Variable radio frequency proton–electron double-resonance imaging: Application to pH mapping of aqueous samples

Abstract

Proton-Electron Double-Resonance Imaging (PEDRI) offers rapid image data collection and high resolution for spatial distribution of paramagnetic probes. Recently we developed the concept of Variable Field (VF) PEDRI which enables extracting a functional map from a limited number of images acquired at pre-selected EPR excitation fields using specific paramagnetic probes (Khramtsov et al. 2010, JMR, 202, 267-273). In this work, we propose and evaluate a new modality of PEDRI-based functional imaging with enhanced temporal resolution which we term Variable Radio Frequency (VRF) PEDRI. The approach allows for functional mapping (e.g., pH mapping) using specifically designed paramagnetic probes with high quality spatial resolution and short acquisition times. This approach uses a stationary magnetic field but different EPR RFs. The ratio of Overhauser enhancements measured at each pixel at two different excitation frequencies corresponding to the resonances of protonated and deprotonated forms of a pH-sensitive nitroxide is converted to a pH map using a corresponding calibration curve. Elimination of field cycling decreased the acquisition time by exclusion periods of ramping and stabilization of the magnetic field. Improved magnetic field homogeneity and stability allowed for the fast MRI acquisition modalities such as fast spin echo. In total, about 30-fold decrease in EPR irradiation time was achieved for VRF PEDRI (2.4 s) compared with VF PEDRI (70 s). This is particularly important for in vivo applications enabling one to overcome the limiting stability of paramagnetic probes and sample overheating by reducing RF power deposition.

Dynamic nuclear polarization properties of nitroxyl radical in high viscous liquid using Overhauser-enhanced Magnetic Resonance Imaging (OMRI)

“…ESR imaging provides the spatial distribution of the nitroxyl radical where as anatomic information is not available. Overhauser-enhanced magnetic resonance imaging (OMRI) is a double resonance technique that uses the presence of paramagnetic agents to enhance the signal intensity from nuclear spins by means of a process known as dynamic nuclear polarization (DNP) or Overhauser effect [10,11]. In this phenomenon, the relatively stronger magnetic moment of the electron is used to enhance the polarization of nuclear spins, thereby enhancing their signal.…”

In Vivo Application of Proton-Electron Double-Resonance Imaging

“…In total, about a 30-fold decrease in EPR irradiation time was achieved for VRF PEDRI (2.4 s) (69) compared with VF PEDRI (70 s) (33), as tested with similar aqueous solutions of the NR1 radical. This is particularly important for in vivo applications enabling one to overcome the limiting stability of paramagnetic probes and sample overheating by reducing RF power deposition.…”

In vivo Spectroscopy and Imaging of Nitroxide Probes

“…EPR-measured pHe values show higher heterogeneity in tumor compared with normal tissue with mean pHe, 6.67, significantly lower than mean tissue pHe in healthy leg, 7.17. Recently we made significant progress towards pH mapping of living tissue using functional PEDRI approaches Efimova et al, 2011). Fig.…”

“…Moreover, continuous waves (CW) EPR (Halpern et al, 1994;He et al, 2002) and pulsed EPR (Yasui et al, 2010) instruments with lower radio frequencies (RF) down to 250 MHz have been constructed allowing for spectral-spatial functional imaging in larger animals, and potentially in humans. Recently, a functional proton-electron doubleresonance imaging (PEDRI) approach Efimova et al, 2011) based on MRI detection with EPR excitation of paramagnetic probes at pre-selected EPR fields/frequencies, has been developed. The latter approach inherits high resolution, fast image acquisition and the availability of anatomical information from MRI techniques.…”