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. 2025 Mar 19:16:1483138.
doi: 10.3389/fneur.2025.1483138. eCollection 2025.

Automatically quantified follow-up imaging biomarkers predict clinical outcomes after acute ischemic stroke

Sonya Abraham #  1 , Davide Carone #  2   3 , Orell Mielke  4 , Mark Heise  1 , Agnieszka Swierczak  5 , Greg Bass  5 , Stephen Gerry  6 , Zoe V J Woodhead  2 , Rafael Namias  2 , James Garrard  2 , David Kallmes  7 , Waleed Brinjikji  7 , Daniel Vaclavik  8 , Petr Mikulenka  9 , Patrick Nicholson  10   11 , John Thornton  10   11 , Gary A Ford  3   12 , George Harston  2   3
Affiliations

Automatically quantified follow-up imaging biomarkers predict clinical outcomes after acute ischemic stroke

Sonya Abraham et al. Front Neurol. .

Abstract

Background: Follow-up infarct volume (FIV) is a proposed surrogate endpoint for proof-of-concept clinical studies in acute ischemic stroke (AIS). This study aimed to provide clinical validation of an automated FIV algorithm, demonstrating the association of imaging biomarkers with clinical outcomes to support the use of these imaging endpoints in clinical trials.

Methods: Data were gathered for adult AIS patients undergoing mechanical thrombectomy with follow-up imaging 12-96 h from initial assessment. Non-contrast computed tomography was used to quantify infarct volume. Image processing used the AI-powered software Brainomix 360 Stroke (Brainomix Ltd., Oxford, United Kingdom) and Brainomix core lab research software. Measures included total FIV and components-ischemic injury corrected FIV (cFIV), hemorrhagic transformation (HT), anatomical distortion (AD; a marker of edema) and infarct growth (IG). The primary clinical endpoint was modified Rankin Scale (mRS) at 90 days; secondary clinical endpoint was NIH Stroke Scale (NIHSS) score at 24 h.

Results: Of 986 patients, 843 (85.5%; median age 72 years, 56.7% male) had complete data and were included in the study analysis. Median baseline NIHSS score was 17 (IQR: 12-21). Median imaging follow-up time was 24 h (IQR 20-28). Median 24 h NIHSS score was 11 (5-17); 34% of patients had mRS 0-2 at 90 days. Median FIV was 30.2 mL (12.5-120.8 mL). FIV was significantly associated with 90-day mRS (concordance = 0.819, p < 0.001) and NIHSS at 24 h (concordance = 0.722, p < 0.001). cFIV, HT, AD, and IG were also significantly associated with good clinical outcomes in both 90-day mRS (concordance = 0.702, p < 0.001; 0.660, p < 0.001; 0.591, p = 0.002; and 0.663, p < 0.001, respectively) and NIHSS at 24 h (0.774, p < 0.001; 0.652, p = 0.004 L; 0.694, p < 0.001; and 0.716, p < 0.001, respectively). In multivariate analysis, FIV remained strongly associated with 90-day mRS. FIV showed a bimodal distribution consistent with success/failure of recanalization during thrombectomy.

Conclusion: Of the algorithm outputs assessed, FIV was most strongly associated with clinical outcomes. Ischemic injury, HT, edema and IG were also independently significantly associated with clinical outcome. This study validates the prognostic significance of automated FIV and its composites as mechanistic endpoints to improve early-stage trials of therapeutics in AIS.

Keywords: artificial intelligence; follow-up studies; imaging; ischemic stroke; neuroimaging; thrombectomy.

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Conflict of interest statement

DC, GH, RN, JG, and ZW are employees of and have share options in Brainomix Limited. AS, GB, MH, OM and SA are employed by and own stocks in CSL Behring. The authors declare that this study received funding from CSL Behring. Representatives of the funder had the following involvement in the study: conception and design, interpretation of the results, and manuscript review.

Figures

Figure 1
Figure 1
(A) Histogram showing distribution of follow-up infarct volume (FIV) as a function of recanalization status, with patients with good recanalization (TICI 2b–3) in blue and patients with poor recanalization (TICI 0–2a) in red. (B) Plot showing the association between FIV and mRS at 90 days. Cases were grouped into five bands on the basis of FIV (on the y-axis), and the proportion of patients within each band at each NIHSS score is shown using the color scale along the x-axis. (C) The same plot is repeated for the association between FIV and NIHSS at 24 h. FIV, final infarct volume; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; TICI, thrombolysis in cerebral ischemia.
Figure 2
Figure 2
Association between recanalization status (TICI 0–2a versus TICI 2b–3) and (top) long-term clinical outcome, i.e., mRS 90; and (bottom) short-term clinical outcome, i.e., 24 h NIHSS. mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; TICI, thrombolysis in cerebral infarction.
Figure 3
Figure 3
Comparison of biomarkers (AIV, FIV, cFIV AD, rAD and HT) in patients with successful recanalization (orange; TICI 2b–3) versus patients with unsuccessful recanalization (gray; TICI 0–2a). AD, anatomical distortion; AIV, acute ischemic volume; cFIV, corrected FIV; FIV, follow-up infarct volume; HT, hemorrhagic transformation; ns, non-significant; rAD, relative anatomical distortion; TICI, thrombolysis in cerebral infarction. ****p < 0.0001.
See this image and copyright information in PMC

References

    1. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al. . Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. (2016) 387:1723–31. doi: 10.1016/S0140-6736(16)00163-X, PMID: - DOI - PubMed
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. (2009) 45:228–47. doi: 10.1016/j.ejca.2008.10.026, PMID: - DOI - PubMed
    1. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. . Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. (2019) 50:e344–418. doi: 10.1161/STR.0000000000000211, PMID: - DOI - PubMed
    1. Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, et al. . European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischaemic strokeendorsed by Stroke Alliance for Europe (SAFE). Eur Stroke J. (2019) 4:6–12. doi: 10.1177/2396987319832140, PMID: - DOI - PMC - PubMed
    1. Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, et al. . European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. (2021) 6:I–LXII. doi: 10.1177/2396987321989865, PMID: - DOI - PMC - PubMed

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