The proposed investigation represents an application of nuclear magnetic resonance (NMR) to study tissue characteristics of tumors. Two approaches (proton NMR imaging and standard NMR spectroscopy) will be used for the detection of tumors and monitoring their response to therapy. NMR imaging is a new technique of constructing tomographic images using magnetic and radiofrequency (Rf) fields and avaoids the use of ionizing radiation. An exicitng and promising aspect of the technique is the potential to extract information from the images related to tissue biochemistry. The intensity in the images is related to proton density and is modified by local NMR relaxation times (T1 and T2) and the Rf pulse sequence. Initial studies will be performed to optimize the Rf pulse sequence for tumor detection. It is well known that tumors have an elevated cell water content and an associated elevation in proton relaxation times. In this study, NMR image relaxation time data for tumors will be correlated with spectroscopic data obtained on the same tissue. Spin density, T1 and T2 spectrometer measurements as well as % of tissue water will be calculated. To determine if NMR can accurately monitor tumor therapy, tumor bearing animals will have serial NMR images while undergoing various anticancer therapy. It is anticipated tht changes in relaxation time versus eventual outcome can be determined early in the course of successful therapy using NMR imaging. Many tumors have the characteristic of developing cellular acidosis when given a glucose challenge (Warburg effect). P-31 NMR spectrometer analysis is able to accurately measure cellular high energy phosphates and pH. Serial pH measurement will be made of control and various tumor cells during low and high glucose infusion. A significant fall in pH in Walker sarcoma cells has been demonstrated in our laboratory using P-31 NMR. After baseline studies experiments will be repeated during the course of various anticancer therapies. It is anticipated that the Warburg effect will abate with adequate therapy. P-31 spectra from extracts of various animal and human tumors will be obtained and analyzed for the presence of tumor specific compounds. It is hoped that these two approaches (NMR imaging and P-31 NMR) will become clinically useful for detecting tumors and monitoring therapy as the field of medical NMR progresses.
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