Abstract Details

Title Magnetization Transfer Saturation Reveals Subclinical Optic Nerve Demyelination in Pediatric Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-044

Objective

This pilot study assesses the suitability of Magnetization Transfer (MT) saturation (MTsat) as a tool for quantifying myelin density within the optic nerve in pediatric multiple sclerosis (POMS).

Background MTsat is an MRI technique sensitive to myelin density. MTsat compensates for T1-relaxation and flip angle inhomogeneities, thus overcoming limitations of previous MT-based methodologies.

Design/Methods Standardized brain MRI including MTSat (3T Siemens Prisma) was acquired in 19 healthy children (HC) (10 females (F), mean (SD) age [years (y)] 16y (2)), and 11 POMS (7F, 17y (1.3), disease duration (DD) 2.5y (1.9)). Only POMS participants without a history of optic neuritis were included. Brain white matter lesion volume (LV) was determined according to standardized pipeline previously described. MTsat maps were calculated as described in Helms, 2008, DOI 10.1002/mrm.21732. Coregistered Mton and Mtoff sequences and MTsat maps were used to manually segment the left and right optic nerve. To minimize movement and susceptibility artifacts, only voxels within the posterior one-third of the intraorbital optic nerve or the intracranial optic nerve, and that appeared to be part of the nerve on all three contrasts, were included. Mean optic nerve Mtsat was then computed for each side. A multivariable mixed effects model was used to model optic nerve MTsat in each group (POMS, HC), accounting for sex, age, DD, LV, and a random effect for subject, accounting for correlation between measurements from right and left optic nerve.

Results Optic nerve MTsat averaged 3.04 units (U) in HC. POMS showed lower optic nerve MTsat (-0.48 U vs HC, p=0.0073). Sex (males: -0.16 U vs females, p=0.29), age (0.031 U/year, p=0.32), DD (-0.026 U/year, p=0.59), and LV (-0.000014 U/mm³, p=0.38) did not significantly affect optic nerve MTsat.

Conclusions Subclinical optic nerve demyelination seems to occur in POMS. MTsat emerges as a sensitive metric to detect microstructural optic nerve alterations in POMS.

Authors/Disclosures
Giulia Longoni, MD (The Hospital for Sick Children) PRESENTER	Dr. Longoni has nothing to disclose.
Robert A. Brown, PhD (ShadowLab Reseaerch)	Dr. Brown has received stock or an ownership interest from ShadowLab Research Inc.. Dr. Brown has received intellectual property interests from a discovery or technology relating to health care. Dr. Brown has a non-compensated relationship as a consultant with the Population Council that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stephanie Grover, MSc, CCRP (The Hospital for Sick Children)	No disclosure on file
Fiona E. Costello, MD (Fiona Costello Professional Corporation)	Dr. Costello has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Costello has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Costello has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Costello has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Costello has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Accure Therapeutics. Dr. Costello has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for the Sumaira Foundation.
	No disclosure on file
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Ruth-Ann Marrie, MD, PhD (University of Manitoba)	The institution of Dr. Marrie has received research support from CIHR. The institution of Dr. Marrie has received research support from MS Canada. The institution of Dr. Marrie has received research support from National MS Society. The institution of Dr. Marrie has received research support from Crohn's and Colitis Canada. The institution of Dr. Marrie has received research support from US Department of Defense. The institution of Dr. Marrie has received research support from The Arthritis Society. The institution of Dr. Marrie has received research support from CMSC.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
Sridar Narayanan (Montreal Neurological Institute)	Sridar Narayanan has received personal compensation for serving as an employee of NeuroRx Research. Sridar Narayanan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech Inc.. The institution of Sridar Narayanan has received research support from Immunotec Inc.
Brenda L. Banwell, MD, FAAN (Johns Hopkins University)	Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.
	No disclosure on file
	No disclosure on file
E. Ann Yeh, MD, MA, FRCPC (Hospital for Sick Children)	Dr. Yeh has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pipeline therapeutics. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for SCN. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from MSSC. The institution of Dr. Yeh has received research support from Garry Hurvitz Foundation. The institution of Dr. Yeh has received research support from Leong Centre. The institution of Dr. Yeh has received research support from OMSLife. The institution of Dr. Yeh has received research support from Canada's Drug Agency. Dr. Yeh has received personal compensation in the range of $0-$499 for serving as a Author with Medscape. Dr. Yeh has a non-compensated relationship as a Editorial Board with Neurology that is relevant to AAN interests or activities. Dr. Yeh has a non-compensated relationship as a Editorial Board with MSJ that is relevant to AAN interests or activities.

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