PROJECT SUMMARY The overall goal of this proposal is to develop novel diffusion-weighted (DW)-MRI methods to enable high image quality and improved quantification of diffusion properties in the abdomen. Diffusion-weighted (DW)-MRI has a unique ability to probe tissue microstructure without the need for ionizing radiation or intravenous contrast agents. DW-MRI of the abdomen is utilized in detection, staging, and treatment surveillance of malignancies, and has shown great promise in various other applications, including for the assessment of fibrosis in the liver, pancreas, kidneys, and other organs. However, despite its enormous potential, DW-MRI in the abdomen has been limited by two unaddressed major technical challenges. The first major challenge is motion in the abdomen. The presence of cardiovascular related motion leads to signal loss in affected tissues (eg: left lobe of the liver, pancreas). This signal loss also results in biased and imprecise (poor test-retest repeatability and reproducibility) quantitative measures of diffusion, such as the apparent diffusion coefficient (ADC), rendering these values highly unreliable as a quantitative imaging biomarker. The presence of respiratory motion leads to blurring and poor quantification. The second major challenge is severe image distortion. DW-MRI commonly relies on single-shot echo planar imaging (ssEPI) acquisitions, where the entire image is acquired following a single excitation. Importantly, ssEPI has limited spatial resolution and introduces severe image distortions in complex magnetic susceptibility environments, such as in the abdomen. Although “low-distortion” acquisitions such as multi-shot (ms)-EPI and non-EPI strategies are effective in the brain, these methods remain unreliable in the abdomen due to the presence of substantial motion-induced inter-shot errors. We have recently proposed several novel methods to address these major challenges, including: i) optimized motion-robust DW waveforms to address cardiovascular motion and signal loss; ii) free-breathing DW-MRI with motion-corrected averaging to address respiratory motion; and iii) the combination of these motion-robust methods with state-of-the-art msEPI methods. In this proposal, we will develop and validate these methods in order to: Obtain reliable motion-robust (Aim 1) and low-distortion (Aim 2) DW-MRI in the abdomen, and validate these methods for the assessment of liver metastases (Aim 3). Upon successful completion, these methods will have broad applications, including the assessment of cancer, fibrosis and other disease processes in various abdominal organs such as the liver, pancreas, kidneys, bowel and beyond.