Early Detection and Monitoring of Osteonecrosis of the Femoral Head

股骨头坏死的早期发现和监测

基本信息

批准号：
10562069
负责人：
Casey Peter Johnson
金额：
$ 22.29万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10562069
关键词：
Address Adolescent Adult Affect Age Animal Model Animals Apoptosis Automobile Driving Bone necrosis Cell Death Child Clinical Clinical Management Clinical Treatment Contralateral Contrast Media Degenerative polyarthritis Detection Diagnosis Diffusion Disease Disease Progression Early Diagnosis Early treatment Evaluation Failure Family suidae Fibrosis Gadolinium Goals Hip Joint Hip Osteoarthritis Hip region structure Histologic Image Imaging Techniques Implant Injury Intervention Ischemia Joints Legg-Perthes Disease Magnetic Resonance Imaging Maps Marrow Measures Medical Imaging Methods Monitor Motion Necrosis Operative Surgical Procedures Osteogenesis Outcome Patient-Focused Outcomes Patients Perfusion Pilot Projects Regional Perfusion Relaxation Replacement Arthroplasty Research Risk Second Look Surgery Severities Specimen Study models Surgical Decompression Techniques Therapeutic Intervention Time Total Hip Replacement Translating Vascular blood supply Work bone chronic pain clinical imaging disability disease diagnosis efficacy evaluation experimental study femur head hip replacement arthroplasty imaging modality improved improved outcome in vivo in vivo imaging injury and repair ischemic injury novel therapeutics pediatric patients perfusion imaging porcine model predict clinical outcome preservation prevent radiological imaging repaired response treatment response young adult

项目摘要

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.

项目摘要：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人，可能导致股骨头塌陷、骨关节炎以及需要髋关节早期 ONFH 年轻患者的临床管理重点是年轻时的更换。防止股骨头塌陷，此时几乎无法挽救髋关节。早期 ONFH 的主要髋关节保留治疗、核心减压手术（涉及钻孔）进入股骨头），但未能阻止 30% 或更多患者的疾病进展。部分归因于诊断延迟以及使用药物来预测和监测治疗反应的能力有限当前的临床成像方法（放射线照相术和传统的 T1 和 T2 加权磁共振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。 ONFH 通过影像学和治疗的协同进步该 R01 提案的目标是：通过表征敏感性来满足更好的成像技术的需求，为早期 ONFH 的治疗提供信息我们的中心假设是利用先进的 MRI 技术来评估骨缺血、坏死和修复。 MRI 方法对于检测早期 ONFH 非常敏感，并提供以下指标的定量测量：我们将基于我们的承诺来确定缺血性损伤的程度以及随后对股骨头的修复。使用缺血性 ONFH 的仔猪模型进行工作，该模型证明了定量的、非对比的增强 MRI 技术，包括弛豫时间映射、扩散成像和灌注成像，在检测股骨头缺血性损伤方面灵敏且可靠在目标 1 中，我们将扩展我们的仔猪。模型研究，以确定驱动定量 MRI 方法对缺血的敏感性的细胞变化损伤和钻孔引起的股骨头修复将通过 3T MRI 和股骨头进行体内成像。随后将对头部进行组织学评估在目标 2 和 3 中，我们将采取初步临床步骤。通过进行初步研究来检测早期损伤并监测，从而转化定量 MRI 方法在目标 2 中，我们将评估 ONFH 患者对核心减压治疗的反应。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。在目标 3 中，我们对患有青少年特发性 ONFH（也称为 Legg-Calvé-Perthes 病）的儿童进行了初步研究。将评估定量 MRI 方法是否可以检测对核心减压的修复反应对接受早期 ONFH 治疗的成年人进行的一项试点研究，以及这些患者的反应是否不同治疗未能预防股骨头塌陷的患者与治疗成功预防股骨头塌陷的患者总的来说，这些目标是改善长期状况的关键一步。通过影像学的进步，为患有早期 ONFH 的年轻患者提供新的结果治疗干预和评估新疗法疗效的机会。