Neutrophil‐Mimetic MRI Enables Ultra‐Early Detection of Vascular Inflammation After Stroke

Following ischemic stroke, neutrophil adhesion to activated cerebral endothelium triggers the initial inflammatory cascade. Real-time, quantitative in vivo detection of this early interaction could help identify individuals most likely to benefit from immunomodulatory therapies. To achieve this, we analyzed single-cell RNA sequencing data from brain tissue and identified E-selectin (Sele) as one of the earliest adhesion molecules selectively upregulated in activated endothelial cells with a venous-like transcriptional signature. We then developed iron oxide microparticles targeting E-selectin, designed to mimic neutrophil adhesion and to function as MRI probes for early endothelial activation. Within seconds of injection, these probes adhered to inflamed vessels in models of LPS-induced neuroinflammation and ischemic stroke, allowing rapid emergency imaging. We observed an MRI-detectable signal as early as 4 h following LPS stimulation and 8 h post-stroke. This binding was significantly associated with neutrophil infiltration, but not with lesion volume, blood-brain barrier disruption, or the accumulation of T cells and monocyte-derived cells. These findings demonstrate its specificity for neutrophil-driven inflammation and its relevance as a biomarker of ultra-early immune activation. These results suggest that neutrophil-mimetic MRI probes could represent a promising approach for detecting the initial phase of stroke-induced inflammation and for guiding personalized immunomodulatory strategies.