PROJECT SUMMARY/ABSTRACT According to Council for Disability Awareness, diseases of the musculoskeletal system and connective tissue, such as the ligaments, tendons and bone are the #1 cause of disability in the United States. MR imaging has been increasingly becoming the diagnostic tool of choice for evaluation and management of these diseases and injuries due to its potential of providing information on not only anatomic structure but also function noninvasively. However, the capability of MRI in studying human ligaments, tendons and bone is limited by inadequate sensitivity and slow acquisitions of conventional MR technology. Semi-solid/solid tissues, including collagen-rich tissues such as calcified ligaments and tendons, as well as periosteum, cortical bone and trabecular bone, provide very little MR signal with traditional MRI due to their very short transverse (T2) relaxation time of a few milliseconds or less. In addition, during the long acquisition times, involuntary movements of human subjects introduce motion artifacts, posing a critical challenge in obtaining high- resolution images with diagnostic value. Several recently developed technologies have the potential to address these limitations. Ultrahigh field 7T MRI, parallel imaging, and compressed sensing have demonstrated unique advantages of high sensitivity and fast acquisitions in vivo. Studies on musculoskeletal imaging using ultra- short echo time (UTE) and zero echo time (ZTE) methods have shown unparalleled capability to image short T2 species normally invisible in MRI. However, the implementation of these technologies at ultrahigh fields is challenging due to design difficulties of the required high frequency multichannel coil arrays, as well as the problems associated with ultrahigh fields, e.g. increased susceptibility, B1 inhomogeneity, and increased SAR. In this study, through a synergistic bioengineering research partnership, we propose a comprehensive project for developing advanced hardware and imaging methods at 7T to enable morphological and functional characterization of human ligaments, tendons and bone. These developments aim to produce highly sensitive, isotropic ~100-150um resolution images of semi-solid connective tissues with clinically relevant contrast in 1 minute scan time. Hardware developments will include multichannel coil arrays for knee and extremities using quadrature and flexible array technology with metamaterial decoupling, as well as application of pyrolytic graphite materials for reducing susceptibility artifacts. Imaging acquisition developments will be based on improved UTE/ZTE sequences, and we propose new integrated techniques for improved semi-solid tissue contrast, motion correction, and acceleration using parallel imaging and compressed sensing. We will also validate the methods developed and assess the performance and safety/SAR. This research would provide sensitive imaging tools for morphological and functional characterization of ligaments, tendons and bone, which are highly demanded and essential for studying semi-solid connective tissues. We expect this research will have a long-term clinical impact in the management of musculoskeletal system diseases and injuries.

Relevance to Public Health: The successful outcome of the proposed project will provide a whole new imaging technique with highly efficient acquisition technique and RF hardware dedicated to human ligament, tendon and bone MR imaging. With this package of novel hardware and software, people can visualize the invisible structures in regular MR technology. This would advance and benefit the biomedical research and clinical diagnosis on musculoskeletal diseases, joint/cartilage disorders, connective tissue diseases and injuries, rheumatism, osteoporosis, and complications associated with diabetes in lower and upper extremities.