Understanding tumor physiology is useful in the diagnosis and treatment of solid tumors. More than 30% of tumors are known to contain hypoxic regions (< 10 mm Hg). Tumors with hypoxic regions are usually associated with higher metastatic potential as well as being resistant to chemotherapy and radiotherapy as well. While currently used pO2 measuring techniques are invasive and used only in tumors, which are accessible, the data obtained from these studies suggest the valuable prognostic information, which they have provided suggest the importance of these measurements. Some of the desirable features in a clinically useful pO2 measuring technique are: 1) non-invasive; 2) quantitative; 3) repeatable; and 4) sensitive to hypoxia/ischemia. Based on these considerations, we have been developing imaging techniques based on spectroscopic technique called Electron Paramagnetic Resonance (EPR), which is similar to Nuclear Magnetic Resonance (NMR), but probes species with unpaired electrons such as free radicals. The intrinsic EPR property of the paramagnetic probes used to extract oxygen is the oxygen dependent line width. Extraction of this parameter on a pixel-by-pixel basis thereby makes it possible to image oxygen in a given object. Based on this principle three independent approaches were considered for small animal imaging applications, which have the potential to be translated to human use as well. Project 1: We have developed, validated and tested the capability of non-invasive pO2 imaging in tumor bearing mice using Time-domain EPR Imaging.. We have optimized the imaging time, contrast agent dosing, gradients etc. The imaging modality is validated with standard pO2 measuring techniques. Feasibility of providing non-invasive and quantitative images of tissue oxygen status was demonstrated in tumor bearing mice. Data acquisition strategies: Integration of a low cost data acquisition system has been accomplished using commercially available high-speed digitizers. Additionally, novel data acquisition strategies such as time-locked sub-sampling are being developed. Project 2: Continuous Wave EPR Imaging unit capable of small animal imaging has been developed. This technique can monitor tissue redox status by following the levels of a redox-sensitive contrast agent. Additionally, endogenous free radicals can be detected using spin traps in pathological conditions. Recent efforts focus on improving the detection sensitivity, imaging speed, and image processing. Resolution recovery in EPR imaging has been attempted with some degree of success with iterative algorithms. Proof-in-principle of redox status imaging has been demonstrated using simple in vivo models. Project 3: Overhauser enhanced MRI is a combination of EPR amd MRI. The MRI aspect of this technique provides anatomical information and the EPR aspect information pertaining to pO2. The MRI is implemented at 15 mT. The loss in resolution inherent at such low fields is recovered using a paramagnetic contrast agent. This method has been tested and validated in phantom objects as well as in in vivo studies. The quantitative pO2 imaging capabilities of OMRI have been also validated using standard techniques such as Polarography. Preliminary studies on tumor perfusion and oxygenation and the changes in response to radiotherapy or
