Despite the development of new imaging modalities, x-ray mammography remains the main tool for screening, diagnosis and management of breast cancers. However, the limited sensitivity and superimposition of calcifications and masses on the breast parenchyma have compromised its value in these procedures. Recent development of flat panel (FP) based cone beam CT (CBCT) techniques have initiated a new approach referred to as the dedicated or pendant geometry cone beam breast CT technique which couples high contrast sensitivity with true 3-D rendition of breast anatomy and lesions. However, although the spatial resolution offered by FP based CBCT is potentially higher than those provided by the conventional CT techniques, it is still significantly lower than those of mammographic imaging techniques as required for detecting and visualizing small calcifications. In this project, we propose to develop, investigate and evaluate a new technique referred to as the dual-resolution CBCT (DRCBCT) technique to allow the spatial resolution of the 3D breast images to be improved beyond those achievable with FPCBCT. With this technique, a FP detector is used to acquire full field CBCT images which are used to select a volume-of-interest (VOI). The breast is then re-positioned to have the VOI centered to the iso-center. A collimator is added to limit the x-ray field to the VOI and a small field of view CCD detector is used to acquire high resolution projection images for the VOI at an appropriate exposure level. Limited height, full width FP images are then obtained by re- scanning or by computing the re-projections from previously obtained FPCBCT images to fill in the truncated area as required for high resolution VOI CBCT. Because high resolution image acquisition and reconstruction are limited to the VOI, both patient dose and computation time can be kept at a reasonable level, making it more practical to implement and use for clinical applications. In the R21 phase (Year 1), we propose to investigate and demonstrate the feasibility of the dual resolution CBCT technique with computer simulation and bench top imaging experiments. In the R33 phase (Years 2, 3 and 4), we propose to construct, optimize and investigate a prototype system for dual resolution CBCT. Both phantom and patient images will be obtained to demonstrate the performance improvement by the dual resolution CBCT techniques and potential applications in the diagnosis and management of breast cancers. Successful development and investigation of the dual resolution CBCT technique may provide a powerful tool for 3-D breast imaging. The addition of high resolution capability, coupled with improved contrast sensitivity and the true 3-D nature of breast CT images may allow the dual resolution CBCT technique to replace and even surpass conventional mammography for improved diagnosis and management of breast cancers, including image guided biopsy, surgical planning, and needle localization. Proposal to be submitted to the NIH-NCI as R21/R33 project Title A Dual Resolution Cone Beam CT System for 3-D Breast Imaging Project Narrative Despite the development of new imaging modalities, x-ray mammography remains the main tool for screening, diagnosis and management of breast cancers. However, the limited sensitivity and superimposition of calcifications and masses on the breast parenchyma have compromised its value in these procedures. Recent development of flat panel (FP) based cone beam CT (CBCT) techniques have intitiated a new approach referred to as the dedicated or pendant geometry cone beam breast CT technique which couples high contrast senstivity with true 3-D rendition of breast anatomy and lesions. However, although the spatial resolution offered by FP based CBCT is potentially higher than those provided by the conventional CT techniques, it is still significantly lower than those of mammographic imaging techniques as required for detecting and visualizing small calcifications. In this project, we propose to develop, investigate and evaluate a new technique referred to as the dual-resolution CBCT (DRCBCT) technique to allow the spatial resolution of the 3D breast images to be improved beyond those achievable with FPCBCT. With this technique, a FP detector is used to acquire full field CBCT images which are used to select a volume-of-interest (VOI). The breast is then re-positioned to have the VOI centered to the iso-center. A collimator is added to limit the x-ray field to the VOI and a small field of view CCD detector is used to acquire high resolution projection images for the VOI at an appropriate exposure level. Limited height, full width FP images are then obtained by re- scanning or by computing the re-projections from previously obtained FPCBCT images to fill in the truncated area as required for high resolution VOI CBCT. Because high resolution image acquisition and reconstruction are limited to the VOI, both patient dose and computation time can be kept at a reasonable level, making it more practical to implement and use for clinical applications. In the R21 phase (Year 1), we propose to investigate and demonstrate the feasibility of the dual resolution CBCT technique with computer simulation and bench top imaging experiments. In the R33 phase (Years 2, 3 and 4), we propose to construct, optimize and investigate a prototype system for dual resolution CBCT. Both phantom and patient images will be obtained to demonstrate the performance improvement by the dual resolution CBCT techniques and potential applications in the diagnosis and management of breast cancers. Successful development and investigation of the dual resolution CBCT technique may provide a powerful tool for 3-D breast imaging. The addition of high resolution capability, coupled with improved contrast sensitivity and the true 3-D nature of breast CT images may allow the dual resolution CBCT technique to replace and even surpass conventional mammography for improved diagnosis and management of breast cancers, including image guided biopsy, surgical planning, and needle localization.