Many disease processes are characterized by substantially different mechanical properties than surrounding normal tissue. This accounts for the efficacy of palpation as a clinical technique to detect cancer and other abnormalities. Indeed, many tumors of the thyroid, breast, and prostate are still first detected by this centuries- old diagnostic technique. Unfortunately, palpation is a subjective technique and small or inaccessible abnormalities cannot be detected by touch. Conventional imaging methods such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) do not provide information that is in any way analogous. The goal of this research is to develop, validate, explore and identify high-impact applications of a new diagnostic imaging technology for quantitatively assessing the mechanical properties of tissues. We call this technique Magnetic Resonance Elastography (MRE). Mechanical waves are generated in tissue and a remarkably sensitive phase-contrast MRI technique, using synchronous motion-sensitizing gradients, is used to directly image the pattern of wave propagation. Specially-developed mathematical algorithms are used to analyze the wave images and to generate quantitative images depicting the stiffness and other mechanical properties of tissue. At the onset of this research, the central hypothesis was that MRE can be successfully implemented as a practical scientific and clinical tool and that it would be useful for detecting and characterizing focal and diffuse disease processes that may be difficult to investigate by other methods. The research in the last cycle of this grant has confirmed this hypothesis by developing, validating, and introducing into clinical research an MRE- based technique for diagnosing chronic liver disease. The research has indicated that in this role, MRE is a more-comfortable, safer, less-expensive alternative to biopsy. The research plan for the next grant cycle includes investigations to further understand and develop the underlying technology of MRE, to develop practical methods for applying other applications, and to explore promising new applications in diagnosing disease. The research plan involves theoretical work, basic MRI pulse sequence development, device engineering, studies of animal and human tissue specimens, and protocol testing studies with normal and patient volunteers. Further progress is expected to provide an increasingly useful imaging tool with capabilities to: (1) noninvasively palpate by imaging regions of the body that are beyond the reach of the physician's hand, (2) delineate tumors and other abnormalities before they are severe enough to detect by touch, (3) provide greater sensitivity for assessing changes in tissue mechanical properties, and (4) provide useful new quantitative imaging biomarkers for characterizing tissue properties.