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

Zhao, Xunxiao; Li, Xue; Gong, Yan; Wu, Menglin; Li, Jiang; Wang, Huiying; Chai, Chao; Zhao, Chenxi et al. · Biomaterials · 2026

basic_science · Level V

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Abstract

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 Fe<sub>3</sub>O<sub>4</sub> nanoprobe (MS-Fe<sub>3</sub>O<sub>4</sub>-Nanoagents). Rather than employing complex nanoarchitectures, we utilized a minimalist biomimetic co-precipitation approach to yield ultrasmall Fe<sub>3</sub>O<sub>4</sub> 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 T<sub>1</sub>-T<sub>2</sub> dual-modal contrast profile (r<sub>1</sub> = 11, r<sub>2</sub> = 59, and r<sub>2</sub>* = 131 mM<sup>-1</sup> s<sup>-1</sup> at 3.0 T) with an optimal r<sub>2</sub>/r<sub>1</sub> ratio. Phantom and in vivo MRI confirmed that the administration of MS-Fe<sub>3</sub>O<sub>4</sub>-Nanoagents robustly drives multi-sequence signal modulation-enhancing T<sub>1</sub>-weighted/mapping signals while effectively attenuating T<sub>2</sub>/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.