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

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 μB) 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.