Portable brain imaging system for early stroke detection

Stroke is the third-leading cause of death in the U.S. and the leading cause of disability. While some 1.5 million people in the US report stroke-like symptoms annually, half of them have actually not suffered a stroke. Making a reliable assessment of stroke in just minutes would provide timely information for treating the victims faster, at lower cost, and with less risk. Jan Medical developed the first and so far the only portable brain sensing device for rapid detection of ischemic stroke. The device is aimed to be used in the ER or ambulance, before a thorough evaluation can be made in a hospital setting with a CT or MRI. The device operation is based on an interesting principle of detecting the ultrasonic waves emitted by the skull. The device does not measure back-reflection of the emitted ultrasound from the brain; instead, it measures natural mechanical vibrations of the skull. These vibrations are generated by a pressure wave of blood rushing from the heart toward the skull during each pulse.  In 5 minutes, the device collects enough information to detect a variety of cerebrovascular anomalies: an intracerebral or subarachnoid hemorrhage, epidural or subdural hematoma, intracranial aneurysm, arteriovenous malformations, ischemic stroke, or transient ischemic attack. The device consists of two primary components: a headset with sensors and a controller for decoding the collected ultrasonic information connected to a computer. Jan Medical markets its device primarily for early detection of stroke as well as the traumatic brain injury, such as sports-related concussion that is often not detected on the field leaving it to a discretion of a team physician to clear the player for return to the game. The device can also be used for rapid military diagnostics of traumatic brain injury at the battlefield.

Treating brain glioblastoma with alternating electric fields

Glioblastoma is the most common type of brain tumor affecting 0.002-0.003% of general population. In glioblastoma, the astrocytes (neuron-supporting glial cells) turn into cancerous cells, start to divide frequently  and gradually form a large mass pressing against the brain. Glioblastoma is a challenging disease to treat as dosages of radiotherapy and chemotherapy are limited by their toxicity to the brain tissue. The use of alternating electrical fields is a novel approach that aims to suppress the division (mitosis) of malignant cells while sparing non-dividing neuronal cells in their vicinity. An Israeli-based company NovoCure Ltd. developed a stimulation device, Novo-TTF, which delivers alternating electric fields through insulated electrodes attached on the scalp surface. The scientific foundation of this approach comes from the study by the Technion scientists showing that alternating electrical fields can stop the cells from dividing and can even destroy them, if the cells are oriented roughly along the field direction. Importantly, the dividing cells inside the blood vessels appear to be unaffected. The key concern for the therapeutic use of alternating electric fields relates to their effects on neurons. At low frequencies, under 1 kHz, alternating electric fields stimulate neurons. As the frequency of the electric field increases above 1 kHz, the field can better penetrate through the cellular membrane, and its effect on neuronal excitability is diminished. At even higher frequencies, above 100 MHz, the brain exposure becomes localized and significant local heating can occur. Faced with these possible side-effects of low and high frequencies, the scientists decided to stick with intermediate frequencies of 100–200 kHz.  The electric fields at these frequencies might be relatively safe as long as their intensity is kept below the threshold for inducing the pore formation in the cellular membrane, through a phenomenon called electroporation. A recently completed phase III trial of the Novo-TTF device alleviates some of these concerns by showing no change in incidences of headaches or seizures in patients. The device is likely to be approved for use in the US within the next three months.

Medtronic introduces the prototype of a tiny wireless pacemaker … but lacks the technology to power the device

Dr. Stephen Oesterle, Medtronic’s senior vice president for medicine and technology, made an announcement about an interesting new device at works at the world’s largest medical device company – the tiny injectable pacemaker. Judging by the provided photo of the prototype, its width is ~2 mm and length is ~6 mm, allowing it to be implanted into the heart via a small catheter rather than an invasive surgery. Medtronic’s R&D department has already developed an ASIC chip featuring most of the components—an oscillator to generate current, a capacitor to store and rapidly dispense charge, memory to store data, and a data telemetry system. “What we don’t have that is fundamental to a pacemaker is a way to power the chip,” said Oesterle. It is not clear whether Medtronic will try to develop this crucial piece of technology in-house or to buy the patent rights from others. Considering that the device would have to deliver tens of mA of current (perhaps more), the power telemetry development might be not an easy task. Additional challenges facing the device developers include deep device placement and limited space for the antenna given the small device size. For these reasons, it might not be feasible to use the existing RF inductive-coupling power telemetry technologies developed for superficially-placed neurostimulation devices, such as the RF-BIONTM Implantable Microstimulator from AMF and the SAINTTM from MicroTransponder Inc. Other possibilities do exist, such as the resonant antennas operating at microwave frequencies, but these technologies have a long way to go before they are applied for any biomedical applications. I guess, we will be more certain about the Medtronic’s plans once they start hiring the microwave antenna engineers.

First clinical trial of a brain-controlled artificial arm to begin by summer’s end

Since 2005, DARPA (the Defense Advanced Research Projects Agency) has invested more than $100M into development of the brain-machine interfaces (BMIs) by sponsoring two programs, Revolutionizing Prosthetics and Human-Assisted Neural Devices. Most of that funding went into creation of two BMI-controlled artificial arms – the 10-degrees-of-freedom (DoF) DEKA “Luke” Arm by DEKA R&D Corp. and the 22-DoF Modular Prosthetic Limb (MPL) by Johns Hopkins University together with University of Pittsburgh and California Institute of Technology. A smaller effort to develop the 3-DoF BMI-controlled artificial arm is also underway in Germany by the company Otto Bock HealthCare GmbH. It now appears that DARPA’s investment into neuroprosthetic control of the arm may begin to materialize as early as this summer. The BMI control of the MPL arm will be made possible by the array of penetrating electrodes implanted into the motor cortex of five quadriplegic patients. The silicon-based array will record the multi-unit activity in the cortical area that controls the arm movement and the recorded information will be used to predict the intended direction and force of movement. Penetrating silicon-based arrays have been already successfully tested in monkeys, demonstrating the feasibility of decoding the intent of different movements from cortical signals. The biggest remaining problem is a rapid deterioration in the quality of neural recordings from cortical arrays, ranging from several months to a year.  A range of strategies can potentially overcome this problem: 1) by making the electrodes less stiff, 2) by removing the wires tethering the array to the skull, and 3) by using a biomimetic array coating to improve its biocompatibility and reduce the immune response. It is unlikely that any of these novel strategies will actually be used in the first generation of cortical arrays for the MPL control. Nevertheless, the upcoming clinical trial will be a positive event for the BMI R&D community after suffering a setback from the failed BrainGate trial three years ago. Progression of the BMI-MPL clinical trial will be closely monitored and guided by the FDA, which, after extensive talks with DARPA, recently created the Innovation Pathway specifically for such pioneering and transformative medical technologies. By utilizing this Pathway, the FDA aims to cut the premarket approval process time in half (to 150 days or less), suggesting a smooth commercialization path for the BMI-MPL after conclusion of its clinical trials.

Penetrating electrode arrays for retinal stimulation

On the heеls of the previous post, here is another news bit on the topic of retinal implants. Over the years, we have witnessed a variety of approaches being applied for retinal stimulation, including the epiretinal, subretinal, and suprachoroidal. One feature, however, remained unchanged in those varied types of implants – a planar geometry of the stimulation array.  At least until now. As the competition in the retinal implant sector is heating up,  the issues of low-power operation and improved electrode contact with retinal neurons is fueling the development of stimulation arrays featuring the 3D geometries. Improved charge delivery to retinal neurons has been achieved a few years ago by fabricating the protruding 3D nanoelectrodes in Daniel Palanker’s lab at Stanford University and at Dong-Il Dan Cho’s and Sung June Kim’s labs at Seoul National University. Now, preparing to reach even deeper into the retina, the Israeli company Nano-Retina Inc., co-founded by Rainbow Medical Ltd. and Zyvex Labs. , is developing the Bio-Retina implant featuring the array of 100-µm-sized penetrating electrodes. Their length should allow the electrodes to reach the layer of bipolar cells that are spared in AMD and other degenerating retinal disorders. The first-generation array will have 24×24 electrodes and the second – 72×72. Power to the device will be delivered wirelessly using the infrared light beamed from the glasses. To expedite their efforts in developing the low-power IC chip with the built-in photodetector array and power telemetry, Nano-Retina has teamed up with CMES (Centre Suisse d’Electronique et de Microtechnique), a non-profit R&D center in Switzerland. According to their (perhaps too optimistic) estimates they plan to have the functional device ready for clinical trials by 2013 and even have estimated the target price of $60K for the Bio-Retina implant. We wish the best of luck to this young ambitious company, hoping it has what it takes to develop a device from scratch in such a short period of time.

Harvesting light and heat energy from the body with a hybrid device

Rechargeable batteries are increasingly more common in neural implants, removing the need for multiple surgeries to replace a depleted battery. Alternative strategies are being developed for replenishing the energy of the battery. The most established method of energy delivery is via radio waves. Recent shift toward the use of higher frequencies in the 0.1-1 GHz band made the rectenna (receiving antenna) extremely small. This allowed the implant to fit within an injectable needle for a minimally invasive delivery at a location near a peripheral nerve. In order to eliminate the need for coupling the implant with an external charging device, methods are being developed for harvesting the energy from the human body. These methods utilize the energy of light (visible or infrared), heat, or vibration.  Harvesting of visible light can be done most efficiently in the retina, while infrared light can penetrate the skin and be used for transcutaneous powering of the implants. In the body, amount of energy available for harvesting is rather limited, so that multiple forms of energy – such as light and heat, or light and vibrations – can be used simultaneously in order to collect a sufficient amount for practical use. This can be achieved by combining different kinds of energy transducers. In pursuit of this approach, Fujitsu Laboratories has developed a new hybrid harvesting device that captures energy from either light or heat in a single device. Their device is manufactured from inexpensive organic materials, keeping the production costs low. The device contains two types of semiconductor materials – P-type and N-type semiconductors – allowing it to function as a photovoltaic cell or thermoelectric generator. Importantly, their hybrid device can be fabricated on flexible substrate for easy accommodation into different implant shapes.  The company is currently refining the technology to increase its performance, and aims to commercialize it by around 2015.

Neurotech exploration setup for a curious child: price – $100, experience – priceless

Take a look at this self-explanatory video from Backyard Brains, a web store founded by two grad students at U. Michigan. It shows how to teach the basics of neural stimulation and recording on a slim budget. Their Spikerbox setup consists of a simple op-amp circuit, a few filters, an A/D, and a speaker, all connected to an iPhone for stimulus generation or recording. If you have a kid interested in neuroscience, don’t pass up this opportunity for a fun educational evening with the Spikerbox.

Neural probe with integrated microfluidics and pumps for intracranial drug delivery

Chemical stimulation using channels in a so-called “puffer” neural probe has been a challenging endeavor, originated by Prof. Kendal Wise’s laboratory in U. Michigan back in 1997. The early probes were fabricated using the reactive ion etching (RIE) technology, and despite their initial promise, so far have not been successfully used in chronic animal studies.  Multiple issues, ranging from the outlet biofouling to the hydraulic resistance inside a microfluidic channel, have been identified. A commercial probe combining the drug delivery and electrical recording/stimulation was recently developed by the NeuroNexus Technologies (D/DM-series); it consists of the silicone probe glued to the fused silica fluidic channel. Opting for an integrated probe solution, engineers at the Institute of Micromachining and Information Technology and the Institute of Microsystem Technology at the University of Freiburg etched the channels with heights of 50 µm and more inside the wafer using the deep RIE (DRIE) technology. Their effort is a part of the NeuroProbes project, funded by a European Sixth Framework Programme (FP6), which includes 13 other partners from Belgium, Germany, Sweden, Switzerland, UK, Italy, France, Hungary, Spain, and Netherlands. The probes, fabricated by German engineers, remained unclogged in an acute in vivo test, while the chronic implant studies are still ongoing. The fluid pumping action inside the microfluidic channels was achieved by a MEMS device built into the probe. The MEMS device functions by constricting fluid-filled micro-chambers (volume = 0.25 μL each) using a thermally expandable material coupled to heating microelements. The microchambers are connected in series and can be constricted individually with a 3-second temporal precision. Having the chemical stimulation and electrical recording on the same probe, may soon allow a detailed examination the chemical signaling inside the brain in vivo with a high spatiotemporal precision.

Hypoglossal nerve stimulation for obstructive sleep apnea: revival of the old technology

Obstructive sleep apnea (OSA) is a condition in which breathing is periodically obstructed during sleep, often due to a prolapsed tongue or swollen throat. OSA affects 3-5% of people (18 millions in the US alone) and is often associated with obesity and old age. The hypoglossal nerve (HGN) controls the tongue and soft palate muscles. The closed-loop HGN stimulation, synchronized with the inspiratory phase of respiration, was shown (by Johns Hopkins U. researchers in mid-90es) to reduce the severity of OSA. In 1996-1997, Medtronic Inc. tested the first implantable HGN stimulator, Inspire I, in humans but soon abandoned the device due to concerns about its safety. Fast-forward to 2010: we have an expired patent on the HGN stimulation and several companies vying for dominance in this lucrative market. Charging ahead of the competition is a Medtronic’s spinout Inspire Medical Systems, with its device, Inspire II, that just received the CE Mark for clinical use in Europe. Not far behind are the Apnex Medical and ImThera Medical, who are undergoing clinical trials for their versions of the HGN stimulation devices. It is worth mentioning that other neurostimulation technologies are being applied for sleep apnea. Cardiac Concepts Inc. is developing a device for the phrenic nerve stimulation to restore a more natural breathing pattern in patients with the central sleep apnea, a related medical condition. Inspiration Medical Inc. holds several patents for the diaphragm pacing as yet another method for OSA treatment. Finally, there are some less-invasive approaches including tongue stimulation with sublingual electrodes and the repelling magnetic implants in the tongue base and posterolateral pharynx. Perhaps, it is too early to predict which of the technologies will ultimately prevail, so let’s not lose our sleep over this for now.

Hi-def and infrared vision in a subretinal implant from Retina Implant AG

A remarkable milestone has been reached in the resolution of retinal implants – a whopping 1520 pixels! In addition to vision restoration, the implant provides a first-ever vision-enhancing capability – the sensitivity to near-infrared light.

A remarkable milestone has been reached in the resolution of retinal implants – a whopping 1520 pixels (38×40)! Following on the heels of a recent success of Argus II retinal implants developed by the Second Sight, this implant by the German Retina Implant AG brings a 25-fold increase in resolution and several other unique features. Its subretinal placement is closer to the retinal pigment epithelium than can be achieved with epiretinal placement. This provides more selective stimulation of photoreceptors and results in further improvement in the implant’s resolution. The light sensing circuitry (silicon photodiodes) is built into the implant allowing it to move along with the eye movements.  This is beneficial for more natural cortical processing of visual information, as the visual map in the visual is adjusted during each saccade. Other types of retinal implants use an external videocamera (usually mounted on the glasses) that does not adjust the video information during the eye movements. The implant is 3 x 4 mm and 50 µm thick.  In addition to vision restoration, the implant provides a first-ever vision-enhancing capability – the sensitivity to near-infrared light. Extending the spectrum of perceived light can have some interesting implications, such as the ability to see a thermal shape of the object (the black body radiation) even in complete darkness. The ongoing research by Prof. Eberhart Zrenner at the University of Tuebingen aims to evaluate these implants to develop strategies for further improvements in the sensitivity and targeting of the implants. According to the paper published in the November issue of Proceedings of Royal Society B, the implants have been tested in three patients with hereditary retinal degeneration. All patients could locate bright objects on a dark table, and one patient discerned shades of grey with only 15% contrast. An important question for the retinal implant community, so far not answered by the study, is: how many pixels in the implant provide truly unique information to the retina and whether this spatial threshold has been reached with a 70-µm spacing used in the implant. The answer to this question has far-reaching implications for further technology developments: 1) whether further improvements in the density of planar arrays will translate into more focal stimulation and 2) whether the stimulating sites should be microfabricated to extend from the chip toward the retina in order to achieve the intended 70-µm spatial resolution.

Modified cochlear implant restores vestibular function

Cochlear implants have been around for decades restoring hearing in profoundly deaf people. Now, with the help of Jay Rubinstein, James Phillips, and other scientists at University of Washington, the old “dog” from Cochlear Ltd has learned a new trick: restoring the sense of balance. The Nucleus® cochlear implant was modified to include three leads with multiples stimulation sites. The leads are implanted into all three semicircular canals of the inner ear to restore the 3D rotational information. The details of the implant design and surgery are provided in this video.