CHICAGO – With the use of a new method that provides objective and specific measurement of iron deposition in brain tissue in vivo, investigators have been able to quantify the increased iron accumulation in the deep gray matter of patients with multiple sclerosis.
The iron accumulation was positively correlated with both lesion load and neuropsychological test performance, according to Dr. Yulin Ge, who presented his findings at the annual meeting of the American Society of Neuroradiology.
The reason why iron has accumulated in these regions “is probably because the axons are transected by the MS lesions, interrupting iron outflow from iron-rich deep gray matter nuclei to projected cortical sites,” he said.
Dr. Ge's work was awarded the 2007 ASNR Cornelius G. Dyke Memorial Award for excellence in original, unpublished research in neuroradiology.
Using magnetic field correlation (MFC) imaging, Dr. Ge and his colleagues studied 17 patients with relapsing-remitting multiple sclerosis (MS) and 14 age-matched normal controls with a 3-T MR system. MFC imaging is a recently developed MR method that applies a unique iron contrast mechanism for measuring the iron deposition in vivo.
There was significantly more iron deposition in the deep gray matter of patients with MS than that in normal controls (P less than .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. Low iron concentrations in patients relative to controls were noted in the frontal white matter and the genu and splenium of the corpus callosum.
Increased iron deposition measured with MFC in the deep gray matter of MS patients was positively correlated with total number of brain lesions (thalamus: P = .01; globus pallidus: P = .02).
Increased iron in deep gray matter was correlated inversely and significantly with performance on several neuropsychological tests, including the Rey Complex Figure Test, the California Verbal Learning Test, and the Digit Span Backward test, Dr. Ge reported. “This is very exciting,” says Dr. Ge, a radiologist at New York University, New York. “Researchers used to feel MS is a white matter disease. Now we know there are deep gray matter neurodegenerative abnormalities, which we think are mainly due to excessive iron accumulation in these regions.”
Abnormal iron deposition is a causal factor of neurodegenerative pathology in MS, said Dr. Ge, who noted that his MFC findings support observations made using diffusion tensor imaging and MR spectroscopy demonstrating gray matter involvement in MS. In addition to providing mechanistic clues of MS pathophysiology, MFC will be a sensitive tool to evaluate MS patients and to monitor the effects of iron chelating agents and other neuroprotective MS treatments, he said.
T2-weighted images (left) and MFC color maps (right) in a 29-year-old MS patient (top) and a 32-year-old control (bottom). High iron levels are seen in deep gray matter regions (arrows) in MS. Courtesy Dr. Yulin Ge