The treatment of primary malignant cerebral neoplasms remains a significant challenge Median survival in the most recent Brain Tumor Study Group report was 50 weeks for valid study patients receiving BCNU and whole brain radiotherapy. Factors influencing chemotherapy effectiveness with cerebral neoplasms include regional cerebral blood flow (rCBF), blood-brain barrier surface area and permeability, cellular permeability, extracellular and intracellular drug half-life and the drug diffusion coefficient. The long term objectives of this proposal are to focus the use of various quantitative metabolic imaging techniques on the measurement of these factors in primary cerebral neoplasms. The unifying hypothesis is that quantitative information of pharmacokinetic parameters will help in the selection of chemotherapy and in finding new methods to increase delivery of agents to their site of action in the neoplasm. These quantitative metabolic imaging techniques will include stable xenon CT, single photon emission computerized tomography and nuclear magnetic resonance. It is well recognized that the rCBF and capillary permeability are two of the major factors in the modeling of effective chemotherapy. The immediate specific aims of this proposal are to study the rCBF and capillary permeability in primary cerebral neoplasms using stable xenon CT, SPECT-HIPDm and iodine-enhanced CT. The hypotheses are that the use of rCBF and capillary permeability will help model chemotherapy selection, aid in prognosis of survival and may help to differentiate tumor types and radiation necrosis. The effects of steroid therapy and radiation therapy will be studied. Finally, the stable xenon CT and SPECT modalities of determining rCBF will be contrasted to evaluate their use, ease and safety. The extended aims of this application are to investigate further methods of quantitating capillary permeability in patients with cerebral neoplasms using SPECT-glucoheptonate and NMR studies with paramagnetic agents. Studies will also measure and determine the usefulness of regional cerebral blood volume. Finally, the role of NMR studies will be addressed, including comparison to conventional CT in following white matter changes due to radiation therapy, use of paramagnetic agents and metabolic phosphorous spectroscopy.
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