Among the causes of death due to cancer, brain tumors are ranked second in the pediatric age group and fourth in middle-aged man and malignant gliomas are uniformly fatal with only 50 percent of patients surviving one year from initial diagnosis. These stark statistics underscore the urgent need for improved therapies along with capabilities that would provide for early therapeutic assessment of efficacy in these patients. A sensitive and early predictor of therapeutic outcome for patients would provide for improved care and the opportunity to individualize and adjust the treatment to each patient. The central hypothesis of this project is that the effectiveness of therapeutic interventions can be determined prior to tumor shrinkage using quantitative MR diffusion, perfusion and 1H spectroscopic methods. Both animal and human brain tumors will be evaluated using MR following therapeutic intervention including chemotherapy, radiation, gene, nanoparticles and antiangiogenic therapies. This research program will provide new mechanistic insights into: The use of MRI/S for the early detection of brain tumor response to therapy and the effects of neovascularization on therapy (Project 1); The sensitivity and resolution of MRI/S for the detection of therapeutic transgene delivery, function and therapeutic efficacy in brain tumors (Project 2); The capability of using NanoPlatforms for the delivery of image contrast agents and potentially therapeutic drugs to brain tumors (Project 3); and The predictiveness of MRI for the early assessment of human brain tumor response to therapy (Project 4). This research plan is an outgrowth of the progress made with previous NCI support. Four interactive projects and four cores are proposed. The Administrative Core A provides administrative support along with internal and external review for all projects. The Animal MR Imaging Core B provides the necessary MRI/S services for Projects 1-3. The Digital Image Processing Core C provides a centralized and high-throughput capability for the digital post processing of all acquired MR data for all projects (Projects 1-4). The Biostatistical Core D provides statistical support to all projects.
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