Malignant brain tumors remain one of the deadliest forms of cancer despite maximal surgical intervention, radiation therapy and chemotherapy. Limitations in neuroimaging technology complicate the clinical management of patients with gliomas and impede efficient testing of new therapeutics. Recently, we have designed a new magnetization transfer-based MRI technique, dubbed amide proton transfer (APT) imaging, that detects a variety of amide protons of endogenous mobile proteins and peptides, such as those in the cytoplasm. Our preclinical studies and pilot clinical data using single-slice acquisition suggest that APT may provide unique information about the presence and grade of brain tumors based on increased cellular content of proteins and peptides, as revealed by MRI-guided proteomics and in vivo MR spectroscopy. However, many technical problems have to be resolved before this technique can be applied reliably for whole-brain imaging in a clinical setting. The overall goals of this proposal are to develop a fast whole-brain APT methodology for use in the clinic and to assess the capability for APT to provide unique visual data about heterogeneous portions of gliomas when compared to standard MRI sequences. To achieve this goal, we have assembled a multidisciplinary team of basic scientists and clinicians, within the framework of a national brain cancer program, who will each contribute their particular expertise in the fields of physics, biostatistics, oncology, neurosurgery, pathology, and neuroradiology. Our specific aims are: (1) Develop a time-efficient whole-brain APT imaging technique at 3T for clinical application, (2) Determine the sensitivity and specificity of APT imaging at 3T in evaluating heterogeneous brain tumors by distinguishing tumor core from peritumoral edema and low- from high-grade gliomas, (3) Explore the origin of the APT contrast for brain tumors using APT-image guided biopsy to allow histologic validation, and (4) explore the feasibility and optimal quality of APT imaging at 7T. This work has the potential to yield a clinically applicable new MRI technique that is unique in its ability to image tissue at the protein and peptide level. This may improve the diagnostic accuracy of brain MRI for malignant gliomas and, potentially, other diseases of the brain and, hence, is of enormous clinical importance. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a novel protein and peptide-based MRI technique, called amide proton transfer (APT) imaging, and to determine the sensitivity and specificity of APT imaging for the detection of brain tumors. APT-MRI may improve the diagnostic and surgical accuracy in treating malignant gliomas.