In Vivo Application of Proton-Electron Double-Resonance Imaging

Abstract

Significance: Proton-electron double-resonance imaging (PEDRI) employs electron paramagnetic resonance irradiation with low-field magnetic resonance imaging so that the electron spin polarization is transferred to nearby protons, resulting in higher signals. PEDRI provides information about free radical distribution and, indirectly, about the local microenvironment such as partial pressure of oxygen (pO 2 ), tissue permeability, redox status, and acid-base balance. Recent Advances: Local acid-base balance can be imaged by exploiting the different resonance frequency of radical probes between R and RH + forms. Redox status can also be imaged by using the loss of radical-related signal after reduction. These methods require optimized radical probes and pulse sequences. Critical Issues: High-power radio frequency irradiation is needed for optimum signal enhancement, which may be harmful to living tissue by unwanted heat deposition. Free radical probes differ depending on the purpose of PEDRI. Some probes are less effective for enhancing signal than others, which can reduce image quality. It is so far not possible to image endogenous radicals by PEDRI because low concentrations and broad line widths of the radicals lead to negligible signal enhancement. Future Directions: PEDRI has similarities with electron paramagnetic resonance imaging (EPRI) because both techniques observe the EPR signal, directly in the case of EPRI and indirectly with PEDRI. PEDRI provides information that is vital to research on homeostasis, development of diseases, or treatment responses in vivo. It is expected that the development of new EPR techniques will give insights into novel PEDRI applications and vice versa. Antioxid. Redox Signal. 28, 1345Signal. 28, -1364

Development of a fast‐scan EPR imaging system for highly accelerated free radical imaging

“…Overhauser effect–based MRI allows increased resolution due to intrinsic advantages of acquiring proton MRI signal. Resolution of about 0.6 mm was achieved in a matrix of 64 × 64 and FOV of 40 × 40 mm in 4.2 minutes or 1.6 mm in 8.4 seconds using functional nitroxides as spin probes . Rapid‐scan EPR has been shown to provide substantially higher SNR than CW for the same amount of data acquisition time .…”

“…Therefore, major efforts were devoted to accelerate the EPR image acquisition. On par with key advances in pulsed EPR imaging, 3,10,29 Overhauser effect-based MRI, 13,[30][31][32] and development of rapid scan approaches, 4,8,33,34 traditional CW with field modulation and phase-sensitive detection has undergone major improvements. Pulsed EPR image modality allows functional (oxygen map) images of legs of living mice with matrices of 31 × 31 pixels and submillimeter resolution to be obtained in 264 seconds, 3 or for 3D imaging in vivo, the scan time is under 10 minutes and resolution is 1.4 mm to 2 mm.…”

“…Electron paramagnetic resonance–related imaging techniques that are capable of detecting paramagnetic substances in vivo have been developed and continue to be improved. These include methods that enable direct detection of paramagnetic compounds such as continuous wave (CW) EPR, time domain pulsed EPR and rapid scan EPR, as well as MRI‐based indirect techniques such as T 1 contrast imaging, which visualize a radical‐induced enhancement, and EPR/proton MRI hybrid methods that enable visualization of radical‐induced Overhauser enhancement …”

“…These include methods that enable direct detection of paramagnetic compounds such as continuous wave (CW) EPR, 1,7 time domain pulsed EPR 3 and rapid scan EPR, 4,8 as well as MRI-based indirect techniques such as T 1 contrast imaging, 9,10 which visualize a radicalinduced enhancement, and EPR/proton MRI hybrid methods that enable visualization of radical-induced Overhauser enhancement. [11][12][13] In vivo or ex vivo CW EPR imaging (EPRI) has been established as a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. EPRI can provide a broad range of important information; however, its application to preclinical models of disease as well as its potential for clinical use is limited by the long acquisition time required to generate high-quality images, due to the fact that in conventional EPR systems each projectionacquisition magnetic field scan requires durations of at least 1-2 seconds.…”

Direct and indirect assessment of cancer metabolism explored by MRI

“…However, a few approaches of profiling cancer metabolism directly or indirectly by magnetic resonance using exogenously administered probes have been investigated. In this review, such imaging studies focusing on cancer preclinical research, using electron paramagnetic resonance imaging (EPRI), PEDRI, and hyperpolarized (HP) 13 C MRI, are summarized. EPRI is a technique to observe the electron spin of paramagnetic probes.…”