The IEEE website places cookies on your device in order to provide you with the best user experience. By using our website, you agree to the placement of these cookies. To learn more, please read our privacy policy.
Implantable device can promote blood flow to help stroke recovery, but the test data is still questionable
BrainsGate hopes that its ischemic stroke system nerve stimulation device can help stroke patients recover better.
After a stroke, time is of the essence. Doctors need to restore the blood supply to the affected brain area as soon as possible-otherwise, due to lack of oxygen, millions of neurons and supporting cells will die quickly, leading to paralysis, loss of sensation or worse.
A new nerve stimulation device may help. The ischemic stroke system (ISS500 for short) stimulates a group of nerve cells behind the nose to promote the release of neurotransmitters and other signaling molecules, thereby enhancing blood circulation in the brain.
More blood flow means fewer cell deaths-which ultimately leads to improvements in muscle strength, walking ability and other motor functions.
However, experts are still divided on whether the Israeli company BrainsGate behind the equipment has made it clear that the ISS500 system is working as expected.
On December 10, an advisory panel from the U.S. Food and Drug Administration (FDA) unanimously voted that the device was safe. But the committee members are divided on whether the clinical trials have fully demonstrated the efficacy.
"It seems that there is indeed a safe level of biological effects here," said Michael Hill, a stroke expert at the University of Calgary in Canada, who advises BrainsGate. "This is a very interesting technology."
However, it is not clear whether the existing data volume is sufficient for BrainsGate to be approved. Hill said: "They may just need a little evidence to cross the finish line."
Out of concerns about the study design, 7 of the 13 members of the group insisted that another trial is needed to confirm the benefits of the device. But others pointed out that the regulatory threshold for device approval is usually lower than that of drugs, and they either wish ISS500 or give up making a final decision.
The FDA does not need to follow the recommendations of its panel, but it usually does. European regulators approved the device last year, but BrainsGate has been waiting for a US decision before starting any form of large-scale commercial promotion.
Jeffrey Saver, a vascular neurologist at the UCLA Stroke Center, co-led the clinical testing of the device and served as a scientific advisor to BrainsGate. He hopes the FDA will make a favorable ruling. "This is not my device," he said. "This is a new way of caring for patients."
For now, there are two main treatment options for patients with "ischemic" strokes (the most common type caused by blocked arteries to the brain). They can take drugs that destroy blood clots to clear the blockage, or insert tiny tubes in their blood vessels to physically remove harmful waste.
However, approximately 10% to 15% of patients do not qualify for these interventions. Medication must be started shortly after the onset of stroke, and the increased possibility of cerebral hemorrhage will make some people too risky for thrombus destruction therapy. At the same time, some people’s blood vessel networks are twisted and tangled, and this maze-like structure makes it impossible to navigate them with any catheter guiding device.
ISS500, if approved, will provide a treatment option for stroke patients who currently have no other options.
The neurostimulator is built around a toothpick-sized device that consists of a bipolar electrode at one end, an electronic circuit board at the other end, and a curved connector in the middle. "The biggest engineering challenge is to minimize everything, to make the implant strong on the one hand and flexible on the other," said Eyal Shai, BrainGate's vice president of corporate stroke work.
The doctor uses an image-guided program-through CT scans, dental impressions, stereo cameras, and optical tracking software-to inject the device through the roof of the mouth into the correct location next to the neural target collection, the sphenopalatine ganglia (SPG). An ice hockey-shaped transmitter is placed on the cheek, and then wirelessly transmits energy to the implant through magnetic induction.
This rendering shows the disk-shaped transmitter powering the ISS500 after implantation. BrainsGate
More than 30 years ago, a pioneering research team led by Australian neurologist Peter Goadsby and Swedish neurophysiologist Lars Edvinsson first showed that electrical stimulation of SPG can promote blood flow in the brain of rats and cats.
But at the time, "the idea that nerves can change cerebral blood flow was destructive," said Goadsby, who now works at King's College London and UCLA. The metabolic activity of the brain—not the wires—is thought to drive blood circulation in the brain. Goadsby and Edvinsson, like most others in the field, continue to study more direct connections between SPG and nerve signals related to headaches.
For example, two years ago, a trial led by Goadsby showed that using a remotely controlled activation device implanted through the upper gums to stimulate the nerve bundles with high frequency and on-demand can help relieve the pain of patients with cluster headache attacks. But Autonomic Technologies, the company behind the device, went bankrupt in 2018-the new owner of the platform, a startup called Realeve, may still take a few years to bring this type of SPG neurostimulator to the market.
In principle, the ISS500 system can be used for headache treatment. BrainsGate co-founder and neurophysiologist David Yarnitsky of Rammbam Medical Center in northern Israel demonstrated in a proof-of-concept experiment in rats and dogs in the mid-2000s that it can also help drugs enter the brain.
However, BrainGate has long prioritized stroke rehabilitation. By gently stimulating the SPG in the right way—instead of over-exciting nerve bundles, as people might block headache pain pathways—the company has honed its technology to increase blood flow to the brain and restore nerve function.
Clinical testing of the ISS500 system began in 2006. A small feasibility test proved the device's potential in post-stroke care. Two subsequent randomized, sham-controlled trials jointly showed that SPG stimulation works best for stroke patients who affect the cerebral cortex (rather than other brain structures located deep in the head).
In these patients, the 4-hour daily ISS500 system treatment started within 24 hours after the ischemic attack and was performed within five consecutive days. Compared with sham treatment, it significantly reduced disability and improved quality of life indicators.
The response is especially obvious when doctors treat with low to medium intensity (stimulating the sweet spot). The strength of the hand has increased. Some people who have lost the ability to understand or express language begin to speak again soon after nerve stimulation.
However, BrainsGate initially did not position its device specifically for the treatment of cerebral cortical stroke. The importance of stroke positioning is only partially mentioned in the company's clinical development plan. In a key trial of 1,000 people—but before anyone knows the results of the trial—BrainsGate decided to modify its analysis plan and introduce a key test of the device's efficacy based solely on the results of cortical stroke participants.
Finally, the device showed little benefit in the entire research population. It only produced a meaningful improvement in disability measures in the subgroup of cerebral cortical stroke.
This analytical shift has angered some outside observers-as a result, many FDA consultants have decided not to recommend authorization for the time being. In their view, BrainsGate needs to conduct a better-designed confirmatory test.
It is now up to agency staff to decide whether such tests are required. A decision is expected to be made in February.
If approved, the ISS500 system will become the second implantable device authorized to treat stroke in less than a year. As early as August, the FDA approved the MicroTransponder Vivistim system, which provides gentle electrical impulses to the vagus nerve in the neck, and has been shown to be combined with physical therapy to help with long-term stroke recovery.
Other supplementary equipment will follow up soon. Stroke clinics are experimenting with wearable hats that can provide magnetic or direct current stimulation to precise points in the brain. According to Realeve CEO Jon Snyder, his company is planning to test its research SPG neurostimulator as a stroke rehabilitation aid.
Saver, a neurologist at the University of California, Los Angeles, welcomed the arrival of these various nerve-stimulating treatment options. As he pointed out: "Stroke neurology first has a pharmacological age. Then it has an era of endovascular devices. And I think we have now begun the era of the third set of models-neuromodulation."
Copenhagen Suborbital is crowdfunding its manned rocket
Volunteers from Copenhagen Suborbitals build manned rockets at night and on weekends. The team includes [from left] Mads Stenfatt, Martin Hedegaard Petersen, Jørgen Skyt, Carsten Olsen and Anna Olsen.
This is one of the most beautiful sights I have ever seen: our homemade rockets fall from the sky and are slowed down by the white and orange parachutes I have been working on for many nights at the table. The 6.7-meter-high Nexø II rocket is powered by a dual-element engine designed and built by the Copenhagen Suborbital Team. The engine mixes ethanol and liquid oxygen to produce a thrust of 5 kilonewtons, and the rocket rises to an altitude of 6,500 meters. More importantly, it became one piece.
The successful mission in August 2018 was a big step towards our goal of sending an amateur astronaut to the edge of space on one of our DIY rockets. We are now building the Spica rocket to complete this mission, and we hope to launch the manned rocket in about 10 years.
The Copenhagen suborbital is the world's only crowdsourced manned space program, and hundreds of generous donors around the world provide nearly 100,000 U.S. dollars each year. Our project consists of various volunteers who are engaged in various daily tasks. We have many engineers and pricing managers like me who have a hobby of skydiving. I am also one of the three candidates for the position of astronaut.
We are in a new era of space flight: the National Space Agency is no longer the only game in the city, and space is becoming more and more accessible. Rockets manufactured by commercial companies such as Blue Origin are now sending private citizens into orbit. Having said that, Blue Origin, SpaceX, and Virgin Galactic all have the support of billionaires with huge resources, and they all expressed their intention to sell flights for hundreds of thousands to millions of dollars. The Copenhagen Suborbital has a very different vision. We believe that anyone who is willing to invest time and energy should be able to fly into space.
The Copenhagen Suborbital Company was founded in 2008 by a self-taught engineer and a space architect who had worked at NASA. From the beginning, the mission was clear: manned spaceflight. Both founders left the organization in 2014, but by then the project had about 50 volunteers and sufficient motivation.
The founding principle of the group is that the challenges involved in building a manned spacecraft at low cost are all engineering problems that can be solved one by one by a group of smart and dedicated diligent teams. When people ask me why I want to do this, I sometimes answer: "Because we can."
Volunteers use a can of argon gas [left] to fill a tube in which engine components are fused together. The team recently built a fuel tank for the Spica rocket [right] in their workshop.
Our goal is to reach the Carmen Line, which defines the boundary between the Earth’s atmosphere and outer space, at an altitude of 100 kilometers. Astronauts who reach that altitude will have a few minutes of silence and weightlessness after the engine is turned off, and will enjoy stunning views. But this will not be an easy journey. During the descent, the capsule will withstand an external temperature of 400 °C and a gravity of 3.5 as it gallops through the air at a speed of up to 3,500 km/h.
I joined the organization in 2011, when the organization had moved from a maker space on a decommissioned ferry to a hangar near the Copenhagen waterfront. Earlier that year, I watched the first launch of the Copenhagen suborbital, when the HEAT-1X rocket took off from a mobile launch platform in the Baltic Sea-but unfortunately, it crashed into the ocean when most of its parachutes failed to deploy. . I have brought to the organization some basic knowledge of sports parachutes acquired during my years of skydiving. I hope this knowledge can be transformed into useful skills.
The team’s next milestone came in 2013, when we successfully launched a sapphire rocket, which was our first rocket that included guidance and navigation systems. Its navigation computer uses a 3-axis accelerometer and a 3-axis gyroscope to track its position, and its thrust control system moves the four servo-mounted copper jet blades inserted into the exhaust pipe to keep the rocket on the correct trajectory part.
We believe that anyone who is willing to invest time and energy should be able to fly into space.
HEAT-1X and sapphire rockets use a mixture of solid polyurethane and liquid oxygen as fuel. We are keen to develop a two-component rocket engine that mixes liquid ethanol and liquid oxygen because this liquid propellant engine is both efficient and powerful. The HEAT-2X rocket, scheduled to be launched at the end of 2014, aims to demonstrate this technology. Unfortunately, its engine caught fire during static tests a few weeks before the scheduled launch. The test should be a controlled 90-second combustion; on the contrary, due to welding errors, a large amount of ethanol poured into the combustion chamber in just a few seconds, causing a large-scale fire. I stand a few hundred meters away, and even at that distance, I can feel the heat on my face.
The engine of the HEAT-2X rocket was unable to run and the mission was cancelled. Although this was a major disappointment, we learned some valuable lessons. Until then, our design has been based on our existing capabilities-the tools in our workshop and the people in the project. Failure forces us to step back and consider what new technologies and skills we need to master in order to achieve the ultimate goal. This rethinking prompted us to design the relatively small Nexø I and Nexø II rockets to showcase key technologies such as parachute systems, dual-element engines, and fuel tank pressure adjustment components.
For the Nexø II launch in August 2018, our launch site is located 30 kilometers east of Bornholm, the easternmost island of Denmark, in the part of the Baltic Sea used by the Danish Navy for military exercises. We left the port of Nexø in Bornholm at 1:00 in the morning. rice. Arrive at the designated sea area on time to launch at 9 am, which is the time approved by the Swedish air traffic control. (When our ship is in international waters, Sweden monitors the airspace over that part of the Baltic Sea.) Many of our crew have been testing various rocket systems the day before and stayed up all night before launch. We are drinking coffee.
When Nexø II was launched and separated neatly from the launch tower, we all cheered. The rocket continued its trajectory, abandoning its nose cone when it reached the apogee of 6,500 meters, and kept sending telemetry data back to our mission control ship. When it begins to descend, it first deploys its parachute, a balloon-shaped parachute used to stabilize spacecraft at high altitudes, and then deploys its main parachute, gently carrying it into the waves.
In 2018, the Nexø II rocket successfully launched [left] and safely returned to the Baltic Sea [right].
This launch brings us one step closer to mastering the logistics of launching and landing at sea. For this launch, we also tested the ability to predict the rocket path. I created a model and estimated that there was a splash drop 4.2 kilometers east of the launch platform; it actually landed 4.0 kilometers east. This kind of controlled water landing-our first landing under a fully inflated parachute-is an important proof of concept for us, because soft landing is absolutely necessary for any manned mission.
In April of this year, the team tested its new fuel injector in a static engine test. Carsten Olsen
The engine of Nexø II, which we call BPM5, is one of the few parts that has not been fully machined in our workshop. A Danish company manufactures the most complex engine parts. But when these parts arrived in our workshop shortly before the launch date, we realized that the exhaust nozzle was a bit deformed. We didn't have time to order new parts, so one of our volunteers, Jacob Larsen, hammered them into shape with a sledgehammer. The engine doesn't look pretty-we nicknamed it the Franken engine-but it does work. Since the Nexø II flight, we have conducted more than 30 pilot fires on the engine, sometimes pushing it beyond the design limit, but we have not killed it yet.
The 15-minute interstellar journey of the Spica astronauts will be the product of more than two decades of work.
The mission also showcased our new dynamic pressure regulation (DPR) system, which helps us control the flow of fuel into the combustion chamber. Nexø I used a simpler system called pressure blowdown, where the fuel tank is filled with one-third of the pressurized gas to drive the liquid fuel into the chamber. With DPR, the fuel tank is filled with fuel and connected to a separate helium tank under high pressure through a set of control valves. This setup allows us to adjust the amount of helium flowing into the tank to push fuel into the combustion chamber, allowing us to program different thrusts at different points during the rocket's flight.
The Nexø II mission in 2018 proved that our design and technology are fundamentally reasonable. It's time to start studying the human-rated Spica rocket.
The Copenhagen Suborbital Company hopes to send an astronaut to high altitude on its Spica rocket in about ten years. Caspa Stanley
The Spica rocket equipped with a crew compartment is 13 meters high and has a total lift-off weight of 4,000 kg, of which 2,600 kg is fuel. It will be, to a large extent, the largest rocket built by an amateur.
The Spica rocket will use the BPM100 engine that the team is currently manufacturing. Thomas Pedersen
Its engine 100-kN BPM100 uses the technology we have mastered for BPM5 with some improvements. Like the previous design, it uses regenerative cooling, where some of the propellant passes through channels around the combustion chamber to limit the temperature of the engine. In order to push fuel into the chamber, it combines the simple pressure blowdown method of the first stage of flight and the DPR system, which allows us to better control the rocket's thrust. The engine parts will be stainless steel, and we hope to manufacture most of the parts ourselves from rolled sheet metal. The trickiest part, the hyperbolic "throat" connecting the combustion chamber and the exhaust nozzle, requires computer-controlled processing equipment that we don't have. Fortunately, we have good industry contacts who can help.
A major change is the conversion from Nexø II nozzle injectors to coaxial swirl injectors. The nozzle injector has about 200 very small fuel passages. It is difficult to manufacture, because if we have a problem in making one of the channels-such as a stuck drill bit-we have to throw the whole thing away. In the coaxial swirl injector, the liquid fuel enters the combustion chamber in the form of two rotating liquid sheets, and when the liquid sheets collide, they are atomized to produce burning propellant. Our swirl jet uses approximately 150 swirler elements, which are assembled into a structure. This modular design should be easier to manufacture and test to ensure quality.
The BPM100 engine will use a coaxial swirl injector [left] to replace the old nozzle injector [right], which will be easier to manufacture. Thomas Pedersen
In April of this year, we conducted static tests on several types of injectors. We first conducted experiments with easy-to-understand nozzle jets to establish a baseline, and then tested brass swirl jets manufactured by traditional machine milling and steel swirl jets manufactured by 3D printing. We are satisfied with the overall performance of the two swirl jets, and we are still analyzing the data to determine which one is better. However, we do see some combustion instability-that is, the flame between the injector and the engine throat oscillates, which is a potentially dangerous phenomenon. We are well aware of the reasons for these oscillations, and we believe that some design adjustments can solve the problem.
Volunteer Jacob Larsen holds a brass injector that performed well in the 2021 engine test. Carsten Olsen
We will soon begin to build a full-scale BPM100 engine, which will eventually include a new rocket guidance system. In our previous rocket, there are metal blades in the exhaust nozzle of the engine, and we can move it to change the thrust angle. But these blades create resistance in the exhaust flow and reduce the effective thrust by approximately 10%. The newly designed universal joint can rotate the entire engine back and forth to control the thrust vector. To further support our belief that smart and dedicated people can solve difficult engineering problems, our gimbal system was designed and tested by 21-year-old undergraduate Jop Nijenhuis from the Netherlands, who used gimbal design as a thesis project (he obtained Got the highest score).
The guidance, navigation and control (GNC) computer we use is the same as the one we use in the Nexø rocket. A new challenge is the crew capsule; once the space capsule is separated from the rocket, we must control each part ourselves to send them back to Earth in the desired direction. When the separation occurs, the GNC computers of the two components will need to understand that the parameters for optimal flight have changed. But from a software point of view, this is only a small problem compared to the problems we have solved.
Bianca Diana is working on a drone that she will use to test the new guidance system of the Spica rocket. Carsten Olsen
My specialty is parachute design. I have studied Balllute, which is inflated at an altitude of 70 kilometers to slow down the speed of the manned space capsule during the high-speed initial descent, and the main parachute, which inflates when the space capsule is 4 kilometers above the sea. We tested both types by letting skydivers jump out of the plane with a parachute, the most recent time being in the 2019 ballet test. The pandemic forced us to suspend parachute testing, but we should resume it as soon as possible.
For the parachute that will be deployed from Spica's booster rocket, the team tested a small prototype of a ribbon parachute. Mads Stenfatt
For the cone parachute that will be deployed from the booster rocket, my first prototype is based on a design called Supersonic X, which is a kind of parachute that looks a bit like a flying onion and is very easy to make. However, I reluctantly switched to a ribbon parachute, which has been more thoroughly tested under high pressure conditions and found to be more stable and robust. I say "reluctant" because I know how much work it takes to assemble such a device. I first made a parachute with a diameter of 1.24 meters. It has 27 ribbons passing through 12 panels, and each ribbon is connected in three positions. So on that small prototype, I had to sew 972 connections. The full-size version will have 7,920 connection points. I try to remain open to this challenge, but if further testing shows that the Supersonic X design is sufficient for our purposes, I have no objection.
We tested two crew cabins in past missions: Tycho Brahe in 2011 and Tycho Deep Space in 2012. The next-generation Spica crew cabin will not be spacious, but it will be large enough to accommodate an astronaut and will maintain a seat during a 15-minute flight (and a two-hour pre-flight check). The first spacecraft we are building is a heavy-duty steel "model" space capsule, which is the basic prototype we use to achieve practical layout and design. We will also use this model to test the design of the hatch, the overall resistance to pressure and vacuum, and the aerodynamics and fluid dynamics of the shape, because we want the capsule to splash into the sea with minimal impact on the astronauts inside. Once we are satisfied with the prototype design, we will make a lightweight flying version.
There are currently three astronaut candidates flying for the first time in the Copenhagen suborbital: From left, Mads Stenfatt, Anna Olsen and Carsten Olsen. Messtanfat
The three members of the Copenhagen suborbital team are currently candidates for our first manned mission as astronauts-me, Carsten Olsen and his daughter Anna Olsen. We all understand and accept the risks involved in flying a homemade rocket into space. In our daily operations, our astronaut candidates have not received any special treatment or training. So far, one of our additional responsibilities has been to sit in the passenger compartment seat and check its dimensions. Since our first manned flight is still ten years away, the shortlist is likely to change. As for me, I think it’s a great honor to be part of the mission and help build the rocket that will send the first amateur astronaut into space. Whether I eventually become an astronaut or not, I will be proud of our achievements.
Astronauts will enter space in a small crew capsule on the Spica rocket. The astronaut will remain seated during the 15-minute flight (and the previous 2-hour flight check). Carsten Brandt
People might wonder how we can live on a meager budget of about $100,000 per year—especially when they learn that half of our income is used to pay for workshop rent. We reduce costs by purchasing as many standard off-the-shelf parts as possible, and when we need custom designs, we are lucky to work with companies that provide us with generous discounts to support our projects. We launch from international waters, so we don’t need to pay for launch facilities. When we went to Bornholm for the press conference, each volunteer paid for it themselves. We lived in a sports club near the harbour, slept on a mat on the floor, and took a shower in the locker room. I sometimes joke that our budget is about one-tenth of what NASA spends on coffee. However, this may be enough to complete the job.
We originally planned to launch Spica for the first time in the summer of 2021, but our schedule was delayed due to the COVID-19 pandemic, which caused our studio to close for several months. Now we hope to conduct a test launch in the summer of 2022, when conditions in the Baltic Sea will be relatively mild. For this initial test of Spica, we will only fill up the fuel tank midway and launch the target to an altitude of approximately 30 to 50 kilometers.
If this flight is successful, Spica will carry more fuel and fly higher in the next test. If the flight in 2022 fails, we will find the problem, fix the problem, and try again. It is remarkable to think that the final 15-minute interstellar journey of the Spica astronauts will be the product of more than two decades of work. But we know that our supporters are counting down until the historic day when amateur astronauts board a homemade rocket and wave goodbye to the earth, ready to take a big step towards the DIY style.
One reason for the slow progress of the Copenhagen suborbital towards the ultimate goal of manned spaceflight is our concern for safety. We test our components extensively; for example, we conducted approximately 30 tests on the engine that powers the 2016 Nexø I rocket before launch.
When we plan and execute the launch, our bible is a safety manual from Wallops Flight Facility, which is part of NASA's Goddard Space Flight Center. Before each launch, we will simulate the flight profile to ensure that it will not cause harm to our crew, ships, and any other personnel or property. We launch from the sea to further reduce the possibility of our rockets damaging anyone or anything.
We recognize that the Spica rocket and crew compartment of our manned spacecraft must meet higher safety standards than anything we have built before. But we must face our situation honestly: if we set the standard too high, we will never be able to complete the project. We cannot test our system like a commercial company (which is why we will never sell our rockets). Every astronaut candidate understands these risks. As one of these candidates, if every friend of mine who works in Rockets can look into my eyes and say "Yes, we are ready", I will have enough confidence to board the plane.
This article will appear in the December 2021 print edition as "the first crowdfunding astronaut".
Mads Stenfatt first contacted the Copenhagen Suborbital Company and put forward some constructive criticisms. In 2011, while viewing the photos of the DIY rocket's latest rocket launch, he noticed a camera installed near the parachute device. Stenfatt sent an email detailing his concern that the parachute ropes could easily get tangled around the camera. "The answer I got was basically,'If you can do better, join us and do it yourself,'" he recalled. This is how he became a volunteer for the world's only crowdfunded manned space program.
As an amateur skydiver, Stenfatt understands the basic principles of parachute packaging and deployment. He began to help the Copenhagen Suborbital Company design and package the parachute, and a few years later he also took over the sewing of the parachute. He has never used a sewing machine before, but he learns quickly at the dining table in the evenings and weekends.
One of his favorite projects is the design of high-altitude parachutes for the Nexø II rocket launched in 2018. While making a prototype and being confused about the design of the air intake, he found himself looking at the bra components on the Danish sewing website. He decided to use bra steel rims to strengthen the air intake and keep it open. The effect was very good. Although he eventually turned to a different design direction, this episode is a classic example of the spirit of the Copenhagen suborbital: collect inspiration and resources from anywhere you find to get the job done.
Today, Stenfatt serves as the chief parachute designer, frequent spokesperson and astronaut candidate. He continued to skydive in his spare time, jumping hundreds of times under his name. With a wealth of experience zooming down in the sky, he was very curious about what it would be like to move in the other direction.