Project Details
Projekt
Ultrasound methods for quantitative imaging of the distribution of magnetic nanoparticles in biological tissue in connection with drug delivery concepts and magnetic hyperthermia for localized tumor treatment
Subject Area
Biomedical Systems Technology
Measurement Systems
Measurement Systems
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 452821018
The aim of the project is to develop an ultrasound-based imaging method for local tumor therapies based on superparamagnetic iron oxide nanoparticles (SPIONs). This includes magnetic drug targeting and magnetic hyperthermia. This involves visualizing the SPIONs during therapy. Magnetomotive ultrasound (MMUS) uses tissue displacements caused by an alternating magnetic field to detect SPIONs. As this method has so far only provided qualitative information on particle distribution, the Inverse MMUS (IMMUS) was developed for quantitative analysis. For phantom development, manufacturing processes were developed that can model SPION-induced as well as vascular and non-vascular structures. The research on MMUS led to the development of a new measuring setup, determining tissue movement using laser Doppler vibrometry, and the extension of lateral tissue displacement. Strain elastography and shear wave elastography were assessed as unsuitable. In parallel, alternative ultrasound-based methods for tissue characterization such as vibrational and transient elastography were investigated. Imaging using scattering and attenuation did not meet the specific requirements of the project. Work on the development of a clinical setup and 3D imaging is currently in the implementation phase. At the beginning of the project, it turned out that the original particle system was not suitable. Therefore, a new particle system was developed based on a dopamine functionalization strategy. For this purpose, dopamine was applied to the surface of lauric acid-stabilized SPIONs via ligand exchange. In a further step, human serum albumin was bound to the SPIONs (HSA-SPIONs). Biological studies showed that the HSA-SPIONs exhibited better stability and advantageous properties. In addition, various stability studies were carried out, including susceptibility measurements, toxicity tests and dynamic pumping tests, which enabled a detailed characterization of the particles. The planned animal studies could not yet be carried out due to the initial challenges with particle synthesis, but are now in the preparation phase. As the quantification methods for the iron and active ingredient content in tissues are based on the results of the animal studies, it has not yet been possible to work on this part of the project. The focus of the project will be on the development of MMUS and IMMUS for therapy monitoring. This includes refining ultrasound-based tissue characterization, improving the MMUS-algorithms and further developing the simulation models. In addition, the clinical setup will be finalized and then tested in animal studies with the redeveloped SPION systems.
DFG Programme
Research Grants
Co-Investigators
Professor Dr. Christoph Alexiou; Professor Dr.-Ing. Helmut Ermert
