HypoIntense Lesions In Multiple Sclerosis

Recent MRI studies in Multiple Sclerosis have highlighted the potential role of Brain Atrophy evaluation as a putative marker of disease progression.

In the present study, we evaluated the SupraTentorial and InfraTentorial Brain Volume in patients with Relapsing/Remitting Multiple Sclerosis (RR MS) and in healthy subjects.

Moreover, we determined whether Brain Volumes of MS patients are associated with different aspects of Brain MRI abnormalities and clinical findings.

Two-dimensional acquired MRI was performed on 52 Relapsing/Remitting Multiple Sclerosis and 30 healthy subjects. The volume of SupraTentorial and InfraTentorial structures was measured in selected representative slices.

Gd-enhancement, T₂ HyperIntense, T₁ HypoIntense (i.e. 'Black Holes') total Lesion Load, as well as the area of Corpus Callosum was calculated in the MS group and related to Brain Volume measures.

Correlations between MRI parameters and clinical features were also considered. MS patients had significantly lower SupraTentorial, InfraTentorial Brain Volume and Corpus Callosum area than healthy subjects (P<0.01).

SupraTentorial Brain Volume was significantly related to Corpus Callosum area (r=0.58; P<0.01) and T₁ HypoIntense Lesion Load (r=0.48; P<0.01), but not with T₂ HyperIntense Lesion Load.

InfraTentorial/SupraTentorial ratio was significantly associated with disease duration and EDSS score (r=-0.34; P=0.02 and r=-0.49; P<0.01, respectively).

This study documents that Brain Atrophy is an early MRI finding in R/R MS and it is closely related to 'Black Holes' burden.

The use of InfraTentorial/SupraTentorial ratio (relative values) may increase the conspicuity of correlation between clinical and MRI findings.

Purpose
To determine the evolution of Magnetization Transfer (MT) in White Matter regions before and after Plaque development in patients with Multiple Sclerosis (MS).

Materials And Methods
In a 5-year longitudinal evaluation, 30 patients with MS underwent conventional Magnetic Resonance (MR) imaging, MT MR imaging, and clinical assessment.

Cross-sectional data in 12 healthy subjects were also collected.

Semiautomated lesion classification with use of T₂-weighted MR images was used to measure the time course of the MT Ratio.

Calculated with MR data acquired without and with MT saturation, in every Voxel and to help analyze the relationship with the status of lesions depicted on T₂-weighted images.

Results
There was a significant (P <.001) temporal decline in Lesion MT Ratio after lesion appearance on T₂-weighted images.

A significant (P <. 001) progressive decline in MT Ratio was also present in Voxels (volume element) that later became Lesions, prior to initial detection on T₂-weighted images.

Even 1^1/2 years prior to lesion appearance, the MT Ratio (33.3%) in regions destined to become such lesions was significantly (P <.001) lower than that in both White Matter in healthy subjects (41.3%) and other Normal-Appearing White Matter in patients with MS (38.1%).

Conclusion
The MT Ratio reveals progressive Focal abnormalities in MS that antedate by up to 2 years the appearance of lesions on T₂-weighted MR images.

MRI findings are increasingly used as outcome measures in therapeutic trials in MS.

The discrepancy between the extent of the lesions on conventional T₂ images and the clinical condition of the patient is one of the problems encountered in such studies.

This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between HypoIntense lesions on T₁ MRI and disability.

To assess in more detail the correlation of changes in HypoIntense Lesion Load on T₁-weighted Spin-Echo MR images (''Black Holes'') with changes in disability in MS, we studied 46 patients with Clinically Definite MS at baseline and after a median follow-up of 40 months.

There was a significant correlation between baseline disability and HypoIntense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001).

In Secondary/Progressive patients, the rate of accumulation of these ''Black Holes'' was significantly related to progression rate (SRCC = 0.81, p < 0.0001).

We speculate that the appearance of HypoIntense lesions is the MRI equivalent of a failure of remission.

Overall, T₁ lesion load measurements correlated better with clinical assessments than T₂ Lesion Load measurements.

Quantification of HypoIntense lesion load on T₁ weighted Spin-Echo MRI helps to resolve the clinical-radiological paradox between Disability and MRI and has the potential to be a surrogate marker of disability in MS.

The aim of the study was to monitor the natural history of new enhancing lesions in Multiple Sclerosis (MS) by means of serial Gadolinium-enhanced Magnetic Resonance Imaging (MRI).

Out of the 63 new enhancing lesions seen on the baseline scan, belonging to 26 Relapsing/Remitting MS patients, 26 (40%), nine (14%) and four (6%) Lesions showed persisting enhancement at first, second and third follow-up scan, respectively.

At the end of 5 months of follow-up
1. 58 (92%) of the new enhancing lesions were
   • detected as T₂ HyperIntensities
2. 24 (38%) as T₁ HypoIntensities ('Black Holes')
3.    5 lesions (8%) disappeared
   • in both T₂ and T₁ weighted images

Duration of Gadolinium enhancement of at least two consecutive scans significantly influenced the development of 'Black Holes'.

No significant correlation was observed between volume, location, configuration of enhancement at baseline and final outcome of the Lesion. In individual cases, different evolution of new enhancing lesions was observed at the same time.

In conclusion, this study documented that different outcomes of new lesions are unrelated either to the individual patient or to the baseline MRI characteristics.

However, prolonged Blood-Brain Barrier disruption as shown by persisting enhancement significantly influences the lesion outcome.

Copyright 1999 Lippincott Williams & Wilkins

Background
Preliminary observational studies with Multiple Sclerosis (MS) patients have reported strong correlations between an increase in HypoIntense lesion load (Black Holes) on T₁ weighted Spin Echo images, and an increase in disability.

Objective
We assessed the relationship of HypoIntense lesions to the clinical course of disease among 50 Relapsing/Remitting MS patients in the controlled setting of a randomized clinical trial.

Methods
Fifty patients with Relapsing/Remitting disease were enrolled in a randomized double-blind two-arm (Cladribine vs. Placebo) clinical trial of 1-year duration.

All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics.

Results
At baseline, clinical severity is weakly related to counts of Black Holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3.

Rates of appearance of new Black Holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS >/= 4) than for the less severe patients.

Changes in clinical severity over the course of the trial are best predicted by baseline Neurologic scores and numbers of Exacerbations, with Black Holes adding no further improvement in prediction.

Conclusions
Numbers of exacerbations seem more critical to short-term clinical outcomes in Relapsing/Remitting MS, as reflected by patients' clinical scores, rather than Black Holes.

Various imaging methods and MRI indices capture Complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.

Copyright 2000 S. Karger AG, Basel

We compared the changes of the volumes of T₁-HypoIntense lesions seen on the Magnetic Resonance Imaging scans of the Brain from 159 Progressive Multiple Sclerosis (MS) patients who were enrolled in a double-blind, placebo-controlled trial assessing the efficacy of two doses of Cladribine.

Although in patients treated with Cladribine there was a tendency to have a lower increase of T₁-HypoIntense Lesion volumes than those treated with placebo, no statistically significant effect of Cladribine on T₁-HypoIntense lesion accumulation was found over the one-year double-blind phase.

Furthermore, no significant treatment effect was also detected in a subset of 22 patients who received placebo during the double-blind phase of the study and Cladribine during the subsequent one-year open-label phase.

We conclude that Cladribine does not have a major impact on the mechanisms leading to severe tissue destruction in Progressive MS.

Magnetic Resonance Imaging (MRI) is being used as an outcome criterion in therapeutic trials in Multiple Sclerosis (MS) on the assumption that it, as a sensitive marker of biologic disease activity, could serve as a surrogate marker of Disability.

We evaluated the relation between MRI findings and Disability in a quantitative follow-up study of 48 MS patients. Median duration of follow-up was 24 months (range, 10 to 42 months).

Computer-assisted volume measurements employing a seed-growing technique yielded a standard error of measurement of 0.275 cmT₂.

The median total area of the HyperIntense lesions on the initial T₂-weighted images was 8.4 cmT₂.

The median increase was 0.76 cmT₂/yr (9%). In a subgroup (n = 19) with short-TR/short-TE Spin-Echo (SE) images, we measured the HypoIntense lesion load.

The median total area of the lesions at entry was 0.70 cmT₂, with a median increase of 0.28 cmT₂/yr (40%).

The total area of the HyperIntense Lesions on the initial T₂-weighted images showed a weak correlation with the Expanded Disability Status Scale score at entry (Spearman rank correlation coefficient [SRCC] = 0.30; 0.02 < p < 0.05).

The increase in Disability showed a positive correlation (SRCC = 0.19) with the increase in HyperIntense Lesion Load on the T₂-weighted SE images, but this correlation did not reach statistical significance (p = 0.09), probably because of lack of clinical Progression.