MRI Criteria In Multiple Sclerosis

To test the reliability of four previously proposed MRI criteria for the diagnosis of MS, we reviewed 1,500 consecutive Brain scans.

For the presence, number, size, and location of Areas of Increased Signal (AIS [Lesions]) on Proton-Density and T₂-weighted images.

Unaware of the patients' clinical presentations and ages. This series included 134 subjects with a Clinical Diagnosis of MS.

Relying exclusively on the presence of at least three or four AIS for a positive diagnosis of MS resulted in high sensitivity (90% for three AIS and 87% for four).

But inadequate specificity (71% for three AIS and 74% for four) and positive predictive value (23% for three AIS and 25% for four).

If one of these lesions was required to border the Lateral Ventricles, specificity was 92% and positive predictive value was 50% at a sensitivity of 87%.

Using the Fazekas Criteria, at least three AIS and two of the following features:
• Lesion abutting body of Lateral Ventricles,
• InfraTentorial Lesion location,
• Lesions larger than 5 mm

Led to a further highly significant improvement of specificity (96%; p = 0.0000).

And increase of the positive predictive value (65%) at the expense of a less significant decrease in sensitivity (81%; p < 0.01).

Because of the major difficulties in measuring clinical end points in Multiple Sclerosis (MS) treatment trials, there has been much enthusiasm for using Magnetic Resonance Imaging (MRI) findings as an alternative outcome.

To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened, recommendations of the task force are presented in this review.

Given the high sensitivity for detecting pathological activity in Relapsing/Remitting and Secondary/Progressive MS, monthly T₂-weighted and Gadolinium-enhanced Brain MRI is an excellent tool for short-term exploratory trials of new agents, where it serves as the primary end point.

In particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study.

However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical.

Although serial MRI at 6- to 12-month intervals is a useful secondary end point in providing an index of pathological progression.

In trials of patients presenting with Clinically Isolated Syndromes suggestive of MS, MRI findings can be used in the entry criteria, and as a secondary outcome measure.

But, conversion to Clinically Definite MS should be the primary outcome. The pathological substrates of irreversible Disability are DeMyelination and Axonal Loss.

Putative MR markers for these processes include:
1. Decreased N-AcetylAspartate on Proton MR Spectroscopy
2. Decreased Magnetization Transfer Ratios
3. HypoIntensity on T₁-weighted images
4. Loss of short-T₂ water fractions

Some of which relate more closely to disability than conventional MRI findings.

Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations.

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 EDSS) 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.

This study evaluates the distribution of Areas Of Intense Signal (AIS) in 189 patients with Multiple Sclerosis (MS) and 83 patients presenting high-risk factors of CerebroVascular injuries.

Two multivariate statistical analyzes (multifactorial discriminant analysis and logistic regression analysis) with two AIS scores and several subpopulations of patients (according to age and/or the number of AIS) were tested.

The results of these analyzes were expressed with the usual screening test.

The results obtained in this study even without the help of any clinical information are very promising, since they established that the specificity of MRI could be improved by using the distribution of the AIS in the various anatomical areas as a criterion.

Five regions of the Brain display were particularly significant in the discrimination between MS and non-MS patients:

In decreasing order we found that the Temporal, Occipital, BrainStem, and Parietal regions were more specific with respect to the diagnosis of MS, while only the Basal Ganglia could account for non-MS patients.

With multifactorial discriminant analysis and logistic regression analysis respectively, 78.9 (+/- 2.8)% and 85.1 (+/- 2.8)% of the patients were correctly classified by MRI.

The results obtained on the main group were confirmed by a predictive test carried out on an other population of 40 patients, which produced similar results.

The comparison between our method and Fazekas's Imaging Criteria showed a 20% improvement in favor of our approach and it is hoped that it will contribute to make the most of MRI as a tool for the diagnosis of MS.

Background And Purpose
In Multiple Sclerosis (MS), the severity of tissue damage can vary from Edema and inflammation to irreversible DeMyelination and Axonal Loss.

Compared with conventional T₂-weighted MR imaging, Magnetization Transfer (MT) and Diffusion Tensor (DT) MR imaging provide quantitative indices with increased specificity to the most destructive aspects of MS.

To increase our understanding of the pathophysiologic processes of MS, we assessed the correlations between MT and DT MR imaging-derived metrics.

And the correlations between these quantities and measures derived from conventional MR in patients with MS.

Methods
T₂-weighted, T₁-weighted, MT, and DT MR images of the Brain were obtained from 34 patients with Relapsing/Remitting MS (RRMS) and 15 age-matched control subjects.

T₂ and T₁ Lesion Volumes (LV) and Brain Volume were measured.

MT Ratio (MTR), Mean Diffusivity (), and Fractional Anisotropy (FA) Histograms from the overall Brain Tissue (BT) and the Normal-Appearing Brain Tissue (NABT) were obtained.

Average lesion MTR, , and FA were also calculated. The correlations between T₂ and T₁ LV, Brain Volume, MT-, and DT-derived metrics were assessed with the Spearman rank correlation coefficient.

Results
No significant correlations were found between MT and FA Histogram-derived metrics and quantities derived from conventional MR scans (T₂ and T₁ LV and Brain Volume).

On the contrary, T₂ and T₁ LV (but not Brain Volume) were significantly correlated with the average values of BT and NABT (r values ranging from 0.52 to 0.78).

No significant correlation was found between MT- and DT-derived metrics.

Conclusion
These results suggest that MT and DT MR imaging provide, at least partially, independent measures of Lesion Burden in patients with RRMS.

This suggests that a multiparametric MR approach has the potential for increasing our ability to monitor MS evolution.

This study was performed to assess how established diagnostic criteria for Brain Magnetic Resonance Imaging (MRI) interpretation in cases of suspected Multiple Sclerosis (MS)

(Fazekas' Criteria) would perform in the distinction of MS from other diseases and whether other MR techniques (Cervical Cord imaging and Brain Magnetization Transfer Imaging [MTI]), might help in the diagnostic work-up of these patients.

We retrospectively identified 64 MS and 59 non-MS patients. The latter group included patients with systemic Immune-Mediated Disorders (SID; n=44) and Migraine (n=15).

All patients had undergone MRI scans of the Brain (dual echo and MTI) and of the Cervical Cord (Fast Short-Tau Inversion Recovery). The number and location of Brain T₂-HyperIntense lesions and the number and size of Cervical Cord lesions were assessed.

Brain images were also postprocessed to quantify the Total Lesion Volumes (TLV) and to create Histograms of Magnetization Transfer Ratio (MTR) values from the whole of the Brain tissue.

Barkhof's Criteria correctly classified 108/123 patients, thus showing an accuracy of 87.8%.

"False negative" MS patients were 13, while 2 patients with Systemic Lupus Erythematosus (SLE) were considered as "false positives". Using Brain T₂ TLV, nine of the "false negative" patients were correctly classified.

Correct classification of 10 MS patients and both the SLE patients was possible based upon the presence or absence of one Cervical Cord lesion.

Two MS patients with negative Barkhof's Criteria and no Cervical Cord lesions were correctly classified based on their Brain MTR values.

Overall, only one MS patient could not be correctly classified by any of the assessed MR quantities.

These preliminary data support a more extensive use of Cervical Cord MRI and Brain MTI to differentiate between MS and other disorders in case of incondusive findings on T₂-weighted MRI scans of the Brain.

Purpose
To determine the value of Magnetic Resonance (MR) imaging in the Spinal Cord to differentiate Multiple Sclerosis (MS) from other Inflammatory Disorders and CerebroVascular Diseases (together, Other Neurologic Disease [OND]).

Materials And Methods
The study population included 66 patients with OND and 25 patients with MS, who were matched for age, sex, and symptom duration or severity.

Brain MR imaging included Gadolinium-enhanced T₁-weighted and Dual-Echo T₂-weighted Spin-Echo sequences to assess the number, size, and appearance of lesions, contrast enhancement, and compatibility with diagnostic criteria for MS.

Spinal cord MR imaging included cardiac-triggered Gadolinium-enhanced sagittal T₁-weighted Spin-Echo and Dual-Echo T₂-weighted sequences to assess the general appearance (normal, focal lesion, Diffuse abnormality) and number or size of focal lesions.

Images obtained in MS and OND patients were compared. Specificity, sensitivity, accuracy, and positive and negative predictive values with MR images were calculated.

Results
Brain images were abnormal in all MS patients and in 65% of OND patients. Abnormal Cord images were found in 92% of MS and 6% of OND patients.

The combination of Brain and Spinal Cord images increased accuracy of diagnosis compared with use of Brain images alone.

Conclusion
In contrast to MS, Cord lesions are very uncommon in OND. This finding can help differentiate these disorders.

Traditionally, Multiple Sclerosis (MS) has been diagnosed on the basis of clinical evidence of dissemination in time and space.

Previously, it could not be diagnosed in patients with single clinical episodes of DeMyelination known as Clinically Isolated Syndromes.

New diagnostic criteria from the International Panel of McDonald and colleagues incorporate MRI evidence of dissemination in time and space to allow a diagnosis of MS in patients with Clinically Isolated Syndromes.

From clinical and MRI examinations performed prospectively at baseline, 3 months, 1 year, and 3 years of follow-up, the frequency of developing MS was ascertained by the application of both the new McDonald Criteria and the Poser Criteria for Clinically Definite MS.

The specificity, sensitivity, positive and negative predictive value, and accuracy of the new criteria for the development of Clinically Definite MS were assessed.

At 3 months, 20 of 95 (21%) patients had MS with the McDonald Criteria, whereas only 7 of 95 (7%) had developed Clinically Definite MS. After 1 year, the corresponding figures were 38 of 79 (48%) and 16 of 79 (20%), and after 3 years, they were 29 of 50 (58%) and 19 of 50 (38%).

The development of MS with the new MRI criteria after 1 year had a high sensitivity (83%), specificity (83%), positive predicative value (75%), negative predictive value (89%), and accuracy (83%) for Clinically Definite MS at 3 years.

Use of the new McDonald Criteria more than doubled the rate of diagnosis of MS within a year of presentation with a Clinically Isolated Syndrome.

The high specificity, positive predictive value, and accuracy of the new criteria for Clinically Definite MS support their clinical relevance.

Aim Of The Study
To evaluate and compare the capacity of OligoClonal Bands (OB) and three sets of MR imaging criteria to predict the conversion of Clinically Isolated Syndromes (CIS) to Clinically Definite Multiple Sclerosis (CDMS).

Patients And Methods
One hundred and twelve patients with CIS were prospectively studied with MR imaging and determination of OB.

Based on the clinical follow-up (conversion or not conversion to CDMS), we calculated the sensitivity, specificity accuracy, positive and negative predictive value of the OB, and MR imaging criteria proposed by Paty et al, Fazekas' et al and Barkhof et al.

Results
CDMS developed in 26 (23.2%) patients after a mean follow-up of 31 months (range 12-62). OB were positive in 70 (62.5%) patients and were associated with a higher risk of developing CDMS.

OB showed a sensitivity of 81%, specificity of 43%, accuracy of 52%, Positive Predictive Value (PPV) of 30% and negative predictive value (NPV) of 88%.

Paty and Fazekas criteria showed the same results with a sensitivity of 77%, specificity of 51%, accuracy of 57%, positive predictive value of 32% and negative predictive value of 88%.

Barkhof Criteria showed a sensitivity of 65%, specificity of 70%, accuracy of 69%, PPV of 40% and NPV of 87%.

The greatest accuracy was achieved when patients with positive OB and three or four Barkhof's Criteria were selected.

Conclusions
We observed a high prevalence of OB in CIS. OB and MR imaging (Paty's and Fazekas' Criteria) have high sensitivity. Barkhof's Criteria have a higher specificity.

Both OB and MR imaging criteria have a high negative predictive value.

Background
Recently developed diagnostic criteria for MS (McDonald Criteria) indicate that in patients with a single DeMyelinating episode (Clinically Isolated Syndromes [CIS]), evidence for dissemination in space and time, essential for diagnosis, may be provided by MRI.

Objective
To assess the usefulness of these new criteria in patients with CIS suggestive of MS.

Methods
A total of 139 patients with CIS followed for a median of 3 years underwent Brain MRI within 3 months of their first attack and again 12 months later.

The number and location of Lesions at baseline, the development of new lesions at follow-up, and the results of CSF examination (which, if positive, requires fewer MR abnormalities for diagnosis) were analyzed.

The new McDonald Criteria (incorporating MRI) were compared to the existing Poser Diagnostic Criteria and their accuracy was evaluated.

Results
At 12 months, 11% had Clinically Definite MS according to the Poser Criteria compared to 37% with the McDonald Criteria.

Eighty percent of patients fulfilling these new criteria developed a second clinical episode within a mean follow-up of 49 months. The new criteria showed a sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to Clinically Definite MS.

Conclusion
One year after symptom onset, more than three times as many patients with CIS were diagnosed with MS using new diagnostic criteria incorporating MRI results compared to older criteria.

However, the proposed MRI criteria require further prospective studies to optimize sensitivity and specificity.

Background
In patients with Clinically Isolated Syndromes (CIS) suggestive of Multiple Sclerosis (MS), the extent of Brain Magnetic Resonance Imaging (MRI) lesion load influences the probability and time to development of Clinically Definite MS.

Cerebral Atrophy is recognized in established MS, but its time of onset and whether, in early disease, it is related to MRI lesion load or clinical outcome is less certain.

Objectives
This study investigated Ventricular enlargement over one year in CIS patients and explored its relation with lesion load and clinical outcome.

Methods
A semi-automated thresholding technique for measuring Ventricular Volume (MIDAS) was applied to MRI scans in a cohort of 55 patients with CIS, recruited consecutively and imaged within three months of the onset of symptoms and again after one year.

Results
Clinical MS had developed after one year in 16 of 40 patients with an abnormal baseline T₂ scan and 2 of 15 with a normal scan.

Significant Ventricular enlargement was seen in 27 of 55 patients who fulfilled the new McDonald MRI Criteria for MS using all available MRI at clinical follow up (median increase 0.3 cm(3), p=0.005).

Significant increase in Ventricular Volume was also seen in the 18 of 55 patients who developed clinical MS over the follow up period (median increase 0.5 cm(3), p=0.006).

There were significant but modest correlations between baseline lesion measures and subsequent Ventricular enlargement.

Conclusions

1. Lesions and Atrophy are both associated with early relapse leading to a diagnosis of clinical MS
2. While lesions contribute to the development of Atrophy, Atrophy may also develop by other mechanisms (Wallerian Degeneration)
3. This suggests that MR measures have a complementary role in monitoring the course of MS, even from the earliest clinical stage

Objectives
With increasing evidence that permanent tissue damage occurs early in the course of Multiple Sclerosis, it is important that treatment trials include patients in the earliest stages of the disease.

For many patients with Multiple Sclerosis the first presentation is a Clinically Isolated Syndrome. Not all patients with a Clinically Isolated Syndrome develop Multiple Sclerosis, however, and treatment of all such patients would be unwarranted.

A single abnormal Brain MRI identifies patients at a higher risk for the early development of Multiple Sclerosis, but current criteria are limited by either poor specificity (T₂ lesions) or sensitivity (contrast enhancing lesions).

The aim of the study was to assess the positive predictive value, sensitivity, and specificity of MRI indices for the development of Multiple Sclerosis after 1 year from two MRI examinations obtained 3 months apart.

Methods
MRI examinations were performed in 68 patients with a Clinically Isolated Syndrome, with a clinical assessment after 1 year.

Results
Contrast enhancing lesions at both time points were the most predictive indices for developing Multiple Sclerosis (positive predictive value 70%) but had low sensitivity (39%).

The combination of T₂ lesions at baseline with new T₂ lesions at follow up had the best overall positive predictive value (53%), sensitivity (83%), and specificity (76%).

In patients with T₂ lesions at baseline, the presence or absence of new T₂ lesions at follow up significantly altered the risk of Multiple Sclerosis.

Within 1 year (55% and 5% respectively, p < 0.001). Multiple Sclerosis also developed in 10% of patients with a normal baseline MRI.

Conclusions
Serial imaging in patients with Clinically Isolated Syndromes improved the positive predictive value, sensitivity, and specificity of MRI for the development of early Multiple Sclerosis.

And, also identified patients at a lower risk of early Multiple Sclerosis than would have been expected from their abnormal baseline MRI.

Selection of patients with Clinically Isolated Syndromes for therapeutic intervention or clinical trials may benefit from serial MRI, to target those at greatest risk of early development of Multiple Sclerosis.