Contributions
Abstract: 63
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Pediatric-onset MS is characterized by accrual of focal lesions, disruption of normal brain growth and loss of tissue integrity. Monophasic acquired demyelinating events (monoADS) during childhood also impact brain development. Magnetization transfer ratio (MTR) imaging is sensitive to myelin density. Signal mass (SM) combines density and volume to quantify amount of tissue. During normal maturation, white matter (WM) volume increases, MTR decreases due to increasing axonal calibre and a relative reduction in myelin ratio. The effect of maturation on SM is unknown.
Objectives: To measure WM volume, MTR, and SM in pediatric-onset MS and monoADS to quantify the impact of acquired demyelination on brain development.
Methods: 213 participants enrolled in the Canadian Pediatric Demyelinating Disease Study had serial 1.5 T MRI: pediatric onset MS (n=87, 23 male, median [IQR] age at first scan 16.5 [4.5] yr, median [IQR] follow-up 2.2 [2.8] yrs), monoADS (n=102, 54 male, median [IQR] age at first scan 11.7 [6.3] yr, median [IQR] follow-up 3.8 [2.5] yrs) and healthy controls (HC, n=24, 7 male, median [IQR] age at first scan 17.3 [2.9] yr, median [IQR] follow-up, 1.1 [0.5] yrs). MTR scans were linearly registered to the MNI template, then serial scans were nonlinearly registered to the first scan. The Jacobian determinant was computed for the entire transform path, giving the cumulative volume change (ΔV). ΔMTR was the difference between a scan (MTR2) and the baseline (MTR1). SM change (ΔSM) was (MTR2·V·ΔV) - (MTR1·V) where V was the volume of a voxel. Normal appearing WM (NAWM) was segmented on baseline scans, and mean quantitites expressed as a % difference. We used mixed effects models to analyze each metric, with effects for group (HC/monoADS/MS) and age.
Results: NAWM ΔV: HC 0.5%/y (p = 0.058), monoADS: 0.2%/y (p=0.00002); MS 0.01%/y (p=0.82); monoADS vs. MS p=0.019. ΔMTR: HC -0.8%/y, p=0.11; monoADS -0.6%/y, p< 10-6; MS -0.9%/y, p< 10-6. ΔSM: HC -0.3%/y, p=0.57; monoADS -0.5%/y, p< 10-6; MS -0.9%/y, p< 10-6 ; monoADS vs. MS p=0.0071. Trajectories did not differ between sexes (min p > 0.5).
Discussion: We confirm that WM volume increases and MTR decreases with maturation in healthy children. MS significantly disrupts WM growth and integrity. SM changes relatively little in healthy youth, declines slightly in children who experienced monoADS, but declines significantly in MS. SM may be more sensitive to MS pathology than measures of tissue volume.
Disclosure: R.A. Brown: has received personal compensation for consulting services from NeuroRx Research and Biogen Idec.
D. Arnold has served on advisory boards, received speaker honoraria, served as a consultant, or received research support from Adelphi, Biogen, Celgene, Genentech, Genzyme, Medday, NeuroRx Research, Novartis, Pfizer, Receptos, Roche, Sanofi, the Canadian Institutes of Health Research, and the Multiple Sclerosis Society of Canada; and holds stock in NeuroRx Research.
Dr. Narayanan reports personal fees from NeuroRx Research and a speaker´s honorarium from Novartis Canada, unrelated to the submitted work.
E. A. Yeh has received funds from NMSS, CIHI, CIHR, OIRM, MS Society of Canada, Mario Battaglia Foundation, SickKids Foundation, CBMH Innovation Fund, CMSC, Rare Diseases Foundation and Guthy Jackson Foundation. She serves as a relapse adjudicator for ACI. She has served on a scientific advisory panel for Juno Therapeutics and has received a speaker's honorarium from Novartis.
R. A. Marrie: receives research funding from Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, National Multiple Sclerosis Society, Rx & D Health Research Foundation, the Waugh Family Chair in Multiple Sclerosis, Crohn's and Colitis Canada, and has conducted clinical trials funded by Sanofi- Aventis.
A. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Biogen Idec, Diogenix, Roche/Genentech, Sanofi-Genzyme, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Teva Neuroscience, Celgene/Receptos Inc, and Merck/EMD Serono.
B. Banwell serves as a central MRI reviewer for Novartis in the context of a clinical trial, and as a non-remunerated advisor on clinical trial design to Sanofi-Aventis, Novartis, Biogen-IDEC, and Teva Neuroscience. Dr. Banwell has received grant support as listed above, as well as from the MS Society of Canada, CIHR, NIH, and NMSS.
Abstract: 63
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Pediatric-onset MS is characterized by accrual of focal lesions, disruption of normal brain growth and loss of tissue integrity. Monophasic acquired demyelinating events (monoADS) during childhood also impact brain development. Magnetization transfer ratio (MTR) imaging is sensitive to myelin density. Signal mass (SM) combines density and volume to quantify amount of tissue. During normal maturation, white matter (WM) volume increases, MTR decreases due to increasing axonal calibre and a relative reduction in myelin ratio. The effect of maturation on SM is unknown.
Objectives: To measure WM volume, MTR, and SM in pediatric-onset MS and monoADS to quantify the impact of acquired demyelination on brain development.
Methods: 213 participants enrolled in the Canadian Pediatric Demyelinating Disease Study had serial 1.5 T MRI: pediatric onset MS (n=87, 23 male, median [IQR] age at first scan 16.5 [4.5] yr, median [IQR] follow-up 2.2 [2.8] yrs), monoADS (n=102, 54 male, median [IQR] age at first scan 11.7 [6.3] yr, median [IQR] follow-up 3.8 [2.5] yrs) and healthy controls (HC, n=24, 7 male, median [IQR] age at first scan 17.3 [2.9] yr, median [IQR] follow-up, 1.1 [0.5] yrs). MTR scans were linearly registered to the MNI template, then serial scans were nonlinearly registered to the first scan. The Jacobian determinant was computed for the entire transform path, giving the cumulative volume change (ΔV). ΔMTR was the difference between a scan (MTR2) and the baseline (MTR1). SM change (ΔSM) was (MTR2·V·ΔV) - (MTR1·V) where V was the volume of a voxel. Normal appearing WM (NAWM) was segmented on baseline scans, and mean quantitites expressed as a % difference. We used mixed effects models to analyze each metric, with effects for group (HC/monoADS/MS) and age.
Results: NAWM ΔV: HC 0.5%/y (p = 0.058), monoADS: 0.2%/y (p=0.00002); MS 0.01%/y (p=0.82); monoADS vs. MS p=0.019. ΔMTR: HC -0.8%/y, p=0.11; monoADS -0.6%/y, p< 10-6; MS -0.9%/y, p< 10-6. ΔSM: HC -0.3%/y, p=0.57; monoADS -0.5%/y, p< 10-6; MS -0.9%/y, p< 10-6 ; monoADS vs. MS p=0.0071. Trajectories did not differ between sexes (min p > 0.5).
Discussion: We confirm that WM volume increases and MTR decreases with maturation in healthy children. MS significantly disrupts WM growth and integrity. SM changes relatively little in healthy youth, declines slightly in children who experienced monoADS, but declines significantly in MS. SM may be more sensitive to MS pathology than measures of tissue volume.
Disclosure: R.A. Brown: has received personal compensation for consulting services from NeuroRx Research and Biogen Idec.
D. Arnold has served on advisory boards, received speaker honoraria, served as a consultant, or received research support from Adelphi, Biogen, Celgene, Genentech, Genzyme, Medday, NeuroRx Research, Novartis, Pfizer, Receptos, Roche, Sanofi, the Canadian Institutes of Health Research, and the Multiple Sclerosis Society of Canada; and holds stock in NeuroRx Research.
Dr. Narayanan reports personal fees from NeuroRx Research and a speaker´s honorarium from Novartis Canada, unrelated to the submitted work.
E. A. Yeh has received funds from NMSS, CIHI, CIHR, OIRM, MS Society of Canada, Mario Battaglia Foundation, SickKids Foundation, CBMH Innovation Fund, CMSC, Rare Diseases Foundation and Guthy Jackson Foundation. She serves as a relapse adjudicator for ACI. She has served on a scientific advisory panel for Juno Therapeutics and has received a speaker's honorarium from Novartis.
R. A. Marrie: receives research funding from Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, National Multiple Sclerosis Society, Rx & D Health Research Foundation, the Waugh Family Chair in Multiple Sclerosis, Crohn's and Colitis Canada, and has conducted clinical trials funded by Sanofi- Aventis.
A. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Biogen Idec, Diogenix, Roche/Genentech, Sanofi-Genzyme, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Teva Neuroscience, Celgene/Receptos Inc, and Merck/EMD Serono.
B. Banwell serves as a central MRI reviewer for Novartis in the context of a clinical trial, and as a non-remunerated advisor on clinical trial design to Sanofi-Aventis, Novartis, Biogen-IDEC, and Teva Neuroscience. Dr. Banwell has received grant support as listed above, as well as from the MS Society of Canada, CIHR, NIH, and NMSS.