Understanding Skeletal Growth Using Diffusion Tensor Imaging of the Physis and Metaphysis

PROJECT SUMMARY Serial assessment of the main organ of longitudinal skeletal growth, the growth plate or physis, with a novel MR technique, diffusion tensor imaging of the physis and metaphysis (DTI-P/M), can improve clinical decision making for conditions that lead to short stature in children. Treatment of short stature using growth hormone (GH) therapy leads to healthcare costs that can rise to $11 billion per year. Assessing response to GH requires determination of height velocity, which currently relies on insensitive external measurements of length or stature and requires height measurements at least 1 year apart. Predicting growth potential, crucial to identifying who will benefit from growth-enhancing treatment, is currently estimated by assessing physeal changes on the hand that only indirectly reflect those of the knee, where most skeletal growth occurs. This proposal addresses an unmet clinical need for a better tool to determine height velocity and predict growth potential. We have pioneered DTI-P/M of the knee, a technique that generates tracts based on anisotropic diffusion of water through the physeal and metaphyseal columns, to measure tract volume, tract length, and fractional anisotropy (FA), a marker of tissue organization. Our proposal overcomes current gaps in knowledge regarding DTI-P/M measurements over time and in response to GH. Our specific aims will test the central hypothesis that DTI-P/M of the distal femur can be established as a diagnostic and predictive tool for height velocity, growth potential and GH response: Aim 1) Predict height velocity using DTI-P/M parameters during the adolescent growth spurt in 60 children; Aim 2) Predict growth potential during cessation of adolescent growth in 40 children; and Aim 3) Assess response to GH therapy based on early changes in DTI-P/M parameters by analyzing tract volume and length and FA in 50 children prior to initiation of GH therapy and at 4, 8, and 12 month clinical follow-ups. Achieving these aims will validate DTI-P/M as a tool for precision therapy with growth enhancing medications and improved timing of orthopedic procedures.