Multiharmonic electron paramagnetic resonance imaging as an innovative approach for in vivo studies

Gonet, Michał; Baranowski, Mikołaj; Czechowski, Tomasz; Kucińska, Małgorzata; Plewiński, Adam; Szczepanik, Piotr; Jurga, Stefan; Murias, Marek

doi:10.1016/j.freeradbiomed.2020.03.018

Cited by 10 publications

(7 citation statements)

References 20 publications

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“…With longer time acquisitions or further improvements in sensitivity, image resolutions approaching 100 µm should be possible. Approaches to achieve this EPR sensitivity enhancement include direct digitizing of the EPR signal at the carrier frequency [44,45], use of high modulation amplitudes with multiharmonic analysis [46,47], and implementation of rapid scan EPR techniques with the use of higher microwave power and direct detection of the EPR signal [43,48]. We are working to implement direct detection in conjunction with multiharmonic analysis that should provide the additional sensitivity required to further enhance the attainable image resolution to approach the theoretical limit.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Fast Scan EPR for High-Resolution Imaging Using Nitroxide Radical Probes at 1.2 GHz

2021

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Nitroxide probes have been commonly used for biomedical EPR imaging applications; however, image quality has been limited by the number of image projections, as well as the probe linewidth and hyperfine structure. In the current study, we evaluate the use of fast millisecond scan EPR projection acquisition along with a novel reconstruction algorithm optimized for 3D spatial EPR image reconstruction from a high number of noisy projections. This reconstruction method utilizes the raw image projection data and zero gradient spectrum to account for EPR line shape and hyperfine structure of any given paramagnetic probe without the need for deconvolution that is poorly suited for high noise data. Using fast scan EPR imaging with this reconstruction method, we image non-deuterated, deuterated and 15 N substituted nitroxide probes in experimental phantoms of complex geometries. We evaluate the image resolution that can be obtained and the imaging time required. With 16,384 projections acquired over 1 min, and a field gradient of 8 G/cm, with a 250 3 voxel 3D matrix, spatial resolutions of up to 100 µm are theoretically possible for a cubical volume of 25 × 25 × 25 mm 3 . In experiments with a variety of phantoms with mM nitroxide radical probes, resolutions of 600-250 µm were obtained with 1-10 min acquisitions, respectively. The presently obtainable signal sensitivity and noise levels of these acquisitions limited the obtainable resolution. With longer time acquisitions or further improvements in sensitivity and noise reduction, image resolutions approaching 100 µm should be possible.

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Section: Resultsmentioning

confidence: 99%

Evaluation of Fast Scan EPR for High-Resolution Imaging Using Nitroxide Radical Probes at 1.2 GHz

2021

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“…The resonator and the receiver systems in the EPR spectrometer are critically essential to reduce the noise on the spectral baseline and improve the sensitivity of signal detection. However, such technical investigations on the EPR spectrometer setup are beyond the scope of this article ( 14 , 37 , 38 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

Redox-Sensitive Mapping of a Mouse Tumor Model Using Sparse Projection Sampling of Electron Paramagnetic Resonance

Kimura

Iguchi

Nakano

et al. 2022

Antioxidants & Redox Signaling

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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 (CS) 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 ( 15 N-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 4-fold compared to conventional image acquisition with FBP.

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“…The spin probe was delivered intravenously through the tail vein. Three-dimensional EPR images were obtained using the ERI TM600 spectroscopic imager (Novilet, Poland), equipped with a volume resonator (38 mm diameter, 27 mm long) . The loaded quality factor (Q-value) of the resonator was measured once the mouse was installed.…”

Section: Methodsmentioning

confidence: 99%

“…Three-dimensional EPR images were obtained using the ERI TM600 spectroscopic imager (Novilet, Poland), equipped with a volume resonator (38 mm diameter, 27 mm long). 32 The loaded quality factor (Q-value) of the resonator was measured once the mouse was installed. The Q-values were 120 for the control mouse and 90 for the tumor-bearing mouse.…”

Section: ■ Introductionmentioning

confidence: 99%

Dynamic Electron Paramagnetic Resonance Imaging: Modern Technique for Biodistribution and Pharmacokinetic Imaging

Baranowski

Gonet

Czechowski³

et al. 2020

J. Phys. Chem. C

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The imaging of the biodistribution and pharmacokinetics is critical in understanding the complexity of drug delivery mechanisms, the status of the disease, and the monitoring of the treatment progress. The imaging techniques, such as magnetic resonance imaging, computed tomography, and positron emission tomography, are suitable for clinical applications. However, with regards to the biodistribution and pharmacokinetics, their availability is often limited due to the requirements of ionizing radiation or high magnetic fields, low spatial and temporal resolution (applicable for animals), and high maintenance costs. Electron paramagnetic resonance (EPR) imaging is a technique that allows for the minimal invasive mapping of unique parameters, such as the oxygen concentration, the redox state, the thiol concentration, or the pH level, in vivo. In this work, a high temporal resolution 3D EPR imaging technique was used for assessing the trityl spin probe pharmacokinetics in mice. The results demonstrate the preliminary outcomes in the application of EPR imaging for the comparison of the trityl spin probe pharmacokinetics between that of a healthy mouse and a tumor-bearing mouse. This study will stimulate further investigation into the use of imaging strategies, such as EPR imaging, to analyze pharmacokinetics.

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Multiharmonic electron paramagnetic resonance imaging as an innovative approach for in vivo studies

Cited by 10 publications

References 20 publications

Evaluation of Fast Scan EPR for High-Resolution Imaging Using Nitroxide Radical Probes at 1.2 GHz

Evaluation of Fast Scan EPR for High-Resolution Imaging Using Nitroxide Radical Probes at 1.2 GHz

Redox-Sensitive Mapping of a Mouse Tumor Model Using Sparse Projection Sampling of Electron Paramagnetic Resonance

Dynamic Electron Paramagnetic Resonance Imaging: Modern Technique for Biodistribution and Pharmacokinetic Imaging

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