Improved Temporal and Spatial Resolution In Vivo Oxymetry Using Time-Domain EPR Imaging

Abstract Time-domain Electron paramagnetic resonance imaging (EPRI) is being developed at 300 MHz for the purpose of developing quantitative in vivo oxymetry in animal models. Unlike other imaging modalities, EPR can provide direct measurements of tissue oxygen concentration in a manner that is independent of complex biological processes such as ligand binding specificity or tracer metabolism. We describe the implementation of single-point imaging (SPI) a purely phase-encoded imaging modality in mouse tumor models and present the techniques for performing rapid quantitative oxygen imaging in phantoms and in vivo. Results from mouse tumor experiments as the mouse breathed alternately air or carbogen® (95% O2, 5% CO2). The reconstructed images demonstrate that the SPI EPR imaging technique readily distinguishes between the normal and tumor legs and can track the changes in tissue oxygen concentration in response to percentage of oxygen in breathing gas. Introduction Since EPR spectroscopy has the ability to perform direct and noninvasive detection, characterization, and quantification of paramagnetic species, it promises to become a prominent clinical diagnostic tool. Although closely related to nuclear magnetic resonance (NMR) spectroscopy, EPR is still under development as an imaging modality. In contrast to MRI, in which water protons (being in high concentration in vivo), are readily imaged, endogenous paramagnetic species that are present in vivo are well below the detection levels of the EPR technique. In order for EPR imaging to be performed, stable free radicals must be introduced into or generated in the living system. With the recent availability of biologically compatible spin probes with optimal toxicologic, pharmacologic, and spectroscopic properties, it has become possible to implement in vivo EPR imaging and extract valuable physiological information, noninvasively, in small animals. The time-course of spin distribution in organs and metabolism of drugs tagged with spin labels can be observed directly via EPR. The most attractive characteristic of EPR is its ability to image in vivo oxygen concentration in tissue noninvasively. In radiation oncology, it is known that hypoxic tumor fractions are at least three times more resistant to radiation compared to normoxic regions. The only accepted way of assessing in vivo pO2 is to use Clarke electrodes which are invasive. As an alternative and non-invasive method, EPR can be of great benefit to radiation therapy in the scheduling of radiation dose to maximize killing of cancer cells at minimal dose. Experimental, results & discussion The single-point imaging (SPI) scheme is essentially a phase-encoding technique that operates by acquiring a single data point in the free induction decay (FID) after a fixed delay (the phase encoding time), in the presence of static magnetic field gradients. A single point of intensity data is collected as a function of gradients (in ∆G steps from –Gmaxto Gmax) at a constant delay τ from the pulse.