The Journey of MRI Guided Interventions and Focused Ultrasound

Written by S. Morry Blumenfeld, PhD

Ferenc, or – as he was called in the US – Frank, was born on May 21, 1946, in Budapest, Hungary, to Holocaust survivors. Budapest is a beautiful city – and I always enjoyed going there with Ferenc, although now I wish I had done this more often. Because of its beauty, I understand why he felt so close to it all the time.

Ferenc (right) had an interesting career in Budapest. He graduated summa cum laude in medicine from Semmelweis University in 1971. But instead of practicing medicine, he served as a research fellow in biomedical engineering and computer science at the Kálmán Kandó College of Electrical Engineering in Budapest. He then completed a residency at the National Institute of Neurosurgery, also in Budapest.

He, his wife Anna, and their two daughters, Klara and Marta, moved to Boston in 1979, where he initially worked as a research fellow in the Department of Neurology at Massachusetts General Hospital. This was followed by a research fellowship in physiology at Harvard Medical School. He joined the Radiology Department of Brigham and Women’s Hospital (BWH) in 1982, first as a resident, then as a clinical fellow in neuroradiology.

He made a pretty swift progression at BWH:

  • 1982: Clinical Fellow, Dept. of Neuroradiology
  • 1982-1985: Resident, Diagnostic Radiology, Dept. of Radiology
  • 1985: Staff Neuroradiologist
  • 1985-1989: Assistant Professor of Radiology
  • 1987-1988: Director, Neuro MR Imaging Section
  • 1988-2014: Director, Division of MRI
  • 1989-1996: Associate Professor of Radiology
  • 1996-1998: Professor of Radiology
  • 1998-2014: B. Leonard Holman Professor of Radiology
  • 2000-2009: Vice-Chairman of Research, Dept. of Radiology
  • 1993-2014: Director, Image-Guided Therapy Program
  • 2001-2014: Director, Advanced Imaging Center, Harvard Medical School, NeuroDiscovery Center

He thus progressed from professor to a chaired professor to vice chair responsible for research. But most importantly – and this is where he focused much of his energy and thought – were his responsibilities for image-guided therapy (IGT) and advanced imaging, primarily to enable adoption of IGT. This became the key to our relationship.

Jolesz and TempanyFerenc had fantastic colleagues at BWH and entertained a constant succession of important visitors from all over the world. An indispensable colleague was Clare Tempany, MD (right, with Ferenc), who now has the crucial role of continuing his legacy.

How was I lucky enough to get involved with Ferenc and IGT?

In 1967, I joined the Imaging Group at General Electric’s Research and Development Center in Schenectady, NY. Then, in 1975, I moved from the R&D Center to GE Medical Systems (GEMS) in Milwaukee to help start the computed tomography (CT) business. I was in CT until 1981, when I started the magnetic resonance program at GEMS, and I did that for about eight years. This is when I first met Ferenc. Then, when my boss, Joe Williams, asked me to look for the “next big thing,” I became intrigued by the concept of using imaging and particularly MRI to help in surgery and other forms of therapy delivery. I started by trying to understand the roles of the medical imaging modalities that GE was not invested in. Foremost among these was laparoscopy, which was started by Georg Kelling who performed the first experimental laparoscopy in Berlin in 1901. He used a cystoscope to peer into the abdomen of a dog after first insufflating it with air.

By the late 1980s the most exciting use of laparoscopy was to perform a laparoscopic cholecystectomy – the first of which was performed by Professor Erich Mühe on September 12, 1985. (It took me almost a month to be able to pronounce “laparoscopic cholecystectomy” without stumbling!)

However, the problem with laparoscopy is that it only is able to view the surface and is unable to “get inside.” I became very intrigued with the whole idea of looking inside and using imaging – specifically MRI – to provide planning, guidance, monitoring, and control capabilities for surgery. This advance would ultimately assist in the transition to minimally invasive procedures, which were becoming important in the late ’80s and early ’90s. To my mind, instant visual control is essential to make sure that any surgical procedure is carried out appropriately. No one would advocate doing open surgery with a surgeon who could not see what he was doing; the same should be true of minimally invasive procedures.

About the same time, in 1989, Ferenc gave a famous lecture at GEMS, and interestingly enough, it was the first time that the CEO of Medical Systems, John Trani, actually sat through a scientific lecture. Ferenc pointed out that at the time, unlike with radiology that used computers and advanced software techniques, surgeons were still using basically the same surgical tools that were used by the Egyptians 5,000 years ago, and the whole process depended on the hand-eye coordination of the surgeon.

Ferenc’s point was that it was time for a change!

My imaging background helped me understand the potential importance of imaging in patient management. There were four key places where imaging was important in this process: screening, diagnosis, staging, and therapy. The appropriate imaging could provide improved visualization for minimal access therapy procedures and in this way broaden the role of interventional radiology. This was increasingly desirable, as there were a lot of new therapies beginning to be used in the late ’80s and early ’90s, including:

  • chemoablation techniques
  • brachytherapy
  • interstitial laser therapy
  • radiofrequency ablation
  • cryosurgery, and, on the horizon …
  • focused ultrasound

These approaches were both percutaneous and non-incisional. Hence, imaging had a four-fold role in therapy:

  1. Planning: Better planning and training to reduce procedure time,
  2. Guidance: Improved visualization to increase the potential range for minimally invasive surgery,
  3. Monitoring: Viewing what you are doing in real time, and
  4. Control: It is particularly important to be able to control the new therapies such as the thermal therapies, brachytherapy, and chemoablation.

Ferenc was particularly instrumental in convincing me that the “next big thing” was to use MR to guide, monitor, and control therapy. MR provided superior image guidance, and with the right MR system, it would also provide the ability to monitor and control what was happening in real time.

So … the “next big thing” was image-guided therapy, and I soon became responsible for developing IGT at GE. In figuring out how to do this, I was constantly consulting and “colluding” with Ferenc.

At about that time, in the late 1989-90 period, Peter Jakab and Ferenc came up with a unique concept to perform lithotripsy within an MR system.

Lithotripsy at that time was very primitive and was done without online monitoring of any sort. Peter came up with the concept of placing an array of wires inside a donut-shaped water bag within the MR system around the patient that was parallel to the bore of the MR system. One then sent sharp electrical pulses into the wires, which, since they were inside a static magnetic field, would vibrate (just like the gradient coils vibrate during any MR imaging acquisition). If the wires were pulsed with the correct phasing, a shock wave would be created and focused on the target of interest. Aside from the fact that this system used a shock wave and the application was lithotripsy, this was clearly an ancestor of our current focused ultrasound system. This concept became US Patent #5131392, filed February 13, 1990, and published on July 21, 1992.

Concurrently, in 1988-89, Trifon Laskaris and his colleagues at GE’s R&D Center were developing a novel magnet for an unnamed government agency, which they described as a pair of Hula Hoops! They were using a niobium-tin alloy, which was superconducting at 10 degrees Kelvin, instead of niobium-titanium, which required cooling to 4 degrees Kelvin. The question was whether we could make a magnet using this concept. The first step was to create a feasibility system which eventually was named the IGMIT magnet (right).

This program was not financed by GE, so to get it done we needed to use OPM – “other people’s money.” We were fortunate that, with the help of the GE medical sales team in Toronto and its leader, Joe Sardi, we received funding from the Ontario government in order to build a simple head-only magnet that could be used to perform neurosurgery. The condition was that we had to build two systems – a prototype to be built and installed at the Sunnybrook Health Sciences Centre (left) and a final system for neurosurgery at Toronto Western Hospital.

The configuration turned out to be extremely difficult and expensive to build. In the end, we decided on a simpler configuration for the second system to be installed at Western Hospital. This was to take a standard 0.2T bi-planar magnet that was built by the GE subsidiary, Yokagawa Medical Systems, and turn it 90 degrees. It was sited in a fully equipped neurosurgical operating room at the Toronto Western Hospital. Although the 46-cm gap was not spacious enough for larger patients or surgeons, it did allow surgery to proceed with rapid imaging for guidance and monitoring, as well as controlling the progress of the surgery.

There is an excellent article on this and the topic of interventional magnets by Scott Hinks, Michael Bronskill, Bruce D. Collick, R. Mark Henkelman, Walter Kucharczyk, and Mark Bernstein, who were the key members of the GE, Sunnybrook, and Western teams.

However, this did give us the experience and the impetus to create what was called the Signa SP MR System, and also called the MRT (for MR therapy). But it was usually called the “double donut” from its appearance (right). It took a while to design and build this system, initially mostly done at the GE R&D Center, but in the end, it was completed. The key was that this system enabled the doctor to see what he or she was doing inside the patient while they were doing it.

There were some very unique features to the system. It was a 0.5T system, which allowed flexible patient entry and positioning, with the patient table entering either axially or transversely. It also allowed the patient to be examined while sitting, which enabled the radiologist to see any spinal issues that were not evident with the patient lying down.

This created a lot of excitement, and we made a real splash within GE, even being featured on the cover of GE’s 1994 Annual Report (left).

Ferenc’s enthusiasm was very instrumental in creating this excitement. The first system was delivered to BWH in March 1994, and below is a picture of the team (right) from GE’s Research Center, GE Medical Systems, and BWH that worked together on that first system.

GE teamWhile this intraoperative system did not in itself create the revolution in healthcare that we had hoped for, it definitely led to the creation of MR-guided focused ultrasound, which today is creating a revolution in healthcare.

One of the key issues that we encountered while using the MRT was the difficulty in finding appropriate tools that could work inside a magnet. Most surgical tools were magnetic and could not be used inside a magnetic field. We were on the constant lookout for appropriate new devices that would enable us to deliver therapy in a minimally invasive way, while monitoring the delivery of the therapy using MR temperature imaging.

In the summer of 1990, Ferenc called to tell me that GE had purchased a medical laser company. I said that I was very surprised because I knew nothing about it. It turned out that GE had purchased the majority share in Tungsram, a light bulb company in Budapest, earlier in that year. Apparently, Tungsram had a small medical laser project within a subsidiary company. I was very interested and contacted a number of people within the GE’s Lighting Business, but it took a few months to verify that indeed there was a laser project within Tungsram. It was clear to me that medical lasers would not be a business focus for GE Lighting, and I suggested that we visit the company and see what they were doing before this project was spun off or sold. So we organized a trip to Budapest, for four of us – myself, Ferenc, Dan Castro (a surgeon doing ENT laser surgery at UCLA), and Bill Lotshaw (a laser physicist from GE’s R&D Center).

On our way to Budapest, we stopped at Graz in Austria where the European Laser Association was holding a very large meeting, an important part of which was devoted to the use of lasers in medicine. Lasers had been used primarily for cosmetic purposes in the past, but now the first interstitial uses were surfacing. At this meeting we were joined by Dr. Tividar Lippényi, the managing director of Tungsram Laser Technology Ltd. – the company within Tungsram that we were to visit the next week in Budapest.

The Hungarians had established Tungsram Laser Technology Ltd. in order to facilitate the transfer of knowledge and technology from Israel to the Soviet Union in the field of lasers in the late ’80s. Russia had broken off relations with Israel, and there was no official way for them to talk, so, as the Hungarians told us, the Russians would sit in one room and the Israelis in another room and the Hungarians would act as go-betweens, going from one room to the other. In order to develop some expertise in understanding the questions and the responses, Tungsram initiated these laser programs, which included the medical laser project.

Lippényi met us in Graz on Friday, November 9, 1990, before our planned meeting a few days later in Budapest, because he was very excited about an idea he had for the use of lasers in surgery. He wanted to use lasers to create a hologram of the tumor, using data from CT and MR images. The hologram of the tumor would be superimposed directly on the tumor – this he felt, would be the best possible way to destroy the tumor.

We agreed with him that, if you could do this, it could work. However, we pointed out to him that there was a very big barrier: The tumor was inside the patient’s body and there was no way that we could put a hologram inside the body without destroying the coherence of the light necessary to create the hologram. It was then that Lippényi made a remark I shall always remember. He told us not to worry about this; it was only a “technical” problem. He said that the University of Budapest, where Dennis Gabor had invented holography, had very smart people and they would solve this problem.

We thanked him for the idea and said we would discuss this further when we got to Budapest the next Monday. The four of us then went for a walk along the Mur River, which flows through Graz. Bill Lotshaw said that even though we were laughing at Lippényi’s idea now, he believed that in 200 years we would be able to put a hologram inside the body. This comment triggered a memory in my mind of a friend at the University of Toronto, Kenny Norwich, who was interested in acoustic holography in the ’60s, and I said that I knew how to do that now – we would use acoustic waves instead of light waves to create the hologram.

realview holoscopeIncidentally, it did not take 200 years, but really only 24 years until an Israeli company, RealView Imaging created the Holoscope, which is capable of putting a real hologram (not just augmented reality) inside the body (right).

We all became very excited by this idea as we discussed its feasibility. Ferenc realized within a day that we did not have to make a hologram, but that we could scan with a focused ultrasound beam through the tumor. Although we continued with the visit to Tungsram in Budapest on November 12, and then London on November 13, where we visited Dr. Steve Bown, the leading laser surgeon in England, our mind was on this idea. Our excitement mounted until we returned to the US, where we discovered that focused ultrasound was a technique developed 50 years before by J.G. Lynn and by the Fry brothers (Francis and William). In addition, Lars Leksell and his collaborators attempted unsuccessfully to develop this technique for brain surgery before he created the Gamma Knife. However, our original thought was to do this within an MR system, so this became the beginning of MR-guided focused ultrasound.

We spent 1991 fleshing out the idea. We built five units at GE’s R&D Center (again using OPM) to be put into standard MR systems. The first unit went to BWH about three years later, followed by systems at the Mayo Clinic, Stanford, MD Anderson, and St. Luc in Montreal, Quebec. These were used to ablate benign breast disease as an initial application. The system was very simple; there was a single transducer that directed the focused ultrasound to the spot in the breast that was determined by the MR imaging procedure. MR imaging also served to monitor the temperature change at the focal point and to control the ablation. These initial experiments were quite successful (right).

breast tumorsHowever, GE decided in 1996 that they were no longer going to perform therapy delivery, but only do imaging of the therapy delivery. This was because of a serious accident that occurred in Spain when a radiation therapy system was miscalibrated and resulted in a number of deaths. I was told by the CEO of GE that I had to find a way to move this program out of GE, but that I had to do this in a way that would not disappoint or antagonize BWH, Mayo, Stanford, MD Anderson, and St. Luc – all of whom were key GE customers with significant influence.

This took about two years, and it was very disappointing, but one day at the end of 1997 I received a phone call from Jack Campo, one of the GE lawyers who was negotiating the purchase by GE of the ultrasound imaging company Diasonics Vingmed from Elbit Medical. He told me that the company was interested in therapeutic ultrasound and were planning to work on it, but that GE was not going to buy that portion of the company. I suggested that we sell our program to Elbit Medical, and this happened and became the progenitor of Insightec. At that time, GE also purchased a number of Israeli companies from Elbit, and I was fortunate to be asked to become the director of GE Medical in Israel, so I was able to watch the incredible development and growth of Insightec under the direction of Kobi Vortman and his team.

Insightec grew, and in 2004, it received FDA approval for the treatment of uterine fibroids with the statement by the FDA in their Talk Paper of Oct 22, 2004, that the “FDA expedited review of the device because it offers significant advantages over existing treatments for uterine fibroids.”

But Ferenc did not stop there. In 1996, he and Kullervo Hynynen submitted a patent for the delivery of therapeutic agents through the blood-brain barrier (BBB). This was granted in May of 1998.

By 2005 the initial brain surgery trials were done at BWH. Ferenc kept creating more and more capabilities for doing IGT, including the Advanced Multimodality Image Guided Operating (AMIGO) suite that houses a complete array of advanced imaging equipment and interventional surgical systems for use before, during, and after surgery. He was also instrumental in creating the National Center for Image-Guided Therapy (NCIGT), which is the NIH’s central resource for image-guided therapy. It is now called the Ferenc Jolesz National Center for Image Guided Therapy.

One thing I clearly remember is the Insightec board meeting of November 2014, a month before Ferenc passed away, when he urged the company to forget everything else and concentrate on the brain and opening the BBB.

His passing was a shock to all of us who had been working with him for more than 25 years. But, we cannot say that there will be no one around to take his place. His legacy continues as we can see from these pictures (below) – one of him and one of his grandson, both at age 2½.

Acknowledgements: This blog could not have been completed without the help of Anna Jolesz, Clare Tempany, Ron Kikinis, Nobuhiko Hata, Scot Hinks, Kirby Vosburgh, Joe Sardi, and of course, Dr. Google.

Morry Blumenfeld is President and CEO of Quescon Consultants, Ltd., a medical device consulting company as well as Founding Partner of Meditech Advisors Management, a General Partner in Ziegler Meditech Equity Partners, LP. Having been with GE for over 34 years until 2002, Morry spent the last 27 years of his career with GE Healthcare, the last four of which were spent as Managing Director of GE Medical Systems in Israel. Dr. Blumenfeld earned his B.A.Sc. in Engineering Physics and Ph.D. in Molecular Physics from the University of Toronto.

Read the originial transcription of the talk, which also includes all 40+ images.