Serial Analyses with Mass Spectrometry Imaging Reveal Chemical and Metabolic Alterations in Liver Tissue Following Thermoembolization

Abstract

Thermoembolization (TE) is a new, minimally invasive approach that could improve outcomes in select patients with hepatocellular carcinoma. However, little is known about the effects of this procedure at the molecular level. To gain greater insight into the molecular effects of TE, we performed a pilot study of transarterial TE with 2-propylpentanoyl chloride in a swine model with 3 animals. Liver tissues were harvested 7 days after the procedure, and formalin-fixed specimens were subjected to serial mass spectrometry imaging (MSI) analyses of metabolites, glycans, and tryptic peptides. We observed striking differences in spatial distributions for multiple features in the TE-treated and untreated areas. Our results show that TE is highly effective in causing coagulative necrosis in the target tissue and based on the data we propose that TE may cause localized chemical alterations in tissues. Our study further demonstrates that MSI is a powerful tool that can provide fundamentally new insights into the potential of using TE or other image-guided in vivo chemistry techniques to alter local biology.