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.     

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.     

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.     

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.     

Macroscopic and microscopic assessments of disease burden by MRI in multiple sclerosis: Relationship to clinical parameters

We have evaluated macroscopic white matter abnormalities (visible lesions) together with microscopic abnormalities in the normal appearing white matter (NAWM) of patients with multiple sclerosis (MS) to determine their relative contributions to the development of disability. The total visible lesion volume (TLV) was computed as a measure macroscopic changes, whereas both texture analysis and T2 were used as possible indicators of diffuse disease in the NAWM. Dual echo T2-weighted SE images were obtained from 41 patients with definite MS: 10 primary progressive (PP), 11 secondary progressive (SP), 10 benign (BE), 10 early relapsing remitting (ERR), as well as from 10 healthy controls. Calculation of T2 and texture parameters were performed in a region of frontal NAWM of patients and controls. The TLV of each patient was measured using a semiautomated lesion detection program. No significant differences were found between the controls and the patients for all texture parameters examined. However, NAWM T2 was longer in the patients than in the controls (P = .02). Mean TLV was highest for SP and lowest for BE and ERR patients. A significant correlation was found between TLV and EDSS (P < .01) but not between NAWM T2 or texture and expanded disability status score (EDSS). Our study suggest that: (a ) diffuse changes are present in NAWM, (b) texture analysis is unable to detect any subtle structure in the NAWM abnormalities, possibly because of the limited image resolution; (c) in the development of disability in MS, macroscopic lesions are more important than microscopic abnormalities in the NAWM.     

Early anisotropy changes in the corpus callosum of patients with optic neuritis

INTRODUCTION: Optic neuritis (ON) and any other early manifestation of multiple sclerosis (MS) are referred to as clinically isolated syndrome (CIS) as long as MS is suspected. In this prospective study we aimed to determine whether diffusion tensor imaging (DTI) could quantify structural changes in patients with early MS. METHODS: A total of 24 patients and 15 control subjects were prospectively followed by clinical examinations and MRI. the main inclusion criterion was presentation with ON. Patients underwent serial MRI scans: MRI1 (baseline, n=24), MRI2 (mean 6.6 months, n=24), MRI3 (mean 13.0 months, n=14), MRI4 (mean 39.4 months, n=5). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were derived from DTI. Four regions of interest (ROIs) were defined in normal-appearing white matter (NAWM). RESULTS: In the temporal course FA decreased in the genu of the callosal body (GCC) from MRI1 to MRI4 (P=0.005) and in the splenium of the callosal body (SCC) (P=0.006). Patients already had lower FA values in the SCC (P<0.01) on MRI1 compared with the controls. Patients had lower FA values in the GCC (P<0.01) starting from MRI2. Patients with definite MS on follow-up (n=9) showed a correlation between FA in the SCC and time (r=-0.40, P=0.004), whereas patients without progression did not. CONCLUSIONS: Our findings suggest that the corpus callosum is an early site for development of anisotropy changes in MS patients with ON. There seems to be a primary FA decrease in all patients with ON that only deteriorates in the group developing definite MS.     

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.     

Spinal cord magnetic resonance imaging in suspected multiple sclerosis

We examined the value of spinal cord magnetic resonance imaging (MRI) in the diagnostic work-up of multiple sclerosis (MS). Forty patients suspected of having MS were examined within 24 months after the start of symptoms. Disability was assessed, and symptoms were categorized as either brain or spinal cord. Work-up further included cerebrospinal fluid analysis and standard proton-density, T2-, and T1-weighted gadolinium-enhanced brain and spinal cord MRI. Patients were categorized as either clinically definite MS (n = 13), laboratory-supported definite MS (n = 14), or clinically probable MS (n = 4); four patients had clinically probable MS, and in nine MS was suspected. Spinal cord abnormalities were found in 35 of 40 patients (87.5 %), consisting of focal lesions in 31, only diffuse abnormalities in two, and both in two. Asymptomatic spinal cord lesions occurred in six patients. All patients with diffuse spinal cord abnormality had clear spinal cord symptoms and a primary progressive disease course. In clinically definite MS, the inclusion of spinal imaging increased the sensitivity of MRI to 100 %. Seven patients without a definite diagnosis had clinically isolated syndromes involving the spinal cord. Brain MRI was inconclusive, while all had focal spinal cord lesions which explained symptoms and ruled out other causes. Two other patients had atypical brain abnormalities suggesting ischemic/vascular disease. No spinal cord abnormalities were found, and during follow-up MS was ruled out. Spinal cord abnormalities are common in suspected MS, and may occur asymptomatic. Although diagnostic classification is seldom changed, spinal cord imaging increases diagnostic sensitivity of MRI in patients with suspected MS. In addition, patients with primary progressive MS may possibly be earlier diagnosed. Finally, differentiation with atypical lesions may be improved. Received: 21 April 1999; Revised: 3 August 1999; Accepted: 7 August 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.     

Proton MR spectroscopic imaging in multiple sclerosis

We studied 24 patients with multiple sclerosis (MS) by proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the neurochemical pathology of the white-matter lesions (WML) and normal-appearing white matter (NAWM). Our 1H-MRSI technique allowed simultaneous measurement of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm slices divided into 0.84 ml single-volume elements. In WML we found significantly lower NAA/Cr and NAA/Cho ratios and a significantly higher Cho/Cr ratio than in NAWM or control white matter. In NAWM, NAA/Cr and Cho/Cr were significantly lower than in control white matter. 1H-MRSI was compatible with damage to myelin in WML, and with axonal damage and/or dysfunction in WML and NAWM. These findings extend data on involvement of NAWM in MS beyond the abnormalities visible on MRI.