A Low-Cost, Tabletop LOD-EPR System for Nondestructive Quantification of Iron Oxide Nanoparticles in Tissues.

Iron oxide nanoparticles (IONPs) have wide utility in applications from drug delivery to the rewarming of cryopreserved tissues. Due to the complex behavior of IONPs (e.g., uneven particle distribution and aggregation), further developments and clinical translation can be accelerated by having access to a noninvasive method for tissue IONP quantification. Currently, there is no low-cost method to nondestructively track IONPs in tissues across a wide range of concentrations. This work describes the performance of a low-cost, tabletop, longitudinally detected electron paramagnetic resonance (LOD-EPR) system to address this issue in the field of cryopreservation, which utilizes IONPs for rewarming of rat kidneys. A low-cost LOD-EPR system is realized via simultaneous transmit and receive using MHz continuous-wave transverse excitation with kHz modulation, which is longitudinally detected at the modulation frequency to provide both geometric and frequency isolation. The accuracy of LOD-EPR for IONP quantification is compared with NMR relaxometry. Solution measurements show excellent linearity (R2 > 0.99) versus Fe concentration for both measurements on EMG308 (a commercial nanoparticle), silica-coated EMG308, and PEG-coated EMG308 in water. The LOD-EPR signal intensity and NMR longitudinal relaxation rate constant (R1) of water are affected by particle coating, solution viscosity, and particle aggregation. R1 remains linear but with a reduced slope when in cryoprotective agent (CPA) solution, whereas the LOD-EPR signal is relatively insensitive to this. R1 does not correlate well with Fe concentration in rat kidney sections (R2 = 0.3487), while LOD-EPR does (R2 = 0.8276), with a linear regression closely matching that observed in solution and CPA.

A frequency-swept, longitudinal detection EPR system for measuring short electron spin relaxation times at ultra-low fields.

A frequency-swept longitudinal detection (LOD) EPR system is described for ultra-low field spectroscopy and relaxometry. With the capability of performing simultaneous transmit and receive with -80 dB isolation, this LOD-EPR can capture signals with decay constants in the nanosecond range and in theory even sub-nanosecond range, at fields close to the earth's magnetic field. The theoretical principles underlying this LOD-EPR are based on a fictitious field that accounts for the Z-axis magnetization polarized by a radiofrequency field alone. The electron spin relaxation time is obtained directly from a previously derived equation that describes the relationship between the relaxation time and the spectral peak position. Herein, the first frequency-swept LOD-EPR system is described in detail, along with experimental measurements of the short relaxation time (∼30 ns) of the free radical, 2,2-diphenyl-1-picrylhydrazyl, at zero to low field.

Ultra-low frequency EPR using longitudinal detection and fictitious-field modulation.

When viewed in a rotating frame of reference, a transverse-plane radiofrequency (RF) field manifests as a longitudinal field component called the fictitious field. By modulating the RF field and thus the fictitious field, detectable longitudinal magnetization patterns have previously been shown to be measurable. By combining fictitious-field modulation and longitudinal detection, here we demonstrate EPR spectroscopy and one-dimensional imaging in a custom-built longitudinal detection system operating at an ultra-low frequency (24 MHz) for detecting electron spins with short (~nanoseconds) relaxation times. Simultaneous transmit and receive with low transmitter leakage level (~80 dB isolation) is also demonstrated.

Continuous SWIFT.

This work describes our first efforts to implement SWIFT (SWeep Imaging with Fourier Transformation) in continuous mode for imaging and spectroscopy. We connected a standard quadrature hybrid with a quad coil and acquired NMR signal during continuous radiofrequency excitation. We utilized a chirped radiofrequency pulse to minimize the instantaneous radiofrequency field during excitation of the spin system for the target flip angle and bandwidth. Due to the complete absence of "dead time", continuous SWIFT has the potential to extend applications of MRI and spectroscopy in studies of spin systems having extremely fast relaxation or broad chemical shift distributions beyond the range of existing MRI sequences.