Abstract Details

Title A Multimodal Neuroimaging Feature Extraction Framework for Biomarker Discovery in Myotonic Dystrophies

Topic General Neurology

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-004

Objective Myotonic dystrophies (DM) are neuromuscular conditions that cause widespread effects throughout the body. New therapeutics are being developed that attack the RNA mechanism underlying DM. Here, we address the urgent need of identifying DM neuroimaging biomarkers that can be used in trials.

Background DTI shows decreased white matter connectivity in DM patients and MRI reveals decreased parietal, frontal, and temporal resting state metabolism. Additionally, DTI studies of DM have shown that the white matter abnormalities are diffuse as opposed to multi-focal.

Design/Methods Extracting important features from neuroimaging data is challenging due to the high feature dimension and low sample-size problem. This work utilizes a sparse matrix decomposition method and a manifold regularization approach to identify the most discriminative features and improves spatial and temporal resolutions of neuroimaging data. To this end, neuroimaging data of 46 DM1, 17 DM2 patients and 92 healthy controls were analyzed using a ten-fold-cross-validation technique. In addition to neuroimaging data, additional clinical assessments including Quebec Muscular Impairment Rating Scale and Quebec Daytime Sleepiness Scale were calculated for DM patients. Wavelet approximation and detailed coefficients were calculated to consider both long term and short-term fluctuations caused by the disease process.

Results Normalized sub-band energy calculated based on wavelet coefficients can characterize DM1 and DM2. Patients with DM1 have widespread white matter volume reductions that are correlated with distal to proximal progression of the muscular involvement in DM1. A significant difference can be seen between DM1 and healthy controls in terms of executive function, motor speed, processing speed, and memory.

Conclusions The proposed method can potentially be used to develop and validate key predictors of DM type, severity, and progression of DM central nervous system abnormalities using brain morphometry. Identified features can also potentially provide multidisciplinary biomarkers that help unravel our understanding of fatigue, sleepiness, and attention.

Authors/Disclosures
Tahereh Kamali, PhD (Stanford University) PRESENTER	Dr. Kamali has nothing to disclose.
John W. Day, MD, PhD (Stanford University School of Medicine)	Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day 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. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Jacinda B. Sampson, MD, PhD	Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viking Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Sampson has received research support from Marigold Foundation. Dr. Sampson has a non-compensated relationship as a Scientific Advisory Committee with Myotonic Dystrophy Foundation that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file

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