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Neurology Genetics
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October 2017; 3 (5) ArticleOpen Access

Design and rationale for examining neuroimaging genetics in ischemic stroke

The MRI-GENIE study

Anne-Katrin Giese, Markus D. Schirmer, Kathleen L. Donahue, Lisa Cloonan, Robert Irie, Stefan Winzeck, Mark J.R.J. Bouts, Elissa C. McIntosh, Steven J. Mocking, Adrian V. Dalca, Ramesh Sridharan, Huichun Xu, Petrea Frid, Eva Giralt-Steinhauer, Lukas Holmegaard, Jaume Roquer, Johan Wasselius, John W. Cole, Patrick F. McArdle, Joseph P. Broderick, Jordi Jimenez-Conde, Christina Jern, Brett M. Kissela, Dawn O. Kleindorfer, Robin Lemmens, Arne Lindgren, James F. Meschia, Tatjana Rundek, Ralph L. Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Slowik, Vincent Thijs, Daniel Woo, Bradford B. Worrall, Steven J. Kittner, Braxton D. Mitchell, Jonathan Rosand, Polina Golland, Ona Wu, Natalia S. Rost; On behalf of MRI-GENIE
First published August 24, 2017, DOI: https://doi.org/10.1212/NXG.0000000000000180
Anne-Katrin Giese
Author affiliations are provided at the end of the article.
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Markus D. Schirmer
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Kathleen L. Donahue
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Lisa Cloonan
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Robert Irie
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Stefan Winzeck
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Mark J.R.J. Bouts
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Elissa C. McIntosh
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Steven J. Mocking
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Adrian V. Dalca
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Ramesh Sridharan
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Huichun Xu
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Petrea Frid
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Eva Giralt-Steinhauer
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Lukas Holmegaard
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Jaume Roquer
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Johan Wasselius
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John W. Cole
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Patrick F. McArdle
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Joseph P. Broderick
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Jordi Jimenez-Conde
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Christina Jern
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Brett M. Kissela
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Dawn O. Kleindorfer
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Robin Lemmens
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Arne Lindgren
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James F. Meschia
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Tatjana Rundek
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Ralph L. Sacco
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Reinhold Schmidt
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Pankaj Sharma
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Agnieszka Slowik
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Vincent Thijs
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Daniel Woo
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Bradford B. Worrall
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Steven J. Kittner
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Braxton D. Mitchell
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Jonathan Rosand
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Polina Golland
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Ona Wu
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Natalia S. Rost
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Citation
Design and rationale for examining neuroimaging genetics in ischemic stroke
The MRI-GENIE study
Anne-Katrin Giese, Markus D. Schirmer, Kathleen L. Donahue, Lisa Cloonan, Robert Irie, Stefan Winzeck, Mark J.R.J. Bouts, Elissa C. McIntosh, Steven J. Mocking, Adrian V. Dalca, Ramesh Sridharan, Huichun Xu, Petrea Frid, Eva Giralt-Steinhauer, Lukas Holmegaard, Jaume Roquer, Johan Wasselius, John W. Cole, Patrick F. McArdle, Joseph P. Broderick, Jordi Jimenez-Conde, Christina Jern, Brett M. Kissela, Dawn O. Kleindorfer, Robin Lemmens, Arne Lindgren, James F. Meschia, Tatjana Rundek, Ralph L. Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Slowik, Vincent Thijs, Daniel Woo, Bradford B. Worrall, Steven J. Kittner, Braxton D. Mitchell, Jonathan Rosand, Polina Golland, Ona Wu, Natalia S. Rost
Neurol Genet Oct 2017, 3 (5) e180; DOI: 10.1212/NXG.0000000000000180

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Abstract

Objective: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI–GENetics Interface Exploration (MRI-GENIE) study.

Methods: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributed MRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants. Neuroimaging analyses include the manual and automated assessments of established MRI markers. A high-throughput MRI analysis pipeline for the automated assessment of cerebrovascular lesions on clinical scans will be developed in a subset of scans for both acute and chronic lesions, validated against gold standard, and applied to all available scans. The extracted neuroimaging phenotypes will improve characterization of acute and chronic cerebrovascular lesions in ischemic stroke, including CCS subtypes, and their effect on functional outcomes after stroke. Moreover, genetic testing will uncover variants associated with acute and chronic MRI manifestations of cerebrovascular disease.

Conclusions: The MRI-GENIE study aims to develop, validate, and distribute the MRI analysis platform for scans acquired as part of clinical care for patients with AIS, which will lead to (1) novel genetic discoveries in ischemic stroke, (2) strategies for personalized stroke risk assessment, and (3) personalized stroke outcome assessment.

GLOSSARY

ADC=
apparent diffusion coefficient;
AIS=
acute ischemic stroke;
CE=
cardioembolic;
CCS=
Causative Classification of Stroke;
CCSc=
causative CCS;
DICOM=
Digital Imaging and Communications in Medicine;
DWI=
diffusion-weighted imaging;
DWIv=
DWI volume;
FLAIR=
fluid-attenuated inversion recovery;
GISCOME=
Genetics of Ischemic Stroke Functional Outcome;
GWAS=
genome-wide association studies;
ICC=
intraclass correlation coefficient;
LAA=
large artery atherosclerosis;
MGH=
Massachusetts General Hospital;
MRI-GENIE=
MRI–GENetics Interface Exploration;
mRS=
modified Rankin Scale;
PHI=
protected health information;
QC=
quality control;
SAO=
small artery occlusion;
SiGN=
Stroke Genetics Network;
SNP=
single nucleotide polymorphism;
SWI=
susceptibility-weighted imaging;
TOAST=
Trial of Org 10172 Acute Stroke Treatment;
VLSM=
voxel-based lesion–symptom mapping;
WMHv=
white matter hyperintensity volume;
XNAT=
eXtensible Neuroimaging Archive Toolkit

Footnotes

  • ↵* These authors contributed equally to the manuscript.

  • Funding information and disclosures are provided at the end of the article. Go to Neurology.org/ng for full disclosure forms. The Article Processing Charge was funded by the NIH.

  • Supplemental data at Neurology.org/ng

  • Received March 9, 2017.
  • Accepted in final form June 30, 2017.
  • Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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