Ultrasmall Nanoprobe Enabling Contrast-Enhanced T₁-Weighted and Susceptibility-Weighted Imaging for Multidimensional Diagnosis of Glioma.

Abstract

Acquiring multidimensional tumor and tumor-associated vascular information is essential for accurate diagnosis and treatment planning of glioma, yet effective imaging methods are still lacking. Here, ultrasmall manganese ferrite nanoparticles (UMFNs) are developed as a dual contrast-enhanced T₁-weighted imaging (T1WI) and susceptibility-weighted imaging (SWI) probe for multidimensional diagnosis of glioma. The UMFNs are synthesized through thermal decomposition and functionalized with polyethylene glycol, ensuring excellent water dispersibility and biocompatibility. Characterization studies confirm the nanoparticles' uniform size (3.8 nm) and high stability in various media. High r₁ (6.8 mm^-1 s^-1) and r₂* (95.1 mm^-1 s^-1) values demonstrate the superior T₁ and T₂* enhancement capabilities of UMFNs. In vivo imaging on a 3.0 T magnetic resonance imaging (MRI) scanner demonstrates that UMFN-enhanced SWI clearly delineates tumor margins and provides sustained tumor enhancement in ultrasmall orthotopic glioma (<2 mm). Besides, UMFN-enhanced SWI reveals distinct vascular structures associated with the glioma, including tortuous, thickened vessels indicative of tumor-induced angiogenesis. Whole-brain histological analysis corroborates these findings, demonstrating dense tumor proliferation and vascular remodeling. These results highlight the potential of UMFNs as a dual-enhanced agent for the early detection and high-resolution vascular mapping of glioma, providing an advanced multidimensional method for precise diagnosis of brain tumors.