In vivo 31-P MR spectroscopy provides a means of non- invasively monitoring tissue metabolism, providing new information about tumor biochemistry, and providing the opportunity to monitor changes occurring in patients during treatment. A number of preliminary studies of human tumors have now been completed. These show that 31-P MR spectra of human cancers in vivo typically have metabolic characteristics which differ from those of normal tissues. These include raised levels of phosphomonoesters (PME), phosphodiesters (PDE) and cellular pH, and reduced phosphocreatine (PCr). In recent studies, these characteristics have provided prognostic information, or early indicators of response to chemotherapy or radiotherapy. In some studies combination of metabolic information with quantitative T2 measurements derived from 1H MR images has increased the accuracy of prediction. Whilst these preliminary studies provide consistent information, they have been relatively small scale single institution studies, with the study size limited by access to machine time and limited patient populations. Recently, there have been significant advances in technology, permitting the wide spread application of chemical shift imaging, decoupling and optimized coil design. Based on these developments and preliminary studies, it is now timely to undertake a definitive trial of the value of 31 P MRS in the management of cancer patients. To achieve this end, a cooperative prospective study in substantial patient groups with appropriate tumors for 31-P MRS investigation is proposed. This proposal is one of 8 Interactive R01 proposals from 8 institutions collaborating to study over 1500 patients with non-Hodgkin's lymphoma, primary breast cancer, soft tissue sarcoma and head and neck carcinoma. This institution will contribute to the first three tumor groups, and will provide an instrument quality control central resource. State of the art techniques will be established at all institutions, including double tuned surface coils designed specifically to access the range of anatomical locations in these diseases; proton decoupling of 31-P to distinguish individual phospholipid metabolites; image guided 3 dimensional chemical shift imaging to accurately localize 31-P MR spectra to tumor; quantification of metabolite levels; and the application of pattern recognition to spectral analysis and characterization. The study will test the hypotheses that a baseline in vivo 31-P MR spectra can predict tumor response to treatment, and that comparison between the baseline spectrum and further spectra taken early in the course of treatment can provide an early indicator of response to treatment. The study will establish standards for cooperative MRS trials in other cancers and treatments, and will provide a basis for use of the technique in accelerating the evaluation of new treatments and in applying the technique in the management of individual patients.
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