The overall goal of this project is to advance the proton-electron double-resonance technique, PEDRI, to a level allowing for functional mapping of physiologically-critical parameters, such as pH, oxygen, redox and intracellular glutathione (GSH), in animals and, potentially, in humans. To reach this goal we will use a new concept of Variable Radio Frequency (VRF) PEDRI in combination with an array of specific paramagnetic probes. This will allow for functional mapping within MRI high quality spatial resolution and short acquisition time. This new proposal is a logical extension of our recent R21 which was successful in validating the concept of functional PEDRI. The success of this proposal will open possibilities for bringing this new PEDRI technique into the leading research and clinical MRI centers. This proposal has promising potential taking into account that VRF PEDRI system allows for the simplified design by elimination of the field cycling coil assembly and its power supplies which will result in a complete utilization of the gap in the magnet system of conventional MRIs.
The specific aims are: (SA1) To enable Variable Radio Frequency PEDRI for in vivo functional imaging. We will focus on the further development and optimization of VRF PEDRI, which is an instrumentally-innovative modification of PEDRI and has been found to be highly efficient for functional applications during the exploratory R21 phase. (SA2) To design PEDRI-oriented pH, oxygen, redox and GSH sensitive paramagnetic probes. The probes with functionally-dependent ratiometric spectral parameters, including dual function probes, with extended aqueous solubility and stability will be synthesized. Synthesis and optimization of the probes is absolutely essential for the overall efficiency of functional PEDRI applications. (SA3) To map in real-time the parameters of a tumor microenvironment using VRF PEDRI. The capacity of the VRF PEDRI for in vivo pH and oxygen mapping will be demonstrated for the most effective probes in PyMT transgenic mice that spontaneously-develop breast cancer. We plan to perform VRF PEDRI imaging and construct real-time, spatially-resolved and stage-specific signature profiles of tumor pO2, pH, redox, and GSH as the mammary tumors progress to malignancy. In summary, the success of this project may have a significant impact on the future of in vivo functional imaging applications to medicine.
This project will advance the proton-electron double-resonance imaging technique, PEDRI, to a level allowing for functional mapping of physiologically-critical parameters, such as pH, oxygen, redox and intracellular glutathione (GSH), in animals and, potentially, in humans. The functional imaging technique will be applied in PyMT transgenic mice that spontaneously-develop breast cancer. This will allow for construction of real-time, spatially-resolved and stage-specific signature profiles of tumor pO2, pH, redox, and GSH as the mammary tumors progress to malignancy. This novel technique may have a significant impact on future applications relating to biomedical imaging.
|Ahmad, Rizwan; Samouilov, Alexandre; Zweier, Jay L (2016) Accelerated dynamic EPR imaging using fast acquisition and compressive recovery. J Magn Reson 273:105-112|
|Driesschaert, Benoit; Bobko, Andrey A; Eubank, Timothy D et al. (2016) Poly-arginine conjugated triarylmethyl radical as intracellular spin label. Bioorg Med Chem Lett 26:1742-4|
|Gorodetsky, Artem A; Kirilyuk, Igor A; Khramtsov, Valery V et al. (2016) Functional electron paramagnetic resonance imaging of ischemic rat heart: Monitoring of tissue oxygenation and pH. Magn Reson Med 76:350-8|
|Elajaili, Hanan B; Biller, Joshua R; Tseitlin, Mark et al. (2015) Electron spin relaxation times and rapid scan EPR imaging of pH-sensitive amino-substituted trityl radicals. Magn Reson Chem 53:280-4|
|Bobko, A A; Khramtsov, V V (2015) Redox properties of the nitronyl nitroxide antioxidants studied via their reactions with nitroxyl and ferrocyanide. Free Radic Res 49:919-26|
|Samouilov, Alexandre; Efimova, Olga V; Bobko, Andrey A et al. (2014) In vivo proton-electron double-resonance imaging of extracellular tumor pH using an advanced nitroxide probe. Anal Chem 86:1045-52|
|Goodwin, Jonathan; Yachi, Katsuya; Nagane, Masaki et al. (2014) In vivo tumour extracellular pH monitoring using electron paramagnetic resonance: the effect of X-ray irradiation. NMR Biomed 27:453-8|
|Takahashi, Wataru; Bobko, Andrey A; Dhimitruka, Ilirian et al. (2014) Proton-Electron Double-Resonance Imaging of pH using phosphonated trityl probe. Appl Magn Reson 45:817-826|
|Tseitlin, Mark; Biller, Joshua R; Elajaili, Hanan et al. (2014) New spectral-spatial imaging algorithm for full EPR spectra of multiline nitroxides and pH sensitive trityl radicals. J Magn Reson 245:150-5|
|Khramtsov, Valery V; Gillies, Robert J (2014) Janus-faced tumor microenvironment and redox. Antioxid Redox Signal 21:723-9|
Showing the most recent 10 out of 15 publications