Analysis of MTR histograms in multiple sclerosis using principal components and multiple discriminant analysis.

Magnetization transfer ratio (MTR) histograms have the potential to characterize subtle diffuse changes in multiple sclerosis (MS) and other white matter disease. A new method is described which gives improved correlation with the Expanded Disability Status Scale (EDSS). Classification of individual subjects into normal and MS subgroups is shown. Principal component analysis (PCA) and multiple discriminant analysis (MDA) are shown to give results superior to methods of MTR histogram analysis using traditional features such as peak height and peak location. Scatterplots confirm the improved separation between groups achieved using the MDA score. The histogram analysis provides a comparison of two classification approaches, based on PCA and MDA, to recognize differences between normal controls and the four different subgroups of MS disease (and all MS patients). Multiple linear regression of these PCs vs. EDSS established an MR-based measure of disease. Using a central 60-mm slab of brain tissue, the success rate of binary classification between control and MS subgroups using MDA was 75-95%, depending on which two groups were being compared. Multiple regression analysis of EDSS with the first three PCs as independent variables was significant (r = 0.83 for secondary progressive MS, and r = 0.80 for all MS patients).     

A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients

Magnetization transfer and T₂ relaxation data were obtained for five white and six gray matter brain structures from 10 normal volunteers and 9 multiple sclerosis patients. Thirty MS lesions were also anatyzed. Magnetization transfer ratios and myelin water percentages were compared. Both techniques showed a significant difference between the average of white and gray matter of the normal volunteers as well as the average of nor mal-appearing white matter and gray matter of the multiple sclerosis patients. The average magnetization transfer ratio and myelin water percentage for lesions were significantly lower than those of normal-appearing white matter. Myelin water per centages and magnetization transfer ratios were uncorrelated in white and gray matter but showed a small (R = 0.5, P = 0.005) but significant correlation in multiple sclerosis lesions. In sum mary, the myelin water percentage and the magnetization trans fer ratio provide quantifiable but largely independent measures of multiple sclerosis lesion pathology.     

Individual voxel‐based analysis of brain magnetization transfer maps shows great variability of gray matter injury in the first stage of multiple sclerosis

In multiple sclerosis (MS), it seems likely that the variability of the long‐term disability might be partly due to the variability of the early gray matter (GM) injury. In the present study, we assessed the variability of GM injury in early MS, using a method designed to determine individual pathological GM patterns. Eighteen patients presenting with a clinically isolated syndrome and 24 healthy matched control subjects were included in this study. Patients were explored using a 1.5 Tesla MR scanner (Magnetom Vision Plus; Siemens). Brain MR protocol included magnetization transfer ratio imaging (MTR). Statistical mapping analyses were performed to compare each subject's GM MTR maps with those of the whole group of control subjects (SPM5). The statistical threshold was taken to be the maximum P value showing no significant cluster when any control individual was compared with the whole control population. GM abnormalities were observed in 83% of the patients, ranging in size from 0.3 to 125 cm³. Among the patients with GM abnormalities, 87% had abnormalities located in the temporal cortex, 80% in the frontal cortex, 80% in the limbic cortex, 73% in the posterior fossa, 53% in the deep GM, 47% in the parietal cortex, and 47% in the occipital cortex. Individual statistical mapping of MTR data, which gives a quantitative assessment of individual GM lesions, demonstrates great variability of grey matter injury in the first stage of multiple sclerosis. J. Magn. Reson. Imaging 2010;32:424–428. © 2010 Wiley‐Liss, Inc.     

Correlation of apparent myelin measures obtained in multiple sclerosis patients and controls from magnetization transfer and multicompartmental T2 analysis.

Two relatively new techniques purport to give measures of the myelin content of brain tissue. These measures are the myelin water fraction from multicompartmental T(2) analysis, and the semisolid proton fraction from analysis of magnetization transfer (MT). The myelin water fraction is the fraction of signal with a T(2) of less than 50 ms measured from a 32-echo sequence. It is believed to originate from water trapped between the myelin bilayers. The semisolid proton fraction is thought to include protons within phospholipid bilayers and macromolecular protons, and may also be a measure of myelin content. Multicompartmental T(2) and MT imaging were carried out on controls and patients with multiple sclerosis (MS), and estimates of the semisolid proton and myelin water fractions were obtained from white matter (WM), gray matter (GM), and MS lesions. These were then correlated for each tissue and subject group. Positive correlations were seen for MS lesions (r approximately 0.2) and in WM in patients (r = 0.6). A negative correlation (r approximately -0.3) was seen for GM. These results indicate that the two techniques measure, to some extent, the same thing (most likely myelin content), but that other factors, such as inflammation, mean they may provide complementary information.     

Quantitative volumetric magnetization transfer analysis in multiple sclerosis: Estimation of macroscopic and microscopic disease burden

Magnetization transfer imaging (MTI) has been shown to be sensitive to both macroscopic and microscopic disease in multiple sclerosis (MS). In this study three-dimensional MTI was used to estimate the global burden of disease in large volumes of brain tissue. MTI was performed in 15 MS patients and 11 normal controls. In seven MS patients MTI was performed on two different occasions. MTI data were displayed as magnetization transfer ratio (MTR) histograms and analyzed. The peak height of the histograms, presumably reflecting the residual amount of normal brain tissue, was lower in MS patients as compared with normal controls (P < 0.001), and was found to correlate with the duration of disease (P < 0.05). A decrease of the MTR histogram peak height was observed in the course of the disease (P < 0.01). These findings suggest that in MS, volumetric MTI provides quantitative information reflecting the global burden of disease.     

Quantitative magnetization transfer mapping of bound protons in multiple sclerosis

Quantitative analysis of magnetization transfer images has the potential to allow a more thorough characterization of the protons, both bound and free, in a tissue by extracting a number of parameters relating to the NMR properties of the protons and their local environment. This work develops previously presented techniques to produce estimates of parameters such as the bound proton fraction, f, and the transverse relaxation time of the bound pool, T(2B), for the whole brain in a clinically acceptable imaging time. This is achieved by limiting the number of data collected (typically to 10); to collect 28 5-mm slices with a reconstructed resolution of 0.94 x 0.94 mm. The protocol takes 82 sec per data point. The fitting technique is assessed against previous work and for fitting failures. Maps and analysis are presented from a group of seven controls and 20 multiple sclerosis patients. The maps show that the parameters are sensitive to tissue-specific differences and can detect pathological change within lesions. Statistically significant differences in parameters such as T(2B) and f are seen between normal-appearing white matter, multiple sclerosis lesions, and control white matter. Whole-brain histograms of these parameters are also presented, showing differences between patients and controls.     

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing–remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing–remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing–remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes—affecting both white and DGM—may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing–remitting multiple sclerosis patients. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

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.     

Added value of double inversion recovery magnetic resonance sequence in detection of cortical and white matter brain lesions in multiple sclerosis

Objective

The aim of this study was to evaluate the value of double inversion recovery (DIR) magnetic resonance (MR) sequence in the detection of brain cortical and white matter lesions in multiple sclerosis (MS).

Patients and methods

Fifteen patients with remitting relapsing MS were included in this study. Imaging was performed on a 1.T MR system using DIR, fluid-attenuated inversion-recovery (FLAIR), and T2-weighted image (T2WI) sequences. The sensitivity of DIR was compared with the corresponding sensitivity of FLAIR and T2WI sequences. The contrast between lesions and normal-appearing gray matter (NAGM), normal-appearing white matter (NAWM), and cerebrospinal fluid (CSF) was determined for all sequences.

Results

DIR showed significantly more MS lesion load overall when compared to T2WI or FLAIR. Significantly higher number of lesions was seen in the supra- and infratentorial locations. DIR detected higher periventricular white matter lesions when compared to FLAIR, but did not detect significantly higher lesions when compared to T2WI. Significantly higher deep white matter, juxtacortical, and intracortical lesions were seen on DIR when compared to both T2WI and FLAIR. The image contrast measurements between the MS lesions and the NAWM in all anatomical locations were significantly higher in DIR sequence compared to both T2WI and FLAIR sequences. However, there was no significant statistical difference between the DIR and both T2WI and FLAIR sequences regarding the contrast of intracortical lesions compared to NAGM.

Conclusion

DIR sequence is valuable in the imaging workup of MS as it can detect more MS lesions compared to the T2W and FLAIR sequences in all anatomical locations. DIR showed better delineation between the white matter, gray matter, and the MS lesions due to its high image contrast. DIR sequence should be included in the routine MR protocol of MS patients especially to answer the question about intra-cortical and juxta-cortical MS lesions.     

Evaluation of Gd-enhancement in brain MR of multiple sclerosis: image subtraction with and without magnetization transfer

The aim of our study was to test the possibility of using image subtraction in detecting enhancing lesions in brain MR scans with and without magnetization transfer (MT) in multiple sclerosis (MS). Ten MS patients underwent 1.5-T MR imaging of the brain with spin-echo T1-weighted sequences with and without MT, repeated after 0.1 mmol/kg of an usual two-compartment paramagnetic contrast agent (Gadoteridol, Gd-HP-DO3A). Precontrast images were subtracted from postcontrast. Enhancing lesions were counted on the postcontrast images only (post-Gd), comparing pre- and postcontrast images by direct visual control (pre/post-Gd), and on the subtracted images (SI) only. Without MT, 36 enhancing lesions were counted on post-Gd, 36 on pre/post-Gd, and 59 on SI; using MT, 69, 52, and 50, respectively. Significant differences were found for pre/post-Gd without MT vs SI without MT ( p=0.028) and vs pre/post-Gd with MT ( p=0.012) as well as for pre/post-Gd with MT vs post-Gd with MT ( p=0.028). With pre/post-Gd, MT allowed the detection of 1.6 enhancing lesions per patient more than without MT. Whereas the SI without MT allow the detection of an increased number of enhancing lesions, SI with MT do not. An off-site final assessment allowed calculation of sensitivity and positive predictive value as follows: without MT were 63 and 94% (post-Gd), 67 and 100% (pre/post-Gd), 96 and 88% (SI); and with MT were 93 and 73% (post-Gd), 96 and 100% (pre/post-Gd), 91 and 98% (SI), respectively. Thus, SI seem to increase the sensitivity without MT; moreover, they could be used to correct the pseudoenhancement that impair post-Gd images with MT.     

Comparison of grey matter atrophy between patients with neuromyelitis optica and multiple sclerosis: a voxel-based morphometry study

Purpose

Previous studies have established regional grey matter (GM) loss in multiple sclerosis (MS). However, whether there is any regional GM atrophy in neuromyelitis optica (NMO) and the difference between NMO and MS is unclear. The present study addresses this issue by voxel-based morphometry (VBM).

Methods

Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 26 NMO patients, 26 relapsing–remitting MS (RRMS) patients, and 26 normal controls. An analysis of covariance model assessed with cluster size inference was used to compare GM volume among three groups. The correlations of GM volume changes with disease duration, expanded disability status scale (EDSS) and brain T2 lesion volume (LV) were analyzed.

Results

GM atrophy was found in NMO patients in several regions of frontal, temporal, parietal lobes and insula (uncorrected, p < 0.001). While extensive GM atrophy was found in RRMS patients, including most cortical regions and the deep grey matter (corrected for multiple comparisons, p < 0.01). Compared with NMO, those with RRMS had significant GM loss in bilateral thalami, caudate, left parahippocampal gyrus, right hippocampus and insula (corrected, p < 0.01). In RRMS group, regional GM loss in right caudate and bilateral thalami were strongly correlated with brain T2LV.

Conclusions

Our study found the difference of GM atrophy between NMO and RRMS patients mainly in deep grey matter. The correlational results suggested axonal degeneration from lesions on T2WI may be a key pathogenesis of atrophy in deep grey matter in RRMS.     

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。     

Quantitative magnetization transfer and myelin water imaging of the evolution of acute multiple sclerosis lesions

Quantitative magnetization transfer imaging provides in vivo estimates of liquid and semisolid constituents of tissue, while estimates of the liquid subpopulations, including myelin water, can be obtained from multicomponent T₂ analysis. Both methods have been suggested to provide improved myelin specificity compared to conventional MRI. The goal of this study was to investigate the sensitivity of each technique to the progression of acute, gadolinium‐enhancing regions of multiple sclerosis. Magnetization transfer and T₂ relaxometry data were acquired longitudinally over the course of 1 year in five relapsing‐remitting multiple sclerosis patients and in five healthy controls. Parametric maps were analyzed in enhancing lesions and normal‐appearing white matter regions. Quantitative magnetization transfer parameters in lesions were most abnormal at the time of enhancement and followed a pattern of recovery over subsequent months. Lesion myelin water fraction was abnormal but did not show a significant trend over time. Quantitative magnetization transfer was able to track the degree and timing of the partial recovery in enhancing multiple sclerosis lesions in a small group of patients, while the recovery was not detected in myelin water estimates, possibly due to their large variability. Our data suggest the recovery is characterized by quick resolution of inflammation and a slower remyelination process. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.