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

项目摘要 用一种新的方法对纵向骨骼生长的主要器官，生长板或生长骨骺板进行系列评估， 磁共振技术，生长骨骺和干骺端扩散张量成像（DTI-P/M），可以提高临床决策 导致儿童身材矮小的条件。使用生长激素治疗身材矮小 (GH)治疗导致每年的医疗保健费用可能上升到110亿美元。评估对GH的反应需要 确定高度速度，目前依赖于对长度或高度的不敏感的外部测量。 身高和需要身高测量至少1年间隔。预测增长潜力，对 确定谁将受益于生长促进治疗，目前估计通过评估骨骺 手部的变化只能间接反映膝盖的变化，而膝盖是骨骼生长最多的地方。这 一项提案提出了一项尚未满足的临床需求，即需要一种更好的工具来确定身高增长速度和预测生长 潜力我们开创了膝关节的DTI-P/M，这是一种基于各向异性 水通过骨骺和干骺端柱的扩散，以测量管道体积、管道长度和 分数各向异性（FA），组织组织结构的标志。我们的建议克服了目前的知识差距 关于DTI-P/M测量随时间的变化和对GH的响应。我们的具体目标将考验中央 股骨远端DTI-P/M可作为身高诊断和预测工具的假设 速度、生长潜力和GH反应：目标1）使用DTI-P/M参数预测生长期间的高度速度 60例青春期生长突增期儿童，目的2）预测青春期终止期的生长潜力 目的3）根据DTI-P/M的早期变化评估对GH治疗的反应 通过分析50名儿童在开始GH治疗前和开始GH治疗后 4、8和12个月临床随访。实现这些目标将验证DTI-P/M作为精确度工具的有效性 用促进生长的药物治疗和改善矫形手术的时机。

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.