Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis

OBJECTIVE: To examine the relation between the frequency of enhancing magnetic resonance imaging lesions and their characteristics of enhancement and atrophy in patients with early relapsing multiple sclerosis. DESIGN: Analysis of number of enhancing lesions, ventricular volumes and diameters, and lesion characteristics on monthly magnetic resonance imaging scans during natural history follow-up. SETTING: A clinical research institution. PATIENTS: Sixteen patients with confirmed early relapsing multiple sclerosis. MAIN OUTCOME MEASURE: Cerebral atrophy as measured by ventricular enlargement. RESULTS: Numbers of enhancing lesions correlated well with an increase of ventricular size. This correlation was strongest for patients with a high proportion of concentric ring-enhancing lesions with central contrast pallor. CONCLUSIONS: Inflammatory events, especially those within lesions with associated blood-brain barrier breakdown, affect the ensuing loss of brain parenchyma. Patients with a high proportion of lesions with central contrast pallor, which is likely associated with more extensive tissue damage, have a higher rate of atrophic changes.     

Pyramidal tract mapping by diffusion tensor magnetic resonance imaging in multiple sclerosis: improving correlations with disability

BACKGROUND: Current magnetic resonance imaging (MRI) outcome measures such as T2 lesion load correlate poorly with disability in multiple sclerosis. Diffusion tensor imaging (DTI) of the brain can provide unique information regarding the orientation and integrity of white matter tracts in vivo. OBJECTIVE: To use this information to map the pyramidal tracts of patients with multiple sclerosis, investigate the relation between burden of disease in the tracts and disability, and compare this with more global magnetic resonance estimates of disease burden. METHODS: 25 patients with relapsing-remitting multiple sclerosis and 17 healthy volunteers were studied with DTI. An algorithm was used that automatically produced anatomically plausible maps of white matter tracts. The integrity of the pyramidal tracts was assessed using relative anisotropy and a novel measure (L(t)) derived from the compounded relative anisotropy along the tracts. The methods were compared with both traditional and more recent techniques for measuring disease burden in multiple sclerosis (T2 lesion load and "whole brain" diffusion histograms). RESULTS: Relative anisotropy and L(t) were significantly lower in patients than controls (p < 0.05). Pyramidal tract L(t) in the patients correlated significantly with both expanded disability status scale (r = -0.48, p < 0.05), and to a greater degree, the pyramidal Kurtzke functional system score (KFS-p) (r = -0.75, p < 0.0001). T2 lesion load and diffusion histogram parameters did not correlate with disability. CONCLUSIONS: Tract mapping using DTI is feasible and may increase the specificity of MRI in multiple sclerosis by matching appropriate tracts with specific clinical scoring systems. These techniques may be applicable to a wide range of neurological conditions.     

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.     

Nuclear magnetic resonance imaging in multiple sclerosis

Ten patients with definite multiple sclerosis underwent hydrogen nuclear magnetic resonance imaging with a 3.5 kilogauss superconducting magnet, using the inversion recovery and spin-echo techniques of signal acquisition. Results were compared with high-resolution x-ray computed tomography. Spin-echo images demonstrated abnormal regions as areas of variably increased signal intensity. The contrast between abnormal and normal white matter improved as the intervals between sequential radiofrequency pulses and between pulse administration and signal sampling were increased. Inversion recovery images demonstrated abnormal areas as regions of decreased signal intensity but did not visualize lesions as well as spin-echo imaging. Spin-echo and inversion recovery imaging each demonstrated more extensive abnormalities than did computed tomography.     

Diffusion magnetic resonance imaging in multiple sclerosis

Multiple sclerosis (MS) is considered the most common inflammatory autoimmune neurologic disorder and the most frequent cause of nontraumatic neurologic disability in young and middle-age adults. This article reviews the basic features of its magnetic resonance (MR) imaging lesions and, primarily, the use of diffusion MR imaging, which is increasingly applied to assess patients with MS, not only to investigate plaques but also the normal-appearing white matter, gray matter, optic nerve, and spinal cord, because of its ability to detect and quantify disease-related pathologic conditions of the central nervous system.     

Enhanced magnetic resonance imaging in multiple sclerosis

Gadolinium-enhanced magnetic resonance imaging (MRI) is very sensitive in the detection of active lesions of multiple sclerosis (MS) and has become a valuable tool to monitor the evolution of the disease either natural or modified by treatment. In the past few years, several studies, on the one hand, have assessed several ways to increase the sensitivity of enhanced MRI to disease activity and, on the other, have investigated in vivo the nature and evolution of enhancing lesions using different non-conventional MR techniques to better define the relationship between enhancement and tissue loss in MS. The present review is a summary of these studies whose results are discussed in the context of MS clinical trial planning and monitoring. Multiple Sclerosis (2000) 6 320 - 326     

Serial magnetic resonance imaging in multiple sclerosis: correlation with attacks, disability, and disease stage

Serial MRI and clinical testing was performed on 45 well-defined untreated multiple sclerosis patients in different categories of disease (relapsing-remitting, progressive, stable). Up to 24 MRIs were scheduled over a 1-year period for each patient. Clinical evaluation was performed monthly and at times of attacks using the Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI). MRI scans were performed both with and without gadolinium enhancement. MRI lesion volume was determined by computerized analysis and gadolinium-enhancing lesions were counted by radiologists. We observed an increase in lesion volume over 1 year in all patient groups except those classified clinically as stable. In relapsing-remitting patients there were correlations between increases in the number of gadolinium enhancing lesions and increases in EDSS and the occurrence of attacks. In chronic progressive patients, increases in lesion volume were correlated with both increases in EDSS and AI. These results demonstrate a linkage between MRI and clinical disease that depends both on the stage of MS and the MRI measures used and support the use of MRI as a surrogate marker of clinical disability in the study of multiple sclerosis.     

Magnetic resonance diffusion weighted imaging in cerebral fat embolism

The use of diffusion weighted imaging with apparent diffusion coefficient mapping in the diagnosis of cerebral fat embolism is shown here to demonstrate infarcts secondary to fat emboli more intensely than T2 weighted sequences 24 hours after the onset of symptoms. Embolic foci are hypointense on apparent diffusion coefficient mapping consistent with cytotoxic edema associated with cell death and restricted water diffusion. This technique increases the sensitivity for detecting cerebral fat embolism and offers a potentially important tool in its diagnosis.     

Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis

CONTEXT: Brain atrophy has emerged as a useful surrogate marker of disease involvement in multiple sclerosis (MS). The relationship between whole-brain or regional atrophy and cognitive dysfunction is poorly understood. OBJECTIVES: To determine whether the bicaudate ratio (BCR)-the minimum intercaudate distance divided by brain width along the same line-is increased in MS and to compare the ability of the BCR, whole-brain atrophy, and other magnetic resonance imaging markers to predict cognitive dysfunction. DESIGN: Case-control study. SETTING: University-affiliated clinic. PARTICIPANTS: Sixty patients with MS and 50 age- and sex-matched control subjects. MAIN OUTCOME MEASURES: Bicaudate ratio, whole-brain atrophy, T2 lesion load, T1 ("black hole") lesion load, and caudate volume were measured quantitatively using fluid-attenuated inversion recovery, T1-weighted, and gradient-echo magnetic resonance imaging scans. Symbol Digit Modalities Test was used to assess cognitive function. RESULTS: The BCR (mean [SD]) was higher in patients with MS (0.11 [0.03]) than in controls (0.09 [0.02]) (P<.001), suggesting subcortical atrophy in MS. The BCR was related to total T2 (r = 0.56, P<.001) and T1 (r = 0.40, P<.002) lesion volumes, but not caudate volume in patients with MS. Regression modeling selected BCR (P<.05), but not whole-brain atrophy, T1 or T2 lesion volume, or caudate volume as predictive of Symbol Digit Modalities Test score in patients with MS. CONCLUSIONS: The BCR is increased in MS and is more closely associated with cognitive dysfunction than are other magnetic resonance imaging surrogate markers including whole-brain atrophy. Increased BCR is best explained by frontal horn ventricular enlargement due to atrophy of deep frontal subcortical white matter. This highlights the close relationship between subcortical atrophy and cognitive impairment in patients with MS.     

Detecting white matter alterations in multiple sclerosis using advanced diffusion magnetic resonance imaging

Multiple sclerosis is a neurodegenerative and inflammatory disease, a hallmark of which is demyelinating lesions in the white matter. We hypothesized that alterations in white matter microstructures can be non-invasively characterized by advanced diffusion magnetic resonance imaging. Seven diffusion metrics were extracted from hybrid diffusion imaging acquisitions via classic diffusion tensor imaging, neurite orientation dispersion and density imaging, and q-space imaging. We investigated the sensitivity of the diffusion metrics in 36 sets of regions of interest in the brain white matter of six female patients(age 52.8 ± 4.3 years) with multiple sclerosis. Each region of interest set included a conventional T2-defined lesion, a matched perilesion area, and normal-appearing white matter. Six patients with multiple sclerosis(n = 5) or clinically isolated syndrome(n = 1) at a mild to moderate disability level were recruited. The patients exhibited microstructural alterations from normal-appearing white matter transitioning to perilesion areas and lesions, consistent with decreased tissue restriction, decreased axonal density, and increased classic diffusion tensor imaging diffusivity. The findings suggest that diffusion compartment modeling and q-spa ce analysis appeared to be sensitive for detecting subtle microstructural alterations between perilesion areas and normal-appearing white matter.     

多发性硬化患者智能改变与头颅磁共振成像测量及弥散张量成像研究

目的　研究多发性硬化 (MS)患者认知功能障碍的发生情况及认知改变的病理解剖基础。方法　对 70例MS患者进行韦氏智力量表测查及头颅MRI检查 ,对其中 5 0例患者的头颅MRI成像进行了定量测量 ;7例患者进行了弥散张量成像 (DTI)扫描。结果　智能测试发现MS组全量表智商低于正常 (<90分 )者为 4 0 % (2 8/ 70 ) ,与正常组比较差异有非常显著意义 (P <0 0 1)。智能测试与MRI测量中的两侧尾状核比率相关性最显著 ,其次为胼胝体指数。DTI显示病灶周围看似正常组织、看似正常白质及灰质较对照组相应部位脑组织的表观扩散系数增高 ,各向异性值减低。结论　MS患者中存在认知障碍。病灶的范围及其严重程度 ,包括看似正常白质中的微小病灶的数量和严重程度决定认知障碍的程度。灰质功能障碍也与认知改变有关。     

Lessons from magnetic resonance imaging in multiple sclerosis

Magnetic resonance imaging is a potent diagnostic tool in multiple sclerosis: it can reveal dissemination of lesions in both space and time in many patients with isolated neurological syndromes. Many more new lesions occur than clinical relapses. A consistent very early event is the breakdown of the blood-brain barrier which is largely repaired over weeks, leading to marked changes in the size of acute lesions. Chronic lesions show persistent oedema and enlarge through cycles of renewed peripheral activity. The vascular changes reflect inflammation: the resulting MRI changes provide, for the first time, a non-invasive means of monitoring disease activity and its modification by treatment.     

Diffusion tensor magnetic resonance imaging in multiple sclerosis

OBJECTIVES: To quantify, using diffusion tensor imaging (DTI), the tissue damage in lesions and normal-appearing white matter (NAWM) from a large cohort of patients with MS and to investigate the magnitude of the correlation between DTI-derived metrics and clinical disability. METHODS: Dual-echo and DTI scans were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive MS and from 20 normal control participants. Post-contrast T1-weighted images were also obtained from the patients. After creating mean diffusivity (D) and fractional anisotropy (FA) images and image coregistration, D and FA values were measured for 4846 lesions (3207 nonenhancing T1-isointense, 1511 nonenhancing T1-hypointense, and 128 enhancing), 497 NAWM areas from patients, and 160 white matter areas from the controls. RESULTS: The average lesion D was higher and the average lesion FA was lower than the corresponding quantities of the NAWM (p < 0.001). The values of enhancing and nonenhancing lesions were not different, whereas enhancing lesions had lower FA (p < 0.001). T1-hypointense lesions had higher D and lower FA than T1-isointense lesions (p < 0.001). NAWM of patients had higher and lower FA than white matter of controls (p = 0.01). Significant correlations were found between T1 and T2 lesion volume and and FA of lesions and NAWM. In the overall patient sample, a moderate correlation was also found between lesion D and the Expanded Disability Status Scale score (r = 0.28, p = 0.01). However, the r value of this correlation was 0.48 in patients with secondary progressive MS, whose disability was also correlated with average lesion FA (r = -0.50). CONCLUSIONS: The results of this study show that DTI is able to identify MS lesions with severe tissue damage and to detect changes in the NAWM. They also indicate that DTI-derived measures are correlated with clinical disability, especially in patients with secondary progressive MS, thus suggesting a role for DTI in monitoring advanced phases of the disease.     

Fatigue and magnetic resonance imaging activity in multiple sclerosis

Fatigue is a frequent and often severe symptom in multiple sclerosis. Pathogenic mechanisms proposed for fatigue include the release of proinflammatory cytokines, which is thought to have an important effect on changes in the blood-brain barrier (BBB). To investigate whether fatigue is related to BBB disruption we studied 11 relapsing-remitting MS patients participating in a multicenter longitudinal study comparing the sensitivity of monthly enhanced magnetic resonance imaging (MRI) after standard-dose and triple-dose injection of gadolinium-diethylene triaminopentoacetic acid (Gd-DTPA). Serial Gd-enhanced MRI studies were performed in two separate sessions every 4 weeks for 3 months. An expanded version of the Fatigue Severity Scale, including 29 items, was administered 24 h before each MRI examination. No relationship was found between the number and volume of Gd-enhancing lesions and fatigue scores at any monthly examination over the study period. Furthermore changes in MRI activity were not significantly related to changes in fatigue scores. These results were obtained on triple-dose delayed scanning, which is more sensitive than standard-dose scanning in detecting areas of BBB disruption. Our preliminary results thus do not support the hypothesis of a relationship between BBB alterations and fatigue severity in multiple sclerosis. Received: 27 March 1998 Received in revised form: 27 October 1998 Accepted: 9 September 1998     

Serial proton magnetic resonance spectroscopic imaging,contrast-enhanced magnetic resonance imaging,and quantitative lesion volumetry in multiple sclerosis

Serial magnetic resonnce (MR) studies that included proton MR spectroscopic imaging (MRSI), contrast-enhanced MR imaging (MRI), and lesion volumetric studies were performed on 25 multiple sclerosis (MS) patients with mild to modest clinical deficits. Each patient was scanned at varying intervals for up to 2 years, resulting in a total of 124 usable MR sessions. In these longitudinal studies, metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Regional changes in metabolite levels were observed to be dynamic and reversible in some patients. Transient changes in N-acetylaspartate (NAA) levels were sometimes found in acute plaques and indicate that a reduced NAA level does not necessarily imply axonal loss. An inverse correlation between the average NAA within the spectroscopic volume and the total lesion volume in the whole brain was observed. This negative correlation implies that NAA can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of gadolinium enhancement and MRI-defined lesions were observed in 4 patients. This observation suggests that demyelination can occur independent of perivenous inflammatory changes and supports the presence of more than one pathophysiological process leading to demyelination in MS.     

1H Nuclear magnetic resonance imaging in multiple sclerosis

Major advances have been made in the diagnosis of MS by using NMR imaging, suggesting that this noninvasive method will permit staging of MS lesions and that conclusions from newer therapeutic trials may be drawn more accurately than heretofore possible.