Contributions
Abstract: P499
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Axonal loss is a main determinant of long-term disability and disease progression in multiple sclerosis (MS), however its non-invasive in vivo detection is challenging. The Composite Hindered and Restricted Model of Diffusion (CHARMED) is an advanced multi-shell diffusion-weighted magnetic resonance imaging (MRI) method that estimates a restricted diffusion fraction (FR) - a surrogate marker for axonal density. We previously provided cross-sectional evidence for the presence of widespread low axonal density in the normal appearing white matter (NAWM) of early MS cases that is, at least in part, unrelated to focal demyelinating lesions. The longitudinal application of CHARMED axonal density estimates, however, remains to be evaluated.
Objective: We aimed to investigate the longitudinal potential of FR axonal density estimates in tracking MS disease progression after 1 year.
Methods: A prospective cohort of 12 early MS subjects (disease duration ≤5 years) were scanned on an ultra-high gradient strength Siemens 3 T Connectom MRI scanner (300 mT/m maximum gradient strength) at baseline and at 1-year follow-up with multi-shell diffusion imaging (b=1k, 5k, 10k s/mm2, 64, 64, 128 directions; 1.5 mm isotropic resolution). Additional imaging included a 3D multi-echo MPRAGE for anatomical segmentations in FreeSurfer and a 3D T2-SPACE-FLAIR (both 1 mm isotropic resolution). Diffusion-weighted data was pre-processed with FreeSurfer and FSL. FR maps were obtained with CHARMED using in-house developed scripts. Lesion masks were drawn by a radiologist using the FLAIR images from both time points independently, and lesions smaller than 12 voxels in diffusion space were discarded. The longitudinal change in FR values was assessed in the NAWM using voxel-wise tract-based spatial statistics (TBSS) while controlling for age, gender and multiple comparisons across clusters. Additionally, the change of FR within lesions was evaluated using one-sample t-tests.
Results: At 1-year follow-up, TBSS analysis revealed decreases in FR in widespread NAWM regions compared with the baseline (p< 0.01). There was also a reduction of the FR within lesions at follow-up (p=0.02).
Conclusion: Our findings show in vivo evidence of progressive axonal loss in both lesions and NAWM of early MS cases. The CHARMED axonal density estimate FR is a sensitive marker for longitudinal change in MS pathology and holds promise as a novel biomarker for early diagnosis and disease-monitoring purposes.
Disclosure: Silvia De Santis: nothing to disclose; Nicola Toschi: nothing to disclose; Tobias Granberg: nothing to disclose; Russell Ouellette: nothing to disclose; Constantina A. Treaba: nothing to disclose; Qiuyun Fan: nothing to disclose; Elena Herranz: nothing to disclose; Jacob A. Sloane: nothing to disclose; Caterina Mainero: Research supported by the National Institutes for Health (R01NS078322-01 A1)
Abstract: P499
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Axonal loss is a main determinant of long-term disability and disease progression in multiple sclerosis (MS), however its non-invasive in vivo detection is challenging. The Composite Hindered and Restricted Model of Diffusion (CHARMED) is an advanced multi-shell diffusion-weighted magnetic resonance imaging (MRI) method that estimates a restricted diffusion fraction (FR) - a surrogate marker for axonal density. We previously provided cross-sectional evidence for the presence of widespread low axonal density in the normal appearing white matter (NAWM) of early MS cases that is, at least in part, unrelated to focal demyelinating lesions. The longitudinal application of CHARMED axonal density estimates, however, remains to be evaluated.
Objective: We aimed to investigate the longitudinal potential of FR axonal density estimates in tracking MS disease progression after 1 year.
Methods: A prospective cohort of 12 early MS subjects (disease duration ≤5 years) were scanned on an ultra-high gradient strength Siemens 3 T Connectom MRI scanner (300 mT/m maximum gradient strength) at baseline and at 1-year follow-up with multi-shell diffusion imaging (b=1k, 5k, 10k s/mm2, 64, 64, 128 directions; 1.5 mm isotropic resolution). Additional imaging included a 3D multi-echo MPRAGE for anatomical segmentations in FreeSurfer and a 3D T2-SPACE-FLAIR (both 1 mm isotropic resolution). Diffusion-weighted data was pre-processed with FreeSurfer and FSL. FR maps were obtained with CHARMED using in-house developed scripts. Lesion masks were drawn by a radiologist using the FLAIR images from both time points independently, and lesions smaller than 12 voxels in diffusion space were discarded. The longitudinal change in FR values was assessed in the NAWM using voxel-wise tract-based spatial statistics (TBSS) while controlling for age, gender and multiple comparisons across clusters. Additionally, the change of FR within lesions was evaluated using one-sample t-tests.
Results: At 1-year follow-up, TBSS analysis revealed decreases in FR in widespread NAWM regions compared with the baseline (p< 0.01). There was also a reduction of the FR within lesions at follow-up (p=0.02).
Conclusion: Our findings show in vivo evidence of progressive axonal loss in both lesions and NAWM of early MS cases. The CHARMED axonal density estimate FR is a sensitive marker for longitudinal change in MS pathology and holds promise as a novel biomarker for early diagnosis and disease-monitoring purposes.
Disclosure: Silvia De Santis: nothing to disclose; Nicola Toschi: nothing to disclose; Tobias Granberg: nothing to disclose; Russell Ouellette: nothing to disclose; Constantina A. Treaba: nothing to disclose; Qiuyun Fan: nothing to disclose; Elena Herranz: nothing to disclose; Jacob A. Sloane: nothing to disclose; Caterina Mainero: Research supported by the National Institutes for Health (R01NS078322-01 A1)