New Studies Show Potential for Dramatically Improved MR

The future of MR imaging may be dramatically improved images and more flexibility in how patients are imaged, new studies indicate.

Contrast Agent Increases Tumor Definition

Kristina Djanashvili, Ph.D. Delft University of Technology, The Netherlands

Philip J. Grandinetti, Ph.D. The Ohio State University

In a study at Delft University of Technology in The Netherlands, a postgraduate researcher has developed a phenylbononate-containing substance that, acting as a contrast agent, does a superb job of defining tumors in mice.

Kristina Djanashvili, Ph.D., recently received her doctorate in organic chemistry and has worked on this research for a few years. She conducted synthetic studies, chemo-physical studies, in vitro cell work to prove the principle and finally the first in vivo studies. She worked with her supervisor, Joop A. Peters, Ph.D., on sugar chemistry and its ability to bind with boronates.

Dr. Djanashvili said the new contrast agent incorporates a lanthanide chelate and a member of the phenylboronate group. The lanthanide chelate makes sure there is a strong and clear MR imaging signal by influencing the behavior of water molecules even inside the human body, leading to water exchange between lanthanide chelate and hydrogen nuclei. The more hydrogen nuclei affected, the better the MR imaging signal. Meanwhile, the phenylboronate group seeks out sialic acid that concentrates on the surface of tumor cells.

The main problem with the new contrast agent, said Dr. Djanashvili, is its propensity to bind with other blood sugars like glucose and to erythrocytes, which also contain sialic acid. The newest research in this area is aimed at overcoming this problem by developing a suitable protection, like liposomes, for the agent until it reaches the tumor site.

"There is still a long way to go until human testing can begin," she said. "Of course the efficiency of the agent is very important but more important is the biostability and safe clearance of the agent from the body."

The Superadiabatic Process The gray path is the magnetic field along the center sphere from North Pole to South Pole as it drags the nuclei to align them in the direction of the magnetic field. Researcher Philip J. Grandinetti, Ph.D., explained that in the sphere on the left, the magnetic field moves infinitely slowly (adiabatic process). On the right, it's too fast (non-adiabatic process). The one in the middle is just right (superadiabatic process). Image courtesy of Gwendal Kervern, The Ohio State University

The new contrast agent won't be turning up in imaging clinics for a couple of years, said Dr. Djanashvili, "but our study demonstrates that molecular recognition of cancer by boronate-containing agents is an extremely interesting approach. We hope that our future work will prove it with new results."

Dr. Djanashvili's research is very exciting, said Martin R. Prince, M.D., Ph.D. "I eagerly await further results," said Dr. Prince, a professor of radiology at Cornell University and chief of MR at New York Hospital. Dr. Prince presided over a scientific paper session in vascular and interventional MR at RSNA 2008.

It makes sense to invest in contrast agent research, said Dr. Prince, noting a trend within the MR imaging research community toward targeted imaging agents with unique biodistribution, versus the one-size fits all approach of current gadolinium-based contrast agents. "MR imaging will become more like nuclear medicine, with many unique imaging agents," he said. "A more molecular approach will "make things more complicated on one hand, but we'll be better able to pinpoint tumors and other pathology more accurately on the other."

Algorithm Improves MR Speed, Images

Another study by researchers in the U.S. and France could potentially help scientists find ways to use MR imaging without putting patients inside magnets. The study, published recently in the Journal of Chemical Physics, reveals a mathematic algorithm that could lead to faster and better MR images and more information.

Philip J. Grandinetti, Ph.D., a professor of chemistry at The Ohio State University, explained that one way to do MR is with the adiabatic process, in which magnetization is slowly moved around a patient to generate an image.

Dr. Grandinetti described adiabaticity as carrying a bowl of soup from the kitchen to the dining room without disturbing the surface—one must use tiny steps the entire way.

Dr. Grandinetti and colleagues at France's National Center for Scientific Research and the University of Lyon looked at superadiabaticity, which occurs during smooth acceleration and deceleration, moving magnetization at a finite rate.

Using the soup analogy for superadiabaticity, Dr. Grandinetti said one starts in the kitchen with tiny steps, gradually increasing the step size to a maximum speed and then gradually decreasing the step size back to tiny steps before stopping at the dining room table, again without disturbing the surface of the soup. Every movement would be in perfect order to get the soup between the kitchen and dining room.

The researchers knew that adiabaticity worked faster but, until now, they didn't understand why. The theoretical picture didn't describe the process properly, said Dr. Grandinetti, because the math algorithm used for years was incomplete. "We now have the proper equation," he said.

With the proper quantum mechanics equation, Dr. Grandinetti said new methods can be designed that are faster and with less image loss. For example, one-sided magnets could be placed under an exam table, he said. "That may be possible in about 20 years and now we are on the right path to figure it out," he said.

Dr. Prince greeted this research enthusiastically as well. "This is the great thing about MR imaging," he said. "Further insights are emerging on how technology works and how to make it better. Sometimes we hear talk of a 'brick wall' in imaging. Then something like this study appears and it smashes that brick wall."