Development of Protein-based Platform Technology to Enhance Magnetic Resonance Imaging

Project: Research project

Project Details

Description

This proposal explores the development of a platform technology for enhancing contrast in magnetic resonance imaging (MRI). The current contrast agent market is dominated by gadolinium and its derivatives; which suffer from inadequate S/N ratio and potential cytotoxicity. Iron-based contrast agents have been explored as an alternative and complement to gadolinium-based contrast agents. MRI contrast agents enhance image contrast by altering the water proton relaxation around tissues. However, despite the promising contrast enhancement, there is a lack of fundamental knowledge about its mechanisms (i.e. the contribution of magnetic and domain structure in the contrast agent). We hypothesize that through understanding such mechanism(s), contrast agents with improved relaxivities (and their respective ratios for appropriate pulse-echo sequence protocols) can be rationally designed. Leveraging on the PI’s published data on iron-loaded and manganese-loaded ferritin protein nanocages (FPNCs), we will perform in-depth study on the contribution of the magnetic and domain structures of the magnetic nanostructures formed within the protein nanocage on water proton relaxation. The aims of this project are (1) Design of magnetic domain structure in caged oxide (iron- and alloy based) and (2) pH and environmental factors sensitive modulation of water access to caged paramagnetic centers for in-situ MRI contrast enhancement. This work is closely related to NU collaborators ongoing research in magnetic nanostructures as theranostic agents and will leverage on state-of-the-art MR facilities. The project will undertake innovative microscopy for elucidating ultrastructure of the nanostructured protein constructs.
The platform technology is aimed to address multiple clinical needs, with the primary focus on cardiac imaging for identification of atherosclerotic lesions. Additional clinical applications include lymph node imaging as well as other inflammatory diseases (e.g. brain, arthritis, other musculoskeletal conditions) and edema. We will demonstrate efficacy of the proposed constructs in collaboration with other appropriate NTU-NU projects to enhance the utility of the mutual programs.
Beyond contrast enhancement of diseased tissues using MRI, the study will also have implications on improvement of nuclear magnetic resonance (NMR) techniques for protein structure determination, which is the strength of the NTU co-PI.
StatusFinished
Effective start/end date11/1/1410/31/19

Funding

  • Nanyang Technological University (Agmt 10/20/2014)

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