MRI And Magnetization Transfer Abstracts

Objectives
To assess the sensitivities of Magnetization Transfer Imaging (MTI)-derived measures in detecting changes over time of Macro- and Microscopic Lesion Burdens in different MS phenotypes and to compare them with those of T₂-weighted and T₁-weighted lesion volumes.

Methods
A total of 96 patients were studied:
• 39 with Relapsing/Remitting MS (RRMS)
• 19 with Secondary/Progressive MS (SPMS)
•   9 with Primary/Progressive MS
•   9 with Benign MS
• 20 with Clinically Isolated Syndromes
         - suggestive of MS at presentation
• 20 healthy subjects

Brain T₂-weighted-weighted, T₁-weighted, and MTI scans were obtained at baseline and after 12 months. The authors measured T₂-weighted and T₁-weighted lesion volumes and average lesion MT Ratio (MTR).

The authors also derived MTR Histograms from Whole Brain Tissue (WBT) and Normal-Appearing Brain Tissue (NABT).

Results
In healthy control subjects, there was no significant change of any of the MTR Histogram parameters.

At follow-up, in the entire patient group, T₂-weighted lesion volume significantly increased and average lesion MTR, WBT-MTR, NABT-MTR, and Histogram peak positions significantly decreased.

Patients with RRMS and SPMS had significantly higher changes in T₂-weighted lesion volume and all the MTI-derived metrics compared with the other subgroups.

MTI changes were more prominent (and significantly different) in patients with SPMS than in those with RRMS.

Compared with patients with Benign MS, patients with RRMS had significantly greater changes in T₂-weighted lesion volume and WBT- and NABT-MTR metrics.

Compared with patients with SPMS, patients with Primary/Progressive MS had similar changes of T₁-weighted and T₂-weighted Lesion volumes, but significantly lower changes of MTI-derived measures.

Conclusions
MTI-derived measures are sensitive for detecting MS-related changes and might provide valuable outcome measures when assessing treatment effects in clinical trials of patients with MS.

Fast Fluid-Attenuated Inversion Recovery (fast-FLAIR) sequences are very sensitive for detecting lesions of patients with Multiple Sclerosis (MS).

Echo Planar Imaging allows to obtain FLAIR images (EPI-FLAIR) with significantly shorter scanning times.

EPI-FLAIR images obtained with 10 measurements are as sensitive as fast-FLAIR for the detection of large MS lesions.

Aim of this study was to compare the numbers of MS lesions seen on EPI-FLAIR images with fewer measurements (and, as a consequence, very short scanning times) with those seen on EPI-FLAIR images with 10 measurements.

EPI-FLAIR scans with 2 (EPI-2), 4 (EPI-4), 6 (EPI-6), 8 (EPI-8) and 10 (EPI-10) measurements were obtained from 29 MS patients.

Lesions seen using each of the five approaches were counted by agreement by two observers. EPI-10 images were used as the "gold standard" for pairwise comparisons.

EPI-FLAIR scans with fewer measurements (EPI-2, -4, -6, -8) were all significantly less sensitive than EPI-10 for the detection of small, intermediate and large MS Lesions.

All the EPI-FLAIR scans, however, fulfilled MR diagnostic criteria for definite MS.

When rapid MR scanning of uncooperative MS patients is needed, EPI-FLAIR images covering the entire Brain in less than one minute may be considered.

Fatigue is a common symptom of Multiple Sclerosis (MS) even in the early phases of the disease, when Neurological Disability is usually still not present.

To investigate the PathoPhysiology of Fatigue we compared NeuroPhysiological Motor Evoked Potentials (MEPs) of the four limbs.

And, Brain Magnetic Resonance Imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) Fatigue.

Fatigue was assessed by an interview and scored by the Fatigue Severity Scale.

The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, Pyramidal Functional System (FS) Score, and Depression Score.

MEPs were abnormal in five patients with Fatigue and in one patient without Fatigue.

A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P< 0.005).

Significantly higher Parietal Lobe (P< 0.05), Internal Capsule (P< 0.05), and PeriVentricular Trigone (P< 0.05) Lesion loads were found in patients with Fatigue than in those without.

Our results agree with a Central Nervous System origin of Fatigue in MS patients.

This symptom might be a consequence either of a functional DeAfferentation of the Cortex due to CorticoSubCortical interconnection damage.

Or, of a DeMyelination in critical sites of the CNS, such as the CorticoSpinal Tract.

In this study we evaluated the correlation between NeuroPsychological Impairment, measured with the Brief Repeatable Battery NeuroPsychological Tests.

And, JuxtaCortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to Spin-Echo MRI sequences in detecting JuxtaCortical MS lesions.

A total of 39 patients with definite MS were evaluated by MRI with a Conventional and Fast Spin Echo sequence and fast FLAIR sequence, and NeuroPsychological tests of the Brief Repeatable Battery NeuroPsychological Tests were performed.

The Z-score of all subtests were used to calculate a Cognitive Impairment Index. The results show that a high number of JuxtaCortical lesions is detected with thin slice FLAIR (30% of all lesions seen).

This percentage was not superior to Spin-Echo, reflecting the thin slice thickness (3 mm) we used. The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques.

While the number of Non-Cortical Lesions correlated with the Expanded Disability Status Scale (r=0.32, P=0.045), the number of JuxtaCortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index.

Our study underlines the high number of JuxtaCortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI.

It also stresses the importance of JuxtaCortical lesions on determining NeuroPsychological Impairment.

Multiple Sclerosis (2000) 6 280 - 285

Introduction And Development
Studies with conventional Magnetic Resonance Imaging (MRI) support the hypothesis that Cognitive Impairment in Multiple Sclerosis (MS) patients is related with the lesion burden.

Patterns of Frontal Lobe Cognitive decline were also found to be related with the corresponding Regional Lesion Load, although the total Lesion Load on T₂-weighted MRI scans of the Brain seems to be more relevant in determining Frontal Lobe deficits.

Other non-conventional MRI techniques with a higher specificity to the heterogeneous substrates of MS pathology, have recently been applied to MS Cognitive studies.

Such as the assessment of HypoIntense lesion load:
1. On T₁-weighted scans
2. On Histogram analysis of Magnetization Transfer Ratio maps

Conclusions
Results from these studies suggest that three factors play a role in the PathoGenesis of MS Dementia:

1. The burden of MS lesions
2. The severity of the pathological damage within individual lesions
3. The Normal-Appearing White Matter

We evaluated whether subtle changes outside T₂-visible lesions are present in the Brain of these patients and whether their extent increases the risk of subsequent development of CDMS.

Methods
Dual-echo, T₁-weighted, and Magnetization Transfer (MT) images of the Brain were obtained from 24 patients with CIS at presentation.

These patients were followed up for a mean period of 33 months (range, 25-42 months). Twenty age- and sex-matched healthy volunteers served as control subjects.

To create MT Histograms of the Normal-Appearing Brain Tissue (NABT), macroscopic lesions were segmented from dual-echo images, were superimposed automatically, and were nulled out from the coregistered and scalp-stripped MT Ratio (MTR) maps.

The following MTR Histogram-derived measures were considered: average MTR, MTR(25), MTR(50), MTR(75), peak height, and peak position.

T₂ and T₁ lesion loads, average lesion MTR, and Brain Volume were also measured.

Results
Patients with CIS had lower average NABT-MTR (P < .0001) and peak position (P = .002) than did control volunteers, but patient Brain size was similar to that of volunteers.

At follow-up, 10 (41%) patients developed CDMS. Patients who developed CDMS during the follow-up period had higher T₂ lesion volume (P = .003) and lower average NABT-MTR (P = .005) and peak position (P = .006) than did those who did not develop CDMS.

T₂ Lesion Volume (odd ratio, 3.54; P = .0005) and average NABT-MTR (odd ratio, 0.81; P = .01) were independent predictors of the subsequent development of CDMS.

Conclusion
Subtle changes occur outside lesions visible on conventional MR images among patients with CIS suggestive of MS at presentation.

The greater the extent of such abnormalities is, the higher is the risk of subsequent development of CDMS.

Magnetization Transfer Imaging (MTI) is a Magnetic Resonance Imaging (MRI) technique that is now used in Multiple Sclerosis (MS) studies, and is thought to have a higher pathological specificity than conventional T₂-weighted imaging.

This review outlines the major contributions given by MTI for the understanding of MS evolution.

MTI studies of individual MS lesions confirm the pathological Heterogeneity of T₂-weighted MRI abnormalities and the potential role of unenhanced T₁-weighted HypoIntensities as specific markers of localized severe White Matter disruption.

Correlative cross-sectional and longitudinal studies using MTI and Gadolinium (Gd)-enhanced MRI reveal that MTI findings may vary in Lesions.

With different patterns of enhancement and that MTI abnormalities are closely related to the onset and recovery of Blood-Brain Barrier disruption in new MS plaques.

MTI Lesion Load (LL) is highly correlated with T₂-weighted MRI lesion load, but it has a limited reliability as a measure of MS lesion burden.

On the other hand, measures obtained from MT scans using whole-Brain Histogram analysis are highly correlated with the extent of MS abnormalities on conventional MRI scans.

And predict patients' clinical Disability well, Since they are sensitive to both macro- and microscopic MS lesion burden in the whole Brain and in specific regions.

These data suggest that:
1. MTI is sensitive to different stages of lesion pathology and pathological evolution in MS patients
2. MTR Histogram analysis can provide a more global assessment of MS lesion burden, since it encompasses both Macro- and Microscopic MS pathology

Purpose
To determine whether the Normal-Appearing White Matter (NAWM) regions surrounding and remote from Multiple Sclerosis (MS) plaques have abnormal Diffusional Anisotropy.

And, to compare Anisotropy maps with Apparent Diffusion Coefficient (ADC) maps for sensitivity in the detection of White Matter (WM) abnormalities.

Materials And Methods
Conventional and Diffusion Tensor Magnetic Resonance (MR) imaging examinations were performed in 26 patients with MS and in 26 age-matched control subjects.

Fractional Anisotropy (FA) and ADC maps were generated and coregistered with T₂-weighted MR images.

Uniform regions of interest were placed on plaques, PeriPlaque White Matter (PWM) regions, NAWM regions in the ContraLateral side of the Brain, and WM regions in control subjects to obtain FA and ADC values, which were compared across the WM regions.

Results
The mean FA was 0.280 for plaques, 0.383 for PWM, 0.493 for NAWM, and 0.537 for control subject WM.

The mean ADC was 1.025 x 10(-3) mm(2)/sec for plaques, 0.786 x 10(-3) mm(2)/sec for PWM, 0.739 x 10(-3) mm(2)/sec for NAWM, and 0.726 x 10(-3) mm(2)/sec for control subject WM.

Significant differences in Anisotropy and ADC values were observed among all WM regions (P < .001 for all comparisons, except ADC in NAWM vs control subject WM [P =.018]).

Conclusion
The Anisotropy and ADC values were abnormal in all WM regions in the patients with MS and were worse in the PeriPlaque regions than in the distant regions.

Diffusion Tensor MR imaging may be more accurate than T₂-weighted MR imaging for assessment of disease burden.

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 (k for) and the native relaxation time (T₁ free) were analyzed 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 k for (F7,166=105.2; p< 0.0001), and by an increase of T₁ free (F7,166=57.3; p< 0.0001).

The drop of k for 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 T₁ free 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.

We investigated the Magnetization Transfer Ratio (MTR) of Normal-Appearing White (NAWM) and Gray Matter (NAGM) in a relatively large group of Multiple Sclerosis (MS) patients, and the relations of MTR changes with clinical disability.

MTR was measured in 66 MS patients (12 PP, 35 RR, 19 SP) and 23 healthy controls, using a Whole-Brain 3D-FLASH technique corrected post-hoc for B1-induced variation.

Histogram parameters of conservatively selected NAWM and Cortical NAGM were analyzed using Bonferroni-corrected ANOVA with age as covariate.

Additionally, manually outlined Regions Of Interest were analyzed using a multilevel method.

Lesions had low MTR (mean 22.7+/-6.9%), but NAWM exhibited limited changes: MTR Histogram peak position was 32.8+/-1.0% in controls and 32.4+/-0.9% in MS patients, with a significant decrease compared to controls only in SPMS patients (31.9+/-1.1%, p=0.045).

Cortical MTR Histogram did not differ significantly between patients and controls. In SPMS, regional mean MTR was significantly decreased in Corpus Callosum and Hippocampus.

MTR Histogram parameters of NAGM and NAWM were correlated with EDSS and MSFC scores, with lesion volume and with Normalized Brain Volume.

We conclude that disease-induced MTR changes were small in MS NAWM and NAGM, but did correlate with clinical decline, Lesion Volume and overall Cerebral Atrophy.