Early Detection and Monitoring of Osteonecrosis of the Femoral Head

股骨头坏死的早期发现和监测

• 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
• 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

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：股骨头的骨分子[ONFH]是一种影响儿童的髋关节疾病 和可能导致股骨头，骨关节炎的年轻人以及需要臀部 在年轻时更换。早期阶段的年轻患者的临床管理专注于 防止股骨头塌陷，此时几乎无法做到以挽救髋关节。但是，其中之一 初级髋关节保存治疗早期的核心减压手术（涉及钻孔） 进入股骨头），无法预防30％或更多患者的疾病进展。这种失败可能是 部分归因于延迟诊断和使用有限的预测和监测治疗反应的能力 当前的临床成像方法（射线照相和常规T1-和T2加权磁共振 成像[MRI]）。我们的长期目标是改善具有或有风险的儿童和成人的临床结果 通过成像和疗法的协同进步。该R01提案的目的是 通过表征敏感性来满足更好成像的需求，以告知早期ONFH的处理 评估骨缺血，坏死和修复的高级MRI技术。我们的中心假设是 定量MRI方法对检测早期ONFH很敏感，并提供了定量测量 缺血性损伤程度和随后对股骨头的修复程度。我们将基于我们的诺言 使用缺血性的小猪模型的工作，该模型证明了定量的，无对比的 增强的MRI技术，包括放松时间映射，扩散成像和灌注成像，是 敏感且可靠地检测股骨头的缺血性损伤。在AIM 1中，我们将扩大仔猪 模型研究以确定驱动定量MRI方法敏感性的细胞变化 损伤和钻孔引起的股骨头修复。动物将在3T MRI的体内成像，股动物 头部将随后通过组织学评估。在目标2和3中，我们将采取初步步骤临床 通过进行试验研究来检测早期损伤并进行监测来翻译定量MRI方法 对ONFH患者的核心减压治疗的反应。在AIM 2中，我们将评估是否 定量MRI方法可以检测股骨头缺血，而无需在A中使用Gadolinium对比剂 少年特发性儿童的试点研究（也称为legg-calvé-perthes疾病）。在AIM 3中，我们 将评估定量MRI方法是否可以检测到对核心解压缩的重新反应 一项针对早期阶段的成年人的试点研究，以及这些患者的反应差异是否差异 其治疗无法防止股骨头崩溃 预防疾病进展。总的来说，这些目标是改善长期的关键一步 通过进步成像的年轻患者的成果，以允许新 治疗干预的机会和新疗法效率的评估。