Early Diagnosis of Growth Disorders Uing MR Imaging

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DESCRIPTION (provided by applicant): The goal of this research is the detection of epiphyseal ischemia and prediction of its growth sequelae using novel non-invasive magnetic resonance (MR) approaches. In animal models, we propose to determine the earliest changes in ischemia, to differentiate early from late ischemia leading to avascular necrosis; and to predict the deverlopment of growth arrest. In addition to conventional MR measures (proton density and T2 relaxation), we will investigate perfusion-related changes by early gadolinum (Gd) enhanced imaging; and diffusion related changes by line diffusion scanning and diffusion tensor imaging. We will also evaluate disturbances of the cartilaginous matrix including glycosaminoglycan depletion revealed by delayed GD enhanced imaging, and collagen content by magnetization transfer imaging. The major hypotheses are that MR parameters can 1) detect early ischemia, 2) differentiate early from late ischemia leading to sequelae, and 3) predict growth deformity through MR parameters that reflect tissue structure and vascularization of the immature epiphysis. Epiphyseal ischemia is a pathogenic pathway shared by many common pediatric disorders. Ischemia leading to avascular necrosis of the femoral head frequently causes hip deformity and disability in childhood. A hip that grows abnormally also predisposes to degenerative joint disease in adult; more than half of all adults with osteoarthritis of the hip suffered hip diseases as children. Imaging of cartilaginous disorders serves to guide early therapy, prevent or minimize deformity, and detect children predisposed to premature cartilage degeneration in adulthood. The specific aims are to: 1) determine the MR tissue characteristics of normal epiphyseal cartilage. Specifically, we wish to test whether the greater cellularity and vascularization of immature epiphyseal cartilage result in different MR tissue characteristics; 2) in early ischemia, determine temporal and spatial differences between diffusion imaging, T2 maps and Gd-enhanced imaging; 3) in prolonged ischemia, determine which MR parameters best predict irreversible damage; and 4) in a model of avascular necrosis, determine which MR parameters predict abnormal growth.