Abstract Details

Title Exploring in-vivo brain microstructural damage in multiple sclerosis through T1w/T2w-ratio mapping: a multicenter study

Topic Multiple Sclerosis

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-009

Objective

To evaluate white (WM) and gray matter (GM) T1-weighted (w)/T2w-ratio in a large multicenter cohort of healthy controls (HC) and multiple sclerosis (MS) patients from 7 European sites, and their association with clinical disability.

Background

T1w/T2w-ratio has been suggested as a clinically feasible method to investigate WM and GM integrity in MS. However, its clinical relevance and suitability in a multicenter setting still need to be fully explored.

Design/Methods

Brain T2-w and T1-w sequences were acquired from 434 MS patients (57 clinically isolated syndrome [CIS], 196 relapsing-remitting [RR], 106 secondary progressive [SP], 75 primary progressive [PP]) and 270 HC. T1w/T2w-ratio maps were obtained after calibration on signal from eyes and temporal fat.

Results

In HC, T1w/T2w-ratio increased with age till 50-60 years for all the structures. Compared to HC, T1w/T2w-ratio was significantly lower in WM lesions of all MS phenotypes, in NAWM and cortex of RRMS and SPMS (p≤0.026), significantly higher in striatum and pallidum of RRMS, SPMS and PPMS (p≤0.042). In relapse-onset MS, compared to HC, T1w/T2w-ratio was significantly lower in WM lesions and NAWM already at mild disability (Expanded Disability Status Scale [EDSS]<3.0) and in the cortex only for EDSS≥3.0 (p≤0.023). Conversely, T1w/T2w-ratio was significantly higher in the striatum and pallidum only for EDSS≥4.0 (p≤0.005). In PPMS, T1w/T2w-ratio was significantly higher in the striatum and pallidum only for EDSS≥6.0 (p≤0.001). In MS, a longer disease duration, higher EDSS, T2-hyperintense lesion load, and a lower normalized brain volume were associated with a lower T1w/T2w-ratio in WM lesions and cortex and a higher T1w/T2w-ratio in the striatum and pallidum (β from -1.168 to 0.286, p≤0.040).

Conclusions

Compared to HC, heterogeneous T1w/T2w-ratio abnormalities were detected in specific brain compartments according to different MS phenotypes and disability. Various pathological substrates such as demyelination, inflammation, neurodegeneration and iron accumulation may explain this metric and its clinical relevance.

Authors/Disclosures
Monica Margoni PRESENTER	Monica Margoni has received research support from MAGNIMS. Monica Margoni has received research support from Merck-Serono. Monica Margoni has received research support from Sanofi-Genzyme.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
Alessandro Meani	Alessandro Meani has nothing to disclose.
Loredana Storelli	Loredana Storelli has nothing to disclose.
Sarlota Mesaros	Sarlota Mesaros has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Sarlota Mesaros has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra Zeneca. Sarlota Mesaros has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. Sarlota Mesaros has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Hemofarm. Sarlota Mesaros has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Jelena Drulovic	Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hemofarm. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PharmaSwiss. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck . Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Actavis TEVA. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Hemofarm. Jelena Drulovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medis. Jelena Drulovic has received research support from Ministry of Science, Technological Development and Innovations of the Republic of Serbia.
Frederik Barkhof, MD, PhD (Image Analysis Center)	Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Frederik Barkhof has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Combinostics. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IXICO. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI.
	No disclosure on file
Antonio Gallo	Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis.
Alvino Bisecco	Alvino Bisecco has nothing to disclose.
	No disclosure on file
Jaume Sastre-Garriga	The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Orchid Pharma. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOGEN. Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal. Jaume Sastre-Garriga has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Revista de Neurologia. The institution of Jaume Sastre-Garriga has received research support from Fondo de Investigación Sanitaria.
Olga Ciccarelli, MD, PhD, FRCP (UCL Institute of Neurology)	Prof. Ciccarelli has received personal compensation in the range of $0-$499 for serving as a Consultant for Lundebeck. Prof. Ciccarelli 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. Prof. Ciccarelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Prof. Ciccarelli has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Prof. Ciccarelli has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEUROLOGY Journal.
	No disclosure on file
Jacqueline Palace (John Radcliff Hospital Oxford Univeristy Hospitals Trust)	Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono, Medimmune, Argenx, Janssen, AMgen, UCB, Roche, Novartis, Amplo, Alexion, . Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx, Sanofi. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Roche, UCB, Alexion, Amgen. Dr. Palace has or had stock in Astra Zenica. The institution of Dr. Palace has received research support from Roche, AMPLO, Alexion, UCB,. argenx, amgen. Dr. Palace has received intellectual property interests from a discovery or technology relating to health care.
Paolo Preziosa (Ospedale San Raffaele)	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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