Characterization of multiple sclerosis plaques with T1-weighted MR and quantitative magnetization transfer.

PURPOSE: To investigate the relationship between the appearance of multiple sclerosis lesions identified on unenhanced T1-weighted images and their corresponding magnetization transfer ratios. METHODS: A total of 119 white matter lesions seen on T2-weighted images in 17 patients with multiple sclerosis were evaluated. Axial T1-weighted images were used to classify the lesions as isointense to white matter (10 lesions), hypointense to white matter but hyperintense to gray matter (44 lesions), hypointense to gray matter (59 lesions), and relatively isointense to cerebrospinal fluid (6 lesions). The magnetization transfer ratio of each lesion was calculated, and an average magnetization transfer ratio for each subcategory was determined. RESULTS: The magnetization transfer ratio values became progressively lower with increasing hypointensity of lesions on T1-weighted images. The average magnetization transfer ratio for lesions isointense to white matter, hypointense to white matter but hyperintense to gray matter, hypointense to gray matter, and relatively isointense to cerebrospinal fluid was 34.90 +/- 2.67 mean +/- SD), 30.93 +/- 3.57, 27.27 +/- 3.56, and 23.62 +/- 2.83, respectively. All groups were significantly different from each other. CONCLUSION: Lesions isointense to white matter exhibited higher magnetization transfer ratio values than lesions that were hypointense. These findings are consistent with relative preservation of the myelin structure in the former, perhaps indicating that these lesions are predominantly inflammatory (edematous) in nature. The proportionately lower magnetization transfer ratio values of lesions that appear progressively more hypointense on T1-weighted images may reflect varying degrees of demyelination, with increasing lesion hypointensity corresponding to more breakdown in the macromolecular structure. These results suggest that T1-weighted images may be useful in characterizing the underlying pathologic substrate in multiple sclerosis plaques.

Magnetization transfer effects in MR-detected multiple sclerosis lesions: comparison with gadolinium-enhanced spin-echo images and nonenhanced T1-weighted images.

PURPOSE: To define the relationship between magnetization transfer and blood-brain-barrier breakdown in multiple sclerosis lesions using gadolinium enhancement as an index of the latter. METHODS: Two hundred twenty lesions (high-signal abnormalities on T2-weighted images) in 35 multiple sclerosis patients were studied with gadolinium-enhanced spin-echo imaging and magnetization transfer. Lesions were divided into groups having nodular or uniform enhancement, ring enhancement, or no enhancement after gadolinium administration. For 133 lesions, T1-weighted images without contrast enhancement were also analyzed. These lesions were categorized as isointense or hypointense based on their appearance on the unenhanced T1-weighted images. RESULTS: There was no difference between the magnetization transfer ratio (MTR) of lesions as a function of enhancement. MTR of hypointense lesions on unenhanced T1-weighted images was, however, lower than the MTR of isointense lesions. CONCLUSION: We speculate that diminished MTR may reflect diminished myelin content and that hypointensity on T1-weighted images corresponds to demyelination. Central regions of ring-enhancing lesions had a lower MTR than the periphery, suggesting that demyelination in multiple sclerosis lesions occurs centrifugally. In addition, the short-repetition-time pulse sequence seems useful in the evaluation of myelin loss in patients with multiple sclerosis.

Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis.

Magnetization transfer imaging (MT) and localized proton spectroscopy (1H-MRS) were utilized in the evaluation of lesions (high signal abnormalities on T2-weighted images) and normal-appearing white matter (NAWM) in multiple sclerosis (MS). Eleven patients with a clinical diagnosis of MS were independently evaluated with both 1H-MRS and MT. The magnetization transfer ratio (MTR) of lesions was compared with the relative concentration of N-acetyl-aspartate (NAA) and a composite peak at 2.1 to 2.6 ppm termed "marker peaks." The MTR of white matter lesions in the MS patients was markedly decreased (6-34%; normal approximately 42%), and correlated well with increase in the marker peaks region (0.94-3.89). There was no correlation between the relative concentration of NAA and MTR. Increased resonance peaks in the 2.1 to 2.6 ppm range and marked decreases in MTR may be a relatively specific indicators of demyelination.

Magnetization transfer: theory and clinical applications in neuroradiology.

Magnetization transfer, a new technique for improving image contrast in magnetic resonance (MR) imaging, is based on application of off-resonance radio-frequency pulses and observing their effects on MR images, as well as measuring the signal intensity with and without application of the pulses (ie, magnetization transfer ratio [MTR]). MTRs can be used to detect changes in the structural status of brain parenchyma that may or may not be visible with standard MR techniques. Use of MTRs may allow subcategorization of multiple sclerosis lesions into those with very low MTR (demyelinated lesions) and slightly decreased MTR (edematous lesions). In cases of wallerian degeneration, use of MTRs appears to allow reliable detection of changes undetectable with MR imaging or even light microscopy. In cases of infection with human immunodeficiency virus, MTRs seem to indicate that the macromolecular structure of white matter remains intact until relatively late in the course of disease. In cases of metastatic disease, MTRs of brain lesions indicate structural changes beyond the extent of the lesions seen on standard MR images. These findings may be due to chronic edema, myelin loss, and perhaps previous undetected tumor. In addition to being a new method of providing contrast, the magnetization transfer technique enables semi-quantitative, reproducible characterization of tissue and pathologic entities, which could substantially improve the specificity of MR imaging.

MR proton spectroscopy in multiple sclerosis.

PURPOSE: To elucidate the natural history of visualized MR abnormalities in patients with multiple sclerosis using proton spectroscopy. METHODS: MR imaging and proton spectroscopy (1H spectroscopy) were performed on 16 patients with clinically definite multiple sclerosis. All patients received gadopentetate dimeglumine (Gd-DTPA). RESULTS: Decreased levels of N-acetylaspartate (NAA) were demonstrated in 17 out of 21 lesions. No correlation was found between decreased NAA and Gd-DTPA enhancement. In five out of seven enhancing lesions, abnormal 1H spectra with extra peaks (termed marker peaks) at 2.1-2.6 ppm (ranging in absolute concentration from 10-50 mM protons) were observed. In nine out of 14 unenhancing lesions, no elevated marker peaks were observed. In the five other unenhancing lesions, the levels of these marker peaks were generally lower than the enhancing group. No correlation was found between the NAA levels and the levels of the marker peaks. We suggest two distinct biochemical processes: 1) decreased NAA reflecting neuronal cell loss, and 2) elevated marker peaks reflecting ongoing demyelination. CONCLUSIONS: Based upon these observations we infer that 1) the majority of enhancing lesions are demyelinating with extra peaks at 2.1-2.6 ppm representing a marker of this process, 2) enhancing lesions without this marker most likely represent edematous regions without significant demyelination, and 3) demyelination may be long in duration compared with transient blood-brain barrier disruption manifested by Gd-DTPA enhancement. Our results suggest that 1H spectroscopy has the ability to further categorize MR-demonstrated enhancing and unenhancing lesions in patients with multiple sclerosis and that it may be more sensitive than contrast enhancement in revealing the true time course of demyelination.

Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging.

Magnetization transfer imaging (MTI) was initially performed in normal guinea pigs and human volunteers. A magnetization transfer ratio (MTR) was calculated in the normal white matter and was found to be 42%-44%, with less than 2.5% variation, which indicates the high reproducibility of the measurement. MTI was then applied to an animal model of white matter disease, acute experimental allergic encephalomyelitis (EAE). In this model of EAE, pathologically proved lesions were edematous with essentially no demyelination. MTRs decreased slightly but significantly (5%-8%) compared with the MTRs of the same tissue region measured before the onset of the lesion [corrected]. Fifteen patients with multiple sclerosis (MS) also underwent MTI. In the 15 patients with MS, all lesions (209 plaques) had a significantly decreased MTR (average, 26%). The authors believe that demyelination produced the lower MTR, and, thus, lesions varied in transfer ratio on the basis of the extent of myelin loss. In patients with MS, particularly those with chronic and/or progressive MS, the MTR of the normal-appearing white matter was significantly decreased. The data suggest that calculated MTR obtained with in vivo MTI may enable differentiation of edema from demyelination, and that MTI can demonstrate white matter abnormalities that cannot be seen with standard spin-echo or gradient-echo magnetic resonance imaging.