Clinical use of H MR spectroscopy in assessment of relapsing remitting and secondary progressive multiple sclerosis

Background

Conventional MRI has a limited ability to provide specific information about axonal pathology in MS, recently, MRI spectroscopy used for assessment of the axonal loss even in normal appearing white matter.

Objective

To assess the axonal degeneration in plaques and normal appearing white matter in patients with relapsing remitting MS and secondary progressive MS, and correlate their clinical disability using expanded disability status scale (EDSS) score with H¹ MRS abnormalities.

Patients and methods

Thirty-two MS patients (20 RRMS, 12 SPMS) and 20 controls were subjected to thorough history taking, clinical examination with special attention to: age at first symptoms, disease duration and the EDSS score. MRS was performed in order to map N-acetylaspartate (NAA), choline (Cho) and creatine (Cr).

Results

In SPMS, the NAA/Cr ratio and absolute concentrations for NAA in MS plaques and NAWM were significantly reduced compared to RRMS and to controls, also, significant relation with this metabolite values and clinical disability using EDSS score.

Conclusion

In SPMS patients group there were significant reduction in the levels of NAA in both plaques and NAWM compared to RRMS and control groups, moreover significant correlation of NAA reduction in the plaques of both groups related to clinical disability and disease progression.     

Relationships of brain white matter microstructure with clinical and MR measures in relapsing‐remitting multiple sclerosis

Purpose:

To assess the relationships of microstructural damage in the cerebral white matter (WM), as measured by diffusion tensor imaging (DTI), with clinical parameters and magnetic resonance imaging (MRI) measures of focal tissue damage in patients with multiple sclerosis (MS).

Materials and Methods:

Forty‐five relapsing‐remitting (RR) MS patients (12 male, 33 female; median age = 29 years, Expanded Disability Status Scale (EDSS) = 1.5, disease duration = 3 years) were studied. T2‐lesion masks were created and voxelwise DTI analyses performed with Tract‐Based Spatial Statistics (TBSS).

Results:

T2‐lesion volume (T2‐LV) was significantly (P < 0.05, corrected) correlated with fractional anisotropy (FA) in both lesions and normal‐appearing WM (NAWM). Relationships (P = 0.08, corrected) between increasing EDSS score and decreasing FA were found in the splenium of the corpus callosum (sCC) and along the pyramidal tract (PY). All FA associations were driven by changes in the perpendicular (to primary tract direction) diffusivity. No significant global and voxelwise FA changes were found over a 2‐year follow‐up.

Conclusion:

FA changes related to clinical disability in RR‐MS patients with minor clinical disability are localized to specific WM tracts such as the sCC and PY and are driven by changes in perpendicular diffusivity both within lesions and NAWM. Longitudinal DTI measurements do not seem able to chart the early disease course in the WM of MS patients. Imaging 2010; 31:309–316. © 2010 Wiley‐Liss, Inc.     

The contribution of diffusion-weighted MR imaging in multiple sclerosis during acute attack

PURPOSE: The aims of the study are firstly, to determine the difference in diffusion-weighted imaging (DWI) in normal appearing white matter (NAWM) between patients with acute multiple sclerosis (MS) and controls; secondly, to determine whether there is a correlation between EDSS scores and DWI in acute plaques and also NAWM. MATERIALS AND METHOD: Out of 50 patients with acute MS attack, 35 patients had active plaques with diffuse or ring enhancement on postcontrast images. Eighteen healthy volunteers constituted the control group. While 26 of 35 had relapsing-remitting, 9 had secondary progressive MS. Apparent diffusion coefficients (ADC) of the active plaques, NAWM at the level of centrum semiovale and occipital horn of lateral ventricle in the patients and NAWM in control group were measured. ADC values of active plaques were compared with WM of the patients and the control group. The relationship of ADC value of active plaques and WM in MS with expanded disability status scale (EDSS) was investigated by using Mann-Whitney U-test. RESULTS: Of 63 plaques totally, 26 and 37 of the active plaques had diffuse and ring enhancement, respectively. There was no statistically significant difference between ADC value of active plaques and EDSS (p>0.05). However, there was a statistically significant difference between ADC value of WM occipital horn and EDSS (p<0.05). ADC value of active plaques were higher than WM in both groups (p<0.001). The difference between ADC value of WM at the centrum semiovale (p<0.05) and occipital horns (p<0.001) in patients and controls was statistically significant. There was no statistically significant difference between EDSS scores, ADC value at centrum semiovale and WM around occipital horn and active plaques in subgroups (p>0.05). CONCLUSION: Apparently normal tissue in MS patients may show early abnormalities when investigated carefully enough, and there is an even though moderate correlation between EDSS and ADC values and early alterations of ADC value are starting in the occipital white matter along the ventricles. This has to be verified in larger series.     

Diffusion tensor imaging for characterizing white matter changes in multiple sclerosis

Purpose

To investigate the diagnostic values of quantitative diffusion tensor imaging parameters in detecting abnormalities in white matter of MS patients and correlate this with lesion load and clinical disability as prognostic factors.

Patients and methods

Diffusion tensor imaging (DTI) was performed in 45 consecutive MS patients and 20 age-matched healthy control volunteers from March 2011 to November 2013. Mean diffusivity (MD), volume ratio (VR) and the fractional anisotropy (FA) were measured in normal appearing white matter (NAWM) and in different types of focal MS lesions during both activity and remission and compared with normal white matter (NWM) of the control group. Evaluation of lesion load was done by the semiautomated method. Clinical assessment of MS was established using the Kurtzke expanded disability status scale (EDSS) and the Kurtzke functional system score.

Results

Significant increase of MD and decrease of FA and VR from normal appearing white matter of the patients to MRI detected active lesions and the least is inactive plaques comparing with NWM of the control group (P value 0.003 for MD, 0.013 for FA, and 0.014 for VR). Correlation and significant difference between {(increase in MD) and (decrease in FA and VR)} and lesion load (strongest in parietal lobes) and also Kurtzke expanded disability status scale (EDSS) and Kurtzke functional system score (KFS-p).

Conclusion

DTI–MRI quantitative parameters are good predictors of tissue damage not only in MRI-defined lesions but also in NAWM as a result of Wallerian degeneration and are helpful as diagnostic and prognostic tools.     

Normal-appearing white matter in optic neuritis and multiple sclerosis: a comparative proton spectroscopy study

We investigated neurochemical abnormalities in the normal-appearing white matter (NAWM) on MRI of patients with optic neuritis (ON) and compared them to those of patients with multiple sclerosis (MS). Patients with ON (42) were classified into three groups according to abnormalities on brain MRI. Patients with MS (55) were devided in two groups: relapsing remitting MS (RRMS) and secondary progressive MS (SPMS). All patients underwent MRI of the brain and localised proton magnetic resonance spectroscopy (MRS) of NAWM. The results were compared to those of 15 controls. Patients with MS had significant abnormalities compared with controls and with patients with ON. Patients with RRMS and those with ON had comparable MRS parameters, while patients with SPMS had significant spectroscopic abnormalities in comparison with controls, but also with patients with RRMS. These changes consisted of a decrease in N -acetylaspartate, a neuronal marker, which may reflect axonal dysfunction and/or loss. MRS abnormalities were detected in 14 patients with ON (27 %). The main abnormalities consisted of a decrease in N -acetylaspartate, an increase in choline-containing compounds at long echo times, and the presence of free lipid peaks at short echo times. MRS of the NAWM on MRI may prove useful for detecting neurochemical brain abnormalities in ON not visible on MRI. Received: 19 January 1999 Accepted: 23 March 1999     

MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0 ± 7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon β-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p < 0.05) and correlated to the MSFC score (r = 0.476, p < 0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p < 0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects. J. Bellmann-Strobl, H. Stiepani and J. Wuerfel contributed equally to this work.     

Use of ultrasmall superparamagnetic particles of iron oxide (USPIO)‐enhanced MRI to demonstrate diffuse inflammation in the normal‐appearing white matter (NAWM) of multiple sclerosis (MS) patients: An exploratory study

Purpose

To explore ultrasmall superparamagnetic particles of iron oxide (USPIO) as a marker for diffuse inflammation in multiple sclerosis (MS) normal‐appearing white matter (NAWM), using quantitative MRI. Disease activity in the NAWM of MS patients partly explains why MRI lesion burden correlates only moderately with disability. USPIO have been shown to visualize the cellular component of inflammation in focal MS lesions. In this study, we aimed to explore USPIO as a marker for the more diffuse inflammation in MS NAWM, using quantitative MRI.

Materials and Methods

In this prospective MRI study, 16 MS patients (eight relapsing‐remitting MS [RRMS] and eight primary‐progressive MS [PPMS] cases) and five healthy control (HC) subjects were included. Using a flip‐angle (FA) array, B1‐corrected T1 maps were generated before and 24 hours after USPIO (SHU555C) injection. White‐matter (WM) T1 histogram and region‐of‐interest (ROI) characteristics were compared between both time points using Wilcoxon signed‐rank test.

Results

Both NAWM ROI and histogram analyses showed T1 shortening after USPIO injection in MS patients (P < 0.01), but not in HCs (P = 0.68).

Conclusion

This exploratory study suggests that USPIO‐enhanced MRI may be a new potential marker for subtle inflammatory activity in MS NAWM. Further studies should focus on relating diffuse inflammation to clinical disease activity and treatment efficacy. J. Magn. Reson. Imaging 2009;29:774–779. © 2009 Wiley‐Liss, Inc.     

Normal-appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T(2).

T(2) relaxation in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients was reexamined using more complete sampling and analysis of decay curves, and to assess focal vs. diffuse abnormalities. Nine MS patients and 10 controls were scanned using a single-slice 32-echo pulse sequence with a 10-ms echo spacing. Decay curves from outlined white and gray matter structures were analyzed using non-negative least-squares (NNLS). Resulting T(2) distributions were each summarized by the geometric mean T(2), T(2). Different white matter structures had different mean (over the subjects in a group) T(2). Mean T(2) in NAWM was always greater than that of controls. Differences were not caused by a few voxels with extreme T(2) (i.e., focal lesions), but rather by shifts of the entire T(2) distribution (diffuse prolongation). This T(2) increase suggests diffuse myelin or axonal pathology.     

Texture analysis of magnetization transfer maps from patients with clinically isolated syndrome and multiple sclerosis

Purpose

To investigate the behavior of texture parameters derived from the gray level co‐occurrence matrix from gray matter (GM) and white matter (WM) (with lesions removed) segments of magnetization transfer ratio maps from controls and patients.

Materials and Methods

Magnetization transfer ratio maps from 23 controls and patients with either a clinically isolated syndrome (CIS) (38 patients) or clinically definite multiple sclerosis (MS) (35) were scanned and texture parameters extracted. The texture parameters were compared between the groups and correlated with clinical measures of disability in the MS patients to investigate any association with disease severity.

Results

No significant differences were found between the texture parameters from controls and CIS patients; however, several parameters differ between MS patients and the two other groups, particularly in the GM, but also in the WM. The expanded disability status score and timed walk test correlate with GM texture measures, while the Paced Auditory Serial Addition Test 3 score, a cognitive measure, correlates with WM texture. Texture abnormalities were seen in MS WM and GM, indicating tissue damage beyond classical WM lesions, the abnormalities being more evident in GM.

Conclusion

The findings highlight potential for texture analysis measures in classifying central nervous system demyelinating diseases that warrants further investigation. J. Magn. Reson. Imaging 2009;30:506–513. © 2009 Wiley‐Liss, Inc.     

Normal appearing white matter permeability: a marker of inflammation and information processing speed deficit among relapsing remitting multiple sclerosis patients

Purpose

Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS).

Methods

Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression.

Results

rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impaired patients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068–2.956; p = 0.026), NAGM (OR 2.138; 1.100–4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120–4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups.

Conclusion

rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.

     

Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis

Objective

The purposes of our study were to employ diffusion tensor imaging (DTI)-based histogram analysis to determine the presence of occult damage in clinically isolated syndrome (CIS), to compare its severity with relapsing-remitting multiple sclerosis (RRMS), and to determine correlations between DTI histogram measures and clinical and MRI indices in these two diseases.

Materials and methods

DTI scans were performed in 19 CIS and 19 RRMS patients and 19 matched healthy volunteers. Histogram analyses of mean diffusivity and fractional anisotropy were performed in normal-appearing brain tissue (NABT), normal-appearing white matter (NAWM) and gray matter (NAGM). Correlations were analyzed between these measures and expanded disability status scale (EDSS) scores, T₂WI lesion volumes (LV) and normalized brain tissue volumes (NBTV) in CIS and RRMS patients.

Results

Significant differences were found among CIS, RRMS and control groups in the NBTV and most of the DTI histogram measures of the NABT, NAWM and NAGM. In CIS patients, some DTI histogram measures showed significant correlations with LV and NBTV, but none of them with EDSS. In RRMS patients, however, some DTI histogram measures were significantly correlated with LV, NBTV and EDSS.

Conclusion

Occult damage occurs in both NAGM and NAWM in CIS, but the severity is milder than that in RRMS. In CIS and RRMS, the occult damage might be related to both T2 lesion load and brain tissue atrophy. Some DTI histogram measures might be useful for assessing the disease progression in RRMS patients.     

Texture analysis of spinal cord pathology in multiple sclerosis.

Texture analysis was applied to MR images of the spinal cord in an attempt to quantify pathological changes that occur in multiple sclerosis (MS). Texture features quantify macroscopic lesions and also the microscopic abnormalities that may be undetectable using conventional measures of lesion volume and number. Significant differences in texture between normal controls and MS patients were seen. Texture differences were detected between normal controls and relapsing-remitting patients before detectable spinal cord atrophy. There was also significant correlation between texture and disability. The segmentation and texture analysis technique demonstrates intraobserver coefficients of variation ranging from 0. 6-8.2%. Texture analysis has potential as a tool for monitoring changes associated with the development of disability in patients with MS. Reproducibility and sensitivity must be improved to use the technique for serial monitoring in individuals. Magn Reson Med 42:929-935, 1999.     

临床孤立综合征和复发缓解型多发性硬化患者表现正常脑白质及脑灰质的MR扩散张量直方图比较

目的 评价扩散张量成像(DTI)对临床孤立综合征(CIS)的研究价值,了解CIS的病理变化机制及与复发缓解型多发性硬化(RRMS)的关系.方法 选择19例CIS患者(CIS组)、19例RRMS患者(RRMS组)和19例性别、年龄与之匹配的健康志愿者(正常对照组)为研究对象.用1.5 T超导型MR机采集数据,经图像后处理得到表现正常脑白质(NAWM),表现正常脑灰质(NAGM)的平均扩散率(MD)、各向异性分数(FA)直方图,其中提取出下列指标:平均值、直方图峰高和峰位置,进行单因素方差分析和秩和检验,并对3组NAWM、NAGM的MD、FA值与扩展残疾状态量表(EDSS)评分进行Spearman相关分析.结果 RRMS组患者表现正常脑白质MD为(0.83±0.04)×10-3mm2/s,较正常对照组(0.78±0.02)×10-3mm2/s、CIS组(0.79±0.02)×10-3mm2/s均显著增高(F=15.304,P＜0.01),但CIS组与正常对照组间差异无统计学意义(P＞0.05);MD图峰高CIS组明显低于正常对照组(P＜0.01);RRMS组平均FA值(0.36±0.03)较正常对照组(0.41±0.01)及CIS组(0.40±0.02)均降低(F=17.965,P＜0.01),但CIS组与正常对照组间差异无统计学意义(P＞0.05),平均FA图峰位置CIS组较正常对照组明显左移.NAGM MD在正常对照组、CIS组、RRMS组分别为(1.03±0.05)、(1.08±0.06)、(1.18±0.12)×10-3mm2/s,依次增高,且差异均有统计学意义(F=15.261,P＜0.01).CIS患者的各项DTI指标与EDSS评分均无显著性相关.RRMS患者NAGM的MD与EDSS评分呈正相关(r=0.568,P＜0.05).结论 DTI直方图可以敏感的显示及量化CIS及多发性硬化(MS)NAWM、NAGM的异常,作为MS最早期表现的CIS患者NAWM、NAGM均已发生了病理改变,但较MS病变轻.     

复发好转型多发性硬化表现正常脑白质DTI研究

目的:利用扩散张量成像(DTI)直方图分析,明确复发好转型多发性硬化(RRMS)患者表现正常脑白质(NAWM)的异常改变及DTI直方图指标与扩展残疾状态(EDSS)评分的相关性。方法:对29例RRMS患者和35例健康志愿者行常规MRI和DTI检查,分割提取NAWM后,绘制出NAWM的平均扩散率(MD)和部分各向异性(FA)直方图,并对其进行分析。结果:与健康志愿者比较,RRMS患者NAWM平均MD直方图右移、峰高降低;平均FA直方图左移、峰高增高。RRMS患者NAWM的平均MD、MD直方图峰位置和FA直方图峰高明显高于健康志愿者(P<0.001),而MD直方图峰高和平均FA明显低于健康志愿者(P<0.001)。在RRMS患者,所有NAWM的MD和FA直方图指标与EDSS评分均无相关性。结论:RRMS患者NAWM内存在明显扩散异常。     

Diffusion abnormality maps in demyelinating disease: correlations with clinical scores

Background and purpose

Magnetic resonance imaging (MRI) has been explored as a noninvasive tool to assess pathology in multiple sclerosis (MS) patients. However, the correlation between classical MRI measures and physical disability is modest in MS. The diffusion tensor imaging (DTI) MRI technique holds particular promise in this regard. The present study shows brain regions where FA and individual diffusivities abnormalities are present and check their correlations with physical disability clinical scores.

Methods

Eight patients and 12 matched healthy controls were recruited. The Multiple Sclerosis Functional Composite was administered. For MR-DTI acquisitions, a Genesis Signa 1.5T MR system, an EP/SE scanning sequence, 25 gradient directions were used.

Results

Tract Based Spatial Statistics (TBSS) group comparisons showed reduced FA and increased individual diffusivities in several brain regions in patients. Significant correlations were found between FA and: EDSS, 9-HPT(NON)DOM and 25FW score; between λ₂ and: P100 (r&;l), 9-HPT(NON)DOM and 25FW; between λ₃ and: 9-HPT(NON)DOM and 25FW score.

Conclusions

Fractional anisotropy and individual radial diffusivities proved to be important markers of motor disabilities in MS patients when the disease duration mean and the disability scores values range are relatively high.     

Gait Profile Score in multiple sclerosis patients with low disability

BackgroundGait abnormalities are subtle in multiple sclerosis (MS) patients with low disability and need to be better determined. As a biomechanical approach, the Gait Profile Score (GPS) is used to assess gait quality by combining nine gait kinematic variables in one single value. This study aims i) to establish if the GPS can detect gait impairments and ii) to compare GPS with discrete spatiotemporal and kinematic parameters in low-disabled MS patients.MethodThirty-four relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score ≤2 (mean age 36.32 ± 8.72 years; 12 men, 22 women; mean EDSS 1.19 ± 0.8) and twenty-two healthy controls (mean age 36.85 ± 7.87 years; 6 men, 16 women) matched for age, weight, height, body mass index and gender underwent an instrumented gait analysis.ResultsNo significant difference in GPS values and in spatiotemporal parameters was found between patients and controls. However patients showed a significant alteration at the ankle and pelvis level.ConclusionGPS fails to identify gait abnormalities in low-disabled MS patients, although kinematic analysis revealed subtle gait alterations. Future studies should investigate other methods to assess gait impairments with a gait score in low-disabled MS patients.     

Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis

Introduction The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Methods Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3–4 and 6–7 months after the initial event. Results Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (−13.4%, P = 0.002) whereas nonconverters (−6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Conclusion Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS.     

T2 relaxation time analysis in patients with multiple sclerosis: correlation with magnetization transfer ratio

The aim of the current study was to perform T2 relaxation time measurements in multiple sclerosis (MS) patients and correlate them with magnetization transfer ratio (MTR) measurements, in order to investigate in more detail the various histopathological changes that occur in lesions and normal-appearing white matter (NAWM). A total number of 291 measurements of MTR and T2 relaxation times were performed in 13 MS patients and 10 age-matched healthy volunteers. Measurements concerned MS plaques (105), NAWM (80), and dirty white matter (DWM; 30), evenly divided between the MS patients, and normal white matter (NWM; 76) in the healthy volunteers. Biexponential T2 relaxation-time analysis was performed, and also possible linearity between MTR and mean T2 relaxation times was evaluated using linear regression analysis in all subgroups. Biexponential relaxation was more pronounced in black-hole lesions (16.6%) and homogeneous enhancing plaques (10%), whereas DWM, NAWM, and mildly hypointense lesions presented biexponential behavior with a lower frequency(6.6, 5, and 3.1%, respectively). Non-enhancing isointense lesions and normal white matter did not reveal any biexponentional behavior. Linear regression analysis between monoexponential T2 relaxation time and MTR measurements demonstrated excellent correlation for DWM(r=–0.78, p<0.0001), very good correlation for black-hole lesions(r=-0.71, p=0.002), good correlation for isointense lesions(r=–0.60, p=0.005), moderate correlation for mildly hypointense lesions(r=–0.34, p=0.007), and non-significant correlation for homogeneous enhancing plaques, NAWM, and NWM. Biexponential T2 relaxation-time behavior is seen in only very few lesions (mainly on plaques with high degree of demyelination and axonal loss). A strong correlation between MTR and monoexponential T2 values was found in regions where either inflammation or demyelination predominates; however, when both pathological conditions coexist, this linear relationship is lost.     

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.     

1H MR spectroscopy of the brain in multiple sclerosis subtypes with analysis of the metabolite concentrations in gray and white matter: initial findings

Many MR spectroscopy (MRS) studies of multiple sclerosis (MS) have focussed on metabolism in normal-appearing white matter (NAWM) and in white matter lesions (WML). In this study, eight patients suffering from primary or secondary progressive MS (PPMS/SPMS) and seven patients with relapsing/remitting MS (RRMS) were examined by ¹H-MRS to assess metabolite levels in gray matter (GM) as well. ¹H-MRS chemical-shift imaging of a cerebral volume of interest of 8×8×2 cm³ above the lateral ventricles revealed differences between the metabolite concentrations in the three groups varying from almost significant [NAWM, choline (cho); P=0.0547] to highly significant [GM, N-acetylaspartate (NAA); P=0.0003]. In PPMS/SPMS patients, the decreases in choline, creatine (Cr) and N-acetylaspartate compared with six healthy controls were significant in GM and to a lesser extent, in NAWM. No significant differences in metabolite concentrations were found between RRMS and controls. In WML, all metabolites were reduced compared with white matter in controls (Cho: P=0.0020; Cr and NAA: P<0.0001, both). In conclusion, the concentrations of Cho, Cr and NAA are reduced in PPMS/SPMS patients, especially in GM and in WML. Despite contrary observations in previous studies, increases in the concentrations of Cr and/or Cho were not observed.