SBIR-STTR Award

The emergence of compact, high-quality digital X-ray imaging detectors, together with nearly exponential growth in computing power and corresponding price reductions, allows for the potential of dedicated 3D breast imaging. X-ray mammography (XRM) has recognized limits including relatively high false negative rates. Other disadvantages include breast compression, relatively high dose to the breast, and low positive predictive value, especially for radiographically dense breasts. The dedicated breast Computed mammoTomography (CmT) solution we are proposing has the potential for improved detection of breast lesions through the removal of contrast-reducing overlying tissue, as well as the added benefits of uncompressed breast imaging for greater patient comfort, and breast dose equal to or less than that of current dual view mammography. Ultimately, we expect this technology to result in improved positive predictive value with earlier cancer detection and reduced morbidity and mortality. In the long term, we seek to demonstrate the feasibility of this device in a clinical setting by overcoming the current limitations in imaging the full breast volume and chest wall. These physical limitations are currently imposed by the fact that the X-ray tube and detector must trace an orbital path which includes moving under a patient support. For other "standard" designs, this makes it difficult to image close to the chest wall, though our prototype device has the 3-dimensional positioning capability to potentially overcome some of these limitations. Specific Aim 1 will investigate of partial angle tomographic scanning using the patient bed to move the breast further into the field of view to capture the entire breast and chest wall while limiting the orbit of the device to the sides of the bed. The assembly will be placed under a patient bed at the Multi-Modality Imaging Lab (MMIL) at Duke University Medical Center and partial angle scans made of available torso, breast, and lesion phantoms. Observers will determine the extent of visibility of lesions close to the chest wall. Specific Aim 2 will demonstrate the feasibility of utilizing current patient bed vertical elevation capabilities to change the relationship between breast and system center of rotation during scans to provide full 360 degree acquisitions while avoiding patient bed limitations. A patient bed with multiple degrees of freedom of movement will be used to lower the patient phantom further into the field of view while the device is perpendicular to the bed axis, then raise the bed to allow to device to move under the bed. Results will be evaluated as in Specific Aim 1. Specific Aim 3 will model patient bed designs to determine the degree to which the chest wall can be moved into the field of view with reasonable patient comfort by potentially utilizing smooth bed contours around a patient's hips and head. Successful implementation of the above alternatives, pending results of Phase I, will result in a next generation advanced system being produced in Phase II that can be placed in a clinical setting for the beginning of patient studies, leading to a commercially available product

This proposal combines the expertise of world renowned medical center collaborators with the experience obtained from our SBIR Phase I project to provide a 3rd generation 3D breast CT scanner suitable for a planned patient trial. X-ray mammography (XRM) has recognized limits including relatively high false negative rates. Other disadvantages include uncomfortable breast compression (possibly reducing participation rates), relatively high dose to the breast, and low positive predictive value, especially for radiographically dense breasts, and 2D images having severely overlapped tissues. The emergence of compact, high-quality digital X-ray imaging detectors, together with nearly exponential growth in computing power and corresponding price reductions, allows for the natural evolution of fully-3D dedicated breast imaging. The contemporary breast imaging approach using tomosynthesis yields morphological, pseudo-3D images (asymmetric volume image resolution with highly aliased and blurred artifacts) and with otherwise no quantifiable metrics due to the highly insufficiently sampled breast volume. The fully-3D dedicated breast Computed mammoTomography (CmT) solution we are developing has the potential for improved detection of breast lesions through the removal of contrast-reducing overlying tissue with images having <500 micron isotropic resolution, as well as the added benefits of uncompressed breast imaging for greater patient comfort, and breast dose equal to or less than that of current dual view screening mammography. Since it is well known that breast compression affects flow of contrast agents, immobilized but uncompressed breast CmT imaging proposed here also allows for contrast enhanced and other kinetic based studies. Ultimately, we expect this technology to result in improved positive predictive value with earlier cancer detection and reduced morbidity and mortality. In NCI-funded work, all Aims have been accomplished in the Phase I SBIR, and we have confirmed that the next generation scanner will be able to fully image the breast and chest wall of a prone patient with uncompressed breasts without unnecessary and uncomfortable contortions of the patient. Our findings have indicated that a unique combination of complex motion capabilities together with modified system and bed components are required to meet this end. As far as we know, this will represent the first dedicated breast CT system with these capabilities and solves one of the major issues remaining for this technology to be commercially successful, namely the ability to image the full breast and chest wall, in a short period of time, without moving the patient during the scan, and maximizing patient comfort. Therefore, the main goals of this Phase II proposal will be to fabricate a clinic-ready scanner containing all modifications indicated in the Phase I and to perform clinical evaluations of this scanner with a small cohort of patients. These goals will be approached through the following Phase II Specific Aims over a two-year period: Specific Aim 1 is to fabricate a clinic-ready scanner using the results of the Phase I SBIR. Tasks will include: (1) implementation of new larger Varian 4030E detector and end-on Comet X-ray tube; (2) implementation of redesigned patient bed specifically adapted to the new system; and (3) implementation and automation of unique orbits and vertical motion capability of system determined in Phase I to maximize the breast volume scanned. Specific Aim 2 is to upgrade front-end and back-end software systems, including (1) implementation of improved synchronization and software robustness to FDA standards; (2) implementation of improved reconstruction algorithm for faster and more practical reconstructions; (3) implementation of front-end GUI for use by trained technician; (4) automation of back-end process for reconstructions and data presentation; and (5) inclusion of literature based scatter correction. Specific Aim 3 is to perform a limited patient trial with a cohort of 25 locally advanced breast cancer patients for three purposes: (1) evaluation of a developed simple mechanism for uncompressed breast immobilization and biopsy capability; (2) evaluation of modified system on women of varying breast and body sizes to confirm system flexibility and ability to image to chest wall; (3) comparison study of CmT versus digital x-ray mammography where patients will undergo both scans. Criteria for success for each Aim are defined in the more detailed Specific Aims section of the proposal. Therefore, the primary goal of this proposal is to produce a clinic-ready and saleable next generation system suitable for placement in practicing clinics to be used for collection of clinical trial results suitable for FDA submission and subsequent sale of systems for commercial use. These systems will be, to our knowledge, the only dedicated breast CT systems with the complex motion capabilities necessary for comfortable and complete breast, and also capable of chest wall imaging. Overall success of this project will be indicated by a complete system useable by trained technicians in a clinical setting and the indication from initial patient trials that the system measures up to the anticipated advantages that have been indicated by our previous results. Phase III is anticipated to involve production of several commercially viable products for placement in several clinics for larger patient trials. The sampling techniques developed here could also be packaged as products in their own right.

Public Health Relevance:
This R44 proposal seeks Phase II funding to produce a clinic-ready, commercially viable, next generation dedicated 3D breast CT device and conduct initial patient trials to evaluate the ability of the system to image breast cancers as compared with conventional digital mammography. In the USA, breast cancer in women is one of the leading causes of malignancy and the second leading cause of death due to cancer (after lung cancer). The earlier a lesion is detected, the better the chances for survival. Our primary hypothesis has been that a dedicated device for 3-dimensional, uncompressed, whole breast imaging will significantly improve cancer detection, thereby reducing morbidity and mortality. Preliminary results have indicated a significant potential advantage and therefore indicate that 3D breast CT should play a prominent role as an important tool in a clinical setting for mammographers. This project serves to provide a clinic-ready scanner able to comfortably image the entire breast without breast compression along with the chest wall of a prone patient, overcoming a major challenge for dedicated breast imaging, and to provide initial patient results confirming patient benefits and therefore commercial potential. Subsequent Phase III activities will involve production of several systems for placement in multiple clinics and conduction of further clinical trials for FDA approval. Academic research markets will also be approached for sale of additional units.

Thesaurus Terms:
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