Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: For cases of multiple sclerosis (MS), magnetization transfer (MT) imaging may provide more pathologically specific and accurate estimates of the disease process than does conventional imaging. In this study, we evaluated changes of the MT ratio (MTR) of newly enhancing lesions, the MTR of normal-appearing white matter (NAWM), the average lesion MTR, and the MT histogram-derived metrics during a 3-year follow-up period for patients with relapsing-remitting or secondary progressive MS. METHODS: Dual-echo, conventional spin-echo, and MT images were obtained from seven patients with relapsing-remitting MS, seven patients with secondary progressive MS, and five age- and sex-matched control subjects at the time of study entry and 1, 13, and 37 months later. RESULTS: Newly enhancing lesions in the patients with secondary progressive MS presented a more severe and significant MTR reduction during the follow-up period as compared with those in the relapsing-remitting group. In cases of secondary progressive MS, we also observed a significant reduction of the MTR values of the NAWM and a trend toward reduction of average lesion MTR values. The patients with MS had mean percentage changes of MT histogram-derived measures that were approximately two to 10 times higher than those of the control subjects. CONCLUSION: This preliminary 3-year follow-up study shows that newly enhancing lesions and NAWM in patients with secondary progressive MS have significantly lower MTR values than do those in patients with relapsing-remitting MS. It also shows that the tissue damage that remains after enhancement ceases is more severe in secondary progressive disease.     

A comparison of magnetization transfer ratio, magnetization transfer rate, and the native relaxation time of water protons related to relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Magnetization transfer (MT) imaging and measurements of the magnetization transfer ratio (MTR) have extended our capability to depict and characterize pathologic changes associated with multiple sclerosis (MS). We wanted to investigate whether the analysis of other MT parameters, such as magnetization transfer rate (k(for)) and relative measure of water content (T1(free)), adds insight into MS-related tissue changes. METHODS: Quantitative MT imaging by use of phase acquisition of composite echoes was performed in nine patients with clinically definite relapsing-remitting MS and eight healthy control subjects on a 1.5-T MR system. We analyzed a total of 360 regions of interest and compared control white matter with various types of lesions and normal-appearing white matter in MS. RESULTS: We found a strong correlation between the MTR and k(for), but this relation was non-linear. A slight but significant reduction of the MTR in normal-appearing white matter of patients with MS was attributable to a reduced transfer rate only, whereas a lower MTR was associated with both a reduction of k(for) and an increase of T1(free) in regions of dirty white matter. Moreover, areas such as edema and T1-isointense lesions had a similar MTR but could be differentiated on the basis of Tl(free). CONCLUSION: Estimates of k(for) and T1(free) appear to complement MTR measurements for the understanding of MT changes that occur with different types of MS abnormalities in the brain.     

Evolution of multiple sclerosis lesions on serial contrast-enhanced T1-weighted and magnetization-transfer MR images

BACKGROUND AND PURPOSE: Magnetization-transfer imaging is a technique that could provide indirect evidence of the characteristics of multiple sclerosis (MS) lesions. The purpose of this work was to study the evolution of MS lesions on T1-weighted MR images over time and to investigate changes in magnetization-transfer ratio (MTR) values of MS lesions with different initial appearances on contrast-enhanced T1-weighted images. METHODS: Eleven patients with relapsing-remitting MS were studied with MR imaging. The MTRs were calculated for 47 lesions that had been classified according to their appearance on contrast-enhanced T1-weighted images. Each patient was examined at four time points over a 1-year period. The MTR changes observed in the selected lesions were compared with their initial T1-weighted appearance. RESULTS: The lowest MTR values were initially found in hypointense nonenhancing lesions and in ring-enhancing lesions, with both types showing a hypointense center. Changes in MTR values were more dynamic and reversible in ring-enhancing than in hypointense nonenhancing plaques. Nodular-enhancing lesions had slightly lower initial MTRs than did isointense non-enhancing lesions. CONCLUSION: The absence or presence of contrast uptake may indicate a different pathologic basis for hypointense MS lesions on T1-weighted MR images. These differences should be kept in mind when considering T1 lesion load as a surrogate marker of disability in MS.     

Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Gray matter may be affected by multiple sclerosis (MS), a white matter disease. Magnetization transfer ratio (MTR) is a sensitive and quantitative marker for structural abnormalities, and has been used frequently in the imaging of MS. In this study, we evaluated the amount of MTR of gray matter among patients with relapsing-remitting MS and healthy control subjects as well as the correlation between gray matter MTR abnormality and neurologic disability associated with relapsing-remitting MS. METHODS: We obtained fast spin-echo dual-echo and magnetization transfer (with and without MT saturation pulses) images from eighteen patients with relapsing-remitting MS and 18 age-matched healthy control subjects. Gray matter was segmented using a semiautomated system. Gray matter MTR histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS), total T2 lesion volume, and gray matter volumes were obtained for statistical analysis. RESULTS: A significant difference was found in gray matter MTR between patients with relapsing-remitting MS and healthy subjects (mean and median). Gray matter MTR histogram normalized peak heights in patients inversely correlated with EDSS (r = -0.65, P =.01). There was also an inverse correlation between mean MTR of gray matter and total T2 lesion volume. CONCLUSION: The MTR of gray matter significantly differed between patients with relapsing-remitting MS and healthy control subjects, suggesting that MS is a more diffuse disease affecting the whole brain, and neuronal damage accumulates in step with T2 lesion volume. Our finding of the relationship between gray matter MTR and EDSS indicates that measurement of gray matter abnormality may be a potentially useful tool for assessing clinical disability in MS.     

Quantitative proton MR spectroscopic imaging in acute disseminated encephalomyelitis.

Serial MR imaging and quantitative proton MR spectroscopic imaging (MRSI) findings of a 4-year-old boy with acute disseminated encephalomyelitis (ADEM) are reported. Over a 2-month period characterized by an initial illness and two relapses, each with full recovery, MR imaging exhibited the appearance and disappearance of multifocal lesions throughout the CNS that correlated only partly with the neurologic impairment. During one relapse, MRSI revealed low levels of N-acetylaspartate (NAA) within the regions of prolonged T2 signal intensity. All other metabolites were normal. At follow-up, the MR imaging and MRSI abnormalities had fully resolved. MRSI might play an important role in the diagnosis of ADEM, as well as in the elucidation of underlying pathophysiologic processes in this poorly defined disorder of children. This case demonstrates that reduced levels of NAA are not always associated with neuronal loss, irreversible tissue damage, or poor neurologic outcome.     

Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon beta-1b.

BACKGROUND AND PURPOSETo determine whether occult disease fluctuates with macroscopic lesions during the natural history of multiple sclerosis (MS) and whether therapeutic interventions affect occult disease, we performed serial monthly magnetization transfer (MT) imaging in patients with relapsing-remitting MS in a crossover trial with interferon beta-lb.METHODSSerial whole-brain magnetization transfer ratios (MTRs) in eight patients with relapsing-remitting MS and in four control subjects were plotted as normalized histograms, and MTR parameters were compared with contrast-enhancing lesions and bulk white matter lesion load.RESULTSIn patients with relapsing-remitting MS, the histographic peak of 0.25+/-0.01 and the histographic mean of 0.21+/-0.01 were statistically lower than corresponding values in control subjects, in whom the histographic peak was 0.27+/-0.01 and the histographic mean was 0.23+/-0.01. When histograms (with MTRs ranging from 0.0 to 0.5) were analyzed by quartiles (quartile 1 to quartile 4) based on histographic area, voxels with low MTRs in quartile 1 (0 to 0.12) increased during the baseline period and corresponded to bulk white matter lesion load. Interferon beta-lb reduced enhancing lesions by 91% and mean bulk white matter lesion load by 15%, but had no effect on MTR in this patient cohort.CONCLUSIONOccult disease in normal-appearing white matter of patients with relapsing-remitting MS measured by MTR parallels the waxing and waning pattern of enhancing lesions and bulk white matter lesion load during the baseline period. MTR is not altered by interferon beta-lb, which raises the possibility of ongoing disease in normal-appearing white matter (not detected by conventional MR sequences).     

Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS. METHODS: Volumetric spiral MRSI was used together with high-resolution MR imaging to derive absolute measures of metabolite concentrations separately in normal-appearing supratentorial cerebral gray matter and white matter in five RRMS patients, five SPMS patients, and nine age-matched controls. Structural MR images were segmented into compartments of gray matter, white matter, CSF, and lesions, and metabolite signals per unit of tissue volume were calculated for gray matter and white matter separately. RESULTS: Only the SPMS group had significantly lower NAA concentrations in normal-appearing gray matter compared with concentrations in controls. NAA in normal-appearing white matter was equally reduced in RRMS and SPMS patients. The functional relevance of this brain metabolite measure was suggested by the observed but statistically nonsignificant correlation between higher disability scores on the Expanded Disability Status Scale and lower gray matter NAA concentrations. CONCLUSION: The otherwise occult abnormality in supratentorial gray matter in SPMS but not RRMS may explain the more severe physical and cognitive impairments afflicting patients with SPMS that do not correlate well with visible lesion burden.     

A new method for analyzing histograms of brain magnetization transfer ratios: comparison with existing techniques

BACKGROUND AND PURPOSE: Previously reported quantitative parameters for the magnetization transfer ratio (MTR) do not give identical results, which can limit their ability to differentiate normal from diseased tissue and render them vulnerable to variations among MR systems. Our purpose was to systematically study different MTR metrics; propose a new MTR histogram parameter, AMTR(2/3); and compare AMTR(2/3) with existing parameters in a study of multiple sclerosis (MS). METHODS: Seven conventional MTR parameters were proposed: global and mean MTR; peak height and position of the histogram; and percentiles MTR25, MTR50, and MTR75. Additionally, we investigated a parameter, AMTR(2/3), to indicate the normalized pixel count (area under the histogram curve) inside the band size of two-thirds MTR histogram peak height. All parameters were measured in 10 patients with relapsing-remitting MS (group A), 10 healthy control subjects from the same imaging center as that of patients (group B), and four healthy control subjects from an outside institution (group C). Comparison of findings was performed between groups A and B to assess the discriminating ability of MTR parameters and groups B and C to evaluate intersystem variations. RESULTS: All MTR parameters differed between groups A and B, but the difference was significant for only global MTR, mean MTR, MTR25, and AMTR(2/3). With the exception of AMTR(2/3), all parameters differed significantly between the two control groups. CONCLUSION: AMTR(2/3) is less sensitive to MR imaging system variations than are other MTR parameters and was most effective in differentiating patients with MS from healthy control subjects. This finding supports the use of AMTR(2/3) in multicenter MT MR imaging studies of MS.     

Correlation of multiple sclerosis measures derived from T2-weighted, T1-weighted, magnetization transfer, and diffusion tensor MR imaging

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), the severity of tissue damage can vary from edema and inflammation to irreversible demyelination and axonal loss. Compared with conventional T2-weighted MR imaging, magnetization transfer (MT) and diffusion tensor (DT) MR imaging provide quantitative indices with increased specificity to the most destructive aspects of MS. To increase our understanding of the pathophysiologic processes of MS, we assessed the correlations between MT and DT MR imaging-derived metrics and the correlations between these quantities and measures derived from conventional MR in patients with MS. METHODS: T2-weighted, T1-weighted, MT, and DT MR images of the brain were obtained from 34 patients with relapsing-remitting MS (RRMS) and 15 age-matched control subjects. T2 and T1 lesion volumes (LV) and brain volume were measured. MT ratio (MTR), mean diffusivity (D macro), and fractional anisotropy (FA) histograms from the overall brain tissue (BT) and the normal-appearing brain tissue (NABT) were obtained. Average lesion MTR, D macro, and FA were also calculated. The correlations between T2 and T1 LV, brain volume, MT-, and DT-derived metrics were assessed with the Spearman rank correlation coefficient. RESULTS: No significant correlations were found between MT and FA histogram-derived metrics and quantities derived from conventional MR scans (T2 and T1 LV and brain volume). On the contrary, T2 and T1 LV (but not brain volume) were significantly correlated with the average D macro values of BT and NABT (r values ranging from 0.52 to 0.78). No significant correlation was found between MT- and DT-derived metrics. CONCLUSION: These results suggest that MT and DT MR imaging provide, at least partially, independent measures of lesion burden in patients with RRMS. This suggests that a multiparametric MR approach has the potential for increasing our ability to monitor MS evolution.     

Proton MR spectroscopy in multiple sclerosis: value in establishing diagnosis, monitoring progression, and evaluating therapy

MR imaging is currently the technique of choice for evaluating brain lesions in patients with multiple sclerosis (MS). In addition to MR imaging, proton MR spectroscopy has shown potential in diagnosing MS and monitoring the progression of treatment. Spatially localized proton spectroscopy has been used to evaluate changes in choline, creatine, N-acetyl aspartate (NAA), lipids, and lactate in MS patients and in animal models of MS. The main spectroscopic findings are a decrease in the NAA:creatine ratio and an increase in the choline:creatine ratio in brain regions that include plaques defined by MR imaging. Proton MR spectroscopy along with MR imaging may be helpful in distinguishing those early lesions that might respond to therapy from late irreversible lesions. Preliminary evidence suggests that although the proton spectra acquired from patients with various brain diseases are similar (high choline, low NAA), there are differences in other resonances (lipids, lactate, glutamate, inositol) that could potentially help in diagnosing MS. Changes in proton metabolites potentially can be used to differentiate between the different stages of the MS lesion (hyperacute and edematous lesions, demyelinated lesions, and subacute to chronic plaques). It is hypothesized that successful treatment of demyelination and neuronal damage will be accompanied by changes in the proton spectrum (high choline:creatine ratio will lower to normal values and low NAA:creatine values will rise to normal values).     

Normal-appearing white matter changes vary with distance to lesions in multiple sclerosis

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) disease processes in normal-appearing white matter (NAWM) may be different close to MR-visible lesions than farther from these lesions. We aimed to investigate the relationship of NAWM changes to the distance to the lesions. METHODS: We measured B(1)-corrected T1 and magnetization transfer ratio (MTR) maps in 63 patients with MS (11 primary progressive, 34 relapsing-remitting, 18 secondary progressive). We used histogram analyses to assess the global properties of lesions, of 4 consecutive 1-mm pixel layers of NAWM around the lesions, and of distant NAWM located at least 4-mm from lesions in all directions. In 22 healthy controls, we measured white matter MTR and T1 histograms. Histogram parameters were statistically analyzed by using a linear mixed model. RESULTS: The first and second NAWM pixel layers around the lesions had a significantly lower MTR histogram peak position than distant NAWM, whereas T1 histogram peak position was similar between all types of NAWM. Furthermore, MTR histograms of distant NAWM were statistically indistinguishable from those of control white matter, whereas T1 histograms of distant NAWM had significantly decreased peak height for relapsing-remitting MS and secondary progressive MS and significantly increased peak position for secondary progressive MS. CONCLUSION: Our results may suggest that axonal damage and demyelination in NAWM mainly arise as a secondary result of visible lesions, with the largest effect close to these lesions. NAWM disease farther from the lesions may be mainly characterized by subtle blood-brain barrier damage, with leakage of fibrinogen into the parenchyma and microplaque formation, processes that are detected with T1 but not with MTR.     

Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis.

BACKGROUND AND PURPOSE: Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures. METHODS: Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS). RESULTS: Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1-22); their median load was 1.4 mL (range, 0.05-12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense lesions shown by fast FLAIR imaging were significantly higher in patients with secondary progressive MS. Significant correlations were found between Expanded Disability Status Scale scores and MR lesion load. A multivariate analysis showed that only the presence of hypointense lesions on fast FLAIR images significantly separated cases of relapsing-remitting MS from cases of secondary progressive MS (relative risk, 7.1; 95% confidence interval, 2.0-25.9). CONCLUSION: The presence of hypointense lesions on fast FLAIR images was a strong predictor of disease severity in cases of MS, although the low sensitivity of this approach might limit its use for the assessment of MS evolution.     

Dirty-appearing white matter in multiple sclerosis: volumetric MR imaging and magnetization transfer ratio histogram analysis

BACKGROUND AND PURPOSE: In contrast to "normal-appearing" white matter (NAWM) in patients with multiple sclerosis (MS), there are subtle, abnormal and diffuse signal intensity changes often seen on T2-weighted MR images, which we have referred to as "dirty-appearing" white matter (DAWM). These areas of DAWM have slightly higher signal intensity than that of NAWM, but lower than that of lesion plaques. Our study was designed to determine the volumetric and magnetization transfer ratio (MTR) features of DAWM in patients with MS. METHODS: Dual-echo fast spin-echo MR imaging and magnetization transfer imaging were performed in 22 patients with relapsing-remitting MS. Slightly hyperintense DAWM areas were manually outlined on the basis of T2-weighted imaging findings. The volume and MTR of DAWM were calculated and compared with the volume and MTR of NAWM and T2 lesion plaques. RESULTS: The average volume of DAWM (18.3 mL) was greater than the average volume of T2 lesion plaques (11.0 mL, P =.04), and the mean MTR in DAWM (38.7%) differed significantly (P <.0001) from that in NAWM (40.7%) and plaques (33.3%). There was a modest negative correlation between either mean MTR (r = -0.60; P =.003) of DAWM or peak height (r = -0.50; P =.02) of DAWM with T2 lesion load. Neither DAWM volume nor total T2 abnormality (DAWM + plaques) volume correlates with the Expanded Disability Status Scale. CONCLUSION: The results of this study indicate that MTR is able to differentiate DAWM from lesion plaques and NAWM and that DAWM might be a different pathologic process of the disease. The notion and quantification of these subtle imaging findings of DAWM areas may improve our understanding of certain stages of disease progression and disease burden in patients with relapsing-remitting MS.     

Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis

BACKGROUND AND PURPOSE: We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS). METHODS: Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis. RESULTS: All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment. CONCLUSION: The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.     

Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis.

PURPOSE: The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. METHOD: Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. RESULTS: Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p 相似文献   

Proton MR spectroscopy and magnetization transfer ratio in multiple sclerosis: correlative findings of active versus irreversible plaque disease.

PURPOSETo characterize plaques of multiple sclerosis (MS) using both proton MR spectroscopy and magnetization transfer (MT) imaging.METHODSThe magnetization transfer ratio (MTR) was calculated from two series of three-dimensional gradient-recalled acquisition in the steady state (GRASS) images obtained with and without an MT saturation pulse. Proton spectra were acquired using the point-resolved spectroscopy (PRESS) sequence with a voxel size of 1.5 x 1.5 x 1.5 cm3. A total of 28 spectra were obtained in 13 patients who had clinically definitive MS. The spectra were analyzed together with the MTR.RESULTSA positive relationship was found between the N-acetylaspartate (NAA)/creatine (Cr) ratio and the MTR in MS plaques, whereas no significant correlation was found between the metabolite ratios and the signal intensity on fast spin-echo T2-weighted MR images.CONCLUSIONSmall changes in the MTR of MS plaques relative to the MTR of normal white matter may reflect inflammatory changes and edema, whereas larger changes in MTR correlate with decreased NAA/Cr ratio and therefore suggest demyelination and irreversible damage from chronic MS plaques.     

Magnetization transfer study of HIV encephalitis and progressive multifocal leukoencephalopathy. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

PURPOSETo ascertain whether the use of magnetization transfer (MT) in MR imaging can characterize tissue destruction in human immunodeficiency virus (HIV)-positive patients with presumed progressive multifocal leukoencephalopathy (PML) or HIV encephalitis.METHODSBrain MR studies that included MT were obtained in three groups: 11 healthy control subjects, 10 HIV-positive patients with clinical and radiologic findings of PML, and 13 HIV-positive patients with HIV encephalitis. MT ratios (MTRs) were calculated in PML and HIV encephalitis lesions and in normal-appearing white matter in the patients and control subjects.RESULTSPML lesions revealed a dramatic decrease in MTR (22% +/- 2.3). HIV encephalitis lesions had statistically significantly higher MTR values (40% +/- 3.8) than PML lesions. The MTR of normal-appearing white matter was significantly higher in the control subjects (47% +/- 2.3) than in the PML group (46% +/- 3.3) or the HIV encephalitis group (44% +/- 2.6).CONCLUSIONMTR determinations suggest the possibility of distinguishing PML from HIV encephalitis and of indicating whether HIV encephalitis is involved in white matter that appears normal on conventional MR images.     

Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images

PURPOSE: To determine the evolution of magnetization transfer (MT) in white matter regions before and after plaque development in patients with multiple sclerosis (MS). MATERIALS AND METHODS: In a 5-year longitudinal evaluation, 30 patients with MS underwent conventional magnetic resonance (MR) imaging, MT MR imaging, and clinical assessment. Cross-sectional data in 12 healthy subjects were also collected. Semiautomated lesion classification with use of T2-weighted MR images was used to measure the time course of the MT ratio (calculated with MR data acquired without and with MT saturation) in every voxel and to help analyze the relationship with the status of lesions depicted on T2-weighted images. RESULTS: There was a significant (P <.001) temporal decline in lesion MT ratio after lesion appearance on T2-weighted images. A significant (P <. 001) progressive decline in MT ratio was also present in voxels that later became lesions, prior to initial detection on T2-weighted images. Even 1(1/2) years prior to lesion appearance, the MT ratio (33.3%) in regions destined to become such lesions was significantly (P <.001) lower than that in both white matter in healthy subjects (41.3%) and other normal-appearing white matter in patients with MS (38.1%). CONCLUSION: The MT ratio reveals progressive focal abnormalities in MS that antedate by up to 2 years the appearance of lesions on T2-weighted MR images.     

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 lesioins (high signal abnormalities on T₂-weighted images) and normal-appearing white matter (NAWM) in multiple sclerosis (MI). 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 Kacetyl-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 ≈?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.     

Whole-brain N-acetylaspartate concentration: correlation with T2-weighted lesion volume and expanded disability status scale score in cases of relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: The T2-weighted MR imaging total lesion volume and Expanded Disability Status Scale (EDSS) score are two common measures of relapsing-remitting multiple sclerosis disability and pathologic abnormality. Because the whole-brain N-acetylaspartate concentration is considered to be a new marker of the disease burden, the purpose of this study was to evaluate the relationship among these three measures. METHODS: The whole-brain N-acetylaspartate concentration and T2-weighted lesion volume were quantified by using MR imaging and proton MR spectroscopy in 49 patients with relapsing-remitting multiple sclerosis (36 female and 13 male patients; average age, 39 years; age range, 24-55 years; average EDSS score, 2; range of EDSS scores, 0-6). Correlations among whole-brain N-acetylaspartate concentrations, T2-weighted lesion volumes, and EDSS scores were obtained. RESULTS: No correlation was found between whole-brain N-acetylaspartate levels and either T2-weighted lesion volumes or EDSS scores. A weak correlation was found between the EDSS scores and T2-weighted lesion volumes (P =.043, r(s) = 0.292). CONCLUSION: Despite the lack of correlation between whole-brain N-acetylaspartate concentration and the clinical disability reflected in the EDSS score, only the former evaluates the global neuronal cell disease in the entire brain, including those lesions that are occult to conventional imaging techniques.