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Thiol redox status is an important physiologic parameter that affects the success or failure of cancer treatment. Rapid scan electron paramagnetic resonance (RS EPR) is a novel technique that has shown higher signal-to-noise ratio than conventional continuous-wave EPR in in vitro studies. Here we used RS EPR to acquire rapid three-dimensional images of the thiol redox status of tumors in living mice. This work presents, for the first time, in vivo RS EPR images of the kinetics of the reaction of 2 H, 15 N-substituted disulfide-linked dinitroxide (PxSSPx) spin probe with intracellular glutathione. The cleavage rate is proportional to the intracellular glutathione concentration. Feasibility was demonstrated in a FSa fibrosarcoma tumor model in C3H mice. Similar to other in vivo and cell model studies, decreasing intracellular glutathione concentration by treating mice with l -buthionine sulfoximine (BSO) markedly altered the kinetic images. [ABSTRACT FROM AUTHOR]

In pulsed magnetic resonance, the excitation power is many orders of magnitude larger than that induced by the spin system in the receiving coil or resonator. The receiver must be protected during and immediately after the excitation pulse to allow for the energy stored in the resonator to dissipate to a safe level. The time during which the signal is not detected, the instrumental dead-time, can be shortened by using magnetically decoupled excitation and receive coils. Such coils are oriented, with respect to each other, in a way that minimizes the total magnetic flux produced by one coil in the other. We suggest that magnetically decoupled coils can be isolated to a larger degree by tuning them to separate frequencies. Spins are excited at one frequency, and the echo signal is detected at another. Sinusoidal magnetic field modulation that rapidly changes the Larmor frequency of the spins between the excitation and detection events is used to ensure the resonance conditions for both coils. In this study, the relaxation times of trityl-CD3 were measured in a field-modulated pulsed EPR experiment and compared to results obtained using a standard spin echo method. The excitation and receive coils were tuned to 245 and 256.7 MHz, respectively. Using an available rapid-scan, cross-loop EPR resonator, we demonstrated an isolation improvement of approximately 20–30 dB due to frequency decoupling. Theoretical analysis, numerical simulations, and proof-of-concept experiments demonstrated that substantial excitation-detection decoupling can be achieved. A pulsed L-band system, including a small volume bi-modal resonator equipped with modulation coils, was constructed to demonstrate fivefold dead-time reduction in comparison with the standard EPR experiment. This was achieved by detuning of the excitation and receive coils by 26 MHz and using sinusoidal modulation at 480 kHz. [ABSTRACT FROM AUTHOR]

Electron paramagnetic resonance (EPR) Imaging (EPRI) is a robust method for measuring in vivo oxygen concentration (pO2). For 3D pulse EPRI, a commonly used reconstruction algorithm is the filtered backprojection (FBP) algorithm, in which the backprojection process is computationally intensive and may be time consuming when implemented on a CPU. A multistage implementation of the backprojection can be used for acceleration, however it is not flexible (requires equal linear angle projection distribution) and may still be time consuming. In this work, single-stage backprojection is implemented on a GPU (Graphics Processing Units) having 1152 cores to accelerate the process. The GPU implementation results in acceleration by over a factor of 200 overall and by over a factor of 3500 if only the computing time is considered. Some important experiences regarding the implementation of GPU-accelerated backprojection for EPRI are summarized. The resulting accelerated image reconstruction is useful for real-time image reconstruction monitoring and other time sensitive applications. [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]

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]

This work propose the balanced TV-CP algorithm for 3D EPR imaging. In the original TV-CP algorithm, the balance mechanism is not used and it corresponds to v = 1 of the new balanced TV-CP algorithm. In this figure, we may see that the original TV-CP algorithm is not convergent, whereas the balanced TV-CP algorithm with the appropriately selected balance parameter, i.e. v = 0.01, may reach convergence and achieve accurate reconstruction, which may be seen from the figure showing the data-divergence iteration-curves in this paper. By use of the balance mechanism, the balanced TV-CP algorithm may guarantee convergence and achieve accurate image reconstruction. [Display omitted] • The balanced TV-CP algorithm is proposed for 3D EPR imaging. • The original TV-CP algorithm cannot guarantee convergence. • The balanced TV-CP algorithm requires user feedback to guide convergence. • We perform simulation and real-data studies to evaluate how the balance parameter impacts convergence. • We give qualitative analysis via the data tolerance ellipse theory and the gradient descent principle. Total variation (TV) minimization algorithm is an effective algorithm capable of accurately reconstructing images from sparse projection data in a variety of imaging modalities including computed tomography (CT) and electron paramagnetic resonance imaging (EPRI). The data divergence constrained, TV minimization (DDcTV) model and its Chambolle-Pock (CP) solving algorithm have been proposed for CT. However, when the DDcTV-CP algorithm is applied to 3D EPRI, it suffers from slow convergence rate or divergence. We hypothesize that this is due to the magnitude imbalance between the data fidelity term and the TV regularization term. In this work, we propose a balanced TV (bTV) model incorporating a balance parameter and demonstrate its capability to avoid convergence issues for the 3D EPRI application. Simulation and real experiments show that the DDcTV-CP algorithm cannot guarantee convergence but the bTV-CP algorithm may guarantee convergence and achieve fast convergence by use of an appropriate balance parameter. Experiments also show that underweighting the balance parameter leads to slow convergence, whereas overweighting the balance parameter leads to divergence. The iteration-behavior change-law with the variation of the balance parameter is explained by use of the data tolerance ellipse and gradient descent principle. The findings and insights gained in this work may be applied to other imaging modalities and other constrained optimization problems. [ABSTRACT FROM AUTHOR]

• Modular semi-digital EPR imaging system was developed. • Digital automatic frequency control minimizes RF reflection. • Digital automatic scan control stabilizes field scans. • Surface loop resonator for RS EPR was developed. • In vivo RS EPR imaging at 800 MHz was demonstrated. An electron paramagnetic resonance (EPR) imaging system has been custom built for use in pre-clinical and, potentially, clinical studies. Commercial standalone modules have been used in the design that are MATLAB-controlled. The imaging system combines digital and analog technologies. It was designed to achieve maximum flexibility and versatility and to perform standard and novel user-defined experiments. This design goal is achieved by frequency mixing of an arbitrary waveform generator (AWG) output at the intermediate frequency (IF) with a constant source frequency (SF). Low noise SF at 250, 750, and 1000 MHz are available in the system. A wide range of frequencies from near-baseband to L-band can be generated as a result. Two-stage downconversion at the signal detection side is implemented that enables multi-frequency EPR capability. In the first stage, the signal frequency is converted to IF. A novel AWG-enabled digital auto-frequency control method that operates at IF is described that is used for automatic resonator tuning. Quadrature baseband EPR signal is generated in the second downconversion step. The semi-digital approach of mixing low-noise frequency sources with an AWG permits generation of arbitrary excitation patterns that include but are not limited to frequency sweeps for resonator tuning and matching, continuous-wave, and pulse sequences. Presented in this paper is the demonstration of rapid scan (RS) EPR imaging implemented at 800 MHz. Generation of stable magnetic scan waveforms is critical for the RS method. A digital automatic scan control (DASC) system was developed for sinusoidal magnetic field scans. DASC permits tight control of both amplitude and phase of the scans. A surface loop resonator was developed using 3D printing technology. RS EPR imaging system was validated using sample phantoms. In vivo imaging of a breast cancer mouse model is demonstrated. [ABSTRACT FROM AUTHOR]

We propose a new iterative reconstruction algorithm without system matrix for EPR imaging. It is based on the idea of image rotation. Thus, the complicated calculation of system matrix may be avoided. For the plane-driven projection method illustrated by the left figure, one must calculate the intersecting area of a plane with a cube. But, for the rotation-driven projection method illustrated by the right figure, one just need rotate the 3D object and sum up the voxel-values of the voxels layer by layer. [Display omitted] • An iterative reconstruction method without system matrix for EPR imaging is proposed. • The core idea is the design of new projection and backprojection methods based on image-rotation. • The new algorithm can achieve the comparable accuracy relative to the traditional algorithm with system matrix. • The new algorithm may avoid the complicated calculation of system matrix. Electron paramagnetic resonance (EPR) imaging is an advanced oxygen imaging modality for oxygen-image guided radiation. The iterative reconstruction algorithm is the research hot-point in image reconstruction for EPR imaging (EPRI) for this type of algorithm may incorporate image-prior information to construct advanced optimization model to achieve accurate reconstruction from sparse-view projections and/or noisy projections. However, the system matrix in the iterative algorithm needs complicated calculation and needs huge memory-space if it is stored in memory. In this work, we propose an iterative reconstruction algorithm without system matrix for EPRI to simplify the whole iterative reconstruction process. The function of the system matrix is to calculate the projections, whereas the function of the transpose of the system matrix is to perform backprojection. The existing projection and backprojection methods are all based on the configuration that the imaged-object remains stationary and the scanning device rotates. Here, we implement the projection and backprojection operations by fixing the scanning device and rotating the object. Thus, the core algorithm is only the commonly-used image-rotation algorithm, while the calculation and store of the system matrix are avoided. Based on the idea of image rotation, we design a specific iterative reconstruction algorithm for EPRI, total variation constrained data divergence minimization (TVcDM) algorithm without system matrix, and named it as image-rotation based TVcDM (R-TVcDM). Through a series of comparisons with the original TVcDM via real projection data, we find that the proposed algorithm may achieve similar reconstruction accuracy with the original one. But it avoids the complicated calculation and store of the system matrix. The insights gained in this work may be also applied to other imaging modalities, for example computed tomography and positron emission tomography. [ABSTRACT FROM AUTHOR]