This Program Project Grant proposal seeks continued support for research directed toward a more comprehensive understanding and novel applications of magnetic susceptibility and other intrinsic NMR contrast mechanisms that provide in vivo physiological information. This research explores the relationship between microscopic biological compartmentalization and macroscopic NMR image contrast. Though much progress has been made in understanding these phenomena as they pertain to measurements of blood volume and iron biochemistry, many unresolved issues, particularly concerning perfusion, oxygen consumption, and targeting effectiveness remain. A coordinated investigation of these effects is provided to enhance the utilization of MR imaging in a variety of organ systems and pathological states, including cancer and coronary artery disease. The availability of real time echo planar imaging as a tool for the study of these questions continues to offer both new opportunities and scientific challenges. This proposal is divided into four research projects which share Core resources and have considerable overlap of methodologies and personnel to allow for constructive interaction. The four projects are: 1) """"""""NMR Imaging in Tumor Angiogenesis"""""""" explores susceptibility and other intrinsic NMR contrast mechanisms for the in vivo assessment of tumor neovascularity and the response to anti-angiogenic therapy; 2) """"""""NMR Studies of Myocardial Perfusion"""""""" addresses the measurement of myocardial flow reserve in animal models and patients using intrinsic T1 and T2* contrast mechanisms; 3) """"""""Susceptibility Contrast in NMR Imaging"""""""" provides theoretical and experimental assessment in several systems in which biological heterogeneity produces quantifiable contrast and that the specifics of the NMR imaging process are crucial to the quantification of the underlying biology. 4) """"""""NMR Receptor Imaging"""""""" explores novel receptor and immunospecific iron oxide contrast agents for the in vivo characterization of cancer. Overall hypotheses to be tested include: 1) that magnetic susceptibility and other intrinsic NMR effects can be used to quantitatively assess blood flow, blood volume and measure the density of vessel size in vivo and 2) that superparamagnetic iron oxide particles can be targeted to tumor specific receptors enabling in vivo characterization with NMR imaging. These projects are supported by three Core laboratories, NMR Facilities, NMR Computer and Technologies, and Contrast Agent Cores, and by an Administrative Core.
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