Small Molecule Imaging
Ultrahigh field magnetic resonance spectroscopy (MRS) is one of those new techniques that is yielding higher resolution images, higher signal-to-noise ratios, and, sometimes, greater speed.
“Ultrahigh fields for magnetic resonance are being used to target molecules other than water,” explains Jullie Pan, M.D., Ph.D., associate professor of neurosurgery at Yale University. We can now image biochemically important molecules such as lactate, glutamate, and GABA with an imaging resolution that is informative and pertinent to living tissue. Ultrahigh field MRS gives researchers a new slant on what they are looking at, how aggressive a tumor is, whether it’s necrotic or proliferative, et cetera,” she elaborates.
Her lab has had success using ultrahigh field MRS to study brain tumors and epilepsy. “The latter condition works with patients who are mainly MRI-negative but who are clearly suffering from a focal brain disease,” she notes.
“The developments and implementation of ultrahigh field MRS imaging opens a distinctively functional and metabolic avenue to imaging the brain, with resolution comparable to that of a PET scan without the issue of radioactivity, which limits repeatability. There also is long-standing research interest in using MRS imaging to study muscle, liver, prostate, and other cancers.”
In the 1990s, Dr. Pan says, typical field strength for human imaging was 1.5 Tesla. In fact, “whether 1.5 Tesla was the optimum field strength was being debated.” Now, the preferred clinical imaging field strength for the human brain is 3 Tesla. However, at higher field strengths, “the size of the human body is closer to the wavelength of the radiofrequency signal at 7 Tesla,” so the detector technology to optimally generate and detect the signals has had to evolve.
“For even higher magnetic fields such as 9.4 and 11.7 Tesla (which exist for human application), this area of work will continue. It’s a long road.” Nonetheless, while technical difficulties of detectors, homogeneity, and relaxation are major challenges, effective approaches are being developed, opening the way to take advantage of the ultrahigh field’s higher signal-to-noise ratio for imaging of anatomy and biochemistry in human study.
At the A. I. Virtanen Institute, University of Eastern Finland, Olli Gröhn, Ph.D., professor of biomedical NMR, is investigating the application of spin-lock MRI contrast in vivo. “T1p, one of the spin-lock MRI contrasts, is currently used mainly for cartilage MRI. However, spin-lock contrasts seem to be more sensitive to tissue changes associated with cell death than conventional MRI.”
During the next several years, he believes that applications of spin-lock MRI will expand to more neurological applications and are likely to include imaging for Parkinson disease and stroke as well as monitoring tumor treatment responses, “especially glioma gene therapy,” he predicts. Already, researchers have successfully demonstrated the utility of spin-lock MRI contrast in these applications in clinical settings.
In earlier work, Dr. Gröhn and colleagues found ways to adjust the sensitivity of that technique. While investigating tissue changes associated with hyperacute stroke, he and researchers from the University of Eastern Finland (formerly the University of Kuopio), the University of Minnesota, Kuopio University Hospital in Finland, and Dartmouth Medical School, determined that the sensitivity of spin-lock MRI contrast could be modified by varying the spin-lock preparation blocks.
Traditionally, acute ischemia lesions have been predicted by their diffusion-perfusion mismatch. Dr. Gröhn and his collaborators, however, determined that using longitudinal relaxation time in the rotating frame obtained by on-resonance continuous wave spin-lock MRI “predicts the tissue outcome in the acute phase when therapies based on clot removal and/or neuroprotection are most likely to be beneficial.”
The limiting factor for the spin-lock MRI contrast technique seems to be the high specific absorption rate (SAR) of energy, which may cause tissue heating. This is a particular concern when tissues within the brain are involved, he points out. That, therefore, is why clinical applications have so far concentrated on monitoring conditions outside the brain.
“Areas outside the brain are easier, as SAR limits are higher,” Dr. Gröhn says. Despite that limitation, he and other researchers have used spin-lock techniques successfully for human brain imaging, allowing researchers to assess slow molecular motions that have an extended range of correlation times.