Early Detection and Monitoring of Osteonecrosis of the Femoral Head

项目概述：股骨头坏死[ONFH]是一种影响儿童的致残性髋关节疾病 和年轻的成年人，可导致股骨头塌陷，骨关节炎，并需要髋关节 年轻时的替补。年轻早期股骨头坏死患者的临床管理重点是 防止股骨头塌陷，此时几乎无法挽救髋关节。不过其中一 早期ONFH的主要髋关节保留治疗，髓芯减压手术（包括钻孔 进入股骨头），未能阻止30%或更多患者的疾病进展。这种失败可能是 部分原因是诊断延迟，以及预测和监测治疗反应的能力有限， 目前的临床成像方法（放射摄影和常规T1和T2加权磁共振 成像[MRI]）。我们的长期目标是改善患有或有风险的儿童和成人的临床结果。 通过影像学和治疗的协同进步治疗ONFH本R 01提案的目的是 通过表征敏感性，满足更好的成像需求，为早期ONFH的治疗提供信息 先进的MRI技术来评估骨缺血、坏死和修复。我们的核心假设是， 定量MRI方法在检测早期ONFH中是敏感的，并提供了定量测量， 缺血性损伤的程度和随后对股骨头的修复。我们将继续努力， 使用缺血性ONFH的小猪模型进行工作，该模型已经证明定量的，非造影剂- 增强MRI技术，包括弛豫时间成像、扩散成像和灌注成像， 对股骨头缺血性损伤的诊断敏感、可靠。在目标1中，我们将扩展我们的小猪 模型研究，以确定驱动定量MRI方法对缺血性疾病敏感性的细胞变化， 损伤和钻孔诱导的股骨头修复。将在3 T MRI下对动物进行体内成像， 随后将对头部进行组织学评估。在目标2和3中，我们将采取初步措施， 通过进行试点研究来翻译定量MRI方法，以检测早期损伤并监测 股骨头坏死患者对髓芯减压治疗的反应。在目标2中，我们将评估 定量MRI方法可以在不使用钆造影剂的情况下检测股骨头缺血， 对患有幼年特发性ONFH（也称为Legg-Calvé-Perthes病）的儿童进行的初步研究。在目标3中， 将评估定量MRI方法是否能检测到髓核减压的修复反应， 一项针对接受早期ONFH治疗的成人的初步研究，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， 预防疾病进展。总的来说，这些目标是改善长期 通过影像学的进步，为年轻的早期ONFH患者提供新的治疗方法， 治疗干预的机会和新治疗的疗效评估。

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.