What Lies Beneath

With around 70,000 admissions per year, 350,000 outpatient visits, 1300 hospital beds and an employee count totaling 28,000 people, Johns Hopkins Medicine is a busy place to work.The department of radiology is no exception, with over 160 faculty members carrying out 550,000 clinical examinations per year. Its research mission is also huge, with $28 million in research projects carried out each year in a bid to discover and deliver world-class solutions and treatments in the area of radiology.

“On the faculty side, we are roughly evenly split between doing research and clinical work in terms of our sources of revenue and our mission,” highlights Jonathan Lewin, Radiologist-in-Chief at the hospital. “The teaching mission is also very strong, both on the clinical side, where we have about 40 residents and around 45 clinical fellows; and on the research side, where we have similar numbers of post-doctoral fellows and graduate students in a number of different areas.”

One of the most innovative focus areas at the department is the use of magnetic resonance imaging and spectroscopy to actively – or interactively – guide and monitor minimally invasive interventions in the body. In the mid-1990s Lewin started trying to develop the hardware and software to enable radiologists and other physicians to use this technology for this type of procedure guidance.

“We began developing the technology for simple procedures, like biopsies, abscess drainage and other needle-directed procedures,” says Lewin. “We then moved on to develop the technology to use MRI to guide ablation procedures for cancer treatment, primarily, using radio frequency ablation and laser ablation. Next we moved into intraoperative MRI, creating the techniques to allow neurosurgeons to use MRI in the operating room. We started with our actual procedures in 1995, doing the first MR-guided radio frequency ablation in early 1996 and our first neurosurgical procedures under MRI guidance in early 1997.”

Lewin describes how much of the work that he did in his former lab at Case Western Reserve University was done with very close collaboration with Siemens Medical Systems. In fact, some early industrial grants from Siemens were very helpful in developing some of the core technologies for using MRI for interventional procedure guidance. Along with this, the hospital was also given critical funding from the Whitaker Foundation with a large special opportunities grant. With significant grant funding for the National Institutes of Health, they were able to move procedures forward.

“Our goal in my former research group was to translate the technology from the computer simulation through animal models and into the clinical realm,” recalls Lewin. “We were very quick to move into patient studies. We did over 500 patients in our first four or five years of interventional MRI work, trying to very quickly create clinically feasible techniques and technologies to work in the clinical realm.”

“When I came to Hopkins, there was already a vibrant interventional MRI program that had been developed with close collaborations with General Electric. There had been a large number of cutting edge and pioneering projects in cardiovascular MR intervention. Over the past few years, industrial grants from both Siemens and Phillips have been critical in development of new technologies at Johns Hopkins, in particular for device tracking and imaging for intravascular devices, as well as the development of new devices for stem cell implantation, islet cell transplantation and other intravascular procedures.”

In addition, the team is also setting up an interventional imaging infrastructure that combines and fuses MR images with X-ray angiography and rotational flat panel-computed tomography with fusion of different imaging modalities within a single imaging suite – all carried out in collaboration with Siemens corporate research.

Assessing the risk

Some believe the MRI process carries certain risks from imaging agents, such as gadolinium, while the potential long-term impact of the magnetic fields has only recently come to light. Lewin, however, thinks the risk of MRI in the greater scheme of things is extremely low, compared to almost any other medical intervention. “Although there are significant risks from gadolinium in a population of patients with severe renal failure, since this has become evident, and since we started to screen for renal function in every patient prior to receiving gadolinium contrast agents, this risk has been almost entirely eliminated. The patients who have been harmed in the past were harmed because this was an unrecognized risk. Now that the risk has been recognized, it can be markedly reduced and eliminated. I don’t think it is a reason for any patient to avoid an MRI study.”

The long-term risks of radio frequency, as well as the risks of the magnetic fields, are also well understood and can be minimized, according to Lewin. For those patients who are getting magnetic resonance imaging studies, or magnetic resonance spectroscopy for clinical work, the risk is really negligible. “I don’t believe that it should preclude imaging for any patient as long as there’s proper screening to make sure there are no implanted devices for which that would be a problem.”

However, for intervention, there is a more complicated scenario since radiologists, surgeons and other medical personnel working within an MRI environment are exposed to much longer duration magnetic fields and radiofrequency than are the patients. “Patients typically will have a relatively short procedure, then they’re out of the magnet, and they’re off recovering. For the medical personnel, those risks need to be well understood and well monitored. Current data shows no evidence of risk to the medical personnel given the amounts of exposure that they’re currently undergoing.”

Neuroradiology and biomedical engineering

Many of the challenges in neuroradiology, biomedical engineering and imaging research in general are very similar, being related to issues of adoption of new technologies into the clinical workflow as well as the costs involved with translating basic research into the clinical realm. “Much of our biomedical engineering work has been done in device development,” says Lewin. “We’re inventing and creating new devices to allow interventional MRI procedures to move forward. These include new types of needles, new types of catheters, and other devices that can go inside the body in an MRI environment for intervention. While we’re able to develop devices that can be used in experimental models at a relatively low cost in the US, the barriers that the Federal Drug Administration puts in front of new technologies makes it extremely costly to take a technology and translate it into the clinical realm.”

“Things like catheters and other devices that are necessary for physicians to use interventional MR in a widely disseminated clinical manner are very difficult to make available. The costs associated with getting all the approvals that are necessary make the larger manufacturing firms hesitant to invest in a new field, or a disruptive technology such as interventional MRI, while the small companies that do make these innovations don’t necessarily have the capital to bring these devices all the way through the clinical regulatory process to full approval.

“Many of the impediments are the regulatory barriers of getting a device into the clinical realm when you have a new or disruptive technology. The same can be seen in molecular imaging where the problems are even higher. For example, a new molecular imaging agent may cost anywhere up to $100 million or $200 million to get through all of the regulatory barriers from development and proof of feasibility through full clinical approval.”

Lewin anticipates that the molecular imaging and personalized medicine market is going to be a major challenge since these are aimed at a smaller number of patients with specific genomic or proteomic profiles. Therefore, the market may never pay back a company that has made an investment into getting approval for some of these new agents. “This is one of the major challenges in some of the new neuroradiology agents that we’re developing here at Johns Hopkins. Cancer molecular imaging agents and even cardiovascular molecular imaging agents for the ultimate market may have tremendous clinical benefits for our patients, but the financial challenges to get to a fully approved clinically available agent are very high.”

On the horizon

Since Lewin arrived at John Hopkins in 2004, the faculty has seen a 40% growth in its size, a 15% growth in its research funding and a 20% growth in its clinical volumes and clinical revenue. Other achievements include an updating of the clinical and research infrastructure, with 13 MRIs installed, along with eight CT systems, eight angio systems and two PET systems, as well as a number of small animal imaging systems and other research equipment.

“During the past four years, we’ve had a marked renovation and update in our clinical and research infrastructure,” says Lewin. “Over the next five years, we would like to see growth continue in targeted areas. In particular, I see us continuing to innovate and grow in our image-guided interventional programs where we’re looking at using not only anatomic imaging information, but also functional and physiological information to guide our minimally invasive interventions.”

Lewin envisions the institution continuing to innovate in developing new types of minimally invasive or noninvasive intervention for therapy, and in advancing molecular imaging techniques to create more personalized medicine approaches, both for the diagnosis and treatment of a number of diseases in cancer, cardiovascular and neurological areas, in particular.

He concludes that, “As medicine and medical research have evolved, it is clear that imaging has become central to the research translation and clinical application of almost every branch of medicine. In many ways, imaging has become the eyes of the physician and the eyes of the researcher. Because of this, radiology and radiological sciences has really become a core to many of the disciplines in biomedical research.

“The need to keep radiology departments and imaging sciences extremely strong has become even more important in this decade and will continue over the coming years ­– just as robotics and other minimally invasive technologies are becoming the hands of the physician, imaging is more and more often becoming the eyes of the physician. The computer processes that we develop become many of the brains of intervention, and the role of imaging becomes even more and more important.”