The Technion Researchers Find to NanoParticles may Threaten Heart

Nanoparticles, extremely tiny particles measured in billionths of a meter, are increasingly everywhere, and especially in biomedical products. Their toxicity has been researched in general terms, but now a team of Israeli scientists has for the first time found that exposure nanoparticles (NPs) of silicon dioxide (SiO2) can play a major role in the development of cardiovascular diseases when the NP cross tissue and cellular barriers and also find their way into the circulatory system. Their study is published in the December 2014 issue of Environmental Toxicology.

Prof. Michael Aviram
The research team was comprised of scientists from the Technion Rappaport Faculty of Medicine, Rambam Medical Center, and the Center of Excellence in Exposure Science and Environmental Health (TCEEH).

“Environmental exposure to nanoparticles is becoming unavoidable due to the rapid expansion of nanotechnology,” says the study’s lead author, Prof. Michael Aviram, of the Technion Faculty of Medicine, “This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Products that use silica-based nanoparticles for biomedical uses, such as various chips, drug or gene delivery and tracking, imaging, ultrasound therapy, and diagnostics, may also pose an increased cardiovascular risk for consumers as well.”

In this study, researchers exposed cultured laboratory mouse cells resembling the arterial wall cells to NPs of silicon dioxide and investigated the effects. SiO2 NPs are toxic to and have significant adverse effects on macrophages. a type of white blood cell that take up lipids, leading to atherosclerotic lesion development and its consequent cardiovascular events, such as heart attack or stroke. Macrophages accumulation in the arterial wall under atherogenic conditions such as high cholesterol, triglycerides, oxidative stress – are converted into lipids, or laden “foam cells” which, in turn, accelerate atherosclerosis development.

“Macrophage foam cells accumulation in the arterial wall are a key cell type in the development of atherosclerosis, which is an inflammatory disease” says co-author Dr. Lauren Petrick. “The aims of our study were to gain additional insight into the cardiovascular risk associated with silicon dioxide nanoparticle exposure and discover the mechanisms behind Si02’s induced atherogenic effects on macrophages. We also wanted to use nanoparticles as a model for ultrafine particle (UFP) exposure as cardiovascular disease risk factors.”

Both NPs and UFPs can be inhaled and induce negative biological effects. However, until this study, their effect on the development of atherosclerosis has been largely unknown. Here, researchers have discovered for the first time that the toxicity of silicon dioxide nanoparticles has a “significant and substantial effect on the accumulation of triglycerides in the macrophages,” at all exposure concentrations analyzed, and that they also “increase oxidative stress and toxicity.”

A recent update from the American Heart Association also suggested that “fine particles” in air pollution leads to elevated risk for cardiovascular diseases. However, more research was needed to examine the role of “ultrafine particles” (which are much smaller than “fine particles”) on atherosclerosis development and cardiovascular risk.

“The number of nano-based consumer products has risen a thousand fold in recent years, with an estimated world market of $3 trillion by the year 2020,” conclude the researchers. “This reality leads to increased human exposure and interaction of silica-based nanoparticles with biological systems. Because our research demonstrates a clear cardiovascular health risk associated with this trend, steps need to be taken to help ensure that potential health and environmental hazards are being addressed at the same time as the nanotechnology is being developed.

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell NYC Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.

American Technion Society (ATS) donors provide critical support for the Technion—more than $1.95 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.

Source: ATS

Adults Sought for Study on Aging and Mobility

                                                               Walking stickman
The Biomechanics Laboratory in the kinesiology department is recruiting volunteers for a study about the effects of age and exercise on walking and muscle function. The researchers hope to learn about how changes in muscle function with age are related to the onset of disability.

The lab is looking for individuals who meet the following criteria: ages 55-70 with healthy body weight who participate in fewer than five 30-minute bouts of exercise per week (or less than a total of 150 minutes of planned exercise per week), no history of reconstructive surgery of the legs, no major health issues (heart disease, diabetes, neurological disease), able to walk for 30 minutes and no contraindications to MRI (metal implant, claustrophobia).

The study consists of two visits: a 1-hour visit to an MRI facility in Amherst and one 3-hour visit to the Biomechanics Lab on campus. During the lab visit researchers will collect data on how participants’ joints move as they walk over the ground and on a treadmill. The study will also collect data on the strength of the muscles in participants’ thighs. All procedures are non-invasive.

Source: UMass

Smart device delivers results for kids with asthma

Smart device

A new smart asthma inhaler with an audio-visual function has dramatically improved child and adolescent use of preventative asthma medication.

The users also experienced significant improvements to their symptoms, well-being and quality of life and needed their reliever medication less frequently.

The University of Auckland study, funded by Cure Kids and the Health Research Council, showed a significant improvement in night time awakening, coughing and wheezing.

Clinical pharmacist, Amy Chan, a doctoral student with the University of Auckland, is the lead author on the paper.  

“We know one of the key reasons for children not taking their medication is parent and patient forgetfulness.  The Smartinhaler reminder system is now clinically proven to be a real solution to the problem,” she says.

“What we’ve been able to establish for the first time with this study is that the ringtone Smartinhaler significantly improves adherence to preventative medication, which results in improved quality of life for children with asthma. It’s hugely exciting,” says Ms Chan.

Children in the study were also given a Smartinhaler tracker for their rescue or ‘blue’ inhaler to measure the amount of rescue medication they used. The device was able to objectively count date and time of rescue medication use. This provided a good indication of asthma being out of control.

When symptoms worsened participants used their rescue reliever inhaler (blue inhaler), which is also known as a rescue medication because it provides immediate relief.  Recent studies have shown that overuse of the blue inhaler is a predictor of worsening asthma and general morbidity.

The study found that use of the rescue medication was significantly reduced in the group using the Nexus6 Smartinhaler reminder device.

Cure Kids Chair of Child Health Research and Ms Chan's supervisor on the study, Professor Ed Mitchell, says he is “absolutely staggered by the size of the effect. To see the improvement in the lives of these children is astounding.”

The participants also reported taking part in more sports and family activities. Parents reported feeling less frightened by their child’s asthma.

New Zealand has the second highest rates of asthma in the world and one in four Kiwi children experiences asthma symptoms. Despite this, regular adherence to asthma medication is poor.

New Zealand digital health company Nexus6 Ltd created the new Smartinhaler device called the SmartTrack, which was used in the study. The device has 14 different ringtones, which are cycled so users don’t get reminder fatigue. The SmartTrack reminder is only triggered when a dose is missed.

The results were published this month in The Lancet Respiratory Medical Journal.  To the researchers’ knowledge, this is the largest study in the world to investigate the effects of an inhaler device with audio-visual reminder function on asthma adherence and outcomes in children and adolescents.

It is also the first to show significant benefits in asthma outcomes and quality of life. The results are expected to gain international interest.

The controlled trial recruited 220 children between the ages of six and 15 who presented to emergency departments with asthma symptoms.

The study was randomised with half of the participants receiving a SmartTrack device for use with their preventative or ‘orange’ inhaler that had the audiovisual elements turned on, and the other half receiving the same device with the audiovisual elements turned off.

Participants were followed up every two months for six months and general asthma control was checked.

Key findings from the study were:

Medication adherence rate for the patient group given the audiovisual enabled SmartTrack inhaler were 84 percent compared to 30 percent for the control group. This equals a 180% increase in medication adherence.
The use of emergency medication or the ‘blue’ inhaler was significantly reduced. The median percentage days on which a reliever was used in the intervention group was 9.5 percent compared to 17.4 percent in the control group. This equals a 45percentreduction in rescue medication use.
Symptoms, well-being and quality of life for the children was significantly improved.

Source: Auckland University

New Weight Loss Device Makes You Feel Full

People who are obese have a new tool in their arsenal for fighting excess weight.

The U.S. Food and Drug Administration approved a medical device called the Maestro Rechargeable System that is implanted in the stomach and, through an external, adjustable controller, helps obese people lose weight. It is approved for patients 18 and older who have a body mass index of 35 to 45, have a condition related to being obese such as type 2 diabetes, and have not been able to lose weight through traditional means. 

The Maestro Rechargeable System targets nerve pathways between the brain and the stomach that are responsible for making a person feel full. In a clinical trial, patients using the device lost 8.5% more weight than people who received an inactive version of it. About 53% of the patients with the device lost at least 20% of their excess weight, and 38% lost at least 25%.

But compared with bariatric surgery, the trial’s results are not as impressive. Eric T. Volckmann, M.D., who specializes in bariatric surgery at University of Utah Health Care, says that after gastric bypass surgery, patients can expect to lose 60% to 80% of their excess body weight.

Bariatric surgery is a highly invasive procedure. But so is implantation of the Maestro Rechargeable System. 

“Any procedure, no matter how small, is still risky,” Volckmann says.

Furthermore, Volckmann says the long-term effects of the device are not as well understood as those of bariatric surgery. He says more research is needed before he would recommend the Maestro Rechargeable System for a severely obese patient.

In the future, the device may make sense for a patient with a BMI between 30 and 35 who is not responding to medical weight loss measures such as lifestyle modifications.

Source: University of Utah

Virtual reality speeds up rehabilitation: Integrating force feedback into therapies

A child is receiving virtual door opening training under the guidance of a therapist. Credit: Copyright The Hong Kong Polytechnic University

The Hong Kong Polytechnic University has successfully developed a novel training programme using haptic technology for impaired hands that cannot function normally. This programme is unique as it provides force feedback, which creates a true sense of weight to the user through the control device.

Our hands are essential to our lives; we need them in all daily tasks including eating, bathing and getting dressed. However, even the simplest tasks are challenging for people with impaired hands due to various conditions such as cerebral palsy, stroke and ageing. Fortunately, they will soon benefit from a new training technology which may greatly improve their conditions.

In response to therapeutic needs, a computerized training programme against impaired hands has been developed at the School of Nursing of The Hong Kong Polytechnic University. Patients being trained are supposed to exercise their hands through playing a series of well-designed computer games that simulate everyday tasks, such as opening a locked door with a key or pouring tea into a cup. While playing, their hand movements are monitored and recorded by a haptic device, which is connected to the control unit held by the patient at one end, and a computer at the other. The haptic device then feeds the data into the computer, resulting in the instant reflection of the patient's actions in the animation on screen.

In addition, the haptic technology which the programme employs is more true-to-life than similar programmes, as feedback is provided through the force created by the control unit to players. For example, they can literally feel the weight of a simulated bottle diminishing as the water is being poured out. Such kind of precision will greatly enhance training effectiveness and improve the patient's coordination.

Game-based therapies are highly motivating. Firstly, playing 3D games in colourful animation is more interesting than monotonous physical exercises. Secondly, a reward system incorporated in the programme is sure to fuel a sense of competition and accomplishment. "Our games are designed to be engaging. When players make successful attempts, they get bonus points. And as they win, they move on to the next level, where more attractive rewards are waiting," said Dr Kup-sze Choi, the leader of the research team. It is satisfying for players to work their way up and keep going with the therapy, thereby improving their hand functions.

Compared to physical training, computer simulated training is a safer option when sharp or breakable objects are involved, making practices on preparing simple meals with a knife possible. It is also less likely to be interrupted by undesired circumstances. Dr Choi explained, "For instance, the hands of cerebral palsy sufferers are usually stiff, weak and prone to uncontrolled movements. If they practise pouring real tea in repeated sessions, they may make spills all over the place and end up soaking wet, requiring the healthcare workers to clean up the mess. That is not a good thing for both the trainee and the trainer." With computer simulation, there will be no such interruptions.

To cater to different degrees of disability, the programme has a built-in difficulty mode with which the level of difficulty can be adjusted with the touch of a button. Therapists can also monitor their patients' progress easily, as the system keeps track of their movements and performance.

The effectiveness of this training programme was preliminarily confirmed, as a similar tool aimed to improve hand-writing was tested on the children at the Hong Kong Red Cross Princess Alexandra School. The results have shown a marked improvement in the time they needed to complete the task after two weeks of training. More tests and trials are on the way, and the team expect that a longer period of computer-assisted training will yield greater benefits. The training system has already won a Silver Medal at the 42nd International Exhibition of Inventions of Geneva in Switzerland.

According to Dr Choi, computer simulated training using haptic technology will widen the access to rehabilitation and help more patients with impaired hands . In the future, the team will work on combining this computer-aided rehabilitation programme with traditional therapy in order to optimize the training system and benefit more patients. The prototype of the haptic platform customized for self-care training Copyright : The Hong Kong Polytechnic University The haptic platform technology developed by Dr Kup-sze Choi and his team has won a Silver Medal at the 42nd International Exhibition of Inventions of Geneva. 

Copyright : The Hong Kong Polytechnic University

Source: The Hong Kong Polytechnic University

Handheld scanner could make brain tumor removal more complete, reducing recurrence

A handheld device that resembles a laser pointer could someday help surgeons remove all of the cells in a brain tumor. Credit: Moritz Kircher

Cancerous brain tumors are notorious for growing back despite surgical attempts to remove them -- and for leading to a dire prognosis for patients. But scientists are developing a new way to try to root out malignant cells during surgery so fewer or none get left behind to form new tumors. The method, reported in the journal ACS Nano, could someday vastly improve the outlook for patients.

Moritz F. Kircher and colleagues at Memorial Sloan Kettering Cancer Center point out that malignant brain tumors, particularly the kind known as glioblastoma multiforme (GBM), are among the toughest to beat. Although relatively rare, GBM is highly aggressive, and its cells multiply rapidly. Surgical removal is one of the main weapons doctors have to treat brain tumors. The problem is that currently, there's no way to know if they have taken out all of the cancerous cells. And removing extra material "just in case" isn't a good option in the brain, which controls so many critical processes. The techniques surgeons have at their disposal today are not accurate enough to identify all the cells that need to be excised. So Kircher's team decided to develop a new method to fill that gap.

The researchers used a handheld device resembling a laser pointer that can detect "Raman nanoprobes" with very high accuracy. These nanoprobes are injected the day prior to the operation and go specifically to tumor cells, and not to normal brain cells. Using a handheld Raman scanner in a mouse model that mimics human GBM, the researchers successfully identified and removed all malignant cells in the rodents' brains. Also, because the technique involves steps that have already made it to human testing for other purposes, the researchers conclude that it has the potential to move readily into clinical trials. Surgeons might be able to use the device in the future to treat other types of brain cancer, they say.

The authors acknowledge funding from the National Institutes of Health.

Source: American Chemical Society

Anemia: One-minute point-of-care test shows promise in new study

Erika Tyburski is shown with a prototype device for point-of-care testing of anemia. The device could enable more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease. Credit: Gary Meek

A simple point-of-care testing device for anemia could provide more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

The disposable self-testing device analyzes a single droplet of blood using a chemical reagent that produces visible color changes corresponding to different levels of anemia. The basic test produces results in about 60 seconds and requires no electrical power. A companion smartphone application can automatically correlate the visual results to specific blood hemoglobin levels.

By allowing rapid diagnosis and more convenient monitoring of patients with chronic anemia, the device could help patients receive treatment before the disease becomes severe, potentially heading off emergency room visits and hospitalizations. Anemia, which affects two billion people worldwide, is now diagnosed and monitored using blood tests done with costly test equipment maintained in hospitals, clinics or commercial laboratories.

Because of its simplicity and ability to deliver results without electricity, the device could also be used in resource-poor nations.

A paper describing the device and comparing its sensitivity to gold-standard anemia testing was published August 30 in The Journal of Clinical Investigation. Development of the test has been supported by the FDA-funded Atlantic Pediatric Device Consortium, the Georgia Research Alliance, Children's Healthcare of Atlanta, the Georgia Center of Innovation for Manufacturing and the Global Center for Medical Innovation.

"Our goal is to get this device into patients' hands so they can diagnose and monitor anemia themselves," said Dr. Wilbur Lam, senior author of the paper and a physician in the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta and the Department of Pediatrics at the Emory University School of Medicine. "Patients could use this device in a way that's very similar to how diabetics use glucose-monitoring devices, but this will be even simpler because this is a visual-based test that doesn't require an additional electrical device to analyze the results."

The test device was developed in a collaboration of Emory University, Children's Healthcare of Atlanta and the Georgia Institute of Technology -- all based in Atlanta. It grew out of a 2011 undergraduate senior design project in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. In 2013, it was among the winners of Georgia Tech's InVenture Prize, an innovation competition for undergraduate students, and won first place in the Ideas to SERVE Competition in Georgia Tech's Scheller College of Business.

Using a two-piece prototype device, the test works this way: A patient sticks a finger with a lance similar to those used by diabetics to produce a droplet of blood. The device's cap, a small vial, is then touched to the droplet, drawing in a precise amount of blood using capillary action. The cap containing the blood sample is then placed onto the body of the clear plastic test kit, which contains the chemical reagent. After the cap is closed, the device is briefly shaken to mix the blood and reagent.

"When the capillary is filled, we have a very precise volume of blood, about five microliters, which is less than a droplet -- much less than what is required by other anemia tests," explained Erika Tyburski, the paper's first author and leader of the undergraduate team that developed the device.

Blood hemoglobin then serves as a catalyst for a reduction-oxidation reaction that takes place in the device. After about 45 seconds, the reaction is complete and the patient sees a color ranging from green-blue to red, indicating the degree of anemia.

A label on the device helps with interpretation of the color, or the device could be photographed with a smartphone running an application written by Georgia Tech undergraduate student Alex Weiss and graduate student William Stoy. The app automatically correlates the color to a specific hemoglobin level, and could one day be used to report the data to a physician.

To evaluate sensitivity and specificity of the device, Tyburski studied blood taken from 238 patients, some of them children at Children's Healthcare of Atlanta and the others adults at Emory University's Winship Cancer Institute. Each blood sample was tested four times using the device, and the results were compared to reports provided by conventional hematology analyzers.

The work showed that the results of the one-minute test were consistent with those of the conventional analysis. The smartphone app produced the best results for measuring severe anemia.

"The test doesn't require a skilled technician or a draw of venous blood and you see the results immediately," said Lam, who is also an assistant professor in the Coulter Department of Biomedical Engineering. "We think this is an empowering system, both for the general public and for our patients."

Tyburski and Lam have teamed up with two other partners and worked with Emory's Office of Technology Transfer to launch a startup company, Sanguina, to commercialize the test, which will be known as AnemoCheck™. The test ultimately will require approval from the FDA. The team also plans to study how the test may be applied to specific diseases, such as sickle cell anemia -- which is common in Georgia.

The device could be on pharmacy shelves sometime in 2016, where it might help people like Tyburski, who has suffered mild anemia most of her life. "If I'd had this when I was kid, I could have avoided some trips to the emergency room when I passed out in gym class," she said.

About a third of the population is at risk for anemia, which can cause neurocognitive deficits in children, organ failure and less serious effects such as chronic fatigue. Women, children, the elderly and those with chronic conditions such as kidney disease are more likely to suffer from anemia.

Source: Georgia Institute of Technology

New way to diagnose brain damage from concussions, strokes, and dementia

A new tool to assess cerebrovascular health: Coherent Hemodynamics Spectroscopy (CHS).
Credit: Tufts University Professor of Biomedical Engineering Sergio Fantini

New optical diagnostic technology developed at Tufts University School of Engineering promises new ways to identify and monitor brain damage resulting from traumatic injury, stroke or vascular dementia -- in real time and without invasive procedures.

Coherent hemodynamics spectroscopy (CHS), developed and published by Tufts Professor of Biomedical Engineering Sergio Fantini, measures blood flow, blood volume, and oxygen consumption in the brain. It uses non-invasive near infrared (NIR) light technology to scan brain tissue, and then applies mathematical algorithms to interpret that information.

"CHS is based on measurements of brain hemodynamics that are interpreted according to unique algorithms that generate measures of cerebral blood flow, blood volume and oxygen consumption," says Fantini. "This technique can be used not only to assess brain diseases but also to study the blood flow and how it is regulated in the healthy brain."

Tufts has licensed CHS on a non-exclusive basis to ISS, a Champaign, Ill.-based company that specializes in technology to measure hemoglobin concentration and oxygenation in brain and muscle tissue.

"Potentially the market for CHS is large as it encompasses several applications from the monitoring of cerebrovascular disorders to assessing neurological disorders," says Beniamino Barbieri, president of ISS. "It reminds me of the introduction of ultrasound technology at beginning of the seventies; nobody back then knew how to utilize the new technology and of course, nowadays, its applications are ubiquitous in any medical center."

How It Works

CHS uses laser diodes which emit NIR light that is delivered to the scalp by fiber optics. Light waves are absorbed by the blood vessels in the brain. Remaining light is reflected back to sensors, resulting in optical signals that oscillate with time as a result of the heartbeat, respiration, or other sources of variations in the blood pressure.

By analyzing the light signals with algorithms developed for this purpose, Fantini's model is able to evaluate blood flow and the way the brain regulates it--which is one marker for brain health.

CHS technology has been tested among patients undergoing hemodialysis at Tufts Medical Center. Published research reported a lower cerebral blood flow in dialysis patients compared with healthy patients.

"Non-invasive ways to measure local changes in cerebral blood flow, particularly during periods of stress such as hemodialysis, surgeries, and in the setting of stroke, could have major implications for maintaining healthy brain function," says Daniel Weiner, M.D., a nephrologist at Tufts Medical Center (Tufts MC) and associate professor of medicine at Tufts University School of Medicine (TUSM), who is a member of the research team.

Josh Kornbluth, M.D., a neurologist at Tufts MC and associate professor of medicine at TUSM, is also working with Fantini to explore CHS's potential to assess the cerebrovascular state of patients who suffer traumatic brain injury or stroke. They hope to test CHS further among neurological critical care patients.

"Having data about local cerebral blood flow and whether it is properly regulated can allow us to more accurately develop individualized therapy and interventions instead of choosing a 'one size fits all' approach to traumatic brain injury, stroke, or subarachnoid hemorrhage," Kornbluth says.

Source: Tufts University

Early results indicate potential for focused ultrasound to treat OCD

Dr. Chang (in sweater) and treatment team with the first patient in the OCD study. Credit: Image courtesy of Focused Ultrasound Foundation

A recently published report in the Journal of Molecular Psychiatry supports the potential of focused ultrasound to treat certain patients with obsessive-compulsive disorder (OCD).

In a study of feasibility, safety and preliminary efficacy, four patients with disabling OCD unresponsive to medical therapy were treated by ablating small targets deep in the brain (anterior internal capsule) using the InSightec ExAblate Neuro MR-guided focused ultrasound system. This proof-of-concept study is being conducted with 12 patients by Jin Woo Chang, MD, PhD, at the Yonsei University Medical Center in Seoul, Korea. The results of the first four patients with six months follow-up were published.

All four patients had the targeted areas of the brain successfully ablated. The procedures were accomplished without complications or side effects and resulted in gradual improvement in obsessive-compulsive thoughts and behaviors as well as showing the nearly immediate and sustained improvement in depression and anxiety over six months.

"There is a need for non-invasive treatment options for patients with OCD that cannot be managed through medication," says Dr. Chang. "Using focused ultrasound, we were able to reduce the symptoms for these patients and help them get some of their life back without the risks or complications of the more invasive surgical approaches that are currently available."

"If these initial results are confirmed in the remaining eight patients in this study as well as in a larger pivotal trial of safety and efficacy, focused ultrasound could emerge as an alternative to surgery for improving quality of life in a cost-effective manner for patients with OCD," said Foundation Chairman Neal F. Kassell, MD. "This could also serve as the predicate for non-invasive therapy for other psychiatric disorders."

Dr. Chang plans to start a study using focused ultrasound to treat depression in 2015.

Current Treatment for OCD

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by recurring anxiety-provoking thoughts (obsessions) that are alleviated only by ritualistic actions (compulsions) such as hand washing. OCD symptoms can be overwhelming and result in severe impairment and dysfunction. Patients also have a high risk for depression, with two-thirds of OCD patients developing major depression.

Although a large portion of OCD patients improve with drug therapy, some patients have debilitating symptoms that are resistant to treatment. For these patients, psychosurgery can be performed to destroy (ablate) a targeted region of the brain (anterior internal capsule) associated with the disorder. The currently available ablative approaches are invasive or involve radiation:

• Radiofrequency ablation requires drilling into the skull and inserting a probe through 
   the brain.

• Stereotactic radiosurgery takes months to achieve an effect and may be associated with
   side effects of radiation.

• Deep brain stimulation has been used as a reversible and adjustable alternative to ablation, but it involves the risks and complications of surgery to implant the system and additional operations for battery changes.

Source: Focused Ultrasound Foundation

High-intensity sound waves may aid regenerative medicine

This is a cross section through a histotripsy lesion created in bovine liver tissue with the liquified cellular contents washed out revealing the remaining extracellular matrix. The scale bar represents 5mm. Credit: T.Khoklova/UW

Researchers at the University of Washington have developed a way to use sound to create cellular scaffolding for tissue engineering, a unique approach that could help overcome one of regenerative medicine's significant obstacles. The researchers will present their technique at the 168th meeting of the Acoustical Society of America (ASA), held October 27-31, 2014, at the Indianapolis Marriott Downtown Hotel.

The development of the new technique started with somewhat of a serendipitous discovery. The University of Washington team had been studying boiling histotripsy -- a technique that uses millisecond-long bursts of high-intensity ultrasound waves to break apart tissue -- as a method to eliminate cancerous tumors by liquefying them with ultrasound waves. After the sound waves destroy the tumors, the body should eliminate them as cellular waste. When the researchers examined these 'decellularized' tissues, however, they were surprised by what the boiling left intact.

"In some of our experiments, we discovered that some of the stromal tissue and vasculature was being left behind," said Yak-Nam Wang, a senior engineer at the University of Washington's Applied Physics Laboratory. "So we had the idea about using this to decellularize tissues for tissue engineering and regenerative medicine."

The structure that remains after decellularizing tissues is known as the extracellular matrix, a fibrous network that provides a scaffold for cells to grow upon. Most other methods for decellularizing tissues and organs involve chemical and enzymatic treatments that can cause damage to the tissues and fibers and takes multiple days. Histrostipsy, on the other hand, offers the possibility of fast decellularization of tissue with minimal damage to the matrix.

"In tissue engineering, one of the holy grails is to develop biomimetic structures so that you can replace tissues with native tissue," Wang said. Stripping away cells from already developed tissue could provide a good candidate for these structures, since the extracellular matrix already acts as the cellular framework for tissue systems, Wang said.

Due to its bare composition, the matrix also induces only a relatively weak immune response from the host. The matrix could then theoretically be fed with stem cells or cells from the same person to effectively re-grow an organ.

"The other thought is that maybe you could just implant the extracellular matrix and then the body itself would self-seed the tissues, if it's just a small patch of tissue that you're replacing," Wang said. "You won't have any immune issues, and because you have this biomimetic scaffold that's closer to the native tissue, healing would be better, and the body would recognize it as normal tissue."

Wang is currently investigating decellularization of kidney and liver tissue from large animals. Future work involves increasing the size of the decellularized tissues and assessing their in-vivo regenerative efficacy.

Source: Acoustical Society of America (ASA)

Powerful imaging for optical point-of-care diagnostics

The new imaging system consists of a handheld probe (on the right), and an ultrasound scanning display system (on the left). It can be easily transported between rooms in a clinic. Credit: Pim van den Berg/ Khalid Daoudi

A new handheld probe developed by a team of university and industry researchers in the Netherlands and France could give doctors powerful new imaging capabilities right in the palms of their hands. The imaging system, which is described in a paper published in The Optical Society's (OSA) open-access journal Optics Express, shrinks a technology that once filled a whole lab bench down to a computer screen and a small probe about the size of a stapler.

The new device combines two imaging modalities: ultrasound and photoacoustics. Ultrasound is a well-established technology that analyzes how sound pulses echo off internal body parts. It is good at revealing anatomical structures and is, perhaps most familiarly, used to image a developing fetus in a mother's womb.

Photoacoustics is a relatively new imaging technique, still making its way toward widespread clinical applications. In photoacoustic imaging, short pulses of light heat up internal tissue. The slight temperature change leads to a change in pressure,
which in turn produces a wave of ultrasound that can be analyzed to reveal information about the body's internal workings. Since this technique ultimately produces ultrasound waves as well, existing technology can be used to analyze and display the images.

The advantage of photoacoustics is that it can reveal important medical information that other imaging techniques cannot, including the presence of molecules like hemoglobin and melanin and the sub-millimeter structure of networks of blood vessels several centimeters beneath the skin. When combined with spectroscopic measurements, photoacoustics can also quantify hemoglobin oxygen saturation within single vessels, providing metabolic information that could be helpful for monitoring tumor progression, for example.

Yet despite these benefits, the cost and size of most photoacoustic systems limit their widespread use, said Khalid Daoudi, a researcher in the Biomedical Photonic Imaging Group at the University of Twente in the Netherlands. Most systems on the market require costly and bulky lasers that make the systems impractical for point-of-care diagnostics. "Our research aimed to break through these hindering factors," Daoudi said.

The project started as collaboration between the University of Twente and three European companies: ESAOTE Europe, a maker of medical diagnostic systems, Quantel, a maker of solid state lasers, and SILIOS Technologies, a maker of optical components.

The team's key innovation, which allowed them to dramatically shrink the system, was the design of an ultra-compact laser based on an efficient and inexpensive laser diode. By stacking multiple diodes to increase the power and carefully designing optical elements to shape the laser beam, the team was able to generate laser pulses with energies higher than had ever been achieved before with diode technology.

Diode lasers can also provide many laser pulses per second, which in turn allows real time imaging, another advantage of the new system, Daoudi noted.

The researchers tested the imaging performance of the system in different types of phantoms -- materials designed to mimic a tissue's optical properties -- and in a healthy human finger joint.

The new compact probe and imaging system can be easily transported between rooms in a clinical setting, an attractive feature for future commercialization, the researchers said.

The team is currently working with a European consortium of industrial and academic partners to take the next steps from the research to the commercialization phase. The current system operates at a single wavelength in the near infrared, but the team has plans to expand the design to multi-wavelength imaging.

"Some applications targeted are rheumatoid arthritis in finger joints, oncology, cardiovascular disease and burn wounds," Daoudi said.

Source: The Optical Society

New biometric watches use light to non-invasively monitor glucose, dehydration, pulse

This schematic diagram shows how the new system can be used to measure a person's glucose levels noninvasively. Credit: Biomedical Optics Express

Monitoring a patient's vital signs and other physiological parameters is a standard part of medical care, but, increasingly, health and fitness-minded individuals are looking for ways to easily keep their own tabs on these measurements. Enter the biometric watch.

In a pair of papers published in The Optical Society's (OSA) open-access journal Biomedical Optics Express, groups of researchers from the Netherlands and Israel describe two new wearable devices that use changing patterns of scattered light to monitor biometrics: one tracks glucose concentration and dehydration levels, and the other monitors pulse.

The glucose sensor is the first wearable device that can measure glucose concentration directly but noninvasively, the authors say.
And while other wearable devices have been made to monitor pulse, the authors claim their new design would be less sensitive to errors when the wearer is in motion, for example while walking or playing sports

Both of the watches described in the two papers make use of the so-called "speckle" effect, the grainy interference patterns that are produced on images when laser light reflects from an uneven surface or scatters from an opaque material. When the material that is scattering the light is moving -- say, in the case of blood flowing through the circulatory system -- "the speckle pattern changes with changes in the flow," explained biomedical engineer Mahsa Nemati, a graduate student in the Optics Research Group at the Delft University of Technology in the Netherlands and the lead author of the Biomedical Optics Express paper on monitoring pulse. Those light variations are a valuable source of information, she says.

The 'Holy Grail' of Diagnostics

In the first paper, bioengineer Zeev Zalevsky of Israel's Bar-Ilan University and his colleagues describe a new wearable biometric system that uses the speckle effect to directly monitor the glucose concentration in the bloodstream, as well as the wearer's relative hydration level.

"Glucose is the holy grail of the world of biomedical diagnostics, and dehydration is a very useful parameter in the field of wellness, which is one of our main commercial aims," Zalevsky said.

The watch-like device consists of a laser to generate a wavefront of light that illuminates a patch of skin on the wrist near an artery, and a camera that measures changes over time in the light that is backscattered off the skin. Unlike other chemicals present in the blood, glucose exhibits a so-called Faraday effect. This means that in the presence of an external magnetic field (generated by a magnet attached to the device) the glucose molecule alters the polarization of the wavefront and thus influences the resulting speckle patterns. 
Analyzing these changing patterns provides a direct measurement of the glucose concentration. Because one of the main signs of mild to moderate dehydration is muscle weakness, which will alter the strength of the signals, the same device can also be used to indicate the relative dehydration level of the user as it changes over time.

Zalevsky and his colleagues are now working to reduce the margin of error in the device's readings. "Around 96 percent of our in vivo measurements were within a range of 15 percent deviation from the readout of a medical reference glucometer device," Zalevsky noted. "The main factor for errors now is the stability of our device on the wrist of the user. We are currently investing efforts in deriving proper calibration and motion cancellation procedures that will allow us to reduce this sensitivity."

Zalevsky says this is the first step toward non-invasive, continuous in vivo measurement of glucose that is based on sensing an effect that is directly related to glucose concentration. The team expects a commercial version of the device to reach the market within two to three years.

Pulse Tracker

In the second Biomedical Optics Express paper, Nemati and her colleagues at Delft and at Phillips Research developed a method that could be used to monitor pulse non-invasively with a sensor that isn't thrown off by the wearer's movement.

Using simulated heart beats generated in milk and measurements performed on the finger of a volunteer, they found that speckle changes can be used to accurately measure flow pulsations -- that is, the heart rate -- even when the light source used to create the speckle pattern is also moving, as would be the case with a wearable biometric sensor. The researchers found that just a couple of pixels from the image were sufficient to extract the pulse rate.

"This paper shows for the first time that a speckle pattern generated from a flowing liquid can give us the pulsation properties of the flow in spite of motion-induced artifacts," Nemati said. "Sophisticated optics is not necessary to implement this, so the costs for devices can be kept low. Another advantage is that the devices can be non-contact or far from the sample," she added.

The team is currently working with companies to integrate their motion-friendly pulse-monitoring technique into existing sensors, for potential use clinically as well as in sports, Nemati said.

Source: The Optical Society

Wearable tech for battlefield, people at risk for heart attacks

The wearable system, under development by Sentient Science and the University at Buffalo, includes electrodes that relay data to a sensor, which connects with a remote computer network.
Credit: University at Buffalo

Wearable devices can count the steps you take and the calories you burn. But can they help soldiers in the field? Or prevent someone from having a heart attack?

Researchers at Sentient Science and the University at Buffalo say yes.

The sensor and software development company is working with UB engineering professor Albert H. Titus to create wearable technology that fuses real-time medical and physiological data with computer models. The system would then send personalized alerts indicating when the individual's level of stress, fatigue and resilience may put them in danger.

The work is funded by a $150,000 grant from the Office of Naval Research's Small Business Technology Transfer program, which enlists small businesses and research institutions to develop technology with military and commercial applications.

"Whether carrying 100 pounds of gear up a mountain or avoiding makeshift bombs, today's soldiers face incredible physical and mental stress," said Titus, PhD, professor and chair of UB's Department of Biomedical Engineering. "Our wearable system aims to measure how the body reacts to those challenges and combine that information with algorithms designed to help keep soldiers as safe as possible."

The wireless system, which is under development, will feature a series of electrodes that measure heart rate, brain activity and other vital signs. The electrodes may be attached to the skin like a Band-Aid or sewn into clothing that hugs the skin -- researchers are still deciding the best method.

The electrodes will relay information to a sensor (slightly smaller than a dime, attached to the skin like a patch), which will deliver that information to a remote computer network.

"It's like the hospital when you have a bunch of wires and equipment monitoring a patient. We're taking that technology and compressing it into a lightweight, wireless system," said the project's principal investigator Jennifer Haggerty, a research scientist and implementations manager at Sentient. Haggerty is an alumnus of UB.

As the information enters the computer network, it will fuse with Sentient's DigitalClone Live software, which has been validated by NASA and used to test the materials and components in the Hubble telescope, the F-35 fighter jet, wind turbines and other products.

The software includes complex algorithms that consider things like the terrain, weather and other environmental information, as well as the soldier's activity level. It will analyze the data and send personalized health alerts to soldiers and, if necessary, emergency medical facilities in the field. The idea is to improve soldiers' cognitive and physical abilities, making them more resilient and less prone to physical and psychological injuries.

In addition to serving the armed forces, the technology has commercial applications as a health-monitoring device. Sentient is exploring how the sensor can be applied to everyday items such as baseball caps. The individual wearing the cap would receive personalized health alerts regarding their risk of suffering a heart attack and other potential danger.

Source: University at Buffalo