Image of the Month

Magnetization transfer imaging (MTI) assays macromolecular protons through their intimate connection and interaction with surrounding tissue water.

“Anywhere it's applied, MTI is very sensitive to macromolecular makeup of the tissue,” said Seth Smith, Ph.D., a postdoctoral fellow at the F.M. Kirby Imaging Center at Johns Hopkins University in Baltimore. In the case of patients with multiple sclerosis (MS), this means myelin. “MTI is a much more sensitive myelin marker than any other conventional imaging technique,” he said.

Conventional MRI targets only water, making it hard to assess the macromolecular subunits of CNS tissue, like myelin. With MTI, an initial off-resonance radiofrequency pulse is applied to the spinal column. This pulse selectively saturates the magnetization of protons attached to such macromolecules as myelin. Some of this magnetization is transferred to free protons in tissue, which reduces the intensity of the observed water signal. Since MT's effect depends on the density of macromolecules in the tissue, “it's a backdoor method for getting at the macromolecular structure,” said Dr. Smith.

The researchers then calculate a slightly modified magnetization transfer ratio, based on the difference in the signal intensity with and without an MT prepulse, to quantify differences between patients with MS and healthy controls.

In the past, it was difficult to ascertain whether or not spinal cord lesions were a significant factor in MS. Conventional MR imaging did not reveal the amount of tissue damage that was actually present in the spinal cord, though inflammation can be seen. MTI reveals much more MS pathology. It is now hypothesized that a lot of the clinical deficit in MS arises from spinal cord damage. “When we use MT imaging, what we find is that every cord [from patients with MS] is damaged in some way,” said Dr. Smith.

The presence of MS spinal lesions on MTI correlates better with the patient's symptoms at presentation than does the presence of brain lesions detected by MRI. A patient with MS brain lesions may be walking at presentation. However, “if I look at the spinal cord and see a bunch of lesions, I can guarantee that the patient is not walking well,” said Dr. Smith.

The researchers have imaged patients of varying ages and at a spectrum of stages in MS: relapsing-remitting, secondary progressive, etc. Since it is difficult to get a patient before he or she has had an attack, information from such studies about the early stages of the disease may prove useful, said Dr. Smith. The researchers also are imaging MS patients periodically (3, 6, 12, and 24 months) to see if they can detect changes in the disease over time.

The researchers are seeking links between MS-induced changes on spinal MTI and brain MTI and the neurologic presentation of patients with MS. The correlation between spinal MTI and the neurologic presentation has been striking.

“We and others find in the brain there is little correlation with clinical presentation. However, the second we look at the spine, everything starts to correlate,” said Dr. Smith. The spine is the main pipeline for nerves in the body, so “if you get a small lesion in something the size of a quarter, the effects could be massive.”

MRI is used to confirm the clinical findings in patients suspected of MS. “We're hoping to make MTI more of a diagnostic tool,” Dr. Smith said. A strong enough correlation between MTI spinal imaging findings and the neurologic presentation could lead to the primary use of MRI to diagnose MS and predict outcome.

MTI also has implications for therapy. Right now, patients with MS often are treated with axonal protection agents, but the effects may take a long time to be seen. “What we hope to see is, can we within a shorter amount of time see that there is any sort of change in the tissue due to therapeutic intervention,” said Dr. Smith.

MTI scans can be done with most higher field MRI scanners using a surface/spine coil and each scan takes only 7 minutes using a 3T magnet. This implies that the technique could easily be integrated into an imaging center or hospital radiology department.

Dr. Smith's collaborators include Dr. Peter Calabresi; Peter van Zijl, Ph.D.; Craig Jones, Ph.D.; Eliza Gordon-Lipkin; and Kathleen Zackowski, Ph.D.

Healthy spine by T2 and T1 3T MRI and MTCSF (top): While T2 and T1 MRI show slight cord atrophy in an MS patient, MTCSF shows hyperintensities in the lateral (green arrow) and dorsal (yellow arrow) column (bottom). Images courtesy Dr. Seth Smith