Visualizing the spatial distribution of inflammation in the depressed brain with a targeted MRI nanoprobe in vivo

Abstract

Depression is a prevalent mental illness that imposes a substantial public health burden. However, the diverse clinical phenotypes observed in patients make it difficult to realize precise diagnosis. Recently, accumulating preclinical and clinical evidence has suggested that inflammation is involved in the pathophysiology of depression. Herein, a molecular imaging–based strategy was proposed as a means to diagnose depression precisely by specifically visualizing the inflammation status associated with depression. Inflammation-targeting MRI nanoprobes were constructed by attaching an intercellular cell adhesion molecule-1 (ICAM-1)-targeting peptide to biocompatible Fe3O4 nanoparticles. Systematic studies demonstrated that the nanoprobes could specifically target inflamed vascular endothelial cells and visualize the spatial distribution of inflammation in the depressed brain in vivo through susceptibility-weighted imaging (SWI), which was further confirmed by histological analysis. Additionally, these inflammatory brain regions identified by nanoprobe-based imaging are consistent with the focal regions closely associated with the symptoms of depression as reported in previous behavioral studies. Overall, this is the first study to directly visualize the distribution of inflammation in the depressed brain in vivo through a molecular imaging strategy, which may not only facilitate insight into the biological mechanism underlying depression but also provide a potential target within the depressed brain for the further development of anti-inflammatory therapies.