Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis

While there is now evidence for thalamic abnormality in established secondary progressive and relapsing-remitting multiple sclerosis (MS), it remains unclear when such abnormality begins. This study investigated the emergence of thalamic abnormality in relapsing-remitting MS by assessing the thalamic magnetization transfer ratio (MTR) in a cohort with clinically early disease. Twenty-three patients with early relapsing-remitting MS (mean age 37; mean disease duration 1.9 years; Expanded Disability Status Scale (EDSS) range 0-3) and 19 healthy controls (mean age 34) were imaged yearly with a magnetization transfer imaging sequence. Twenty-two MS patients and 14 controls completed two-year follow-up. Regions of interest were placed in both thalami and mean thalamic MTR calculated. At baseline, significant differences between patient and control thalamic MTR were not observed. However, at years one and two, the thalamic MTR in patients was significantly lower than control MTR. Although baseline lesion volume did not correlate with baseline thalamic MTR, at year one, an association between baseline lesion volume and year one thalamic MTR emerged. There was also a significant inverse correlation between EDSS and thalamic MTR (r = -0.47, P = 0.02). The study suggests that thalamic involvement occurs within the first five years of MS onset, when most patients are still minimally disabled.     

Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis

OBJECTIVE: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. METHODS: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). RESULTS: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p<0.0001) and of kfor (F7,166=105.2; p<0.0001), and by an increase of T1free (F7,166=57.3; p<0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. CONCLUSIONS: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event     

Brain and spinal cord atrophy in multiple sclerosis

Until recently, atrophy of the brain and spinal chord was thought to occur late in the course of multiple sclerosis (MS) or as a result of rare, fulminant disease. Now atrophy is known to occur early and likely indicates destructive and irreversible pathologic change that may be subclinical. Central nervous system atrophy from MS now can be measured accurately over short time intervals. Atrophy may become an important prognostic indicator in MS and is being evaluated as a treatment outcome measure in population studies, and possibly in the future, in individuals.     

Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study

BACKGROUND: Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). OBJECTIVE: To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. METHODS: Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18-month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. RESULTS: Average cervical cord MTR was correlated with relapse rate (r= -0.56, P=0.037). A moderate correlation (r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached (P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. CONCLUSIONS: This study suggests that a 'snapshot' MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.     

Brain MRI correlates of magnetization transfer imaging metrics in patients with multiple sclerosis.

Previous studies suggested that magnetization transfer ratio (MTR) histograms are highly correlated with other magnetic resonance imaging (MRI) measures and can be used as a reliable method for quantifying overall disease burden in multiple sclerosis (MS). However, the relative influence of burden and severity of macroscopic MS lesions and degree of brain atrophy on various MTR histogram parameters has not yet been fully elucidated. Aim of the present study was to investigate which MRI measure best predicts the values of MTR histogram parameters in MS patients. Forty-two MS patients underwent brain dual-echo. T1-weighted and magnetization transfer imaging (MTI) MRI scans. Hyperintense lesion load (LL) on proton density (PD)-weighted and hypointense LL on T1-weighted images were measured using a local thresholding technique. A measure of brain atrophy was derived from T1-weighted images by computing the volume of brain tissue segmented from a slab of five consecutive slices rostral to the velum interpositum. On MTI scans, MTR histogram analysis was performed for the whole brain and average lesion MTR was also calculated. PD-weighted LL, T1-weighted LL and brain volume were significantly correlated with several MTI-derived measures. When a multivariate analysis was performed, brain volume alone significantly predicted the values of all the MTR histogram-derived measures (P values ranged from 0.003 to 0.0002). The ratio between hypointense T1-weighted and hyperintense PD-weighted LL significantly predicted average lesion MTR (P<0.05). Our results confirm that MTR can be used as a reliable method to assess both the overall disease burden and the individual lesion intrinsic nature in MS patients. The significant influence of brain atrophy on MTR histogram parameters supports the concept that this method also provides information on the loss of brain parenchyma in MS.     

Brain atrophy and cognitive impairment in multiple sclerosis: a review

Journal of Neurology - Multiple sclerosis (MS) is a common neurological disease in the Western hemisphere that leads to neurological dysfunctions and frequently from its onset to cognitive...     

Brain atrophy and cognitive impairment in multiple sclerosis: a review

Multiple sclerosis (MS) is a common neurological disease in the Western hemisphere that leads to neurological dysfunctions and frequently from its onset to cognitive impairment, which together predict quality of life. Recent pathological and imaging studies have focused on brain atrophy representing axonal injury and loss as being crucial for developing disability and neuropsychological impairment. Brain atrophy has therefore been proposed to be a tool for monitoring disease progress. Here, we review the possible origins of brain atrophy and its correlation with cognitive impairment in MS.     

Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis

Although there is substantial brain grey matter pathology in secondary progressive multiple sclerosis (MS), there has been limited investigation of its contribution to disability. This study investigated the correlation of magnetization transfer ratio (MTR) measures taken from brain grey matter, normal appearing white matter (NAWM) and lesions with neurological deficit and disability in 113 people with secondary progressive MS. In order to adjust for the potential effects of focal white matter lesions and global brain atrophy, T2 lesion volume and normalized brain volume (NBV) were also calculated for each subject. Clinical measures included the expanded disability status scale (EDSS) and the multiple sclerosis functional composite (MSFC) scores. Linear regression analysis was used to assess the age- and gender-adjusted correlation of MTR histogram mean, peak height and peak location with the MSFC and individual component measures. Logistic regression analysis was used to determine whether imaging measures could be used to predict if subjects were in the higher disability group (EDSS ≥ 6.5). Significant correlations were detected between MSFC composite and mean MTR in (i) normal appearing white matter (NAWM; r = 0.327, p < 0.0001), (ii) grey matter (r = 0.460, p < 0.0001) and (iii) lesions (r = 0.394, p < 0.0001). Although NBV and T2 lesion volume correlated significantly with MSFC, grey matter histogram mean emerged as the best predictor of MSFC score. None of the MRI measures significantly predicted higher EDSS. These results suggest that brain grey matter pathology plays an important role in determining neurological impairment. The apparent paucity of correlation between MRI measures and EDSS is likely to represent the relative insensitivity of the latter measure in this study group.     

Voxel-based analysis of grey matter magnetization transfer ratio maps in early relapsing remitting multiple sclerosis

Previous studies using magnetization transfer ratio (MTR) histogram analysis have demonstrated the existence of global grey matter (GM) abnormalities in patients with early relapsing-remitting multiple sclerosis (RRMS). However, MTR histogram analysis does not provide any information on the localization of the morphological changes within the GM. The aim of this study was to investigate the localization of GM injury in early RRMS, performing voxel-based analysis of GM MTR maps. Statistical mapping analysis of GM MTR maps was performed in a group of 38 patients with early RRMS and 45 healthy controls. Between-group comparisons (P<0.05, corrected for multiple comparisons) demonstrated significant GM MTR decrease in patients located in the bilateral lenticular nuclei, the bilateral insula, the left posterior cingulate cortex, and the right orbitofrontal cortex. To limit the potential confounding effect of regional GM atrophy, the percentages of GM were assessed in the regions showing significant MTR decrease, and no GM atrophy was evidenced in these regions. This study demonstrates that several GM regions are commonly affected in patients with early RRMS. Predominant involvement of these structures may be partly related to their vulnerability to anterograde or retrograde degeneration from transected axons in the white matter and/or to the predominant localization of GM demyelinating lesions in such regions.     

Short-term brain atrophy changes in relapsing-remitting multiple sclerosis

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.     

Magnetization transfer ratio of the spinal cord in multiple sclerosis: relationship to atrophy and neurologic disability.

The authors compare the spinal cord magnetization transfer ratio (MTR) of multiple sclerosis (MS) patients to healthy volunteers, relate MTR to spinal cord atrophy, and relate these and other magnetic resonance (MR) imaging parameters to disability. Sixty-five patients with MS (14 relapsing remitting [RR], 34 secondary progressive [SP], and 17 primary progressive [PP] MS), and 9 healthy volunteers were studied using MR at 1.0 T. Disability of the patients was assessed using the expanded disability status scale (EDSS). Magnetic resonance parameters were upper spinal cord MTR, number of focal spinal lesions, presence of diffuse abnormalities, and spinal cord cross-sectional area (CSA). Correlations were assessed using Spearman's rank correlation coefficient (r). Magnetization transfer ratio was higher in the controls (median, 33%; range, 30%-38%) than in patients with MS (median, 30%; range, 16-36; p < 0.05). In patients with MS EDSS correlated with spinal cord MTR, albeit weakly (r = -0.25, p < 0.05). Correlation between EDSS and spinal cord CSA was better (SRCC = -0.40, p < 0.01). No correlation was found between MTR and CSA (r = 0.1, p = 0.4). Combining MTR with spinal cord CSA improved correlation with EDSS (r = -0.46, p < 0.001), suggesting an independent correlation between disability and these 2 MR parameters. Expanded disability status scale scores were higher in patients who had diffuse spinal cord abnormality regardless of focal lesions (median, 6; range, 1.5-7.5) than in patients without diffuse abnormalities (median, 3.5; range, 0-8; p < 0.01). CSA was lower in patients with diffuse spinal cord abnormality (median, 62; range, 46-89 mm2) than in patients without diffuse abnormalities (median, 73; range, 47-89 mm2; p < 0.01). MTR was slightly lower in patients with diffuse spinal cord abnormalities (median, 29; range, 21%-33%) than in patients without diffuse abnormalities (median, 31; range, 16-36; t-test, p < 0.05).     

多发性硬化患者的磁化传递及弥散张量成像特点

目的比较多发性硬化(MS)患者脑内病灶、表现正常脑白质(NAWM)及健康志愿者脑白质的磁化传递及弥散特性的差异,探讨MS患者的磁化传递率(MTR)与平均弥散率(MD)的相关性。方法分别对24例复发缓解型MS患者和24名健康志愿者行常规MRI、磁化传递成像(MTI)及弥散张量成像(DTI),经处理后得到相应的MTR、MD及各向异性分数(FA)图。测量MS病灶、对侧NAWM及健康志愿者相应脑白质区域的MTR、MD及FA值。结果MS患者病灶的平均MTR值(23.49%±5.16%)明显低于NAWM组(29.49%±3.38%)及健康对照组(32.78%±3.42%,F=101.44,P<0.01);病灶的平均FA值(0.32±0.09)也明显低于NAWM组(0.42±0.09)及对照组(0.51±0.09,F=95.41,P<0.01);而病灶的平均MD值[(1.10±0.17)×10-3mm2/s]明显高于NAWM组[(0.92±0.13)×10-3mm2/s]及对照组[(0.76±0.04)×10-3mm2/s,F=144.89,P<0.01]。与MS患者T1WI等信号病灶相比,低信号病灶的MTR值及FA值降低,而MD值升高。MS患者病灶的MTR值与MD值显著相关,而NAWM的MTR与MD值无明显相关性。结论MTI和DTI的指标可以反映MS患者脑内不同部位病理变化的不同,为常规MRI提供补充信息。     

Regional specificity of magnetization transfer imaging in multiple sclerosis.

BACKGROUND:The goal of this study was to develop and validate a method for generation of regional magnetization transfer ratio (MTR). We also studied the topography of MTR changes in multiple sclerosis (MS) and in normal controls (NC), and preliminarily examined the clinical usefulness of this method.METHODS:We examined 45 patients with MS (relapsing remitting [RR] = 28 and secondary progressive[SP] = 17] and 19 NC. Mean disease duration was 14.3 years and median Expanded Disability Status Scale was 3.0. Regions of the brain were determined using semiautomated brain region extraction (SABRE). Twenty-six regional masks were automatically applied to MTR maps that were further split into gray matter (GM) and white matter (WM)compartments.RESULTS:Mean MTR from 12 SABRE regions differed significantly between MS patients and NC. For WM, all regional mean MTRs differed significantly between RR, SP, and NC participants(P < .001). In regression analysis, only 3 regions remained significantly different when corrected for total T2-LV. The regression model predicting disability selected GM mean MTR of the right medial inferior frontal region (P = .031).CONCLUSIONS:The study results showed that this regional MTR approach is reproducible, reliable and clinically relevant. MTI changes occur selectively in specific sub-regions.     

Brain atrophy after immunoablation and stem cell transplantation in multiple sclerosis

The authors measured brain atrophy in nine patients undergoing immunoablation and autologous hematopoietic stem cell transplantation for multiple sclerosis. From baseline to 1 month after treatment, atrophy was 10 times faster than before treatment. A patient with non-CNS lymphoma showed comparable acute brain atrophy after analogous therapy. These observations suggest that brain atrophy after immunoablation may not be due entirely to the resolution of edema but may be related to chemotoxicity.     

Correlation of magnetization transfer ration with clinical disability in multiple sclerosis

We performed spin echo magnetic resonance imaging with and without application of an off-resonance saturation pulse in 43 patients with multiple selerosis (MS), 10 age-matched controls, and 4 elderly asymptomatic patients with the radiological diagnosis of small-vessel disease. Magnetization transfer (MT) ration images were obtained from these. All MS subgroups (primary progressive, secondary progressive, benign, early relapsing–remitting) showed significantly lower average lesion MT ratios than small-vessel disease patients. Secondary progressive MS patients showed significantly lower lesion MT ratios than those with benign disease, and there was an inverse correlaion of disability with average lesion MT ratio. The degree of reduction of MT ratios is an indicator of the extent of tissue destruction. Thus, reduced MT ratios in MS may provide an indication of the degree of demyelination and axonal loss, both of which are likely to cause functional deficits in MS. We conclude that MT measurement is (1) a robust quantitative method that may increase the pathological specificity of magnetic resonance imaging, (2) has the potential to differentiate demyelination in MS from less destructive pathological changes, and (3) may be useful in monitoring modifications in tissue structure brought about by treatment.     

Correlation of magnetization transfer and diffusion magnetic resonance imaging in multiple sclerosis

The aim of this study was to correlate diffusion to magnetization transfer (MT) magnetic resonance imaging (MRI) results in multiple sclerosis (MS), in order to establish if the former technique provides complementary information. Magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) were measured in 156 different regions of interest (ROIs) of 14 MS patients, where 84 corresponded to T1 hypointense lesions, 60 to T1 isointense lesions and 12 to regions of normal appearing white matter (NAWM). MTR mean value was higher for T1 isointense than for T1 hypointense lesions, and lower when compared to NAWM. ADC mean value for T1 isointense lesions was higher than for NAWM, but lower than for T1 hypointense lesions. A significant negative correlation was found between ADC and MTR for hypointense lesions (Pearson's r = -0.758, P < 0.001), whereas this correlation was much weaker for T1 isointense lesions (Pearson's r= -0.256, P = 0.049). There was no correlation between ADC and MTR for NAWM. The fact that ADC and MTR show a strong correlation only for T1 hypointense lesions indicates that, when tissue integrity is not severely compromised, as in the case of T1 isointense lesions or NAWM, ADC and MTR might be sensitive to different pathological processes.     

Diffusion tensor and magnetization transfer MR imaging of early-onset multiple sclerosis

Neurological Sciences - Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) with the onset of symptoms typically occurring between the age of 20 and 40...     

Brain atrophy in multiple sclerosis: what we know and would like to know

Brain and spinal cord atrophy measures are becoming standard in multiple sclerosis (MS) clinical trials, yet we know little about the underlying mechanisms resulting in atrophy, or the factors accounting for variable rates of atrophy in individuals and across the MS phenotype. We do not understand, as yet, why apparently effective treatment does or does not affect atrophy. Some limitations of this measure may be accounted for by complex structural and temporal factors that become active at the initiation of injury, but are not immediately expressed. Additional limitations include differential effects related to the focal versus diffuse pathology in MS, and variable expression of the pathology underlying atrophy, depending on location in central nervous system (CNS) tissue.     

Brain MRI lesions and atrophy are related to depression in multiple sclerosis

It is unclear whether brain MRI lesions are associated with depression in multiple sclerosis (MS). Neurological dysfunction in depressed (n= 19) and non-depressed (n = 29) MS patients was rated by expanded disability status scale (EDSS). EDSS was weakly predictive of the presence of (p = 0.03) and severity of (p = 0.01) depression. After correcting for EDSS, the presence of depression was predicted by superior frontal and superior parietal hypointense TI lesions (p<0.01); the severity of depression was predicted by superior frontal, superior parietal and temporal TI lesions, lateral and third ventricular enlargement, and frontal atrophy (p<0.01). Depression was not related to bright T2 lesions or enhancement. We conclude that atrophy and cortical-subcortical disconnection due to frontal and parietal white matter destructive lesions may contribute to depression in MS.