Contributions
Abstract: EP1538
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Magnetic resonance imaging (MRI) plays a key role in tracking disease activity, evaluating treatment efficacy, and predicting long-term disability in multiple sclerosis (MS) patients. Natalizumab (henceforth NA) has been shown to reduce the rate of clinical relapse compared to placebo and slow accumulation of new lesions that appear hyperintense on T2-weighted MRIs. It remains unknown whether NA has quantifiable effects on MRI lesional intensities that could be used as potential markers for therapeutic response or tissue repair.
Objectives: This study assessed differences in MRI intensity within new lesions appearing before and after NA initiation. Secondary objectives tested for intensity changes in chronic lesions that may reflect repair.
Methods: Relapsing remitting MS patients were retrospectively identified who initiated NA at the University of Pennsylvania between 2009-2014. Fluid attenuated inversion recovery (FLAIR) and T1-weighted sequences from two pre-NA scans and one post-NA scan were obtained from a common protocol and preprocessed. Manual segmentations identified chronic lesions, defined by their presence on earliest MRI (1.3 years before NA on average), and acute lesions, defined by first appearance on the MRI immediately prior to NA initiation (0.4 years before NA on average) or after NA initiation (0.6 years after on average). The mean and quartiles of normalized MRI intensities from 214 chronic and 229 acute lesions were analyzed using linear mixed models to estimate changes in lesional intensities after NA initiation.
Results: Although not statistically significant, mean (25th, 50th, 75th quartile) normalized FLAIR intensity decreased by 0.8 (0.5, 1.2, 1.1) units in post-NA new lesions compared to lesions that formed prior to NA, suggesting therapeutic response. Similarly, mean (25th, 50th, 75th quartile) normalized T1 lesional intensity increased by 0.7 (1.0, 0.2, -0.2) units. In chronic lesions, mean (25th, 50th, 75th quartile) normalized FLAIR intensity decreased by 1.0 (0.6, 1.0, 1.2) units and mean (25th, 50th, 75th quartile) normalized T1 intensity increased by 1.4 (2.0, 1.5, 0.7) units, suggesting possible tissue repair after NA initiation.
Conclusions: Natalizumab may lead to decreases (increases) in normalized FLAIR (T1) intensities in new lesions. Lesion-based analyses may provide a useful measure of treatment efficacy. Further investigation using a larger study cohort is warranted.
Disclosure:
Kristin Linn: nothing to disclose.
Gabriel Pilar: nothing to disclose.
Emily Acton: nothing to disclose.
Clyde Markowitz has served as a consultant to: Bayer HealthCare, Biogen, Merck-Serono, Mallinckrodt, Mylan, Novartis Pharmaceuticals, Roche/Genentech, Sanofi/Genzyme, and Teva Pharmaceuticals.
Salim Chahin: nothing to disclose.
Matthew Schindler: nothing to disclose.
Russell Shinohara: nothing to disclose.
Abstract: EP1538
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Magnetic resonance imaging (MRI) plays a key role in tracking disease activity, evaluating treatment efficacy, and predicting long-term disability in multiple sclerosis (MS) patients. Natalizumab (henceforth NA) has been shown to reduce the rate of clinical relapse compared to placebo and slow accumulation of new lesions that appear hyperintense on T2-weighted MRIs. It remains unknown whether NA has quantifiable effects on MRI lesional intensities that could be used as potential markers for therapeutic response or tissue repair.
Objectives: This study assessed differences in MRI intensity within new lesions appearing before and after NA initiation. Secondary objectives tested for intensity changes in chronic lesions that may reflect repair.
Methods: Relapsing remitting MS patients were retrospectively identified who initiated NA at the University of Pennsylvania between 2009-2014. Fluid attenuated inversion recovery (FLAIR) and T1-weighted sequences from two pre-NA scans and one post-NA scan were obtained from a common protocol and preprocessed. Manual segmentations identified chronic lesions, defined by their presence on earliest MRI (1.3 years before NA on average), and acute lesions, defined by first appearance on the MRI immediately prior to NA initiation (0.4 years before NA on average) or after NA initiation (0.6 years after on average). The mean and quartiles of normalized MRI intensities from 214 chronic and 229 acute lesions were analyzed using linear mixed models to estimate changes in lesional intensities after NA initiation.
Results: Although not statistically significant, mean (25th, 50th, 75th quartile) normalized FLAIR intensity decreased by 0.8 (0.5, 1.2, 1.1) units in post-NA new lesions compared to lesions that formed prior to NA, suggesting therapeutic response. Similarly, mean (25th, 50th, 75th quartile) normalized T1 lesional intensity increased by 0.7 (1.0, 0.2, -0.2) units. In chronic lesions, mean (25th, 50th, 75th quartile) normalized FLAIR intensity decreased by 1.0 (0.6, 1.0, 1.2) units and mean (25th, 50th, 75th quartile) normalized T1 intensity increased by 1.4 (2.0, 1.5, 0.7) units, suggesting possible tissue repair after NA initiation.
Conclusions: Natalizumab may lead to decreases (increases) in normalized FLAIR (T1) intensities in new lesions. Lesion-based analyses may provide a useful measure of treatment efficacy. Further investigation using a larger study cohort is warranted.
Disclosure:
Kristin Linn: nothing to disclose.
Gabriel Pilar: nothing to disclose.
Emily Acton: nothing to disclose.
Clyde Markowitz has served as a consultant to: Bayer HealthCare, Biogen, Merck-Serono, Mallinckrodt, Mylan, Novartis Pharmaceuticals, Roche/Genentech, Sanofi/Genzyme, and Teva Pharmaceuticals.
Salim Chahin: nothing to disclose.
Matthew Schindler: nothing to disclose.
Russell Shinohara: nothing to disclose.