RSNA News - October 2004

Scientists Reach Important Milestone in Nanoscale MR Research

To get to the dream of 3D molecular imaging, we need to improve the sensitivity of the technique so that we can see individual protons.
— Daniel Rugar, Ph.D.

Using magnetic resonance technology 10 million times more sensitive than medical MR imaging devices, scientists can detect the faint magnetic signal from a single electron buried inside a solid sample. This discovery is an important step in the quest to achieve three-dimensional imaging of the atomic structure of molecules.

The technique, developed at IBM's Almaden Research Center in San Jose, Calif., is called MR force microscopy (MRFM). It shares some characteristics with MR imaging, but uses a very different type of sensor.

"MR imaging is a very powerful technique because it can look below surfaces and view three-dimensional structures," says Daniel Rugar, Ph.D., manager of nanoscale studies at IBM. "The one disadvantage with MR imaging is that it takes around a million trillion protons in order to generate a detectable signal. Thus each pixel, or voxel, in an MR image requires this very large number of hydrogen atoms. Because so many hydrogen atoms are required, spatial resolution is limited."

Even the most specialized MR microscopes require at least a trillion protons, he says, which limits the spatial resolution to about one micrometer.

Dr. Rugar's team is trying to overcome this sensitivity limitation. They eventually hope to be able to detect an individual proton, which would open up the possibility that an MR imaging-like technique could someday be able to display 3D images of the atomic structure of molecules.

The detection of the magnetic signal from an individual electron spin is an important intermediate milestone. "Spin" is a term physicists often use to refer to the fundamental magnetism of individual atomic particles, such as protons or electrons. An electron spin is easier to detect than a proton spin because the magnetism of an electron is about 650 times larger than the magnetism of a proton.

The key to this detection is the development of a much more sensitive method to detect the weak magnetic signal. "Instead of using a coil to detect a voltage induced by the motion of the spin, we use detection based on magnetic force," says Dr. Rugar.

"Our apparatus uses a tiny, nanoscopic bar magnet—the magnetic tip—mounted on a microscopic cantilever. The cantilever is like a tiny silicon diving board and is responsive to the very small magnetic force that is exerted by the electron on the magnetic tip," he explains. "To see the signal, we vibrate the tip and use a high frequency magnetic field, much like MR imaging, to manipulate the magnetic orientation of the electron."

As the electron flips back and forth in orientation, the magnetic force on the cantilever flips between attraction and repulsion. The net result is that the vibration frequency of the cantilever changes slightly, about one part per million.

"To get to the dream of 3D molecular imaging, we need to improve the sensitivity of the technique so that we can see individual protons," says Dr. Rugar. "To image the positions of hydrogen atoms within a biomolecule will require at least 650 times improvement in sensitivity."

He says his team is also trying to further improve spatial resolution. "While our current 25 nm spatial resolution is 40 times better than the best MR image, it is still a factor of 250 from being able to resolve individual atoms in a molecule."

IBM Almaden's MRFM Research Team

(left to right) Raffi Budakian, John Mamin, Dan Rugar, Ph.D., and Benjamin Chui (not shown) developed and used the MR force microscope to detect the magnetic signal from a single electron. Image courtesy of IBM More photos

Medical Implications

Thomas R. McCauley, M.D., a private practitioner who is also an assistant clinical professor of diagnostic radiology at the Yale School of Medicine, suggests the IBM breakthrough may be a potentially important advance as a research technique for analysis of the microscopic structure of samples. "Possible changes in the technique allowing application to human imaging are always possible," he says, reflecting upon the fact that MR analysis of samples occurred decades before MR imaging of humans.

William G. Bradley Jr., M.D., Ph.D., professor and chairman of the Department of Radiology at the University of California-San Diego Medical Center, sees potential for the new technique. "Right now, I think it's going to have applications in basic chemistry—showing the structure of proteins," he says. "This may reveal certain molecular structures in a way that's never been possible before and that could conceivably help us in design of new molecular therapies."

More information on MRFM is available at www.research.ibm.com/resources/news/20040714_nanoscale.shtml. The new development is also detailed in the July 15 issue of the journal Nature (Vol. 430 No. 6997 p. 300).