The Importance of Quality Imaging

Your three-year-old daughter is deaf. The surgeon explains that a cochlear implant could help her hear again providing the ear's nerve is intact. But the only way to examine the nerve is during surgery. Should you expose your little girl to the risks of major surgery when the nerve damage may be too severe to warrant an implant?

The physicists and physicians in Mayo Clinic's Magnetic Resonance (MR) Research Laboratory hold the key to solving your dilemma. In collaboration with clinical radiologists, they are developing biotechnology that can picture the cochlear nerve in such fine detail that radiologists can evaluate it without your daughter feeling so much as a pin prick.

The project is one of many undertaken by the Department of Radiology's MR Research Lab - a small lab of six investigators that has earned an international reputation for its heady success. The lab consistently applies the physics of magnetic fields and radio waves to invent cutting edge technology - technology that produces safer ways for physicians to see inside the body. Their inventions have been incorporated into every MR scanner and are used to help millions of people all over the world. It is an exciting lab in a dynamic field.

"Our research allows radiologists to diagnose diseases more easily and with greater patient safety and convenience," says Stephen Riederer, Ph.D., Director of the MR lab. "We are finding new ways to use imaging every day."

Spatial Presaturation: An Early Invention to Reduce Interference

When Richard Ehman, M.D., a radiologist, and Joel Felmlee, Ph.D., a medical physicist and biomedical engineer, began their careers they were attracted to Mayo because of its willingness to provide state-of-the-art biotechnology tools.

"In 1983, Mayo purchased the second clinical MRI (Magnetic Resonance Imaging) magnet in the U.S.," says Dr. Ehman. "I was fortunate to start my career when MRI was just being introduced into practice and the basic physics was not well understood."

MRI scanners create a magnetic field around the part of the body to be examined and also send and receive radio waves from gradient coils. A computer processes the way the body responds to these forces to produce the image. Early technology required an extended acquisition time to produce a useful picture. That was a problem because it also increased the amount of artifact, or interference, caused by the motion of blood in the vessels. Drs. Ehman and Felmlee solved the problem in the mid 1980s when they invented a technique, called spatial presaturation, which is now incorporated in every MR scanner produced.

"It was the first time an academic site offered a solution to the vendor to improve their product," says Dr. Felmlee. "What's exciting to me is that our invention is used to help more than a million patients every week all over the world."

Adaptive Motion Correction and Navigator Echoes

Dr. Ehman's interest in motion artifact also led to his invention of the adaptive motion correction, which is now used to identify problems in musculoskeletal structures such as rotator cuff injuries.

The technique involves generation of special signals, called Navigator Echoes, which monitor an object's position as it moves during data acquisition. The information is then corrected to make the image look static.

"It's similar to moving the frame of reference around an object as it moves," explains Dr. Ehman. "It's a concept that has led to many other projects, both in our lab and around the world."

One example is collaboration with Armando Manduca, Ph.D., co-director of the Biomathematics Resource. Dr Manduca is a mathematician who is using navigator echoes to develop algorithms that organize random computerized corrections into an automatic motion correction system.

Inventing a Safer Carotid Angiography Test—MRA

Dr. Riederer focuses his research on magnetic resonance angiography (MRA), the imaging of blood vessels with MRI. By 1998, he had perfected his invention, the elliptical centric contrast-enhanced MRA, to a level of image clarity that rivaled conventional x-ray angiography. The technique was so successful that surgeons were clamoring to use the test routinely even before clinical studies were complete. The technology is now implemented worldwide by all MRI vendors. MRA is a much safer, more convenient, and less expensive test than x-ray angiography.

Angiography is used to determine abnormalities in the blood vessels such as atherosclerotic disease and aneurysms. During X-ray angiography, a catheter is inserted in an artery in the groin and threaded up to the carotid artery. The procedure is associated with the risk of stroke, which can occur if the catheter dislodges a fat plaque that then settles in a smaller vessel and blocks blood supply to part of the brain. Additional risks include bleeding problems and allergic reactions to iodine contrast dye. In MRA, radiologists place the catheter in a vein rather than an artery, and use a contrast dye that rarely causes allergic reaction.

Most MRAs take less than an hour and patients can return to their normal activities immediately. Patients having x-ray angiography must fast the night before the test, remain flat for several hours afterward, and limit their activities for the rest of the day.

"We offered the technology to our patients at least two years before it was available anywhere else," says John Huston, M.D., a neuroradiologist who collaborated with Dr. Riederer and Matthew Bernstein, Ph.D., a medical physicist and biomedical engineer who is also a member of the MR Research Lab. "Being able to work with brilliant basic scientists like Drs. Riederer and Bernstein to bring state-of-the-art biotechnology directly to patient care is what I find exciting about working at Mayo."

Collaboration for this project between Drs. Bernstein and Huston began in 1989. With Dr. Riederer's leadership, the team developed a variety of techniques to produce clearer images and to decrease the acquisition time - the time it takes to scan. There were many challenges.

"The depth of MRI physics required to produce accurate 3-D images of the blood vessels presents a significant challenge," says Dr. Riederer. "The novel aspect that we developed is the ability to get very high resolution scans that demand 40-second acquisition times, yet have immunity to venous signals."

The spatial detail and accuracy of images is generally proportional to the length of the scan. It takes 40-50 seconds to produce the high quality, 3-D images that show plaque in the vessels. But after five seconds, the view of the artery is often blocked by contrast flowing into companion veins. By using his understanding of how physics forms MR images, Dr. Riederer was able to adapt the ordering of the data and make the additional 35-45 seconds of acquisition time useful.

Pioneering Clinical 3T MRI Scanning

The strength of a magnet is measured in Tesla. A 1.5 Tesla magnet is about 30,000 times stronger than the Earth's magnetic field. 1.5 Tesla scanners are typically used in clinical practice. 3.0 Tesla scanners double that field strength - and that means a much higher potential for achieving higher resolution images.

When Mayo installed a 3T scanner in 1999, it was intended solely for use as a research tool - as were all 3T scanners at that time. Mayo's hallmark is teamwork. And Mayo brought together the people with the skills to make our medical center one of the pioneers of clinical 3T imaging. Mayo's 3T clinical practice is now well established - more than 7000 patient exams have been performed.

Dr. Huston and Clifford Jack, M.D., an MRI investigator and the Department of Radiology Research Chair, envisioned using the more powerful magnet to produce higher resolutions that can detect aneurysms and narrowing of the blood vessels within the brain.

After three months of intensive development, Mayo began using 3T scanning for standard patient care. Dr. Bernstein developed the technology to convert the 1.5T data acquisition software to 3T. He collaborated with Drs. Huston and Felmlee to write the necessary code. And Dr. Felmlee worked on designing radio-frequency receiver coils to fit the anatomy of the body parts they planned to scan.

"We are not a big lab but we are effective because we focus on clinical problems," says Dr. Felmlee. "And there aren't many places that have the ability to control the whole process - from how the imager operates, to reconstructing data, to building receiver coils - the way we do."

The MR lab is expanding 3T imaging technology to detect musculoskeletal problems in the cervical spine, wrists and hands. Additional novel clinical applications for high field MRI include:

• High spatial resolution MR angiography—Dr. Bernstein is developing a new motion correction method to salvage MRA exams made unreadable by the motion of patients disoriented by stroke.
• Real-time scans—Dr. Riederer and his colleagues are now taking the MRA techniques they developed to perform full-body scans that pinpoint problems in vessels of patients with peripheral vascular disease and other circulation problems. The technique also is being applied to abdominal, cardiovascular and neurological imaging.
• Measuring Cardiac Function—Kiaran McGee, Ph.D., another biomedical engineer in the MR lab, collaborates with Thoralf M. Sundt, III, M.D., a surgeon in Cardiovascular Surgery, to assess cardiac function analysis using 3T MRI.

Focusing Tumor Destruction: Interventional MRI

Drs. Riederer, Ehman, and Felmlee, collaborate with James Greenleaf, Ph.D., Director of the Ultrasound Research Laboratory, and member of the Department of Physiology and Biomedical Engineering, on refining the use of MRI to guide an ultrasound therapy that destroys tumors.

"I focus on developing methods that identify where to direct the therapy and exactly when to stop it," says Dr. Felmlee. "Currently, we do that by gauging the temperature but we are working on developing a new technique, called MR elastography, which we think will be more accurate."

Dr. Felmlee is pleased that earlier collaboration with Bradley Lewis, M.D, on a technique to treat breast cancer evolved into another successful collaboration with Bobbie Gostout, M.D., a gynecologic surgeon and faculty member of the Tumor Biology Program in the Mayo Graduate School, and clinical radiologists Kathleen Brandt, M.D., and Gina Hesley, M.D.; on a clinical trial that uses the technology to treat uterine fibroids.

Measuring the Progression of Alzheimer's Disease with MRI

Dr. Jack collaborates closely with the Alzheimer's Disease Research Center (ADRC), to develop and validate new MRI tests that will provide earlier diagnosis and differential diagnosis from other causes of dementia. Currently, the diagnosis of Alzheimer's Disease (AD) is an unreliable process of elimination.

The fact that the NIH has continuously funded the development of the Alzheimer's Disease Patient Registry speaks volumes about the importance of this research. Together with Ronald Petersen, M.D., Ph.D., director of the ADRC, Dr. Jack is conducting serial imaging studies to track the progression of AD. Dr. Jack is developing new MRI techniques to do that by measuring brain volume and by assessing metabolite production (spectroscopic MRI). In a related study, Dr. Jack collaborates with Joseph Poduslo, Ph.D., Director of the Molecular Neurobiology Laboratory and member of the Department of Biochemistry and Molecular Biology, on developing an MRI contrast agent that can identify amyloid plaques. They perform weekly studies of transgenic mice using the powerful 9.4T magnet at the University of Minnesota.

MR Elastography: Using MRI Physics to "Feel" Abnormal Tissue

In 1995, Dr. Ehman's studies on elastography, the use of MRI to distinguish materials based on their mechanical properties, were published in Science - a highly respected peer-reviewed scientific journal. He came up with the idea for elastography by considering which property of tissue would be the most valuable to image. He decided on the mechanical property of tissue because of the importance of palpation in diagnosing disease.

"Every physical exam includes palpation," says Dr. Ehman. "Surgeons still discover tumors in the operating room just by feeling their stiffness compared to surrounding tissue. These are tumors that were undetected by state-of-the-art imaging technology. We are optimistic that elastography can change that."

The technique will be valuable in a variety of fields. For example, surgery stimulation programs that train surgeons virtually, would be greatly improved if the consistency of various tissues was known. The MR lab is currently exploring the following elastography projects:

Breast Cancer—Dr. Ehman is collaborating with Lynn Hartmann, M.D., a breast cancer specialist in the Mayo Clinic Cancer Center. Their preliminary study, demonstrating the feasibility of detecting breast cancer with elastography, was published in 2002 (AJR:178, June 2002, 1441-1417). They are now working on distinguishing benign and cancerous tumors by improving the specificity of the technique.

• Brain Injury—Dr. Felmlee conceived of the idea to gently shake the head to produce mechanical waves that propagate through the brain. The team then developed a technique to produce the first images that show stiffness of the brain. This technique has application in diagnosing head injury, and in designing helmets and protective devices in automobiles.
• Alzheimer's Disease—Dr. Ehman hypothesizes that the accumulation of beta amyloid plaques in the brain of patients with Alzheimer's Disease causes increased stiffness. The hope is to develop elastography techniques that can detect Alzheimer's Disease at an early stage.
• Musculoskeletal Disease—Dr. Ehman collaborates with Kai An, Ph.D., Co-director of the Biomechanics and Motion Analysis Lab, on measuring the stiffness of muscle to non-invasively study the tension of muscle in normal and disease states.

How Mayo Supports the MRI Lab

The MR lab was established in 1988 with a major funding initiative from Mayo. Subsequent support included installation of the 1.5 Tesla MR research scanner that is shared by the seven MR researchers for a variety of projects. In addition, Mayo has 18 MRI machines for use in the clinical setting that are also used in clinical trials to test new techniques. One of those is the 3-T scanner, purchased in 1999. A second, more compact and quieter 3-T scanner will be installed by the end of 2003.

Each of the researchers is supported by NIH grants. And, thanks to our generous benefactors, Mayo supplements their funding in a variety of ways—through Mayo Graduate School, for example, which supports the graduate students who accomplish much of the work necessary to test new techniques. The school's Biomedical Engineering Program collaborates with investigators in the MR lab to training the next generation of biomedical engineers in medical imaging.