Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex

Abstract

Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion.Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP).Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP.Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization.

Nanotechnology translation in vascular diseases: From design to the bench

“…Iron oxide is the most commonly used component with NPs for molecular imaging, and it has been widely studied for the diagnosis of vascular diseases, due to its ultrafine size, magnetic properties, and good biocompatibility (de Bortoli et al, 2021; Lee et al, 2015). In the application of MRI, IONPs have been used as T2 contrast agents for approximately 30 years.…”

Mapping the Cerebrovascular Abnormality in Transgenic Alzheimer’s Disease (AD) Mice with deep-learning-based super-resolution cerebral blood volume (CBV)-MRI

“…Magnetic iron oxide nanoparticles (MION)-based cerebral blood volume (CBV) mapping methods have been employed for in vivo brain-wide vasculatures 55 . The spatial resolution of MION-based CBV fMRI is lower than the aforementioned methodology.…”