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

in Biomaterials by Bingjie Li, Jinbin Pan, Ruijie Zhang, Bing Han, Yujie Zhao, Guijun Liu, Yujie Tong, Yujing He, Guangchao Xie, Ruxia Liu, Ting Zhou, Quan Zhang, Shao-Kai Sun

TLDR

  • A novel Ho-based nanoprobe-enhanced susceptibility-weighted imaging (SWI) strategy achieves ultrahigh-resolution imaging of cerebral microvessels at 9.4 T for precise diagnosis and treatment of vascular-related diseases.

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)-NaHoFnanoparticles (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-NaHoFNPs exhibit high r/r(742.7) and T∗ relaxivity (r∗, 73.16 smM) under 9.4 T due to the large magnetic moment (∼10.6 μ) and short electronic relaxation time (∼10s) of Ho. The high susceptibility of PEG-NaHoFNPs 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-NaHoFNPs-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.

Overview

  • The study presents a novel strategy for high-resolution vascular imaging at tens of micrometers in deep tissues in vivo using holmium (Ho)-based nanoprobe-enhanced susceptibility-weighted imaging (SWI).
  • The Ho-based nanoprobe, PEG-NaHoFNPs, is fabricated via coprecipitation synthesis and modification, exhibiting uniform size, appropriate hydrodynamic size, good biocompatibility, and long circulation half-life.
  • The primary objective of the study is to achieve ultrahigh-resolution imaging of cerebral microvessels at 9.4 T and to demonstrate its application in two brain disease models, glioma and stroke.

Comparative Analysis & Findings

  • The PEG-NaHoFNPs exhibit high r1 relaxivity (742.7) and T∗ relaxivity (r∗, 73.16 smM) under 9.4 T due to the large magnetic moment and short electronic relaxation time of Ho.
  • In vivo high-resolution imaging of cerebral microvessels with diameters as small as 10 μm is achieved using PEG-NaHoFNPs-enhanced SWI under 9.4 T.
  • The PEG-NaHoFNPs enable high-resolution visualization of tumor vasculature in glioma and post-stroke collateral circulation in stroke, demonstrating its potential for precise diagnosis and treatment of vascular-related diseases.

Implications and Future Directions

  • This study offers a new paradigm for precise diagnosis and treatment of vascular-related diseases, providing a robust tool for their diagnosis, treatment, and prognosis assessment.
  • Future studies can explore the application of this nanoprobe-enhanced SWI strategy in other diseases models and clinical trials to validate its effectiveness and safety.
  • Additionally, the development of optimized probe designs and imaging protocols will be crucial to improve the resolution and accuracy of the imaging results.
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