MT Imaging In Multiple Sclerosis

Background And Purposes
MR imaging is now widely used to monitor disease progression in patients with Multiple Sclerosis (MS).

The purpose of this study was to explore the relationship between Disability Status and existing and new MR parameters in MS patients.

Methods
Forty-one patients with Clinically Definitive MS were studied. MR imaging included T₂- and T₁-weighted imaging as well as Gradient-Echo Imaging with and without Magnetization Transfer contrast.

We used surface-based thresholding segmentation techniques to obtain T₂ and T₁ lesion load, T₁/T₂ Ratio, and several Magnetization Transfer Ratio (MTR) lesion load parameters.

MTR Histographic analysis included measurements of absolute peak height (aHp), relative peak height (rHp), MTR of the peak (MTRp), mean MTR (MTRm), and MTR25, MTR50, and MTR75, relating to the integrals of the Histogram at 25%, 50%, and 75%, respectively, of the total area under the curve.

All MR parameters were correlated with Expanded Disability Status Scale (EDSS) score, disease duration, and patient's age.

Results
Using surface-based thresholding segmentation techniques, we found relatively low correlations with EDSS. T₁ Lesion Load and T₁/T₂ ratios correlated most strongly.

Regarding MTR Histographic parameters, EDSS correlated best with rHp but only weakly with others. Similar correlations were found with disease duration, but not with age.

Conclusion
The best MR correlations with disability were several MTR Histographic parameters.

Our findings may favor the use of these MR parameters over T₂ lesion load to monitor disease progression in patients with MS, findings that should be explored further in longitudinal studies.

Studies with conventional Magnetic Resonance Imaging (MRI) indicate that Cognitive Impairment in Multiple Sclerosis (MS) patients is not fully explained by the burden of T₂-visible lesions in the Brain.

Other non-conventional MRI techniques with increased specificity to the more destructive aspects of MS pathology, such as Magnetization Transfer MRI, Diffusion-weighted MRI and proton Magnetic Resonance Spectroscopy, have recently been applied to MS Cognitive studies.

The results suggest that the presence and extent of "occult" MS pathological features in the Normal-Appearing Brain Tissue and the location of lesions in eloquent sites play a central role in the pathogenesis of MS NeuroPsychological impairment.

Magnetic Resonance Imaging (MRI) is frequently used to monitor new treatments in Multiple Sclerosis (MS), but its role is limited by the uncertain relationship between MRI parameters and clinical disability.

A Brain MRI study using nine MRI parameters was undertaken in 15 MS patients with a wide spectrum of disability to evaluate the relationship between each parameter and disability.

A strong correlation was found between disability (measured using Kurtzke's DSS) and total Lesion Load on both Proton Density (PD; r = 0.79) and T₁ (r = 0.71) weighted sequences.

There was also a strong correlation of disability with average lesion Magnetization Transfer Ratio (MTR; r = -0.74) and calculated T₁ (r = 0.71).

But, not with calculated T₂ or the average signal intensity of lesions on the conventional T₁-weighted, PD-weighted and heavily T₂-weighted images.

Thus, four parameters which measured either the extent of lesions (PD lesion load) or their pathological severity (MTR, calculated T₁, HypoIntense T₁-Lesion Load) were correlated significantly with disability.

While this suggests that such parameters will be useful in treatment trial monitoring, further multi-parameter MRI studies, of larger cohorts and using a wider range of techniques, are indicated.

Background And Purpose
Magnetization Transfer imaging provides information about the structural integrity of macromolecular substances, such as Myelin.

Our objective was to use this imaging technique and contour plotting to characterize and to define the extent of White Matter lesions in Multiple Sclerosis and Traumatic Brain Injury.

Methods
Magnetization Transfer imaging was performed of 30 Multiple Sclerosis plaques and 10 Traumatic White Matter lesions.

Magnetization Transfer Ratios (MTRs) were calculated for the lesions, for the Normal- or Normal-Appearing surrounding White Matter, and for remote Normal-Appearing White Matter. MTR contour plots were constructed about these lesions.

Results
The contour plot appearance of MS plaques differed from that of Traumatic White Matter lesions.

There was a gradual increase in MTR values at points at increasing distances from the center of the MS plaques.

This was true for those lesions with and without surrounding T₂ signal abnormality (Halos).

In contrast, there was an abrupt transition in MTR values between Traumatic lesions and Normal-Appearing surrounding White Matter.

Additionally, the size of the MTR abnormality exceeded the size of the T₂ signal abnormality for the MS plaques.

Conclusion
MTR contour plots permit characterization and border definition of White Matter lesions.

Analysis of the contour plots suggests that MS is a centrifugal process with the lowest MTR within the center of the lesion.

In contrast, Traumatic White Matter injuries are discrete Lesions with abrupt transitions between the abnormal lesion and normal Brain.

Objective
To evaluate the contribution made by Cervical Cord damage, assessed using a fast Short-Tau Inversion Recovery (fast-STIR) sequence and Magnetization Transfer Ratio (MTR) Histogram analysis to the clinical manifestations of MS.

Background
Previous studies have failed to show significant correlations between the number and extent of T₂ Spinal Cord lesions and the clinical status of patients with MS.

Fast-STIR is more sensitive than T₂-weighted imaging for detecting Cervical Cord MS lesions.

MTR Histogram analysis provides estimates of the overall Disease Burden in the Cervical Cord with higher pathologic specificity to the more destructive aspects of MS than T₂-weighted scans.

Methods
We obtained fast-STIR and Magnetization Transfer (MT) scans from 96 patients with MS (52 with Relapsing/Remitting [RRMS], 33 with Secondary/Progressive [SPMS], and 11 with Progressive/Relapsing [PPMS] MS) and 21 control subjects.

Dual-Echo scans of the Brain were also obtained and lesion load measured.

Results
Eighty-one of the patients with MS had an abnormal Cervical Cord scan. Patients with SPMS had more Cervical Cord lesions and more images with visible Cervical Cord damage than did patients with RRMS or PPMS (p = 0.04).

The entire cohort of patients with MS had lower average MTR of the Cervical Cord (p = 0.006) than control subjects.

Compared to control subjects, patients with RRMS had similar Cervical Cord MTR Histogram-derived measures.

Whereas, those with PPMS had lower average MTR (p = 0.01) and peak height (p = 0.02).

Patients with SPMS had lower Histogram peak height than did those with RRMS (p = 0.03).

The peak position and height of the Cervical Cord MTR Histogram were independent predictors of the probability of having Locomotor disability.

We found no correlation between Brain T₂ lesion load and any of the Cervical Cord MTR Histogram metrics.

Conclusions
This study shows that the amount and severity of MS pathology in the Cervical Cord are greater in the Progressive forms of the Disease.

An accurate assessment of Cervical Cord damage in MS gives information that can be used in part to explain the clinical manifestations of the disease.

Background And Purpose
Magnetization-Transfer Imaging is a technique that could provide indirect evidence of the characteristics of Multiple Sclerosis (MS) lesions.

The purpose of this work was to study the evolution of MS lesions on T₁-weighted MR images over time.

And to investigate changes in Magnetization-Transfer Ratio (MTR) values of MS lesions with different initial appearances on contrast-enhanced T₁-weighted images.

Methods
Eleven patients with Relapsing/Remitting MS were studied with MR imaging.

The MTRs were calculated for 47 lesions that had been classified according to their appearance on contrast-enhanced T₁ -weighted images.

Each patient was examined at four time points over a 1-year period. The MTR changes observed in the selected Lesions were compared with their initial T₁-weighted appearance.

Results
The lowest MTR values were initially found in HypoIntense NonEnhancing lesions and in Ring-Enhancing Lesions, with both types showing a HypoIntense center.

Changes in MTR values were more dynamic and reversible in Ring-Enhancing than in HypoIntense NonEnhancing plaques.

Nodular-enhancing lesions had slightly lower initial MTRs than did IsoIntense non-enhancing lesions.

Conclusion
The absence or presence of contrast uptake may indicate a different pathologic basis for HypoIntense MS lesions on T₁ -weighted MR images.

These differences should be kept in mind when considering T₁ Lesion Load as a surrogate marker of Disability in MS.

This study assessed whether dysfunction of the Blood-Brain Barrier is an obligatory early event in lesion formation in Multiple Sclerosis.

Dual-Echo and T₁ -weighted Magnetic Resonance Imaging after the injection of a triple dose (0.3 mmol/kg) of Gadolinium-DTPA were obtained from ten patients with Relapsing/Remitting Multiple Sclerosis every week for 2 months.

Sixty-four newly active lesions were detected by the two techniques.

All the 44 new lesions seen on Dual-Echo scans enhanced during the early phases of their formation: 33 at their first appearance, 10 1 week before their appearance on the Dual-Echo scans, and one the week thereafter.

When the every fourth (monthly) scan was analyzed, a total of 55 newly active lesions were detected (i.e., 14% active lesions would have been missed compared to the number found on weekly scanning).

Thirty-one of them were detected by both Dual-Echo and triple-dose scans, 15 only by enhanced scans, and nine only by Dual-Echo scans.

This study confirms that with highly sensitive Magnetic Resonance Imaging techniques, dysfunction of the Blood-Brain Barrier is an obligatory early event in new lesion formation in Relapsing/Remitting Multiple Sclerosis.

Objective
To identify differences in pathology between the principal clinical phenotypes of MS using conventional and Magnetization Transfer (MT) MRI.

Methods
T₁-weighted and T₂-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with Clinically Isolated Syndromes suggestive of MS, and 93 MS patients with Relapsing/Remitting, Secondary/Progressive, Benign, or Primary/Progressive course.

Metrics considered: HypoIntense T₁ and T₂ lesion volumes, average lesion MT ratio, average Brain MT ratio, peak height and position from MT Histograms.

Results
MS patients had lower MT metrics than controls.

Patients with Clinically Isolated Syndromes had MT measures similar to controls, whereas Primary/Progressive MS patients had lower Histogram peak height with normal peak position.

Relapsing/Remitting MS patients had lower MT measures, higher T₂ Lesion Loads and ratio of HypoIntense T₁ to T₂ lesion volumes than patients with Clinically Isolated Syndromes, and lower MT Ratio and peak height than Benign MS patients.

Benign MS patients were similar to controls and patients with Clinically Isolated Syndromes.

Secondary/Progressive MS patients had the lowest MT measures and highest lesion loads.

Conclusions
Pathology in patients with Clinically Isolated Syndromes is confined to modest tissue damage in the lesions seen on T₂-weighted scans.

Severe damage is important for the later development of Disability. However, microscopic damage in Normal-Appearing White Matter may be a major contributor to disability in Primary/Progressive MS.

Background And Purpose
For cases of Multiple Sclerosis (MS), Magnetization Transfer (MT) imaging may provide more pathologically specific and accurate estimates of the disease process than does conventional imaging.

In this study, we evaluated changes of the MT Ratio (MTR) of newly enhancing lesions, the MTR of Normal-Appearing White Matter (NAWM), the average lesion MTR, and the MT Histogram-derived metrics during a 3-year follow-up period for patients with Relapsing/Remitting or Secondary/Progressive MS.

Methods
Dual-Echo, conventional Spin-Echo, and MT images were obtained from seven patients with Relapsing/Remitting MS, seven patients with Secondary/Progressive MS, and five age- and sex-matched control subjects at the time of study entry and 1, 13, and 37 months later.

Results
Newly enhancing lesions in the patients with Secondary/Progressive MS presented a more severe and significant MTR reduction.

During the follow-up period as compared with those in the Relapsing/Remitting group.

In cases of Secondary/Progressive MS, we also observed a significant reduction of the MTR values of the NAWM and a trend toward reduction of average lesion MTR values.

The patients with MS had mean percentage changes of MT Histogram-derived measures that were approximately two to 10 times higher than those of the control subjects.

Conclusion
This preliminary 3-year follow-up study shows that newly enhancing lesions and NAWM in patients with Secondary/Progressive MS have significantly lower MTR values than do those in patients with Relapsing/Remitting MS.

It also shows that the tissue damage that remains after enhancement ceases is more severe in Secondary/Progressive Disease.

Fast Fluid-Attenuated Inversion-Recovery (FLAIR) and Proton Density/T₂-weighted Fast Spin Echo (FSE) Brain images with 3-mm slices were acquired monthly for 7 months in 37 Multiple Sclerosis patients.

New and enlarging lesions were counted and compared according to the site of lesions seen with each sequence.

In addition, the number of new enhancing lesions seen on Gadolinium-enhanced T₁-weighted Brain Magnetic Resonance Imaging at the same time points was counted.

All sequences used 3-mm contiguous axial slices.

Overall, 126 new or enlarging lesions were seen on FSE and 135 on fast FLAIR (P = 0.25, Wilcoxon signed ranks test).

Regional comparisons revealed significantly more fast FLAIR lesions only in the Cortical/SubCortical areas.

There was a total of 295 new enhancing lesions over the same period -- a gain in the number of 'active lesions' of 234% seen with FSE and 218% with FLAIR.

It is concluded that serial thin slice fast FLAIR is only slightly superior to FSE in detecting new and enlarging Multiple Sclerosis lesions.

But, the difference is not sufficient to recommend that FLAIR should replace FSE in short-term, exploratory trials in MS using monthly scanning.