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Precise radiation guided by oxygen images has demonstrated superiority over the traditional radiation methods. Electron paramagnetic resonance (EPR) imaging has proven to be the most advanced oxygen imaging modality. However, the main drawback of EPR imaging is the long scan time. For each projection, we usually need to collect the projection many times and then average them to achieve high signal-to-noise ratio (SNR). One approach to fast scan is to reduce the repeating time for each projection. While the projections would be noisy and thus the traditional commonly-use filtered backprojection (FBP) algorithm would not be capable of accurately reconstructing images. Optimization-based iterative algorithms may accurately reconstruct images from noisy projections for they may incorporate prior information into optimization models. Based on the total variation (TV) algorithms for EPR imaging, in this work, we propose a directional TV (DTV) algorithm to further improve the reconstruction accuracy. We construct the DTV constrained, data divergence minimization (DTVcDM) model, derive its Chambolle–Pock (CP) solving algorithm, validate the correctness of the whole algorithm, and perform evaluations via simulated and real data. The experimental results show that the DTV algorithm outperforms the existing TV and FBP algorithms in fast EPR imaging. Compared to the standard FBP algorithm, the proposed algorithm may achieve 10 times of acceleration. [Display omitted] • We propose a DTV algorithm for fast EPR imaging to speed up the scan process 10 times. • This is the first extension and application of DTV algorithm in 3D pulsed EPRI. • We first give a simple but effective model-parameters selection method. • We accelerate the convergence rate by introducing two balanced parameters. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Stochastic RF excitation and resulting data correlation before image reconstruction. • Use of stochastic sequences can result in reduced RF power during EPR imaging. • Reduced RF power brings the SAR of EPR imaging near levels of some MRI imaging. • SAR levels are low enough to explore possible clinical applications. Abstract An excessive RF power requirement is one of the main obstacles in the clinical translation of EPR imaging. The radio frequency (RF) pulses used in EPR imaging to excite electron spins must be very short to match their fast relaxation. With traditional pulse schemes and ninety degree flip angles, this can lead to either unsafe specific absorption rate (SAR) levels or unfeasibly long repetition times. In spectroscopy experiments, it has been shown that stochastic excitation and correlation detection can reduce the power while maintaining sensitivity but have yet to be applied to imaging experiments. Stochastic excitation is implemented using a pseudo-random phase modulation of the input stimulus. Using a crossed coil resonator assembly comprised of an outer saddle coil and an inner surface coil, it was possible to obtain a minimum isolation of ∼50 dB across a 12 MHz bandwidth. An incident peak RF power of 5 mW was used to excite the system. The low background signal obtained from this resonator allowed us to generate images with 32 dB (>1000:1) signal-to-noise ratio (SNR) while exciting with a traditional pulse sequence in a phantom containing the solid paramagnetic probe NMP-TCNQ (N-methyl pyridinium tetracyanoquinodimethane). Using two different stochastic excitation schemes, we were able to achieve a greater than 4-fold increase in SNR at the same peak power and number of averages, compared to single pulse excitation. This procedure allowed imaging at significantly lower RF power levels than used in conventional EPR imaging system configurations. Similar techniques may enable clinical applications for EPR imaging by facilitating the use of larger RF coils while maintaining a safe SAR level. [ABSTRACT FROM AUTHOR]

In rapid scan EPR the rapidly-changing magnetic field induces a background signal that may be larger than the EPR signal. A method has been developed to correct for that background signal by acquiring two sets of data, denoted as scan 1 and scan 2. In scan 2 the external field B 0 is reversed and the data acquisition trigger is offset by one half cycle of the scan field relative to the settings used in scan 1. For data acquired with a cross-loop resonator subtraction of scan 2 from scan 1 cancels the background and enhances the EPR signal. Experiments were performed at an EPR frequency of about 258 MHz, which is in the range that is commonly used for in vivo imaging. Samples include nitroxide radicals, a trityl radical, a dinitroxide, and a nitroxide in the presence of a magnetic field gradient. This method has the advantage that no assumption is made about the shape of the background signal, and it provides an approach to automating the background correction. [ABSTRACT FROM AUTHOR]

In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250 MHz. [ABSTRACT FROM AUTHOR]

The value of any measurement and a fortiori any measurement technology is defined by the reproducibility and the accuracy of the measurements. This implies a relative freedom of the measurement from factors confounding its accuracy. In the past, one of the reasons for the loss of focus on the importance of imaging oxygen in vivo was the difficulty in obtaining reproducible oxygen or pO 2 images free from confounding variation. This review will briefly consider principles of electron paramagnetic oxygen imaging and describe how it achieves absolute oxygen measurements. We will provide a summary review of the progress in biomedical EPR imaging, predominantly in cancer biology research, discuss EPR oxygen imaging for cancer treatment and tissue graft assessment for regenerative medicine applications. [ABSTRACT FROM AUTHOR]

In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are non-invasive technologies used to specifically detect and quantify paramagnetic species. However, the relative instability of spin probes such as triarylmethyl radicals limits their application to conduct oxygen quantification and mapping. In this study we encapsulated tetrathiatriarylmethyl radical (TAM; known as “Finland” probe) in Pluronic F-127 hydrogel (PF-127) in order to limit its degradation and evaluate its in vitro and in vivo EPR properties as a function of oxygen. Our results show that the EPR signal of encapsulated TAM in PF-127 hydrogel is similar to the one in solution. Although it is less sensitive to oxygen, it is suitable for oximetry. We also demonstrated that the incorporation of TAM in PF-127 hydrogel leads to an improved in vivo EPR stability of the radical under anesthesia. This new formulation enables high quality EPR imaging and oximetry and paves the way for the application of TAM radical-based probes in various biomedical fields. [ABSTRACT FROM AUTHOR]

Hypoxic tumors are resistant to radiotherapy, motivating the development of tools to image local oxygen concentrations. It is generally believed that stable or chronic hypoxia is the source of resistance, but more recent work suggests a role for transient hypoxia. Conventional EPR imaging (EPRI) is capable of imaging tissue pO 2 in vivo , with high pO 2 resolution and 1 mm spatial resolution but low imaging speed (10 min temporal resolution for T 1 -based pO 2 mapping), which makes it difficult to investigate the oxygen changes, e.g., transient hypoxia. Here we describe a new imaging method which accelerates dynamic EPR oxygen imaging, allowing 3D imaging at 2 frames per minute, fast enough to image transient hypoxia at the “speed limit” of observed pO 2 change. The method centers on a low-rank tensor model that decouples the tradeoff between imaging speed, spatial coverage/resolution, and number of inversion times (pO 2 accuracy). We present a specialized sparse sampling strategy and image reconstruction algorithm for use with this model. The quality and utility of the method is demonstrated in simulations and in vivo experiments in tumor bearing mice. [ABSTRACT FROM AUTHOR]

Tumors and tumor portions with low oxygen concentrations (pO 2 ) have been shown to be resistant to radiation therapy. As such, radiation therapy efficacy may be enhanced if delivered radiation dose is tailored based on the spatial distribution of pO 2 within the tumor. A technique for accurate imaging of tumor oxygenation is critically important to guide radiation treatment that accounts for the effects of local pO 2 . Electron paramagnetic resonance imaging (EPRI) has been considered one of the leading methods for quantitatively imaging pO 2 within tumors in vivo . However, current EPRI techniques require relatively long imaging times. Reducing the number of projection scan considerably reduce the imaging time. Conventional image reconstruction algorithms, such as filtered back projection (FBP), may produce severe artifacts in images reconstructed from sparse-view projections. This can lower the utility of these reconstructed images. In this work, an optimization based image reconstruction algorithm using constrained, total variation (TV) minimization, subject to data consistency, is developed and evaluated. The algorithm was evaluated using simulated phantom, physical phantom and pre-clinical EPRI data. The TV algorithm is compared with FBP using subjective and objective metrics. The results demonstrate the merits of the proposed reconstruction algorithm. [ABSTRACT FROM AUTHOR]

Continuous wave electron paramagnetic resonance imaging (EPRI) experiments often suffer from low signal to noise ratio. The increase in spectrometer time required to acquire data of sufficient quality to allow further analysis can be counteracted in part by more processing effort during the image reconstruction step. We suggest a simultaneous iterative reconstruction algorithm (SIRT) for reconstruction of continuous wave EPRI experimental data as an alternative to the widely applied filtered back projection algorithm (FBP). We show experimental and numerical test data of 2d spatial images and spectral–spatial images. We find that for low signal to noise ratio and spectral–spatial images that are limited by the maximum magnetic field gradient strength SIRT is more suitable than FBP. [ABSTRACT FROM AUTHOR]

Pulse electron paramagnetic resonance imaging (Pulse EPRI) is a robust method for noninvasively measuring local oxygen concentrations in vivo . For 3D tomographic EPRI, the most commonly used reconstruction algorithm is filtered back projection (FBP), in which the parabolic filtration process strongly influences image quality. In this work, we designed and compared 7 parabolic filtration methods to reconstruct both simulated and real phantoms. To evaluate these methods, we designed 3 error criteria and 1 spatial resolution criterion. It was determined that the 2 point derivative filtration method and the two-ramp-filter method have unavoidable negative effects resulting in diminished spatial resolution and increased artifacts respectively. For the noiseless phantom the rectangular-window parabolic filtration method and sinc -window parabolic filtration method were found to be optimal, providing high spatial resolution and small errors. In the presence of noise, the 3 point derivative method and Hamming-window parabolic filtration method resulted in the best compromise between low image noise and high spatial resolution. The 3 point derivative method is faster than Hamming-window parabolic filtration method, so we conclude that the 3 point derivative method is optimal for 3D FBP. [ABSTRACT FROM AUTHOR]

A new method for fast 2D Electron Paramagnetic Resonance Imaging (EPRI) is presented. To reduce the time of projections acquisition we propose to combine rapid scan of Zeeman magnetic field using high frequency sinusoidal modulation with simultaneously applied magnetic field gradient, whose orientation is changed at low frequency. The correctness of the method is confirmed by studies carried out on a phantom consisting of two LiPc samples. The images from the acquired data are reconstructed using iterative algorithms. The proposed method allows to reduce the image acquisition time up to 10 ms for 2D EPRI, and to detect the sinogram with infinitesimal angular step between projections. [ABSTRACT FROM AUTHOR]

This article describes an improved method for suppressing image artifacts in the visualization of 14 N- and 15 N-labeled nitroxyl radicals in a single image scan using electron paramagnetic resonance (EPR). The purpose of this work was to solve the problem of asymmetric EPR absorption spectra in spectral processing. A hybrid function of Gaussian and Lorentzian lineshapes was used to perform spectral line-fitting to successfully separate the two kinds of nitroxyl radicals. This approach can process the asymmetric EPR absorption spectra of the nitroxyl radicals being measured, and can suppress image artifacts due to spectral asymmetry. With this improved visualization method and a 750-MHz continuous-wave EPR imager, a temporal change in the distributions of a two-phase paraffin oil and water/glycerin solution system was visualized using lipophilic and hydrophilic nitroxyl radicals, i.e., 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy (16-DOXYL stearic acid) and 4-hydroxyl-2,2,6,6-tetramethylpiperidine-d 17 -1- 15 N-1-oxyl (TEMPOL-d 17 - 15 N). The results of the two-phase separation experiment verified that reasonable artifact suppression could be achieved by the present method that deals with asymmetric absorption spectra in the EPR imaging of 14 N- and 15 N-labeled nitroxyl radicals. [ABSTRACT FROM AUTHOR]

Highlights: [•] Novel design of a bimodal resonator for 250MHz in vivo imaging. [•] This design improves signal to noise ratio per unit of time of in vivo images. [•] Alderman–Grant resonator is an optimal choice for excitation coil in bimodal resonator design. [•] Alderman–Grant resonator generates very low E-field in a sample which is important for in vivo imaging. [ABSTRACT FROM AUTHOR]

Abstract: A combination of the constant-time spectral-spatial imaging (CTSSI) modality and projection-reconstruction modality was tested to simplify data acquisition for multi-dimensional CW EPR spectral-spatial imaging. In this method, 3D spectral-spatial image data were obtained by simple repetition of conventional 2D CW imaging process, except that the field gradient amplitude was incremented in constant steps in each repetition. The data collection scheme was no different from the conventional CW imaging system for spectral-spatial data acquisition. No special equipment and/or rewriting of existing software were required. The data acquisition process for multi-dimensional spectral-spatial imaging is consequently simplified. There is also no “missing-angle” issue because the CTSSI modality was employed to reconstruct 2D spectral-spatial images. Extra reconstruction processes to obtain higher spatial dimensions were performed using a conventional projection-reconstruction modality. This data acquisition technique can be applied to any conventional CW EPR (spatial) imaging system for multi-dimensional spectral-spatial imaging. [Copyright &y& Elsevier]

Abstract: A new algorithm for EPR imaging oximetry is described and tested with experimental data for the case of one spatial and one spectral dimension. A single species with variable linewidth is assumed. Instead of creating a 2D image, two one-dimensional profiles are reconstructed: the concentration of the radical and the corresponding oxygen concentration, which reduces the dimensionality of the problem. The algorithm (i) seeks to minimize the discrepancy between experimental data and projections calculated from the profiles and (ii) uses Tikhonov regularization to constrain the smoothness of the results. This approach controllably smoothes profiles rather than the data, while preserving sharp features. [Copyright &y& Elsevier]

Abstract: The CW-EPR method of image reconstruction is based on sample rotation in a magnetic field with a constant gradient (50G/cm). In order to obtain a projection (radical density distribution) along a given direction, the EPR spectra are recorded with and without the gradient. Deconvolution, then gives the distribution of the spin density. Projection at 36 different angles gives the information that is necessary for reconstruction of the radical distribution. The problem becomes more complex when there are at least two types of radicals in the sample, because the deconvolution procedure does not give satisfactory results. We propose a method to calculate the projections for each radical, based on iterative procedures. The images of density distribution for each radical obtained by our procedure have proved that the method of deconvolution, in combination with iterative fitting, provides correct results. The test was performed on a sample of polymer PPS Br 111 (p-phenylene sulphide) with glass fibres and minerals. The results indicated a heterogeneous distribution of radicals in the sample volume. The images obtained were in agreement with the known shape of the sample. [Copyright &y& Elsevier]

Abstract: The resolution and signal to noise ratio of EPR imaging and T1-weighted MRI were compared using an identical phantom. Several solutions of nitroxyl contrast agents with different EPR spectral shapes were tested. The feasibility of T1-weighted MRI to detect nitroxyl contrast agents was described. T1-weighted MRI can detect nitroxyl contrast agents with a complicated EPR spectrum easier and quicker; however, T1-weighted MRI has less quantitative ability especially for lipophilic nitroxyl contrast agents, because T1-relaxivity, i.e. accessibility to water, is affected by the hydrophilic/hydrophobic micro-environment of a nitroxyl contrast agent. The less quantitative ability of T1-weighted MRI may not be a disadvantage of redox imaging, which obtains reduction rate of a nitroxyl contrast. Therefore, T1-weighted MRI has a great advantage to check the pharmacokinetics of newly modified and/or designed nitroxyl contrast agents. [Copyright &y& Elsevier]

Abstract: Methods proposed for in vivo redox status estimation, X-band (9.4GHz) electron paramagnetic resonance (EPR) bile flow monitoring (BFM) and 300MHz in vivo EPR measurement, were compared. The spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) was utilized for both methods, due to its suitable lipophilicity. EPR signal decay of a nitroxyl spin probe in the bile flow and in the liver region (upper abdomen) of several rat groups with different selenium status were measured by both the BFM and the in vivo EPR method, respectively. The nitroxyl radical clearance measured with in vivo EPR method may be affected not only by the redox status in the liver but also by information from other tissues in the measured region of the rat. On the other hand, the time course of nitroxyl radical level in the bile flow of rats was found to be a reliable index of redox status. Measurement site and/or volume limitation, which was achieved by the BFM method in this paper, is quite important in estimating reasonable EPR signal decay information as an index of tissue/organ redox status. [Copyright &y& Elsevier]