Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis

BACKGROUND AND PURPOSE: We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS). METHODS: Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis. RESULTS: All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment. CONCLUSION: The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.     

Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits

Signal shortening of the motor cortex in T2-weighted MR images is a frequent finding in patients with amyotrophic lateral sclerosis (ALS). The cause of signal shortening in ALS is unknown, although iron deposits have been suggested. To test this hypothesis, we acquired T2*-weighted gradient-echo (GRE) MR images in addition to T2-weighted turbo spin-echo in 69 patients with ALS. Signal shortening in T2-weighted images was found in 31 patients. In T2*-weighted GRE images, only three patients had signal shortening. One patient with additional bifrontal haemorrhage had frontal but no motor cortex signal shortening. Iron deposits do not cause cortical signal shortening in patients with ALS predominantly. Other factors are presumably more important in the generation of cortical T2 shortening in ALS.     

Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology

BACKGROUND AND PURPOSE: Cortical lesions constitute a substantial part of the total lesion load in multiple sclerosis (MS) brain. They have been related to neuropsychological deficits, epilepsy, and depression. However, the proportion of purely cortical lesions visible on MR images is unknown. The aim of this study was to determine the proportion of intracortical and mixed gray matter (GM)-white matter (WM) lesions that can be visualized with postmortem MR imaging. METHODS: We studied 49 brain samples from nine cases of chronic MS. Tissue sections were matched to dual-echo T2-weighted spin-echo (T2SE) MR images. MS lesions were identified by means of myelin basic protein immunostaining, and lesions were classified as intracortical, mixed GM-WM, deep GM, or WM. Investigators blinded to the histopathologic results scored postmortem T2SE and 3D fluid-attenuated inversion recovery (FLAIR) images. RESULTS: Immunohistochemistry confirmed 70 WM, eight deep GM, 27 mixed GM-WM, and 63 purely cortical lesions. T2SE images depicted only 3% of the intracortical lesions, and 3D FLAIR imaging showed 5%. Mixed GM-WM lesions were most frequently detectable on T2SE and 3D FLAIR images (22% and 41%, respectively). T2SE imaging showed 13% of deep GM lesions versus 38% on 3D FLAIR. T2SE images depicted 63% of the WM lesions, whereas 3D FLAIR images depicted 71%. Even after side-by-side review of the MR imaging and histopathologic results, many of the intracortical lesions could not be identified retrospectively. CONCLUSION: In contrast to WM lesions and mixed GM-WM lesions, intracortical lesions remain largely undetected with current MR imaging resolution.     

Cortical plaques visualised by fluid-attenuated inversion recovery imaging in relapsing multiple sclerosis

Fluid-attenuated inversion recovery (FLAIR) imaging with prolonged inversion times allows generation of highly T2-weighted images of the brain with suppression of cerebrospinal fluid signal. Such sequences result in high lesion contrast and allow visualisation of abnormalities not seen with conventional T2-weighted spin-echo sequences. We used FLAIR sequences, proton density (PD) and standard T2-weighted images to examine lesion number and distribution in ten patients with clinically definite relapsing multiple sclerosis (MS). We also studied the extent and distribution of blood-brain-barrier breakdown by gadolinium-enhanced T1-weighted images. FLAIR sequences proved feasible both in terms of acquisition time and image quality using a 0.5 T imager. FLAIR imaging allowed identification of 45 % more high-signal lesions than T2-weighted or PD images in the 10 patients. In particular, 60 % more lesions within the cortex and at the grey-white interface were identified. Cortical lesions, none of which enhanced following gadolinium-DTPA injection, were present in seven of the ten patients studied. Of all lesions identified, 8 % were cortical. FLAIR sequences are more sensitive to cortical and subcortical lesions in patients with active demyelination.     

Volume T1-weighted gradient echo MRI in multiple sclerosis patients.

Three-dimensional (3D) volume turbo fast low angle shot (FLASH) techniques have become available which produce heavily T1-weighted images, similar to inversion recovery scans, utilizing the appropriate flip angle and inversion time. The purpose of this study was to compare the sensitivity of a rapid volume gradient echo technique [3D magnetization prepared rapid acquisition gradient echo (MP RAGE)] in identifying multiple sclerosis (MS) plaques with a conventional T2-weighted spin echo (SE) sequence. Ten patients with clinical MS were evaluated. Patients underwent a routine examination consisting of an axial T2-weighted SE sequence (2,500,22/90) and a coronal 3D MP RAGE, 10/4/10, acquired as 128 two mm partitions. In six patients, area measurements of 22 plaques were determined on both the axial T2-weighted SE examinations and the axial reformatted MP RAGE examinations. The overall number of plaques utilizing each technique was approximately the same. One hundred twenty-two plaques were visualized for the 3D MP RAGE sequence, and 128 plaques for the T2-weighted SE sequence. There were differences in detection of plaques in different regions, with plaques in gray matter better demonstrated utilizing the conventional T2-weighted SE sequence. Plaques in the corpus callosum, pons, and brachia pontis were better demonstrated utilizing 3D MP RAGE. No significant difference was found between the areas measured on the MP RAGE sequence and on the T2-weighted SE sequence. Three-dimensional MP RAGE provides a sensitive and complementary method to conventional T2-weighted SE sequences in the evaluation of patients with MS.     

多发性硬化MR扩散张量成像的脑皮质异常:为期3年的纵向研究

目的评价扩散张量成像联合双反转恢复序列是否能够发现多发性硬化(MS)病人脑皮质的结构变化。材料与方法经本地伦理委员会批准并获得知情同意后,纳入168     

T2 shortening in the visual cortex: effect of aging and cerebrovascular disease.

PURPOSETo evaluate the effect of aging and cerebrovascular disease on T2 shortening in the visual cortex at MR imaging.METHODSMR images of 72 neurologically normal subjects (45 men and 27 women, 35 to 92 years old) and 32 (13 men and 19 women, 54 to 92 years old) with cerebrovascular disease were evaluated retrospectively. On T2-weighted spin-echo images, the signal intensity of the visual, motor, and sensory cortices was divided into three grades and compared with the signal intensity of the frontal subcortical white matter.RESULTSDecreased signal intensity (grade III) was rarely seen in the visual and sensory cortices of the neurologically normal subjects who were less than 60 years old. The signal intensity of the motor cortex decreased rapidly after the age of 50 years. At 61 to 70 years of age, 53% of these subjects had grade III intensity, and at age 71 years or older, 94% had reached grade III. The frequency of progression from grade I to grade III was lower in the visual cortex than in the motor cortex; 22% of these subjects had grade III appearance at age 61 to 70 years, and at age 71 years older, 56% had reached grade III. In patients with cerebrovascular disease who were older than 60 years of age, the frequency of grade III signal intensity in the visual cortex was almost equal to that in the neurologically normal subjects.CONCLUSIONST2 shortening in the visual cortex is frequently seen in neurologically normal older persons. These findings are compatible with a previously reported histochemical study of normal iron deposition in the visual cortex. Cerebrovascular disease has no effect on T2 shortening in the visual cortex.     

Visual analysis of serial T2-weighted MRI in multiple sclerosis: intra- and interobserver reproducibility

We evaluated the effect of consensus formation and training on the agreement between observers in scoring the number of new and enlarging multiple sclerosis (MS) lesions on serial T2-weighted MRI studies. The baseline and month 9 MRI studies of 16 patients with a range of MRI activity were used (dual-echo conventional spin-echo sequence, TR 2000, TE 34 and 90 ms, 5 mm contiguous slices, in-plane resolution 1 mm). First, the serial studies were visually analysed for the presence of new and enlarging lesions, on two occasions, by five experienced observers, without adopting any consensus strategy and in isolation. Next, the observers met to identify the common sources of inconsistencies in reporting between observers and formulate consensus rules. Finally, a further independent reading session was performed on the same MRI dataset, this time applying the consensus rules. Agreement between observers was assessed using kappa scores. Without the consensus rules, interobserver kappa scores for the first and second reading sessions for new lesions were only 0.51 and 0.39 respectively; agreement for enlarging lesions was even worse. The mean intraobserver kappa score for new lesions was higher at 0.72, reflecting the fact that the observers were consistently applying their individual assessment strategies. Application of the consensus rules did not lead to a significant improvement in inter observer kappas; the kappa scores adopting the guidelines were 0.46 and 0.21 for new and enlarging lesions respectively. Consensus guidelines thus did not improve the reproducibility of visual analysis of serial T2-weighted MRI, and the level of agreement between observers remained only moderate. Suboptimal repositioning is likely to be a major source of residual variability and this suggests a future role for image registration strategies; until then, a single observer, or pair of observers working in consensus, should be used in MS studies. Received: 6 April 1999 Accepted: 21 April 1999     

Chronically obstructed sinonasal secretions: observations on T1 and T2 shortening

Clinically assessed chronic proteinacious sinonasal secretions usually have long T1 and T2 relaxation times reflecting their high water content. However, in some cases variable combinations of short and long T1 and T2 relaxation times are found. To study the causes of these findings, the magnetic resonance (MR) images of 41 patients with surgically proved, chronically obstructed sinonasal secretions were studied. The relative signal intensities on both T1- and T2-weighted sequences of the sinus specimens were correlated with the gross viscosity of the specimens at surgery. Ten specimens were collected that were not contaminated with either blood or saline. UV spectrophotometric analysis of four of these samples excluded the presence of methemoglobin. Total protein content was determined in five samples, and in vitro T1 and T2 values were measured in one sample. These T1 and T2 relaxation times were accurately predicted with use of a standard pure lysozyme protein solution with the same concentration as the specimen. In addition, the observed T1- and T2-weighted signal intensities on the 41 MR images were predicted from an analysis of pure protein solutions. This study concludes that the primary causes of the variable T1 and T2 relaxation times of chronic sinonasal secretions are the macromolecular protein concentration, the amount of free water, and the specimen viscosity. Furthermore, an orderly and predictable transition of these signal intensities occurs over time.     

In vivo determination of T1 and T2 in the brain of patients with severe but stable multiple sclerosis

In vivo measurements of relaxation processes in multiple sclerosis (MS) lesions by magnetic resonance imaging (MRI) may be important for evaluation of the disease activity in individual MS plaques. To obtain information of presumably chronic plaques, 10 patients with severe, but stable MS were investigated, using a whole-body superconductive MR scanner, operating at 1.5 T. By employing 12-point (or 6-point) partial saturation inversion recovery (PSIR) and 32-echo multiple spin-echo sequences we measured T1 and T2 in MS plaques, white matter, and cortical gray matter. We also focused on the issue, whether T1 and T2 relaxation processes in fact were monoexponential. T1 and T2 in plaques were found to cover a wide range, which could be explained only by inherent biophysical dissimilarity of the plaques, possibly due to differences in disease activity, edema and gliosis. T1 appeared monoexponential in all the plaques, but in seven cases T2 showed biexponential behavior. This was found to be most pronounced near the cerebrospinal fluid of the ventricles, probably caused by partial volume effects or increased free water content. The T2 of apparently normal white matter was significantly longer in MS patients than in healthy subjects.     

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.     

MR identification of white matter abnormalities in multiple sclerosis: a comparison between 1.5 T and 4 T.

BACKGROUND AND PURPOSEAlthough MR spectroscopy and functional MR imaging of the brain have been successful at 4 T, conventional fast spin-echo imaging of the brain at 4 T has not been adequately evaluated. The purpose of this study was to compare the detection of white matter abnormalities in multiple sclerosis (MS) at 1.5 T and 4 T.METHODSFifteen patients with clinically definite MS were imaged at both 1.5 T and 4 T within a 1-week period. Comparison was made between fast spin-echo long-TR images at both field strengths. Pulse sequences were tailored to maximize resolution and signal-to-noise ratio in clinically relevant imaging times (< 7 min). Four interpreters independently reviewed the images obtained at both field strengths in separate sessions and evaluated them for lesion identification, size, characterization, and subjective resolution. Differences in interpretations at 1.5 T and 4 T were subsequently recorded.RESULTSImages obtained at 4 T showed a mean of 88 more lesions as compared with images obtained at 1.5 T. All the lesions measured less than 5 mm and were typically aligned along perivascular spaces. Twenty-five consensually identified lesions on 4-T images were not seen at all on 1.5-T images. Moreover, 4-T images showed 56 additional consensually identified lesions, which were indistinct and seen only in retrospect on 1.5-T images. These lesions were frequently (n = 48) identified in large confluent areas of white matter signal intensity abnormality at 1.5 T. All observers also agreed that 4-T images subjectively enhanced the perception of normal perivascular spaces and small perivascular lesions.CONCLUSIONMR imaging at 4 T can depict white matter abnormalities in MS patients not detectable at 1.5 T through higher resolution with comparable signal-to-noise ratio and imaging times.     

Axial vs sagittal T2-weighted brain MR images in the evaluation of multiple sclerosis

Axial and sagittal proton density and T2-weighted MR images (TR 2,500-3,000 ms, TE 15-22 and 85-90 ms) were performed in 50 patients with multiple sclerosis (MS) on a 1.5 T superconductive system. The number of plaques on the axial and sagittal images in the periventricular white matter, the corpus callosum, the brain stem, the cerebellum, and the basal ganglia were counted separately by two independent observers. A total of 858 lesions (mean 17.40 +/- 21.57) were seen on the axial series and 1,196 (mean 24.32 +/- 26.22) on the sagittal scans. More lesions were visualized on sagittal images in the periventricular region (mean 18.79 +/- 21.69 versus 13.34 +/- 16.45; p less than 0.001) and the corpus callosum (mean 3.00 +/- 2.72 versus 0.57 +/- 1.19; p less than 0.001). In the brain stem more lesions were visualized on the axial images (mean 1.55 +/- 2.55 versus 0.87 +/- 1.20; p less than 0.05). In the cerebellum and basal ganglia, scans in the two planes were equivalent (p greater than 0.5). In three patients lesions were seen on the sagittal series, while the axial scans were normal. Sagittal T2-weighted images appear to demonstrate significantly more MS plaques than transverse images, especially in the periventricular region and the corpus callosum. This is explained by partial volume averaging, by the orientation of some cerebral structures (e.g., corpus callosum) with regard to the section plane, and by the longer diameter of the lesions in the axial plane.     

Normal-appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T(2).

T(2) relaxation in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients was reexamined using more complete sampling and analysis of decay curves, and to assess focal vs. diffuse abnormalities. Nine MS patients and 10 controls were scanned using a single-slice 32-echo pulse sequence with a 10-ms echo spacing. Decay curves from outlined white and gray matter structures were analyzed using non-negative least-squares (NNLS). Resulting T(2) distributions were each summarized by the geometric mean T(2), T(2). Different white matter structures had different mean (over the subjects in a group) T(2). Mean T(2) in NAWM was always greater than that of controls. Differences were not caused by a few voxels with extreme T(2) (i.e., focal lesions), but rather by shifts of the entire T(2) distribution (diffuse prolongation). This T(2) increase suggests diffuse myelin or axonal pathology.     

Cortical activity and gait parameter characteristics in people with multiple sclerosis during unobstructed gait and obstacle avoidance

BackgroundPeople with Multiple Sclerosis (PwMS) present higher cortical activity during walking. However, the cortical activity during gait while avoiding an obstacle is still not clear.ObjectiveTo investigate cortical activity and gait spatial-temporal parameters in PwMS during two different gait tasks (i.e., unobstructed and obstacle avoidance).MethodFifteen PwMS and 15 healthy controls (CG) were recruited. Participants performed ten trials in each gait condition, wearing a 64-electrode cap electroencephalogram (EEG) at 1024 Hz. Kinematic data were obtained through 10 Vicon® cameras at 200 Hz. EEG was analyzed through four cortical areas (frontal, motor, parietal, and occipital cortex areas) and five frequency bands (delta, theta, alpha, beta, and gamma) obtained through the power spectral density. In addition, spatial-temporal gait parameters (e.g., step length and velocity) were measured. Two-way ANOVA (group x gait condition) and MANOVA (group x gait condition) were used to compare gait and EEG parameters, respectively. One-way ANOVA was used to compare groups in the crossing phase of the obstacle avoidance condition.ResultsPwMS presented lower step length and velocity, and higher cortical activity in frontal (beta and gamma) and parietal (gamma) cortical areas in both gait conditions compared to CG. Moreover, PwMS presented increased cortical activation (frontal and parietal) and decreased step length and velocity in obstacle avoidance compared with unobstructed gait. In addition, PwMS required more cortical resources (frontal and parietal) than CG to accomplish both gait conditions. During the obstacle avoidance task, it was further observed that PwMS positioned their feet closer to the obstacle, before and after the task, compared to CG.ConclusionPwMS demand higher cortical resources to accomplish gait tasks, mainly when it is necessary to negotiate an obstacle in the pathway. This higher cortical activity may be a compensatory mechanism to deal with damage in subcortical structures caused by multiple sclerosis.