Weill Cornell Medicine

Author Of 2 Presentations

Imaging Poster Presentation

P0559 - Cluster Analysis discriminates Multiple Sclerosis Patients based on Lesion Size and Myelin Content (ID 1884)

Speakers
Presentation Number
P0559
Presentation Topic
Imaging

Abstract

Background

Clinical heterogeneity among patients with multiple sclerosis (MS) may be driven by genetic and environmental influences that lead to distinctive MRI features.

Objectives

Our objective was to utilize a cluster analysis to determine the variability of quantitative MRI features among a cohort of MS patients and examine the ability of these imaging features to discriminate patients by clinical disability.

Methods

Ninety-six relapsing remitting MS patients and 7 patients with progressive MS underwent Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) sequence, for myelin water fraction (MWF) analysis, and conventional MRI for measures of lesion volume, cortical thickness and thalamic volume. An agglomerative hierarchical clustering algorithm was implemented using lesion level MRI features selected from a Principal Component Analysis (PCA). The final clusters were selected by implementing a comprehensive validation method based on several unsupervised statistical learning techniques. Matched cluster groups with statistically significant clinical covariates (i.e. age and disease duration) were analyzed based on propensity scores.

Results

A total of 1691 chronic MS lesions were identified among the 103 MS patients. Mean patient age was 44.4 (+/- 11.9) years, disease duration was 10.5 (+/- 8.3) years, and expanded disability status scale (EDSS) was 2.2 (+/- 2.0). PCA demonstrated lesion MWF and volume distributions characterized by 25th, 50th and 75th percentiles account for 87% of the total variability. The hierarchical clustering confirmed two distinct patient clusters. The variables in order of importance were individual lesion median MWF, MWF 25th, MWF 75th, volume 75th percentiles, median individual lesion volume, and total lesion volume (all p-values < 0.000001). Cortical thickness and thalamic volume were significant but less important on cluster discrimination. The clustering MRI features discriminated patients based upon EDSS, p=0.0016 at the time of MRI and maintained EDSS difference at five years (n=72), p=0.0016.

Conclusions

The size and extent of demyelination among individual lesions discriminated MS patients into two MRI lesion-based clusters and was associated with clinical disability. These results suggest an inherent difference among patients with regard to lesion pathology and repair.

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Imaging Poster Presentation

P0620 - QSM detects greater rate of reduction in lesion magnetic susceptibility in patients treated with Dimethyl Fumarate over Glatiramer Acetate treatment (ID 1783)

Abstract

Background

Chronic active multiple sclerosis (MS) lesions, characterized by a hyperintense rim (rim+) on quantitative susceptibility mapping (QSM), have been shown to contain iron-enriched, activated microglia and macrophages. QSM is a potential biomarker to monitor treatments directed toward the CNS inflammation. Studies have suggested that dimethyl fumarate (DMF) may reduce the pro-inflammatory innate immune response in the CNS. A comparison to other disease modifying therapies (DMTs) is warranted to evaluate this potential benefit.

Objectives

To determine if dimethyl fumarate (DMF) reduces the iron load, as measured on QSM, in chronic active MS lesions at a greater rate than glatiramer acetate (GA) treatment.

Methods

Sixty-one patients (41 female, 20 male, mean age: 42.1 years +/- 10.9 and EDSS 0.82 +/- 1.2), were considered for this analysis. Fifty-six patients had relapsing-remitting MS and 5 had clinically-isolated syndrome; 37 patients were treated with DMF and 24 with GA. The two treatment groups had similar baseline clinical characteristics; however, DMF patients had less time on treatment as compared to GA (3.86 +/- 1.75 years vs 5.99 +/- 2.67 years, p<0.001). Patients had a QSM scan prior to treatment and a minimum of two on-treatment QSM MRIs. Lesions were classified as rim+ or rim- negative based upon a review of two independent reviewers. To compare longitudinal QSM change in the rim+ lesions among treatment groups, a linear mixed effects model was utilized.

Results

At baseline, patients treated with GA had more QSM rim+ lesions (9.4%) as compared to those starting DMF (4.5%), p=0.0004, however the number of patients having at least one rim+ lesion was similar (16 vs 18 patients) among the treatment groups. DMF patients with rim+ lesions had a longer disease duration as compared to rim+ GA patients (8.15 +/- 6.82 vs 3.55 +/- 4.85 years, p= 0.032). In the subset of patients with QSM rim+ lesions, there was a significantly larger decrease in susceptibility in rim+ lesions with DMF treatment as compared to GA, p< 0.0009. There was minimal reduction of susceptibility in rim- lesions, which was similar among treatment groups; all patients (p=0.92) and QSM rim+ only patients (p=0.11).

Conclusions

This study suggests that DMF reduces the iron load in rim+ MS lesions at a greater rate than GA. These results support QSM to evaluate the effectiveness of various DMTs on the CNS innate immune response in chronic active MS lesions.

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