Towards High Relaxivity Magnetic Resonance Imaging Contrast Agents for use in Biomaterials

Public Deposited

High relaxivity contrast agents are of great importance in the advancement of magnetic resonance imaging diagnostics for use in biomaterials. Biomaterials that are implanted into the body, with the goal of repairing or regenerating lost or damaged tissue, need to be tracked noninvasively, over time. I have completed work using self-assembly as the mechanism to achieve both tissue regenerating materials and their use as a template for noninvasive imaging by MRI. Attachment of a magnetic resonance contrast agent small molecule to a scaffold that self-assembles into high aspect ratio nanofibers allows for the formation of a high relaxivity contrast agent. In this thesis, we explore the underlying properties that affect these contrast agents and their efficacy. Elucidation involved the synthesis of multiple peptide amphiphile contrast agents with varying position, linker length, and peptide amphiphile architecture. The most important variables promoting high relaxivity included the positioning of the chelator closer to the middle of the peptide amphiphile and keeping the linker length between the contrast agent and peptide amphiphile as short as possible. These modifications provided relaxivity values ~20 mM-1 s-1 which are ~7 times greater than the small molecules relaxivity values. When the peptide amphiphile contrast agents were mixed with other peptide amphiphile nanofiber scaffolds and formed into hydrogels, we were able to obtain homogeneous mixing throughout the gels as measured by MRI. The chosen peptide amphiphile contrast agent had the ability to be mixed with various bioactive peptide amphiphiles for imaging. These experiments included in vivo monitoring of porcine hearts and it was found that the bioactive gel could be monitored over a two-week period before loss of the signal shedding light on the degradation time of the peptide amphiphile biomaterial in vivo. Studies were also performed on the templation of the peptide amphiphile nanofibers for the eventual use in drug delivery and fate mapping. A molecular dumbbell was synthesized with the properties that would offset the self-assembling properties of the peptide amphiphile monomers. The dumbbell was found to have a profound effect on the nanofiber formation and effectively stopped the high aspect ratio aggregates from forming

Last modified
  • 05/30/2018
Date created
Resource type
Rights statement