PROJECT ABSTRACT:
The integration of electron paramagnetic resonance (EPR) and magnetic resonance imaging (MRI)
promises to lead to new generations of biomedical imaging technologies. This proposal outlines important
studies en route to this vision by designing EPR imaging (EPRI) probes based on transition-metal ions.
The specific intent is to realize EPRI probes that function with low frequency microwaves at high magnetic
fields. Modern EPR imaging techniques largely rely on open-shell organic radicals as probes for obtaining
biochemical information. However, organic radicals impart a formidable obstacle to merging EPR with
MRI, namely, their requirement for high-frequency microwave radiation at high magnetic field. Such high-
frequency microwaves are strongly absorbed by water, which lowers technique sensitivity and induces
localized heating. The proposed work will develop new imaging agents that function with low-frequency,
biologically inert microwaves at high magnetic field, representing important progress toward the
development of hybrid MRI/EPR imaging techniques.
The significance of this proposal is that it addresses a key, needed innovation in the field of EPR
imaging to circumvent the challenges of high frequency microwave requirements. The proposed
molecules will be designed following an electronic structure hypothesis: that an important facet of
transition metal ions, spin-orbit coupling, will enable such species to function as low-frequency/high-field
EPRI probes. Spin-orbit coupling – largely absent in organic radicals – engenders the presence of EPR
transitions in metal ions that decrease in microwave frequency with increasing magnetic field. Thus, metal
complexes hold significant promise as a valuable family of low-frequency EPR imaging probes capable
of seamless integration with existing high-field MRI technology. This work will seek to disprove the
alternative hypothesis: that the EPR spectroscopic properties of magnetic metal ions will in contrast
prevent utility for EPR imaging. Such properties include (1) difficulty in the design of molecules with an
exact EPR transition field and frequency, (2) broad signal linewidths, and (3) short relaxation times. The
proposed work will directly explore solutions to these challenges through a coordination chemistry
approach. Specifically, tunable molecular features such as electronic structure, rigidity, and chemical
composition will be harnessed to subdue the foregoing detrimental properties. Thus, the anticipated result
of funding this proposal is a set of empirical design principles for a new class of metal-based EPR probe.
In the longer term, such design principles will open the door to probes that function with low frequency
microwaves at high magnetic fields, leading to new, noninvasive diagnostic imaging techniques.