The overall objectives of this proposal are to correlate tumor radiation response with changes in vivo magnetic resonance spectra and evaluate the role of Magnetic Resonance Spectroscopy (MSP) as a predictor and monitor of tumor response to radiation therapy. In addition to intrinsic cellular radiosensitivity, the radiation response of a tumor is influenced by a number of physiological and environmental factors which may have a direct effect on its metabolism such as 02 tension, pH, nutrient concentration and blood flow. In vivo NMR spectroscopy (MRS) provides a noninvasive method of obtaining serial measurements of the tumor oxygenation status, pH and changes in tumor metabolism and may potentially be used to predict and monitor tumor radiation response. Thus far the results of tumor studies using in vivo MRS have been largely anecdotal. Evaluation of the potential clinical application the MRS techniques will require systematic correlation of spectroscopy parameters with reliable indices of tumor viability and tumor cure. In this application we propose to study tumor radiation response with in vivo 31P and 1H MRS and to determine if there is a intracellular pH, the ratios of PCr/NTP, Pi/NTP, PME/NTP, Pi/PCr, lactate/Cr and relative intensities of other phosphorous metabolites and cell survival and tumor cure after radiotherapy using two murine tumors. We will also explore the possible mechanisms underlying the NMR spectral changes by altering the tumor cellular physiological and environmental factors such as 02 and glucose concentration and blood flow and measure their effects on the NMR spectrum and the pH. The results of these studies should provided a basis for further experimental and clinical studies and establish whether in vivo MRS in conjunction with MRI (magnetic resonance imaging) will play a significant role in the diagnosis, selection of treatment modality and prediction of treatment outcome in cancer management.
| Wendland, M F; Iyer, S B; Fu, K K et al. (1992) Correlations between in vivo 31P MRS measurements, tumor size, cell survival, and hypoxic fraction in the murine EMT6 tumor. Magn Reson Med 25:217-32 |
| Fu, K K; Wendland, M F; Iyer, S B et al. (1990) Correlations between in vivo 31P NMR spectroscopy measurements, tumor size, hypoxic fraction and cell survival after radiotherapy. Int J Radiat Oncol Biol Phys 18:1341-50 |
| Cohen, Y; Chang, L H; Litt, L et al. (1990) Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats. J Cereb Blood Flow Metab 10:277-84 |
