Project Summary/Abstract Chronic obstructive pulmonary disease (COPD) and lung cancer are the third and sixth most common causes of death worldwide. One major challenge is that there are no effective screening methods capable of early detection of these diseases and when these diseases are finally detected, they are often at advanced stages for which few effective treatment strategies exist. In the case of lung cancer, more than half of people die within the year of diagnosis. Darkfield (scattering-based) x-ray contrast has been recently demonstrated to provide exciting capabilities for early detection of lung pathologies, including cancer and COPD at doses comparable to conventional chest radiography. This contrast mechanism differs significantly from current approaches, which use the absorption of x-rays for contrast rather than the scattering of x-rays. Accessing information provided by this contrast mechanism requires an emerging grating-based x-ray technique called Talbot-Lau interferometry, which uses three sets of gratings (source, phase, and detector) to achieve contrast. However, a critical bottleneck for using this technique at the high x-ray energies (~60 keV) required for imaging through a human chest is a source grating with the aspect ratios required cannot be fabricated. We propose to develop a lung darkfield imaging prototype using a major x-ray source innovation that removes the need for the x-ray source grating to enable Talbot-Lau interferometry at high x-ray energies. The system will critically enable demonstrations of the clinical potential of darkfield radiography for early detection of lung pathologies. The proposed Phase I 6-month project is a proof-of-principle of a grating-less Talbot-Lau breadboard set-up on a phantom. The proposed Phase II 24-month project is to develop a complete prototype system and experimentally verify its performance.