Institut für Radiologie
Charité – Universitätsmedizin Berlin
Telephone: +49 30 450 539 066
Molecular imaging of inflammation beyond macrophages by magnetic nanoparticle-enhanced MRI
PIs: Taupitz, Schroeder, Makowski
Application area: Cardiovascular
Background: A vast majority of diseases such as atherosclerosis or arthritis take place through inflammatory processes. Advances in the field of molecular imaging have enabled the use of nano-targeting concepts for detection and quantification of inflammation, thereby leading to better understand the critical cellular and molecular mechanisms behind diseases. In this scope, an important focus has been established on exploring the accumulation of phagocytic macrophages in the affected region by magnetic nanoparticle (MNP)-based magnetic resonance imaging (MRI). However, increasing understanding of the pathogenesis of such diseases suggest thorough investigation of major tissue structure alterations of the extracellular matrix (ECM) during the onset and progression of inflammation. Recent research has presented evidence on the accumulation of proteoglycan (PG) and glycosaminoglycan (GAG) molecules that are attractive sites for transchelation of electrostatically stabilized MNPs (ES-MNP) due to their negatively charged molecular structures as well as their ability to act as modulators to activate various information transmitting mechanisms. Such characteristics of these molecules make them excellent targets for molecular MRI. It has been shown that in vivo targeting of sugar-based components of ECM occur within minutes following the administration of MNPs while targeting of phagocytic cells takes hours to days. This could potentially aid clinical workflow and enhance the accuracy of imaging-based quantification methods, thereby offer valuable opportunities for biomedical research and clinical applications.
Aim and Methods: This project aims at: 1) Molecular MRI in small animal models for the detection of ECM changes in inflammation, 2) Monitoring local accumulation of suited imaging probes by in vivo and ex vivo examinations, 3) Assessment of mechanical properties of the inflamed tissue, and 4) correlation of imaging probe based and elastography based methods.