Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: a TBSS study

Objective

To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data.

Methods

Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS.

Results

The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified.

Conclusion

Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.     

Caudate nuclei volume,diffusion tensor metrics,and T2 relaxation in healthy adults and relapsing‐remitting multiple sclerosis patients: Implications for understanding gray matter degeneration

Purpose

To investigate the utility of caudate nuclei (CN) macro‐ and microstructural metrics as markers of gray matter degeneration in healthy adults and relapsing‐remitting multiple sclerosis (RRMS) patients.

Materials and Methods

The normal age‐ and pathology‐related changes in caudate nuclei volume (CNV), the corresponding diffusion tensor metrics, and the T₂ relaxation times were measured in a cohort of 32 healthy adults (12 men/20 women; age range 21–59 years) and 32 age‐matched RRMS patients (8 men/34 women; age range 21–57 years).

Results

Smaller values in both the absolute CNV and the caudate volume ratio relative to the total intracranial volume (CNVp) were observed in the RRMS group relative to healthy controls. The fractional anisotropy (FA), based on the diffusion tensor imaging (DTI) of the CN increased with age in healthy adults (r = 0.52; P = 0.003) but not in patients (r = 0.28; P = 0.12). The caudate FA value was approximately 9% larger in RRMS patients relative to controls (P = 0.001). The mean diffusivity of the CN was greater in the RRMS group compared to controls (P = 0.02). The caudate T₂ relaxation times were smaller in the RRMS group relative to the control group (3% reduction, P = 0.05). T₂ relaxation times did not exhibit age‐related changes (P > 0.35) in either cohort. Strong and significant correlations between CNVp and whole‐brain lesion load (r = ?0.48; P = 0.005) and whole‐brain CSF fraction (r = ?0.46; P = 0.01) were also noted.

Conclusion

These preliminary findings indicate that caudate DTI‐derived metrics can serve as potential quantitative radiological markers of MS pathology. J. Magn. Reson. Imaging 2009;29:70–77. © 2008 Wiley‐Liss, Inc.

     

Multiple sclerosis: Hyperintense lesions in the brain on T1‐weighted MR images assessed by diffusion tensor imaging

Purpose:

To evaluate retrospectively quantitative diffusion tensor imaging (DTI) values of hyperintense lesions on nonenhanced T1‐weighted magnetic resonance (MR) images in patients with multiple sclerosis (MS) to elucidate the degree of demyelination or remyelination associated with T1 hyperintense lesions and study their relationship to MR markers of tissue damage (brain atrophy).

Materials and Methods:

Institutional review board approval was obtained; informed consent was waived for this HIPAA‐compliant study, including 76 patients with MS and 20 healthy control subjects without evidence of MS clinically or on imaging. T1 lesions were compared with normal white matter on nonenhanced images and judged to be hyperintense. Quantitative DTI metrics of T1 hyperintense lesions were examined, and the relationship between DTI parameters and brain atrophy were investigated in this study.

Results:

At least one T1 hyperintense lesion was found in 16 patients (total, 28 lesions). Hyperintense lesions on T1‐weighted imaging (T1WI) had lower mean diffusion (MD) than others signal intensity lesions on T1WI but higher MD than normal white matter (F = 3.931; P < 0.001); Fractional anisotropy (FA; F = 3.24; P < 0.001) and volume ratio (VR; F = 1.664; P < 0.001) were higher in hyperintense lesions on T1WI than hypointense/isointense lesions on T1WI, but were lower than normal‐appearing white matter (NAWM) and normal white matter in controls. There was correlation between FA and VR (r = 0.678; P < 0.001) and inverse correlation between FA and MD (r = ?0.437; P = 0.02), MD and VR (r = ?0.423; P 0.025) for T1 hyperintense lesion. The MD values of T1 hyperintense lesions (r = ?0.304; P < 0.001) and the VR values of T1 hyperintense lesions (r = 0.096; P = 0.042) were significantly (negative) correlated with Brain parenchymal fraction (BPF; higher BPF score); the FA values of T1 hyperintense lesions (r = ?0.111; P = 0.018), the MD values of T1 hyperintense lesions (r = 0.379; P < 0.001) and the VR values of T1 hyperintense lesions (r = ?0.142; P = 0.003) were significantly correlated with third ventricular width (lower width). However, the FA value of T1 hyperintense lesions was not significantly associated with BPF(r = 0.083; P = 0.08).

Conclusion:

The quantitative DTI values of T1 hyperintense MS plaques were between hypo‐/isointense lesions and NAWM or normal white matter, and correlated with BPF and third ventricular width. Our results supports the notion that axonal remyelination may be the reason for T1 hyperintense lesions. J. Magn. Reson. Imaging 2010;31:789–795. ©2010 Wiley‐Liss, Inc.

     

Mapping of iron deposition in conjunction with assessment of nerve fiber tract integrity in amyotrophic lateral sclerosis

Purpose:

To test if and where increased iron accumulation occurs in amyotrophic lateral sclerosis (ALS) by quantitative mapping of iron deposition and to relate these findings to white matter tract degeneration assessed by diffusion tensor imaging (DTI).

Materials and Methods:

Fifteen patients with ALS and 15 age‐ and gender‐matched controls underwent MRI of the brain to obtain R₂* relaxation rate and DTI measurements, focusing on the corticospinal tract (CST) and on deep gray matter structures, using tract‐based spatial statistics (TBSS).

Results:

Compared with controls, ALS patients showed reduced fractional anisotropy values along the mesencephalic CST, suggesting disintegration of fiber tracts. A trend for R₂* values to be elevated was found in the CST of ALS patients. Regarding other brain areas examined, increased R₂* values in ALS patients were observed solely in the caudate nucleus.

Conclusion:

This study extends previous findings on fiber disorganization by additional quantitative evidence for increased iron deposition in closely localized regions along the CST in ALS patients. Longitudinal studies are needed to further explore the pathophysiologic and diagnostic implications of these findings. J. Magn. Reson. Imaging 2010;31:1339–1345. © 2010 Wiley‐Liss, Inc.     

Correlation of cognitive dysfunction and diffusion tensor MRI measures in patients with mild and moderate multiple sclerosis

Purpose

To compare the diffusion tensor imaging (DTI) measures of multiple sclerosis (MS) patients and healthy subjects in every brain voxel and to correlate them with Paced Auditory Serial Addition Test (PASAT) scores.

Materials and Methods

Fractional anisotropy (FA), and mean, longitudinal, and transverse diffusivity are compared between control subjects and MS patients, which were subdivided as mildly and moderately impaired. In addition, PASAT scores are correlated for both MS groups with the diffusion measures. An optimized voxel based analysis (VBA) method, in terms of coregistration, atlas construction, and image smoothing, was thereby used.

Results:

Diffusion differences between the control subjects and the patients with MS were found in the corpus callosum, inferior longitudinal fasciculus, cortico spinal tracts, forceps major, superior longitudinal fasciculus, and cingulum. In addition, we observed significant correlations of the FA and PASAT scores in the left inferior longitudinal fasciculus, the forceps minor, the capsula interna and externa, the genu of the corpus callosum, the left cingulum, the superior longitudinal fasciculus, and the corona radiata.

Conclusion:

Diffusion differences were observed between the mildly impaired MS patients and control subjects. In addition, different diffusion measures correlated with PASAT scores for cognitive decline in parietal, frontal, as well as temporal white matter (WM) regions. J. Magn. Reson. Imaging 2010;31:1492–1498. © 2010 Wiley‐Liss, Inc.     

脊髓型多发性硬化脑白质DTI直方图分析

目的:研究脊髓型多发性硬化(SMS)是否存在脑白质损伤。方法:对25例SMS患者和35例正常志愿者行常规MRI和DTI检查,分割提取脑白质后,研究SMS患者脑白质平均弥散率(MD)和分数各向异性(FA)直方图的异常变化。结果:同正常志愿者比较,SMS患者脑白质的平均MD增高(P=0.005),平均FA降低(P=0.001)和MD直方图峰位置降低(P=0.007)。在SMS患者,脑白质MD直方图峰高与扩展残疾状态评分(EDSS)中度相关(r=0.453,P=0.023)。结论:SMS患者脑白质存在损伤,脑白质MD直方图峰高可用于监测SMS患者的临床进展。     

A diffusion tensor imaging group study of the spinal cord in multiple sclerosis patients with and without T2 spinal cord lesions

Purpose

To examine the T₂‐normal appearing spinal cord of patients with multiple sclerosis (MS) using diffusion tensor imaging.

Materials and Methods

Diffusion tensor images of the spinal cord were acquired from 21 healthy subjects, 11 MS patients with spinal cord lesions, and 10 MS patients without spinal cord lesions on the T₂‐weighted MR images. Different diffusion measures were evaluated using both a region of interest (ROI) ‐based and a diffusion tensor tractography‐based segmentation approach.

Results

It was observed that the FA, the transverse diffusivity λ_?, and the ratio of the longitudinal and transverse diffusivities (λ_∥/λ _?) were significantly lower in the spinal cord of MS patients with spinal cord lesions compared with the control subjects using both the ROI method (P = 0.014, P = 0.028, and P = 0.039, respectively) and the tractography‐based approach (P = 0.006, P = 0.037, and P = 0.012, respectively). For both image analysis methods, the FA and the λ _∥/λ _? values were significantly different between the control group and the MS patient group without T₂ spinal cord lesions (P = 0.013).

Conclusion

Our results suggest that the spinal cord may still be affected by MS, even when lesions are not detected on a conventional MR scan. In addition, we demonstrated that diffusion tensor tractography is a robust tool to analyze the spinal cord of MS patients. J. Magn. Reson. Imaging 2009;30:25–34. © 2009 Wiley‐Liss, Inc.

     

运用白质地图定量分析多发性硬化小脑解剖连接改变的研究

目的 运用基于白质地图(ABA)的扩散张量成像(DTI)分析方法,探讨复发-缓解型多发性硬化(RRMS)患者表现正常小脑解剖连接隐匿损伤及DTI在多发性硬化临床研究中的价值.方法 选择RRMS患者21例及性别、年龄相匹配健康对照19例行常规磁共振及DTI扫描,DTI数据后处理获得小脑解剖连接(小脑中脚、小脑上脚和小脑下脚)的DTI参数值,其参数包括部分各向异性分数(FA)、平均扩散系数(MD)、径向扩散系数(RD)、轴向扩散系数(AD),进行2组数据比较分析,并将DTI参数值与临床残疾扩展评分、病程行相关性分析.结果 与对照组比较,RRMS组小脑中脚、左侧小脑上脚及双侧小脑下脚FA值降低、RD值升高(P＜0.05);小脑中脚及左侧小脑下脚MD值、AD值升高(P＜0.05).小脑中脚FA值与病程呈负相关,小脑中脚及右侧小脑下脚MD值、AD值、RD值分别与病程呈正相关.结论 RRMS患者表现正常小脑解剖连接存在隐匿性损伤,且DTI可在一定程度上监测患者病情.     

Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis.

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal-appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within-subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS.     

Diffusion tensor fractional anisotropy of the normal-appearing seven segments of the corpus callosum in healthy adults and relapsing-remitting multiple sclerosis patients

PURPOSE: To investigate the utility of whole-brain diffusion tensor imaging (DTI) in elucidating the pathogenesis of multiple sclerosis (MS) using the normal-appearing white matter (NAWM) of the corpus callosum (CC) as a marker of occult disease activity. MATERIALS AND METHODS: A high signal-to-noise ratio (SNR) and optimized entire brain DTI data were acquired in 26 clinically-definite relapsing and remitting multiple sclerosis (RRMS) patients and 32 age-matched healthy adult controls. The fractional anisotropy (FA) values of seven functionally distinct regions in the normal-appearing CC were compared between patients and controls. RESULTS: This study indicates that 1) there was a gender-independent FA heterogeneity of the functionally specialized CC segments in normal volunteers; 2) FA in the MS group was significantly decreased in the anterior (P=0.0039) and posterior (P=0.0018) midbody subdivisions of the CC, possibly due to a reduction of small-caliber axons; and 3) the FA of the genu of the CC was relatively intact in the MS patients compared to the healthy age-matched controls (P=0.644), while the splenium showed an insignificant trend of reduced FA values (P=0.248). The decrease in FA in any of the CC subdivisions did not correlate with disease duration (DD) or the expanded disability status scale (EDSS) score. CONCLUSION: The preliminary results are consistent with published histopathology and clinical studies on MS, but not with some published DTI reports. This study provides insights into the pathogenesis of MS, and the role played by compromised axonal integrity in this disease.     

Reducing the impact of white matter lesions on automated measures of brain gray and white matter volumes

Purpose:

To develop an automated lesion‐filling technique (LEAP; LEsion Automated Preprocessing) that would reduce lesion‐associated brain tissue segmentation bias (which is known to affect automated brain gray [GM] and white matter [WM] tissue segmentations in people who have multiple sclerosis), and a WM lesion simulation tool with which to test it.

Materials and Methods:

Simulated lesions with differing volumes and signal intensities were added to volumetric brain images from three healthy subjects and then automatically filled with values approximating normal WM. We tested the effects of simulated lesions and lesion‐filling correction with LEAP on SPM‐derived tissue volume estimates.

Results:

GM and WM tissue volume estimates were affected by the presence of WM lesions. With simulated lesion volumes of 15 mL at 70% of normal WM intensity, the effect was to increase GM fractional (relative to intracranial) volumes by ≈2.3%, and reduce WM fractions by ≈3.6%. Lesion filling reduced these errors to ≈0.1%.

Conclusion:

The effect of WM lesions on automated GM and WM volume measures may be considerable and thereby obscure real disease‐mediated volume changes. Lesion filling with values approximating normal WM enables more accurate GM and WM volume measures and should be applicable to structural scans independently of the software used for the segmentation. J. Magn. Reson. Imaging 2010. © 2010 Wiley‐Liss, Inc.     

多发性硬化灰质病变MRI研究进展

多发性硬化(MS)是以脱髓鞘、炎症、神经胶质过多及神经元丢失为特征的中枢神经系统的神经退化疾病,以时间上的多发性(多次发作)及空间上的多发性(多个部位发作)为特征,病因不明。MS的各个时期均存在灰质损伤并与临床功能障碍有较大的联系。新兴MRI技术能够检测灰质的病灶、微观结构损害、代谢物变化、血氧水平及灌注变化等多方面信息,为深入理解MS的发病机制、制定治疗方案以及评估预后提供大量有价值的信息,就MRI技术在MS灰质病变检测中的研究进展予以综述。     

Using diffusion tensor imaging and immunofluorescent assay to evaluate the pathology of multiple sclerosis

Purpose:

To determine the ability of the principal diffusion tensor imaging (DTI) indices to predict the underlying histopathology evaluated with immunofluorescent assay (IFA).

Materials and Methods:

Conventional T2 and 3D multishot‐diffusion weighted echoplanar imaging (3D ms‐DWEPI) was performed on a fixed, ex vivo human cervical spinal cord (CSC) from a patient with a history of multiple sclerosis (MS). In all, 170 regions of interest (ROIs) were selected within the white matter and categorized as a high intensity lesion (HIL), low intensity lesion (LIL), and normal‐appearing white matter (NAWM). The longitudinal diffusivity (λl), radial diffusivity (λr), and fractional anisotropy (FA) were obtained from each ROI. The underlying histopathology was then evaluated using immunofluorescent assay with antibodies directed to myelin and neurofilament staining.

Results:

The mean values for λl and λr were significantly elevated within HIL relative to NAWM and LIL. IFA analysis of HIL demonstrated significant demyelination, without significant if any axon loss. The FA values were significantly reduced in HIL and LILs. FA values were also reduced in lesions with increased λl and λr values relative to normal.

Conclusion:

Aberrant λl, λr, and FA relative to normal values are strong indicators of demyelination. DTI indices are not specific for axon loss. IFA analysis is a reliable method to demonstrate myelin and axon pathology within the ex vivo setting. J. Magn. Reson. Imaging 2011;33:557–564. © 2011 Wiley‐Liss, Inc.     

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.