Thalamic involvement and its impact on clinical disability in patients with multiple sclerosis: a diffusion tensor imaging study at 3T.

BACKGROUND AND PURPOSE: Several studies suggest that grey matter involvement may play a role in multiple sclerosis (MS) pathology. Diffusion tensor imaging (DTI) at 3T was used to investigate the presence of damage to the normal-appearing thalamus in MS and its relationship with disability. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting (RR, n = 13, age = 41.7 +/- 6.1, Expanded Disability Status Scale [EDSS] score = 2.2 +/- 1.2) and secondary-progressive (n = 11, age = 46.9 +/- 9.6, EDSS = 5.9 +/- 1.0) MS and 24 age- and sex-matched healthy volunteers were studied. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in regions of interest of normal-appearing thalamus. We examined group differences in MD and FA and correlations between DTI-derived metrics and clinical or imaging measures of disease. RESULTS: Patients with MS had higher thalamic FA (P < .0001) and MD (P = .035) than volunteers. MD values correlated with the Paced Auditory Serial Addition Task (r = -0.43, P = .034) and motor EDSS (r = 0.47, P = .021) scores. In patients with RRMS, MD values correlated with global EDSS (r = 0.75, P = .003) and motor EDSS (r = 0.68, P = .010). Correlations were found between MD values and T1 and T2 lesion load (r = 0.58, P < .05) and brain parenchymal fraction (r = -0.46, P < .05). CONCLUSIONS: DTI was able to detect abnormalities in normal-appearing thalamus of patients with MS. The strength of association between thalamic DTI measures and functional impairment was in the same range as those seen with standard MR imaging disease measures. The assessment of the integrity of the thalamus with DTI is a promising metric as a marker of disease for future studies.

Interferon-beta-1b effects on re-enhancing lesions in patients with multiple sclerosis.

Interferon-beta (IFNbeta) reduces the number and load of new contrast-enhancing lesions (CELs) in patients with multiple sclerosis (MS). However, the ability of IFNbeta to reduce lesion sizes and re-enhancements of pre-existing CELs has not been examined extensively. Activity of contrast re-enhancing lesions (Re-CELs) and contrast single-enhancing lesions (S-CELs) were monitored in ten patients with relapsing-remitting (RR) MS. These patients underwent monthly post-contrast magnetic resonance imaging (MRIs) for an 18-month natural history phase and an 18-month therapy phase with subcutaneous IFNbeta-1b, totaling 37 images per patient. The activity was analysed using the first image as a baseline and registering subsequent active monthly images to the baseline. There was a 76.4% reduction in the number of CELs with IFNbeta therapy. The decrease was greater (P = 0.003) for S-CELs (82.3%) than for Re-CELs (57.4%). S-CELs showed no changes in durations of enhancement and maximal lesion sizes with treatment. Exclusively for Re-CELs, IFNbeta-1b significantly decreased maximal lesion sizes, total number of enhancement periods and total months of enhancement. Thus, IFNbeta appears to be effective in reducing the degree of severity of inflammation among Re-CELs, as reflected by their reduced maximal lesion sizes and durations of enhancement.

Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis.

OBJECTIVE: To determine whether lesion evolution in relapsing-remitting multiple sclerosis (RRMS) patients is altered by treatment with interferonbeta1b (IFNbeta-1b) or by intravenous methylprednisolone (IVMP) as measured by magnetization transfer imaging. METHODS: Magnetization transfer ratios (MTR) of 225 contrast enhancing lesions (CEL), in four RRMS patients were serially determined for 12 months before and 12-18 months after contrast enhancement in a baseline vs treatment trial with IFNbeta-1b. During the baseline period, 185 new CEL were identified: 76 were treated with IVMP (1 g/day x 5 days) and designated steroid CEL (S-CEL); the remaining 109 were considered baseline lesions (BCEL). During IFNbeta-1b treatment, 40 CEL (IFN-CEL) were identified. After image co-registration, regions of interest (ROIs) defining new CEL were transferred to the MTR image set to determine the mean lesion MTR on each monthly exam. The lesion MTR was compared to MTR of normal appearing white matter (NAWM) on the same exam. RESULTS: As early as 12 months prior to enhancement, the MTR of CEL was reduced compared to NAWM (mean 9.43 +/- 3.2%; P<0.001). The further reduction in MTR (28% +/- 4.0) at the time of contrast enhancement was not significantly different for BCEL, S-CEL or IFN-CEL Following enhancement, lesion recovery for IFN-CEL (P=0.02) and S-CEL (P=0.002) was significantly higher than BCEL CONCLUSION: IFNbeta-1b and IVMP reduce tissue damage and promote lesion recovery in RRMS patients. The additional benefit of IVMP compared to IFNbeta-1b may be related to its inhibitory effect on demyelination.

Characterization of differences between multiple sclerosis and normal brain: a global magnetization transfer application.

BACKGROUND AND PURPOSE: Although the exact nature of the physiological differences between normal and multiple sclerosis (MS) brains are unknown, it has been shown that their global magnetization transfer ratio (MTR) values are significantly different. To more fully understand these differences, we examined MTR values by using 30 distinct measures. We provide a unique illustration of these differences through a derived normal-to-MS transform. METHODS: Global MTR values for the group of normal subjects and for the group of MS subjects were characterized by 30 different measures involving simple statistics, histographic characteristics, MTR order information, and MTR range information. The measures that were significantly different with respect to these two groups were discovered. From the mean MTR histogram of the two groups, a transform was created to describe a conversion between the two brain states. Normal data were passed through this transform, creating a set of pseudo-MS data. The measures that were significantly different from the normal and pseudo-MS data were also obtained in order to verify the accuracy of the transform. RESULTS: Seventeen of the 30 measures were determined to be significantly different when comparing the sets of normal and MS data. The same set of 17 measures were found to be significantly different when comparing the normal and pseudo-MS data. CONCLUSION: The differences in the global MTR values of normal and MS subjects are statistically significant compared with a large number of measures (alpha = 0.05). A normal-to-MS transform is a novel method for illustrating these differences.

Technical solution for an interactive functional MR imaging examination: application to a physiologic interview and the study of cerebral physiology.

Studies with functional magnetic resonance (MR) imaging produce large unprocessed raw data sets in minutes. The analysis usually requires transferring of the data to an off-line workstation, and this process frequently occurs after the subject has left the MR unit. The authors describe a hardware configuration and processing software that captures whole-brain raw data files as they are being produced from the MR unit. It then performs the reconstruction, registration, and statistical analysis, and displays the results in seconds after completion of the MR image acquisition.

Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon beta-1b.

BACKGROUND AND PURPOSE: To determine whether occult disease fluctuates with macroscopic lesions during the natural history of multiple sclerosis (MS) and whether therapeutic interventions affect occult disease, we performed serial monthly magnetization transfer (MT) imaging in patients with relapsing-remitting MS in a crossover trial with interferon beta-lb. METHODS: Serial whole-brain magnetization transfer ratios (MTRs) in eight patients with relapsing-remitting MS and in four control subjects were plotted as normalized histograms, and MTR parameters were compared with contrast-enhancing lesions and bulk white matter lesion load. RESULTS: In patients with relapsing-remitting MS, the histographic peak of 0.25+/-0.01 and the histographic mean of 0.21+/-0.01 were statistically lower than corresponding values in control subjects, in whom the histographic peak was 0.27+/-0.01 and the histographic mean was 0.23+/-0.01. When histograms (with MTRs ranging from 0.0 to 0.5) were analyzed by quartiles (quartile 1 to quartile 4) based on histographic area, voxels with low MTRs in quartile 1 (0 to 0.12) increased during the baseline period and corresponded to bulk white matter lesion load. Interferon beta-lb reduced enhancing lesions by 91% and mean bulk white matter lesion load by 15%, but had no effect on MTR in this patient cohort. CONCLUSION: Occult disease in normal-appearing white matter of patients with relapsing-remitting MS measured by MTR parallels the waxing and waning pattern of enhancing lesions and bulk white matter lesion load during the baseline period. MTR is not altered by interferon beta-lb, which raises the possibility of ongoing disease in normal-appearing white matter (not detected by conventional MR sequences).

Study of relapsing remitting experimental allergic encephalomyelitis SJL mouse model using MION-46L enhanced in vivo MRI: early histopathological correlation.

MION-46L, a superparamagnetic iron oxide contrast agent, was investigated for its ability to increase the sensitivity of in vivo 3D MRI in the detection of brain lesions in a chronic experimental allergic encephalomyelitis (crEAE) mouse model. Lesion conspicuity on postcontrast 3D MRI was dramatically enhanced as compared to precontrast images corresponding to areas of inflammatory and demyelinating lesions. MION-46L could be detected on Prussian blue iron stain in the vascular endothelium, the perivascular space, and in macrophages within perivascular cuffs and areas of inflammation and demyelination. By taking advantage of the MION-46L induced macroscopic susceptibility effect, acute early lesions measuring only 100 microm in diameter could be detected. MION-46L enhanced MRI may be used to 1) provide a unique sensitivity in EAE lesion detection and correlate imaging to histopathology; 2) help to understand EAE lesion development and its underlying pathophysiology; and 3) eventually assist in preclinical screening of new experimental therapies directed at patients with multiple sclerosis (MS).

Analysis of interpolation effects in the reslicing of functional MR images.

PURPOSE: Typically, the final step in volume registration is the reslicing of the volume of interest. The purpose of this work is to examine the effects of this reslicing on functional MRI (fMRI) data using different interpolation methods. METHOD: Functional whole-brain echo planar imaging (EPI) volumes were resliced using six different interpolation methods: trilinear, tricubic splines, and a 3D sinc function using a rectangular and a Hanning window, both with half-window lengths of 3 and 4 voxels. RESULTS: Interpolation by tricubic spline and 3D sinc using a Hanning window had comparable errors, although tricubic spline interpolation was computationally the fastest. Interpolation by trilinear and 3D sinc using a rectangular window had relatively large errors, although the speed of trilinear makes it desirable for some applications. CONCLUSION: Interpolations using all of the tested methods adversely affected the fMRI data, although these effects differed for each method.

Correspondence of closest gradient voxels--a robust registration algorithm.

A robust, automatic volume registration algorithm based on intensity gradients is presented. This algorithm can successfully perform registrations under conditions of unrelated intervolume voxel intensities, significant object displacements, and/or significant amounts of missing data. It also allows the user to visualize the registration convergence, clearly illustrating any source of registration errors. This algorithm consists of a matching algorithm based on iteratively finding the correspondence of the closest voxels containing a high three-dimensional intensity gradient magnitude. This algorithm was tested by registering T2-weighted MR volumes that had undergone varying displacement transformations to simultaneously acquired proton-density volumes. These transformations involved rotations of up to 25 degrees followed by translations of up to 25 mm along the axis of rotation. For all registrations, the mean registration error was less than one-fifth of a voxel and the mean registration time was less than 30 minutes. In conclusion, this algorithm is shown to be a powerful method of sequence-independent MR volume registration that is simple to both use and understand.