Early Detection and Monitoring of Osteonecrosis of the Femoral Head

项目摘要：股骨头坏死[ONFH]是一种影响儿童的严重髋关节疾病 以及可能导致股骨头塌陷、骨关节炎和需要髋关节的年轻人 在很小的时候就被替换了。青壮年早期股骨头坏死的临床处理 防止股骨头塌陷，在这一点上，挽救髋关节几乎无能为力。然而，其中一个 早期ONFH的主要髋关节保留治疗，核心减压术(涉及钻探 进入股骨头)，在30%或更多的患者中未能阻止疾病的进展。此故障可能是 部分原因是诊断延迟，预测和监测治疗反应的能力有限 目前的临床成像方法(X线片和常规的T1和T2加权磁共振 成像[核磁共振成像])。我们的长期目标是改善患有或有高血压风险的儿童和成人的临床结果。 ONFH通过成像和治疗的协同进步。本R01提案的目标是 通过表征敏感性，满足对更好的成像的需求，以便为早期ONFH的治疗提供信息 先进的核磁共振技术来评估骨缺血、坏死和修复。我们的中心假设是 定量MRI方法对早期股骨头坏死的诊断具有较高的敏感性，可为临床提供定量指标。 股骨头缺血性损伤的程度和随后的修复。我们将在承诺的基础上再接再厉 使用缺血ONFH的仔猪模型进行研究，该模型已经证明了定量的、非对比的- 增强的磁共振成像技术，包括松弛时间图、扩散成像和灌注成像， 对检测股骨头缺血性损伤敏感可靠。在目标1中，我们将扩展我们的小猪 模型研究确定驱动定量MRI方法对缺血敏感性的细胞变化 损伤和钻探导致的股骨头修复。动物将在3T磁共振下进行活体成像，股骨 随后将对头部进行组织学评估。在目标2和目标3中，我们将采取初步步骤在临床上 通过开展试验性研究来检测早期损伤和监测，从而转化定量MRI方法 股骨头坏死患者对核心减压治疗的反应。在目标2中，我们将评估 定量MRI方法可以在不使用Gd造影剂的情况下检测股骨头缺血 青少年特发性ONFH(也称为Legg-Calvé-Perths病)儿童的初步研究。在目标3中，我们 将评估定量MRI方法是否能检测出髓核减压后的修复反应 成人早期ONFH治疗的一项先导性研究，以及这些患者的反应是否不同 治疗未能防止股骨头塌陷的患者与治疗成功的患者相比 防止疾病的发展。总的来说，这些目标是朝着改善长期目标迈出的关键一步。 早期ONFH的年轻患者通过先进的成像技术获得新的预后 治疗干预的机会和新治疗方法的疗效评估。

PROJECT SUMMARY: Osteonecrosis of the femoral head [ONFH] is a crippling hip disorder affecting children and young adults that can lead to collapse of the femoral head, osteoarthritis, and the need for a hip replacement at a young age. Clinical management of young patients with early-stage ONFH focuses on preventing femoral head collapse, at which point little can be done to salvage the hip joint. However, one of the primary hip preservation treatments for early-stage ONFH, core decompression surgery (which involves drilling into the femoral head), fails to prevent disease progression in 30% or more of patients. This failure can be attributed in part to delayed diagnosis and limited ability to predict and monitor treatment response using current clinical imaging methods (radiography and conventional T1- and T2-weighted magnetic resonance imaging [MRI]). Our long-term goal is to improve clinical outcomes for children and adults with or at risk for ONFH through the synergistic advancement of imaging and therapies. The objective of this R01 proposal is to address the need for better imaging to inform treatment of early-stage ONFH by characterizing the sensitivity of advanced MRI techniques to assess bone ischemia, necrosis, and repair. Our central hypothesis is that quantitative MRI methods are sensitive in detecting early-stage ONFH and provide quantitative measures of the degree of ischemic injury and subsequent repair to the femoral head. We will build upon our promising work using a piglet model of ischemic ONFH, which has demonstrated that quantitative, non-contrast- enhanced MRI techniques, including relaxation time mapping, diffusion imaging, and perfusion imaging, are sensitive and reliable in detecting ischemic injury to the femoral head. In Aim 1, we will expand upon our piglet model studies to identify the cellular changes driving the sensitivity of the quantitative MRI methods to ischemic injury and drilling-induced repair of the femoral head. Animals will be imaged in vivo at 3T MRI, and the femoral heads will subsequently be assessed histologically. In Aims 2 and 3, we will take initial steps to clinically translate the quantitative MRI methods by conducting pilot studies to detect early-stage injury and monitor response to core decompression treatment in patients with ONFH. In Aim 2, we will evaluate whether the quantitative MRI methods can detect femoral head ischemia without use of a gadolinium contrast agent in a pilot study of children with juvenile idiopathic ONFH (also known as Legg-Calvé-Perthes disease). In Aim 3, we will evaluate whether the quantitative MRI methods can detect a reparative response to core decompression in a pilot study of adults being treated for early-stage ONFH, and whether the response differs in those patients whose treatment fails to prevent femoral head collapse versus those whose treatment is successful in preventing disease progression. Collectively, these aims are a critical step toward improving long-term outcomes for young patients with early-stage ONFH through advancement of imaging to allow for new opportunities for therapeutic intervention and the evaluation of the efficacy of new treatments.