This research plan will continue our development of Chemical Exchange Saturation Transfer (CEST) MRI acquisition and analysis methods for imaging patients with cancer. AcidoCEST MRI with an exogenous contrast agent is an innovative variation of this technique that measures extracellular pH in solid tumors. We have also developed an exceptionally innovative method that acquires endogenous CEST MR images with multiple powers, which can measure the chemical exchange rate of endogenous proteins that can assess relative differences in pH. We will improve our CEST MRI acquisition methods by accelerating the imaging speed, reducing and eliminating complications due to patient motion, eliminating complications caused by fat signal, and expanding to 3D imaging methods. We will also improve image analysis methods that are required for CEST contrast from endogenous proteins and exogenous contrast agents. Our research has strong impact because acidoCEST MRI can track changes in tumor acidosis in response to chemotherapy and chemoradiation therapy in patients who have breast cancer and head & neck cancer. Endogenous CEST MRI can improve the diagnoses of brain tumor recurrence vs. pseudoprogression, and evaluations of lung cancer vs. lung infection. We will perform clinical studies with our endogenous and exogenous CEST MRI methods to image patients with brain, breast, lung, and head & neck cancers. To amplify the impact of our research, we will develop versions of our CEST MRI acquisition methods for the many versions of the 13 Siemens hardware platforms and software operating systems at the MD Anderson Cancer Center. We will also develop user-friendly CEST analysis methods for many researchers at MD Anderson. We will leverage our unique research environment and expertise with intra-institutional dissemination to provide inter-institutional dissemination, by sharing share these acquisition and analysis tools with other CEST MRI researchers. We will collaborate with NIST to provide the first CEST MRI phantom that can standardize the development and implementation of intra- and inter-institutional CEST MRI methods. Our team of outstanding investigators includes experts in CEST saturation methods, CEST MR image analysis, clinical contrast agents, rapid MRI acquisition methods, high field 7T MRI, clinical radiology, biostatistics, histopathology and oncology. Based on our expertise and years of productivity in clinical CEST MRI, we have developed an exceptional research approach. As the world's largest cancer center and a health destination, the MD Anderson Cancer Center has the patient population that provides very strong institutional support for our clinical studies.