Advances in MRI-Safe Technology: Interview With Michael L. Weiner, CEO, Biophan Technologies, Inc.

How did your collaboration with Wilson Greatbatch begin? When was Biophan created?

There were a lot of early stage innovations, and in setting it up, a friend, Wilson Greatbatch, the National Medal of Technology Award Winner (from President Bush, Sr.), who invented the implantable pacemaker technology which was licensed to Medtronic in 1961 and who also invented the lithium iodine battery, had some new technology that we started working on together. We created what became Biophan Technologies to pursue the technology to find a solution to MRI safety. Wilson was very concerned that pacemakers weren't safe for MRIs, and he wanted to fix that problem. He didn't envision that when he made the first pacemakers they would run into such a conflict in something as important as MRIs. We started working on the problem in 1999, and decided to put the technology initiative into Biophan to get access to capital to increase the R&D. Therefore, Biophan Technologies was formed in December 2000. We merged to become a public company; the reverse merger into a public shell is what they call it. It helped us raise needed capital to fund the R&D. So we began working on the safety problem. Initially we started out with a fiber-optic imaging catheter that replaced the metal wire lead in a pacemaker. We successfully tested it in animals and found it was transparent in MRI as well as safe. However, it was too much of a hurdle for the pacemaker companies to want to re-engineer their products it was too big of a change for them, and used too much power for an implantable device. In parallel, we had begun working with Johns Hopkins Hospital, who has a patent for the use of an RF filter to achieve MR-safe pacemaker leads, and that led us to solve the pacemaker safety problem. One of the main problems with a pacemaker during MRI is tissue heating. The lead causes the tissue to get hot, which can cause scarring of the heart tissue and then the pacemaker might not work. There are also other problems. In interventional medicine, the guidewires get hot. Therefore, one of the reasons they don t use MRI during most catheter functions is because of safety. They can get hot enough to burn a surgeon's fingers with his gloves on.

I was also reading that other complications to pacemaker patients during MRI can include stopping of the battery, reprogramming of the battery, the pacemaker can start beating up to 300 times a minute, or even death?

Yes, all of these problems have been reported in the literature and are confirmed by the studies we are doing, including the one we introduced at the Heart Rhythm Society Conference. The energy in the MRI is like a magnet generating electricity, and if you have enough electricity in the lead, you can make the heart to beat up to 300 times per minute, which can be fatal. Solving the problem for pacemaker leads also solved the problem for guidewire safety, which opens up the opportunity for the interventional world, as well as for the EP lab. The leads get hot, and we know how to solve that. The other main problem for devices in the MRI are that certain products like guidewires create what is called an image artifact in the MRI this makes it difficult to see the image. Imagine you are looking at a picture of a heart with the blood vessels, and there is a catheter similar to what you would see on an X-ray image of a pacemaker for an EP procedure. Under X-ray you will see a white line inside the vessels it will be bright and solid you ll know that's the lead, you will be able to tell. Seeing the tissue it is in is more difficult, due to the limitations of the X-ray. In the same picture, under MRI, you won t see the lead it will be black, and the tissue in which it is situated will also be blacked out by the image artifact. In addition, the artifact may be several inches from the vessel, so you may not even see the tissue surrounding the vessel. Thus, implantable devices in MRIs pose: 1) a safety problem, and 2) an imaging problem. However, since MRIs are not currently safe for these patients, the industry has steadily stayed with using only X-ray and fluoroscopy.

Describe Biophan's technology.

We have licensed the RF filters from Johns Hopkins that go at the end of the electrode lead and eliminate heating. In addition, the thin-film nanomagnetic coating that we developed with Nanoset, LLC, a spin-off from Alfred University, minimizes the artifact. We can also make the tip of the catheter very bright so that now you can see it guiding the catheter through the vessel under MRI. You illuminate the artifact and light up the tip that is the real selling point. We have an additional solution, a special loop we configure in the pacing lead to resolve the induced voltages. Our thin-film coatings resolve the image artifacts. In combination, these solutions can resolve the safety and image artifact problems of many devices. Over four years of research, working with a number of partners, we have also created this solution suite. We are now working with several manufacturers on implementation. I believe in time it will enable a whole new use of the MRI suite for EP/cath labs.

When will the MRI-safe technology be approved? How long before MRI-safe technology becomes commonplace? Right now there are no options for implant patients needing an MRI, is that correct? Can any patient with an implant get an MRI currently? Do you know how many related deaths there have been?

That's right. The only option is if you can find a physician willing to help you, and if you are willing to take the risk. There have been 25 reported deaths we have the FDA reports for some of these listed on our website. There is still a controversy about how dangerous or safe this really is. However, now that there is a definitive solution and we know it is safe, then why not just eliminate the risk? Medtronic has announced they are going to make their future products MRI-safe, and they say that will be the new gold standard. That is wonderful, but to us, the ideal situation would be if they were also imageable. In our mind, the ultimate pacemaker improvement would be that it is safe to go in the MRI, but that it can also be imaged. Therefore, the patient who needs an angiogram can have a MRI angiogram and not have to have an invasive procedure. That is within striking distance what we hope to bring to the industry. It is possible that Medtronic will have a safe pacemaker, while their competition has a solution that is both safe and image compatible. That is the real gold standard. To answer your previous question, what it is going to take is one manufacturer at a time to make a decision, to make a change. That is why we are here at the conference to be available to discuss this issue. It has also been very helpful to alert cardiologists, EPs, and radiologists, because they reinforce those needs to the manufacturers. All other things being equal in a product line, this could be the difference. That may make a physician choose one device over another.

Also, since EP physicians are not dealing with the MRI aspect on a daily basis, I am sure they still would want to make sure that something they implant isn't going to limit or do harm to their patient.

Once there are MRI-safe cath labs in which the EPs and patients will be subject to much less ionizing radiation, and the physician will not have to wear heavy lead aprons. There are some real tragedies every EP physician we talked to has experienced this to some intent. We met a patient that contacted us imploring us to help them, which we couldn't do. They had a pacemaker but were suspected of having a brain tumor. They wanted to get an MRI to get treated earlier, because you can't really detect it any other way, until it gets really big. Unfortunately, all we could say was that there were some physicians that have done studies to say there isn't much of a problem.

Describe the recent study at a major teaching hospital which confirmed the danger using MRI in implant patients.

A large teaching hospital has worked with us to produce several studies. There was a report presented last year at the NASPE - Heart Rhythm Society meeting that said they tested 50 dogs and no leads got hotter than 7 degrees. We do tests every week for pacemaker leads and devices in MRI, and we've seen heating as low as that, but also heating of 25 degrees and up to 60 degrees Centigrade, so there is an inconsistency. What we have discovered in our research is that it really depends on how you do the tests. Whether or not you see the heating depends on this, because the lead, or the metal tip itself, doesn't get hot. It is the tissue near the tip that gets hot. This happens because the energy is racing to try and short circuit itself into the lead and is moving towards that tissue; however, the tissue is resistant to the current, so the tissue gets hot. The problem ensues when the tissue then scars. The patient might not feel it though, and if they go home when there is scarring, then the pacemaker might not be able to hear the heart or the heart hear the pacemaker, and maybe a week later the patient will complain of fatigue or of not feeling good, and it is because the pacemaker ceased to function. There is a debate as to whether this is really a problem. Perhaps, if there were several problems when 50,000 pacemaker patients go into an MRI, some percentage would have a problem. Our experience is that you get the heating pretty often it is there, we just don t know how to measure it. Therefore, we asked the teaching university to work with us on an independent study. They took a pig heart and put an active pacemaker lead in it, put a lode on the end like a pacemaker would be there, put it in the MRI machine, and measured the heating. In one test, it only had 2 degrees heat, in another it had 25 degrees heat. The cooling was variable, but it did get hot, and 25 degrees is enough to scorch. It is hard to know the statistical outcome, though, because every batch of 50 patients is going to be different, but it appears to us to be a problem.

Why is it important to have MRI-safe ICDs? When did you first hear of the risk to patients? What new technology do you have to prevent this?

The FDA contraindication came out in 1997, after several years of noticing problems. From what we can tell, the problems weren t fully understood. The heating problem was better understood than the induced voltages, but there were also problems in odd pacemaker performance, which we have also observed, such as detecting false arrhythmias, or the energy that caused its logic service to cause problems, or it could be pacing you when you didn t need it, or the defibrillator would give off a big blast when the patient didn t need it. The interesting thing is that we have to prove to the pacemaker companies that it is a real problem, not just a perception, and we are in that process. The good news is that Medtronic announced that they are going to have an MRI-safe pacemaker, and this has caused the whole industry to pay attention.

Describe Biophan's recent collaboration with Boston Scientific and with TE-Bio.

We recently did a deal with Boston Scientific it started out exploring safety and image compatibility for one product, and has now extended to several products. TE-Bio technology is developing a biothermal battery, producing power from natural body heat. Currently, the rated life of an implantable device life of a pacemaker may be good for about 7-8 years; for a defibrillator, it might be five or six years. The rated life of neurostimulators used for Parkinson's tremors is about three years. Some devices will last a little longer, but that is the average. We realized that with advances in thermoelectric thin-film technology, which is used by NASA to power spacecrafts by the Department of Energy to generate alternative power, you can get differences in temperatures that cause electricity to flow. You can take the pacemaker device and put thermoelectric material on the case; from the differential of heat in the body you can get power. In the past, thermoelectric materials needed 30-Volt differentials between temperature, such as cold outer space versus inside a satellite where there is a heat source, to generate power. We believe that banotech advances can get this down to a temperature differential of only 2-3 degrees (Centigrade). There is that much of a difference between the organs of your body (heart, lung, liver, brain, stomach, etc.) and the outside surface temperature. Our technology includes polarity reversal if you work in a very hot environment such as the desert. This makes the concept of a biothermal battery within the range of feasibility, where it previously did not appear to be feasible. If you use a thermometer and your body temperature is 98.6 degrees, somewhere down inside in an organ the temperature might be 101 degrees. The body s temperature is different, and if you ve ever been trapped with 10 people in a conference room with the door shut, you know that the body gets hot. People can generate a lot of power! Advances in thermoelectric material are predicting that they ll be able to get 3 degrees Delta we use Delta T as the rating to produce about 50-100 microwatts. A pacemaker only uses about 50 microwatts, so there should be enough power to run a pacemaker. A defibrillator uses more power and has a larger battery, but normally a defibrillator is essentially a pacemaker except when it goes into defibrillation, it charges the full-capacity 800-Volt blast. The average rate of life is five years, but this power system wouldn t be able to replace the defibrillator battery it needs too much power when it delivers its charge. What you can do is recharge the battery 24/7, and whenever it is discharged and is low, you can bring it back up to full power this way. You might get a five-year life or go any number more years. However, the manufacturer wouldn t want it to be 20 years, because they will want to be able to replace it occasionally. That way, people will have the benefit of the most modern versions. They will also always have the competitive advantages; if it lasts a year or two longer, it is a big deal. We are getting a lot of people here at the conference asking about the biothermal battery the drug pumps, sensors, neurostimulators, pacemakers, defibrillators, and other devices.

Are Greatbatch Technologies' products also MRI-safe?

The heating and the voltages that can cause the rapid heartbeat happens in the lead. Therefore, if you fix the lead, the device should be fine. They also make a battery that goes in the device. They do not make a biothermal battery, though no one else does. The only other biothermal batteries out are by Seiko, which makes a watch powered by body heat transmitting out it is a limited edition, and is very expensive. However, it is not an implantable design. Of the entire industry, no one thought this was real, but Stuart MacDonald predicted that the nano revolution would enable biothermal batteries to put thousands of small semi-conductive nodes on the surface of a postage stamp that today might take up the size of a wall; that would allow them to have very low power output, but quite a few walls something like in a pacemaker. Initial studies say this will work. However, it is probably one to two years before we can prove it to a battery or pacemaker company that it will work. We ll work with either one or both to get the product to market and to go through FDA, although that could be another year.

Describe the patents held by Biophan. I see that about 50 patents are still pending; when do you think they will be approved?

We have nine issued and six more have been allowed, which will make a total of 15 issued or allowed. There are 45 more pending, not including TE-Bio they have the license for that. It covers everything, from the fiber-optic solution, the heating problem, reduced voltages, the image artifacts the whole range is covered by those 60 patents. The patents have been allowed, which means they will issue; if you wait awhile, you get them. As far as the license, we announced the deal with Boston Scientific, which includes an exclusive right to a first right of negotiation, under which we can only talk to them about their licensing of certain technologies of their products. If that relationship continues to be successful, then that will convert into a license for several products. At the same time, we are talking to several other companies who are getting close to potential licenses. I would hope that we will have something more to announce probably one or more deals this year.