Zurab Nadareishvili, MD, PhD; Devon Kelley, BSc, MSc; Marie Luby, PhD; Alexis N. Simpkins, MD, PhD; Richard Leigh, MD; John K. Lynch, DO, MPH; Amie W. Hsia, MD; Richard T. Benson, MD, PhD; Kory R. Johnson, MS, PhD; John M. Hallenbeck, MD; Lawrence L. Latour, PhD;
Perfusion-weighted -diffusion-weighted imaging mismatch (PD MM) using acute MRI approximates ischemic penumbra. We aimed to characterize gene expression dynamics using next generation sequencing (NGS) in peripheral blood of acute ischemic stroke patients with PD MM at baseline and 24 hours. 
Baseline PD MM was defined as the difference in perfusion lesion volume as measured on mean transit time map and DWI ischemic lesion volume. Whole blood was collected within 30 minutes of MRI at baseline and 24 hours. Baseline blood was obtained prior to the thrombolytic therapy. NGS RNA-sequencing platform was used for the gene expression analysis. 
We studied 23 patients within 12 hours of stroke onset. Twenty patients (87%) were treated with IV tPA and 3of these patients also received endovascular therapy. Expression was detectable for 26,182 genes. Baseline PD MM volume significantly (p< 0.05 and > 1.5-fold change) correlated with the expression of 24 genes including those related to inflammation, SUMOylation, and coagulation. Inhibition of lipopolysaccharide was found to be an upstream regulator of these processes. At 24 hours, PD MM volume significantly correlated with expression of 93 genes including pathways related to Eph (erythropoietin-producing hepatocellular receptor), MAP/ERK (mitogen-activated protein kinases, ERK-extracellular regulated kinases), phospholipase C, and protein kinase A, while tretinoin (retinoic acid receptor ligand) upregulation was found to be an upstream regulator. 
Multimodel pathways and upstream regulators are associated with penumbral tissue at baseline and 24 hours follow-up that can be detected in the peripheral blood of patients with stroke.

ASSOCIATION OF PERIPHERAL BLOOD GENE EXPRESSION WITH PENUMBRAL TISSUE DYNAMICS IN PATIENTS WITH ACUTE ISCHEMIC STROKE: MRI BASED NEXT GENERATION SEQUENCING STUDY