A unified magnetic nanoprobe enables multi-sequence MRI mapping of post-stroke cerebrovascular and glymphatic injuries.

The coupled impairment of the cerebrovascular network and the glymphatic system is a critical pathological feature of stroke. However, comprehensively assessing this dual-pathway damage remains a significant clinical challenge. Current clinical MRI contrast agents are fundamentally limited by single-modality contrast, restricted sequence compatibility, and safety concerns, falling short of multi-parametric evaluation at clinical 3.0 T magnetic fields. To address this gap, we propose an integrated multi-sequence MRI strategy enabled by a highly translatable, bovine serum albumin (BSA)-templated Fe3O4 nanoprobe (MS-Fe3O4-Nanoagents). Rather than employing complex nanoarchitectures, we utilized a minimalist biomimetic co-precipitation approach to yield ultrasmall Fe3O4 cores (∼4.5 nm) with an optimized hydrated diameter (∼20 nm). The BSA shell creates a hydrophilic, exchange-rich interface that modulates the rotational motion of water protons, achieving a balanced T1-T2 dual-modal contrast profile (r1 = 11, r2 = 59, and r2* = 131 mM-1 s-1 at 3.0 T) with an optimal r2/r1 ratio. Phantom and in vivo MRI confirmed that the administration of MS-Fe3O4-Nanoagents robustly drives multi-sequence signal modulation-enhancing T1-weighted/mapping signals while effectively attenuating T2/SWI signals. In rat models of ischemic and hemorrhagic stroke, the versatile compatibility of this nanoprobe significantly amplified the signal-to-noise ratio and spatial resolution across multiple sequences. This capability enabled the dynamic and quantitative mapping of venous hemodynamics, microbleeds, blood-brain barrier (BBB) disruption, and delayed glymphatic clearance without the need for sequence-specific contrast agents. By repurposing a biocompatible nanomaterial into a unified multi-sequence platform, this study provides a robust diagnostic tool for the precise prognostic evaluation and therapeutic monitoring of complex post-stroke injuries.