia’s team, led by Benoit Delhaye and Erik Schluter, tested the finger’s ability to distinguish different touch locations, different pressure levels, the direction and speed of surfaces moving across it and the identity of textures scanned across it. The robotic finger (with the help of machine learning algorithms) proved to be almost as good as a human at most of these sensory tasks. By combining such high-quality input with the algorithms and data Bensmaia and Tyler produced in the other study, researchers can begin building neuroprosthetics that approximate natural sensations of touch.

Without realistic, natural-feeling sensations, neuroprosthetics will never come close to achieving the dexterity of our native hands. To illustrate the importance of touch, Bensmaia referred to a piano. Playing the piano requires a delicate touch, and an accomplished pianist knows how softly or forcefully to strike the keys based on sensory signals from the fingertips. Without these signals, the sounds the piano would make would not be very musical.

“The idea is that if we can reproduce those signals exactly, the amputee won’t have to think about it, he can just interact with objects naturally and automatically. Results from this study constitute a first step towards conveying finely graded information about contact pressure,” Bensmaia said.

Computer Program Beats Physicians At Brain Cancer Diagnoses

Computer programs have defeated humans in Jeopardy!, chess and Go. Now a program developed at Case Western Reserve University has outperformed physicians on a more serious matter.

The program was nearly twice as accurate as two neuroradiologists in determining whether abnormal tissue seen on magnetic resonance images (MRI) were dead brain cells caused by radiation, called radiation necrosis, or if brain cancer had returned.

The direct comparison is part of a feasibility study published in the American Journal of Neuroradiology today.

“One of the biggest challenges with the evaluation of brain tumor treatment is distinguishing between the confounding effects of radiation and cancer recurrence,” said Pallavi Tiwari, assistant professor of biomedical engineering at Case Western Reserve and leader of the study. “On an MRI, they look very similar.”

But treatments for radiation necrosis and cancer recurrence are far different. Quick identification can help speed prognosis, therapy and improve patient outcomes, the researchers say.

With further confirmation of its accuracy, radiologists using their expertise and the program may eliminate unnecessary and costly biopsies Tiwari said. Brain biopsies are currently the only definitive test but are highly invasive and risky, causing considerable morbidity and mortality.

To develop the program, the researchers employed machine learning algorithms in conjunction with radiomics, the term used for features extracted from images using computer algorithms. The engineers, scientists and physicians trained the computer to identify radiomic features that discriminate between brain cancer and radiation necrosis, using routine follow-up MRI scans from 43 patients. The images were all from University Hospitals Case Medical Center.

The team then developed algorithms to find the most discriminating radiomic features, in this case, textures that can’t be seen by simply eyeballing the images.

“What the algorithms see that the radiologists don’t are the subtle differences in quantitative measurements of tumor heterogeneity and breakdown in microarchitecture on MRI, which are higher for tumor recurrence,” said Tiwari, who was appointed to the Department of Biomedical Engineering by the Case Western Reserve School of Medicine.

More specifically, while the physicians use the intensity of pixels on MRI scans as a guide, the computer looks at the edges of each pixel, explained Anant Madabhushi, F. Alex Nason professor II of biomedical engineering at Case Western Reserve, and study co-author.

“If the edges all point to the same direction, the architecture is preserved,” said Madabhushi, who also directs the Center of Computational Imaging and Personalized Diagnostics at CWRU. “If they point in different directions, the architecture is disrupted—the entropy, or disorder, and heterogeneity are higher. “

In the direct comparison, two physicians and the computer program analyzed MRI scans from 15 patients from University of Texas Southwest Medical Center. One neuroradiologist diagnosed seven patients correctly, and the second physician correctly diagnosed eight patients. The computer program was correct on 12 of the 15.

Tiwari and Madabhushi don’t expect the computer program would be used alone, but as a decision support to assist neuroradiologists in improving their confidence in identifying a suspicious lesion as radiation necrosis or cancer recurrence.

Next, the researchers are seeking to validate and the algorithms’ accuracy using a much larger collection of images from across different sites.

Electron Microscopy Reveals How Vitamin A Enters The Cell

Using a new, lightning-fast camera paired with an electron microscope, Columbia University Medical Center scientists have captured images of one of the smallest proteins in our cells to be “seen” with a microscope.

The protein – called STRA6 – sits in the membrane of our cells and is responsible for transporting vitamin A into the cell interior. Vitamin A is essential to all mammals and is particularly important in making the light receptors in our eyes, and in the placenta and fetus where it’s critical for normal development.

Images of the protein – which revealed several unusual features –– were published in the August 26 issue of the journal Science, by structural biologist Filippo Mancia, PhD, assistant professor of physiology and cellular biophysics, who lead a team of other scientists including Wayne Hendrickson, Larry Shapiro, Joachim Frank and Bill Blaner at Columbia University Medical Center, Loredana Quadro at Rutgers University, Chiara Manzini at George Washington University and David Weber at the University of Maryland School of Medicine.

Until the new study, the way STRA6 transports vitamin A into the cell had been a mystery. Most transporters interact directly with the substances they transport. But STRA6 only interacts with Vitamin A via an intermediary protein that carries the greasy vitamin A in the bloodstream. Revealing the structure of STRA6 may not only give the researchers insight into Vitamin A transport, but also clues about how other related transporters may work.

A new type of camera technology was a key element to getting the images of STRA6. When paired with an electron microscope – the camera allows biologists to see tiny, never-seen-before structural details of the inner machinery of our cells.

“We can now get near atomic resolution because the new camera is much faster and allows us to take a movie of the molecules,” says Oliver Clarke, PhD, an associate research scientist in the Hendrickson lab at Columbia University Medical Center. “Even under the electron microscope, the molecules are moving around by a tiny amount, but when you take a picture of something moving, it comes out blurry. With such a movie, we can align the frames of the movie to generate a sharper image.”

Imaging the molecule also depended on painstaking biochemical procedures, developed by Yunting Chen, PhD, and associate research scientist in the Mancia lab, to generate large quantities of the protein and separate them from the cell’s other components. “It’s a very delicate protein, and we had to mimic its environment to keep it from getting out of shape,” she says. Those efforts took about two years to perfect.

The researchers used approximately 70,000 individual pictures of STRA6 to generate a 3-dimensional map of the protein, which was used to construct an atomic model accurate to the smallest detail.

The images and model reveal STRA6 is “a bit of a freak,” says Dr. Clarke. Even more surprising was the fact that STRA6 does not work alone, but is instead tightly associated with another protein, calmodulin, which plays a key role in calcium signaling.

Although Vitamin A moves through STRA6 to enter the cell, there is no channel in STRA6 like most transporters. Instead, vitamin A enters the top of STRA6, but then appears poised to exit through a side window that opens directly into the cell membrane, not the cell interior.

Though this needs to be verified, the mechanism may be a way to protect cells from too much vitamin A. “Vitamin A is actually somewhat toxic,” says Dr. Mancia. “Trapping vitamin A inside the membrane may keep control of the amount inside the cell.”

The new model of STRA6 advances the understanding of a critical cellular function and may help researchers understand how other, still mysterious cellular components, work.

PinnacleHealth Implants Aortic Valve To First Patients In United States After FDA Approval For Commercial Use

This week, PinnacleHealth became the first hospital in the country to implant the EDWARDS INTUITY Elite valve, a rapid deployment device for surgical aortic valve replacement, after U.S. Food and Drug Administration (FDA) approval.

The team, led by Mubashir Mumtaz, MD, FACS, FACC, chief of cardiothoracic surgery and surgical director of the structural heart program at PinnacleHealth, replaced the aortic valve in two patients using a technique called intercostal surgical aortic valve replacement (iSAVR). This minimally invasive approach accesses the heart through the rib space without dividing any major muscle groups, rib or cartilage. The EDWARDS INTUITY Elite valve system facilitates this approach, which was developed at PinnacleHealth.

“We are able to offer our patients with aortic stenosis less invasive surgical options such as iSAVR. This can mean less trauma, quicker recovery and decreased need for blood transfusions,” states Dr. Mumtaz.

The EDWARDS INTUITY Elite valve system is designed to facilitate and streamline complex aortic valve replacements, thereby offering a cutting-edge treatment option for patients with aortic valve disease.

PinnacleHealth was among the top enrollers in the U.S. in TRANSFORM clinical trial, which evaluated the safety and efficacy of the EDWARDS INTUITY valve system. The FDA recently approved the INTUITY valve due to its positive clinical performance. Results showed that, at one year, the valve system was highly effective and may reduce cross-clamp time and cardiopulmonary bypass time, compared to times recorded in the Society of Thoracic Surgeons’ (STS) Adult Cardiac Database. This may provide patient benefits such as decreased mortality and morbidity, less time in an intensive care unit and reduced total hospital stay.

“Participation in clinical trials can lead to improved care and innovations, particularly for our complex cardiac patients,” states Dr. Mumtaz. “This milestone in cardiac treatment can reassure the community that nationally recognized heart care is available close to home.”

According to an article published in the Journal of the American College of Cardiology, aortic stenosis (AS) is the most common valvular heart disease in developed countries with prevalence estimated between 3 and 23 percent.1 Aortic stenosis mainly affects older people, due to scarring and calcium buildup in the valve cusp. With a growing elderly population, aortic stenosis is anticipated to become a major public health concern.

PinnacleHealth CardioVascular Institute surgeons perform more coronary artery bypassand valve surgeries than any other hospital in the region and is in the top five acute care hospitals in Pennsylvania. While maintaining this high volume, important quality indicators such as mortality and readmission rates remain low,” states Michael A. Young, president and CEO for PinnacleHealth.

Implanted Neuroprosthesis Improves Walking Ability in Stroke Patient

A surgically implanted neuroprosthesis—programmed to stimulate coordinated activity of hip, knee, and ankle muscles—has led to substantial improvement in walking speed and distance in a patient with limited mobility after a stroke, according to a single-patient study in the American Journal of Physical Medicine & Rehabilitation, the official journal of the Association of Academic Physiatrists. The journal is published by Wolters Kluwer.

“An implanted stimulation system for multi-joint control is a promising intervention to provide assistance to stroke survivors during daily walking,” write Nathaniel S. Makowski, PhD, and colleagues of the Louis Stokes Cleveland Veterans Affairs Medical Center. With technical refinements and further research, such implanted neuroprosthesis systems might help to promote walking ability for at least some patients with post-stroke disability.

Initial Experience Shows ‘Clinically Relevant Improvements in Gait’
The researchers report their experience with an implanted neuroprosthesis in a 64-year-old man with impaired motion and sensation of his left leg and foot after a hemorrhagic (bleeding) stroke. After thorough evaluation, he underwent surgery to place an implanted pulse generator and intramuscular stimulating electrodes in seven muscles of the hip, knee, and ankle.

Dr. Makowski and colleagues then created a customized electrical stimulation program to activate the muscles, with the goal of restoring a more natural gait pattern. The patient went through extensive training in the researchers’ laboratory for several months after neuroprosthesis placement.

In a ‘before-and-after’ study design, the patient showed significant gains in walking speed and distance. Gait speed increased from 0.29 meters per second (m/s) before surgery, to 0.35 m/s after training but without muscle stimulation—a nonsignificant improvement.

But when muscle stimulation was turned on, gait speed increased dramatically: to 0.72 m/s. Detailed analysis of the patient’s walking ability also showed evidence of a “more symmetrical and dynamic gait.”

In addition, the patient was able to walk much farther. When first evaluated, he could walk only 76 meters before becoming fatigued. After training but without stimulation, he could walk about 300 meters (in 16 minutes). With stimulation, the patient’s maximum walking distance increased to more than 1,400 meters (in 41 minutes) with stimulation. “Thus his walking distances increased by 370 percent with stimulation while walking nearly twice as fast,” Dr. Makowski and colleagues write.

Even though the patient wasn’t walking with stimulation outside the laboratory, his walking ability in daily life improved significantly. He went from “household-only” ambulation to increased walking outside in the neighborhood.

“The therapeutic effect is likely a result of muscle conditioning during stimulated exercise and gait training,” according to the authors. “Persistent use of the device during walking may provide ongoing training that maintains both muscle conditioning and cardiovascular health.”

While the results of this initial experience in a single patient are encouraging, the researchers emphasize that large-scale studies will be needed to demonstrate the wider applicability of a neuroprosthesis for multi-joint control. If the benefits are confirmed, Dr. Makowski and colleagues conclude, “Daily use of an implanted system could have significant clinical relevance to a portion of the stroke population.”

New Technology Aims to turn Complicated Lab Tests into Point-of-Care Tests for First Responders

Carbon monoxide (CO) poisoning can have tragic consequences if victims are not rescued or treated. First responders at the scene may not know immediately if a conscious patient is a victim of CO poisoning.

Normally, these type of tests are taken with an arterial blood sample (typically an artery in the arm), and are then sent off to a central lab, where a bench top unit uses spectroscopy and electrochemical sensor measurements to provide results.  It can take hours to get the results.

But what if a lab in a hospital is not an option and time may be ticking for first responders at a scene of a possible CO poisoning?

Rapid Response

Toronto-based ChroMedx, a medical technology company focused on the development of novel medical devices for in vitro diagnostics and point-of-care testing is working to address this. Their flagship device, the HemoPalm utilizes a small sample of blood via the finger, providing a result on the spot, with no specialist required. Central to the HemoPalm, is its ability to fully integrate CO-oximetry, measured through spectroscopy (the only method for CO-oximetry) which allows the user to measure total hemoglobin (Hb), Oxy-Hb, Deoxy-Hb, Met-Hb and carboxy-Hb, simultaneously with blood gases and electrolytes measured with electrochemical sensors.

The technology is especially beneficial to first responders, who can take the blood sample right at the scene and have the data available upon arrival to the hospital before the patient even arrives into the ER. The information can also be transmitted back to the hospital before the patient is wheeled into the ER triage.

Hospital Setting

In a hospital setting, the HemoPalm could simplifying sample collection and expediting patient results, both in the emergency department and the operating room, where the device could replace multiple machines currently in use. Another use would be for respiratory care, allowing respiratory therapists and visiting nurses to optimize treatment in the hospital and at home with comprehensive results of oxygen in the blood.

A second cartridge, the HemoPalm B, is being developed to measure bilirubin (which may be used to monitor liver function).  Bilirubin in high levels is an indication of jaundice, a potentially dangerous condition for newborns of which approximately 15% will develop this condition.  The heel-prick method of sampling, as provided by the HemoPalm system, makes sample collection easy with minimal trauma to the baby and minimal blood loss.   Once diagnosed, treatment is relatively straightforward, and pre-discharge testing could predict virtually all cases of jaundice and ensure proper parental response and care.

Future Tests

Other cartridges planned for development include testing for lactate, which is an indication of sepsis (blood poisoning), a common and deadly condition in the Emergency Department; creatinine, a measure of kidney function; and beta-hydroxybutyrate, elevated in diabetic emergencies.

Wayne Maddever, ChroMedx’s CEO said he expects to see HemoPalm in studies for FDA approvals within a year.  For more information, log on to http://www.chromedx.com

 

 

 

Introducing the Dario: The world’s largest glucose monitoring market, gets user-centric mHealth product that brings diabetes management into the digital age

Americans living with diabetes are now able to incorporate their phones as a tool for managing their blood glucose measurements. Labstyle Innovation’s user-centric mHealth product, the Dario Blood Glucose Monitoring System, neatly brings diabetes management into the digital age.

The Dario Blood Glucose Monitoring System consists of an all-in-one Smart Meter that plugs directly into smartphones coupled with a robust, real-time mobile app, that allows users to track and monitor data such as: blood glucose measurements, carbs and insulin intake, as well as physical activity directly on their mobile devices, making diabetes data management much simpler. Additionally, users can share this data with their community, family and medical staff.

Dario is a leading pocket-sized all-in-one diabetes management solution that provides users all over the world with important disease management features such as emergency hypoglycemia contacts, actionable insights and easy information sharing with medical staff. This technology is now available for people with diabetes in the USA.

The Dario app integrates with popular apps such as RunKeeper, helping diabetics better manage exercise and fitness activities, and FatSecret, which allows for better food intake management. Instantly generated, personalized reports help users better understand why their blood glucose levels may change.

Direct-to-consumer sales are now being done via LabStyle’s U.S. website at usa.mydario.com/shop and are now available and supported through a U.S. based customer service center and hotline. LabStyle’s membership-based pricing for direct-to-consumer test strip sales offers users a very cost-effective and convenient solution. The Dario App is now also available through the App Store and ready for download by users across the U.S. Sales through various non-exclusive third party distributors and medical equipment suppliers are anticipated over the first half of 2016.

“The U.S. is the world’s largest market for glucose monitoring and the launch of national availability represents a transformative achievement not only for Dario, but more importantly for users,” said Erez Raphael, Chairman and CEO of LabStyle Innovations.

“Our unique ability to deliver a user-centric approach to monitoring glucose levels and other important behavioral factors will help usher in a new era for diabetes management in the U.S., delivering significant value to users, healthcare providers and the entire American healthcare system,” added Todd Durniak, LabStyle’s Executive Vice President and General Manager for North America.

In keeping with Dario’s user-centricity, the company has also focused on a new business model that will revolutionize the way people with diabetes acquire strips. Dario’s exclusive membership program will allow people to sign up to a simple and hassle-free program which will deliver the right quantity of strips to their door, every 90 days at competitive prices.

For more information, log on to: usa.mydario.com/shop