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.
Letters: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
