The overall goal of this proposal is to develop new and safe imaging methods that use red and infrared light to monitor and image the re-growth of blood vessels in healing bones. These methods are based on diffuse optical tomography (DOT) and diffuse correlation tomography (DCT) as scientific research tools to provide non-invasive, deep-tissue longitudinal monitoring of vascularization of engineered tissues. Tissue engineering is a strategy for using artificial or combinations of natural and artificial materials to assist re-growth of damaged tissues, such as broken bones. The optical methods being developed in this project are based on shining a source of light into the tissue of interest (bone in this case), through the skin, and then analyzing light that is reflected back by the tissues. Techniques that non-invasively monitor and longitudinally assess the vascularization process could significantly accelerate the tissue-engineering field, which will lead to new methods for healing damaged tissues.
Towards this goal, a comprehensive DOT and DCT system will be optimized for monitoring the vascularization of bone grafts. The utility of this approach will be established using well-established murine femoral defect models and bone tissue-engineering strategies. Although there have been various applications of diffuse optical tomographic techniques, their utility in bone-vascularization monitoring, especially in engineered tissue, has never been explored. The proposed research objectives are: (1) Expand an existing optical system into a 3D imaging DOT-DCT system and develop a comprehensive tomography algorithm for longitudinal imaging of murine leg; (2) Compare total hemoglobin concentration from DOT and blood flow from DCT to contrast-enhanced micro-CT and histology and a fluorescent microsphere technique, respectively, using live murine autograft models; (3) Characterize the longitudinal vascular changes due to autografts, devitalized allografts, and allografts with tissue-engineered periosteum using the DOT-DCT system and develop a predictive model for graft healing. Educationally, the proposed research will provide stimulating research topics for graduate and undergraduate students, with opportunities to interact with national and international collaborators in various interdisciplinary fields. The project will also involve educational outreach to underrepresented high school student groups at the University of Rochester.
