TY - JOUR
T1 - Deep profiling of multiple ischemic lesions in a large, multi-center cohort
T2 - Frequency, spatial distribution, and associations to clinical characteristics
AU - the MRI-GENIE GISCOME Investigators, the International Stroke Genetics Consortium
AU - Bonkhoff, Anna K.
AU - Ullberg, Teresa
AU - Bretzner, Martin
AU - Hong, Sungmin
AU - Schirmer, Markus D.
AU - Regenhardt, Robert W.
AU - Donahue, Kathleen L.
AU - Nardin, Marco J.
AU - Dalca, Adrian V.
AU - Giese, Anne Katrin
AU - Etherton, Mark R.
AU - Hancock, Brandon L.
AU - Mocking, Steven J.T.
AU - McIntosh, Elissa C.
AU - Attia, John
AU - Cole, John W.
AU - Donatti, Amanda
AU - Griessenauer, Christoph J.
AU - Heitsch, Laura
AU - Holmegaard, Lukas
AU - Jood, Katarina
AU - Jimenez-Conde, Jordi
AU - Kittner, Steven J.
AU - Lemmens, Robin
AU - Levi, Christopher R.
AU - McDonough, Caitrin W.
AU - Meschia, James F.
AU - Phuah, Chia Ling
AU - Ropele, Stefan
AU - Rosand, Jonathan
AU - Roquer, Jaume
AU - Rundek, Tatjana
AU - Sacco, Ralph L.
AU - Schmidt, Reinhold
AU - Sharma, Pankaj
AU - Slowik, Agnieszka
AU - Sousa, Alessandro
AU - Stanne, Tara M.
AU - Strbian, Daniel
AU - Tatlisumak, Turgut
AU - Thijs, Vincent
AU - Vagal, Achala
AU - Woo, Daniel
AU - Zand, Ramin
AU - McArdle, Patrick F.
AU - Worrall, Bradford B.
AU - Jern, Christina
AU - Lindgren, Arne G.
AU - Maguire, Jane
AU - Wu, Ona
AU - Frid, Petrea
AU - Rost, Natalia S.
AU - Wasselius, Johan
N1 - Funding Information:
The MRI-GENIE study was funded by NIH NINDS (R01NS086905). AB was supported by a Massachusetts General Hospital Executive Committee on Research (MGH ECOR) Fund for Medical Discovery (FMD) Clinical Research Fellowship Award. MB was supported by the Société Française de Neuroradiologie, Société Française de Radiologie and Fondation ISITE-ULNE. AV was in part supported by National Institutes of Health and National Institute of Neurological Disorders and Stroke (NIH-NINDS, R01 NS103824, RF1 NS117643, R01 NS100417, U01NS100699, and U01NS110772). CJ was supported by the Swedish Research Council (2018-02543 and 2021-01114), the Swedish state under the agreement between the Swedish government and the county councils, the “Avtal om Läkarutbildning och Medicinsk Forskning” (ALF) agreement (ALFGBG-720081); the Swedish Heart and Lung Foundation (20190203). AL was supported by the Swedish Research Council (2019-01757), The Swedish Government (under the “Avtal om Läkarutbildning och Medicinsk Forskning, ALF”), The Swedish Heart and Lung Foundation, Region Skåne, Lund University, Skåne University Hospital, Sparbanksstiftelsen Färs och Frosta, Fremasons Lodge of Instruction Eos in Lund and National Institutes of Health (NIH, 1R01NS114045-01). NR was in part supported by National Institutes of Health and National Institute of Neurological Disorders and Stroke (NIH-NINDS, R01NS082285, R01NS086905, and U19NS115388). JW received funding from the Crafoord Foundation (#20180610 and #20200548), the Swedish state under the agreement between the Swedish government and the county councils, the “Avtal om Läkarutbildning och Medicinsk Forskning” (ALF) agreement (YF-aALF-43435), and the Skåne University Hospital Research Funds (#96437 and 96438). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
ME had received personal fees for consulting from Astra Zeneca and WorldCare Clinical Group. CG had received consulting honoraria from Microvention and Strykere and research funding from Medtronic and Penumbra. AV had received research funding from Cerenovus. AL had received personal fees from Bayer, Astra Zeneca, BMS Pfizer, and Portola. NR had received compensation as scientific advisory consultant from Omniox, Sanofi Genzyme and AbbVie Inc. TU received personal fees for consulting from AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher Copyright:
Copyright © 2022 Bonkhoff, Ullberg, Bretzner, Hong, Schirmer, Regenhardt, Donahue, Nardin, Dalca, Giese, Etherton, Hancock, Mocking, McIntosh, Attia, Cole, Donatti, Griessenauer, Heitsch, Holmegaard, Jood, Jimenez-Conde, Kittner, Lemmens, Levi, McDonough, Meschia, Phuah, Ropele, Rosand, Roquer, Rundek, Sacco, Schmidt, Sharma, Slowik, Sousa, Stanne, Strbian, Tatlisumak, Thijs, Vagal, Woo, Zand, McArdle, Worrall, Jern, Lindgren, Maguire, Wu, Frid, Rost and Wasselius.
PY - 2022/8/25
Y1 - 2022/8/25
N2 - Background purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methods: Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. Results: We analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL. Conclusion: Multiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.
AB - Background purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methods: Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. Results: We analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL. Conclusion: Multiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.
KW - Bayesian hierarchical regression
KW - acute ischemic stroke
KW - lesion volume
KW - magnetic resonance imaging
KW - multiple acute ischemic lesions
KW - quantitative imaging
UR - http://www.scopus.com/inward/record.url?scp=85138101263&partnerID=8YFLogxK
U2 - 10.3389/fnins.2022.994458
DO - 10.3389/fnins.2022.994458
M3 - Article
C2 - 36090258
AN - SCOPUS:85138101263
SN - 1662-4548
VL - 16
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 994458
ER -