Abstract
Aims: This work aimed to establish an accelerated imaging system for redox-sensitive mapping in a mouse tumor model using electron paramagnetic resonance (EPR) and nitroxyl radicals.Results: Sparse sampling of EPR spectral projections was demonstrated for a solution phantom. The reconstructed three-dimensional (3D) images with filtered back-projection (FBP) and compressed sensing image reconstruction were quantitatively assessed for the solution phantom. Mouse xenograft models of a human-derived pancreatic ductal adenocarcinoma cell line, MIA PaCa-2, were also measured for redox-sensitive mapping with the sparse sampling technique.Innovation: A short-lifetime redox-sensitive nitroxyl radical (15N-labeled perdeuterated Tempone) could be measured to map the decay rates of the EPR signals for the mouse xenograft models. Acceleration of 3D EPR image acquisition broadened the choices of nitroxyl radical probes with various redox sensitivities to biological environments.Conclusion: Sparse sampling of EPR spectral projections accelerated image acquisition in the 3D redox-sensitive mapping of mouse tumor-bearing legs fourfold compared with conventional image acquisition with FBP. Antioxid. Redox Signal. 36, 57–69.
Highlights
Areduction–oxidation balance called the redox state is a critical part of homeostasis in a living organism [52]
Sparse sampling of electron paramagnetic resonance (EPR) spectral projections accelerated image acquisition in the 3D redoxsensitive mapping of mouse tumor-bearing legs fourfold compared with conventional image acquisition with filtered back-projection (FBP)
We developed an accelerated EPR-based redox-sensitive mapping system by deploying fast-scan CW-EPR acquisition at 750 MHz [41, 43], sparse modeling [22], the 3D golden mean (GM) sampling strategy [5], fast iterative shrinkage-thresholding algorithm (FISTA) [2], and an improved multiple-imagereconstruction protocol
Summary
Areduction–oxidation balance called the redox state is a critical part of homeostasis in a living organism [52]. Dysfunction of redox homeostasis leads to many diseases; an altered redox state can be seen as evidence of a disease’s pathological status [15]. Several imaging modalities have been developed for redox-sensitive mapping in animal models of disease, including magnetic resonance imaging (MRI) [19], dynamic nuclear polarization (DNP) MRI [50], fluorescence imaging [7], photoacoustic imaging [13], and electron paramagnetic resonance (EPR) spectroscopy and imaging [9, 48]. Redox-sensitive imaging techniques use exogenous redox-sensitive molecular probes, such as nitroxyl radicals for MRI, DNP-MRI, and EPR [8, 21, 40]; fluorescent probes and protein for fluorescence imaging [11, 24]; and fluorescent probes for photoacoustic imaging [56]. While the reduction reaction of nitroxyl radicals leads to EPR-silent hydroxylamines, the oxidation reaction of hydroxylamines leads to EPR-active
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