Variable Field Proton-Electron Double-Resonance Imaging: Application to pH mapping of aqueous samples.

Davis Heart and Lung Research Institute and the Division of Cardiovascular Medicine, The Ohio State University, College of Medicine, 420 West 12th Ave., Room 611B, Columbus, OH 43210, USA.
Journal of Magnetic Resonance (Impact Factor: 2.3). 11/2009; 202(2):267-73. DOI:10.1016/j.jmr.2009.11.017
Source: PubMed

ABSTRACT A new concept of Variable Field Proton-Electron Double-Resonance Imaging (VF PEDRI) is proposed. This allows for functional mapping using specifically designed paramagnetic probes (e.g. oxygen or pH mapping) with MRI high quality spatial resolution and short acquisition time. Studies performed at 200 G field MRI with phantoms show that a pH map of the sample can be extracted using only two PEDRI images acquired in 140 s at pre-selected EPR excitation fields providing pH resolution of 0.1 pH units and a spatial resolution of 1.25mm. Note that while concept of functional VF PEDRI was demonstrated using the pH probe, it can be applied for studies of other biologically relevant parameters of the medium such as redox state, concentrations of oxygen or glutathione using specifically designed EPR probes.

0 0
  • [show abstract] [hide abstract]
    ABSTRACT: The in vivo quantification of extracellular pH (pHe ) in tumours may provide a useful biomarker for tumour cell metabolism. In this study, we assessed the viability of continuous-wave electron paramagnetic resonance (CW-EPR) spectroscopy with a pH-sensitive nitroxide for the measurement of extracellular tumour pH in a mouse model. CW-EPR spectroscopy (750 MHz) of C3H HeJ mice hind leg squamous cell tumour was performed after intravenous tail vein injection of pH-sensitive nitroxide (R-SG, 2-(4-((2-(4-amino-4-carboxybutanamido)-3-(carboxymethylamino)-3-oxoproylthio)methyl)phenyl)-4-pyrrolidino-2,5,5-triethyl-2,5-dihydro-1Н-imidazol-1-oxyl) during stages of normal tumour growth and in response to a single 10-Gy dose of X-ray irradiation. An inverse relationship was observed between tumour volume and pHe value, whereby, during normal tumour growth, a constant reduction in pHe was observed. This relationship was disrupted by X-ray irradiation and, from 2-3 days post-exposure, a transitory increase in pHe was observed. In this study, we demonstrated the viability of CW-EPR spectroscopy using R-SG nitroxide to obtain high-sensitivity pH measurements in a mouse tumour model with an accuracy of <0.1 pH units. In addition, the measured changes in pHe in response to X-ray irradiation suggest that this may offer a useful method for the assessment of the physiological change in response to existing and novel cancer therapies. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 01/2014; · 3.45 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (JMR 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at EPR frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analog linewidth of 2.1 G allowing for an increase of Overhauser enhancements and reduction in RF power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis - a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pHe). In vivo VRF PEDRI was performed on PyMT tumor-bearing mice. Compared to normal mammary glands with a neutral mean pHe (7.1±0.1), we observed broader pH distribution with acidic mean pHe (6.8±0.1) in tumor tissue. In summary, VRF PEDRI in combination with newly developed pH probe provides an analytical approach for spatially-resolved noninvasive pHe monitoring, in vivo.
    Analytical Chemistry 12/2013; · 5.70 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The development of electron paramagnetic resonance (EPR)-based mapping of pH is an important advancement for the field of diagnostic imaging. The ability to accurately quantify pH change in vivo and monitor spatial distribution is desirable for the assessment of a number of pathological conditions in the human body as well as the monitoring of treatment response. In this work we introduce a method for EPR-based pH mapping utilizing a method of spectral-spatial imaging of sequentially scanned spectra to decrease the missing gradient rotation angle, without increasing the spatial field of view. Repeated in vitro measurements of pH phantom tubes demonstrated higher precision measurements of the hyperfine coupling constant (HFC) compared to previous EPR-based methods, resulting in mean pH values accurate to less than 0.1 pH across a range of physiologically observed values.
    Analytical Chemistry 03/2012; 84(8):3833-7. · 5.70 Impact Factor


Available from
Mar 11, 2013