Treatment Efficacy Analysis in Acute Ischemic Stroke Patients Using In Silico Modeling Based on Machine Learning: A Proof-of-Principle

Interventional neuroradiology is characterized by engineering- and experience-driven device development with design improvements every few months. However, clinical validation of these new devices requires lengthy and expensive randomized controlled trials. This contribution proposes a machine learning-based in silico study design to evaluate new devices more quickly with a small sample size. Acute diffusion- and perfusion-weighted MRI, segmented one-week follow-up imaging, and clinical variables were available for 90 acute ischemic stroke patients. Three treatment option-specific random forest models were trained to predict the one-week follow-up lesion segmentation for (1) patients successfully recanalized using intra-arterial mechanical thrombectomy, (2) patients successfully recanalized using intravenous thrombolysis, and (3) non-recanalizing patients as an analogue for conservative treatment for each patient in the sample, independent of the true group membership. A repeated-measures analysis of the three predicted follow-up lesions for each patient revealed significantly larger lesions for the non-recanalizing group compared to the successful intravenous thrombolysis treatment group, which in turn showed significantly larger lesions compared to the successful mechanical thrombectomy treatment group (<i>p</i> < 0.001). A groupwise comparison of the true follow-up lesions for the three treatment options showed the same trend but did not reach statistical significance (<i>p</i> = 0.19). We conclude that the proposed machine learning-based in silico trial design leads to clinically feasible results and can support new efficacy studies by providing additional power and potential early intermediate results.