Visualizing and quantifying acute inflammation using ICAM-1 specific nanoparticles and MRI quantitative susceptibility mapping.

Abstract

As intense and prolonged inflammation correlates with the progression of various inflammatory diseases, locating specific regions of the body with dysregulated levels of inflammation could provide crucial information for effective medical diagnosis and treatment. In this study, we demonstrate high resolution spatiotemporal imaging of inflammation in mice treated with systemic injection of lipopolysaccharides (LPS) to mimic systemic inflammatory response or sepsis. Diagnosis of organ-level inflammation was achieved by magnetic resonance imaging (MRI) of inflammation-sensitive superparamagnetic iron oxide (SPIO)-based nanomicelle termed leukocyte-mimetic nanoparticle (LMN), designed to preferentially localize to cells with inflammation-induced overexpression of intercellular adhesion molecule (ICAM)-1. Using a novel MRI quantitative susceptibility mapping (QSM) technique for non-invasive quantification of SPIO nanoparticles, we observed greater accumulation of LMN in the liver, specific to ICAM-1 induction due to LPS-induced inflammation. However, the accumulation of nanoparticles into the spleen appeared to be due to an ICAM-1 independent, phagocytic activity, resulting in higher levels of both LMN and control nanoparticles in the spleen of LPS-treated than untreated mice. Overall, the amounts of nanoparticles in liver and spleen estimated by QSM were in a good agreement with the values directly measured by radioactivity, presenting an idea that spatiotemporal mapping of LMN by MRI QSM may provide a reliable, rapid, non-invasive method for identifying organ-specific inflammation not offered by existing diagnostic techniques.