Biomimetic MRI Nanoprobe for Mapping Cerebrovascular Inflammation After Traumatic Brain Injury
Rousseau, J.; Simmons, A. M.; Kim, M.; Ortega, D.; Alzubi, O.; Wang, T.-Y.; Bartelle, B. B.; Stabenfeldt, S. E.; Wang, K.-C.
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Cerebrovascular inflammation is a critical driver of secondary injury following traumatic brain injury (TBI), yet no noninvasive tool currently exists to map its spatial heterogeneity across the injured brain. Here, we report MoNP-SPION, a monocyte-mimetic nanoprobe that selectively targets activated cerebrovascular endothelium after TBI and enables quantitative MRI of spatiotemporally heterogeneous cerebrovascular inflammation. MoNP-SPION binding to inflamed brain endothelium scaled with activation state, enabling rapid, spatially heterogeneous targeting of injured cerebral vasculature. MoNP-SPION-enhanced MRI revealed dynamic reductions in T2* throughout the brain that extended beyond the injury penumbra and captured both subacute vascular injury and therapy-induced recovery. Importantly, spatiotemporal reductions in T2* strongly correlated with VCAM1 upregulation, supporting MoNP-SPION as a molecularly specific readout of endothelial activation. Together, these findings establish MoNP-SPION as a promising platform for longitudinal, noninvasive monitoring of cerebrovascular inflammation in TBI and other neurological disorders involving vascular dysfunction. TEASERCell-mimicking MRI nanoprobe maps cerebrovascular injury and recovery dynamics following brain trauma.
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