Vascular magnifier for ultrahigh-resolution visualization of cerebral vessels in vivo.

Abstract

High-resolution vascular imaging at tens of micrometers in deep tissues in vivo remains a critical challenge. Ultrahigh field susceptibility-weighted imaging (SWI) holds promise but lacking compatible high-sensitivity imaging probes. Herein, we show a holmium (Ho)-based nanoprobe-enhanced SWI strategy for ultrahigh-resolution imaging of cerebral microvessels at 9.4 T. The polyethylene glycol (PEG)-NaHoF₄ nanoparticles (NPs) fabricated via coprecipitation synthesis combined with PEG modification possess uniform size, appropriate hydrodynamic size (20 nm), good biocompatibility, and long circulation half-life (710 min). Notably, the PEG-NaHoF₄ NPs exhibit high r₂/r₁ (742.7) and T₂∗ relaxivity (r₂∗, 73.16 s^-1 mM^-1) under 9.4 T due to the large magnetic moment (∼10.6 μ_B) and short electronic relaxation time (∼10^-13 s) of Ho³⁺. The high susceptibility of PEG-NaHoF₄ NPs in blood vessels induces a significant blooming effect, resulting in a magnified vascular appearance on SWI. In vivo high-resolution imaging of cerebral microvessels with diameters as small as 10 μm is achieved using PEG-NaHoF₄ NPs-enhanced SWI under 9.4 T. In two representative brain disease models, glioma and stroke, this nanoprobe enables high-resolution visualization of tumor vasculature and post-stroke collateral circulation, respectively. Our study offers a new paradigm for precise diagnosis of vascular-related diseases, providing a robust tool for their diagnosis, treatment, and prognosis assessment.