? Despite the abundance of proteins inside many cell types, these proteins do not provide intense signals in proton magnetic resonance (MR) spectra, and little has been studied about cellular proteins in vivo or in cells, in particular, there are presently no magnetic resonance imaging (MRI) methods to spatially assess protein content and status in vivo. Yet, most cellular activities are performed by proteins, and various lesions, such as those found in cancer and stroke, may show changes in protein content and amide proton exchange properties, and thus the interpretation of the nature of these proteins is important for earlier detection, better spatial definition, and improved characterization of diseases. We will develop novel MRI and MRS (magnetic resonance spectroscopy) methods for studying mobile cellular proteins and their properties in tissue. We hypothesize that detection sensitivity enhancement through selective saturation transfer via water-exchangeable amide protons of mobile proteins allows spatial assessment of protein content and status in biological tissue via the water signal. The overall goal of this study is to develop a completely new MRI technique, called amide proton transfer (APT) imaging, which opens the possibility of adding intrinsic protein-based contrast to the diagnostic capability of high-field MRI. The clinical use of this type of imaging will first be demonstrated for human brain tumors. Therefore, the specific aims of this application are: (1) To develop new MR spectroscopy methods with a WATERGATE detection scheme and to quantify amide proton content and exchange rates in the human brain on a 3T clinical MRI system. (2) To develop and implement a new single-slice amide proton transfer imaging technique and to quantify amide proton transfer contrast for imaging of brain tumors on a 3T human MRI system. (3) To determine brain tumor boundary and volume using multi-slice amide proton transfer imaging on a 3T human MRI system. APT imaging can be used to study a host of potentially abnormal proteins in cancer, stroke, metabolic disorders, and other diseases. The successful outcome of this application will offer a sensitive and specific modality in the clinical MRI examination of diseases. ? ? ?
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