Ultrashort Echo Time Magnetic Resonance Imaging of Hemophilic Arthropathy

项目摘要/摘要 血友病是一种x连锁的出血性疾病，其特征是凝血因子VIII或IX缺乏。病人 患有频繁的关节出血，可能导致虚弱的血友病关节病(HA)。两者都有 有症状的和无症状的出血，以及未被注意的微出血，会产生含铁血黄素沉淀物， HA关节退行性变的主要病因。含铁血黄素及其后续的无创性成像 它对软骨和软骨下骨造成的损害对于优化昂贵的预防性治疗很重要 计划和监测疾病进展。而磁共振成像(MRI)是诊断的黄金标准 对于HA的评价，它有很大的局限性，包括不精确，只能半定量地评价 含铁血黄素沉积，以及无法检测到软骨和软骨的早期铁沉积和退变 软骨下骨。超短回波时间(UTE)MRI序列，TES比TES短100倍 临床序列，可以克服这些限制。使用定向UTE序列，快速横向松弛 含铁血黄素和骨软骨连接(OCJ)的信号可以直接检测到，对比度高。 本研究旨在开发一套完整的评估HA的UTE MRI技术，包括1) 通过T1、T2*和敏感性的体积图准确定量含铁血黄素；2)评估 通过监测蛋白多糖和胶原蛋白来评估早期软骨损伤；以及3)OCJ的评估，目的是 将该软件包应用于三组HA患者(轻度、中度、 和严重)，以及年龄匹配的对照组。在目标1中，我们将进一步优化速度、对比度、 用于形态和定量评估的一系列3D UTE MRI技术的分辨率和准确性 滑膜中含铁血黄素的含量，并使用临床试验评估关节软骨的健康和OCJ的变化 3T磁共振扫描仪。在目标2中，我们将评估优化的3DUTE和临床MRI序列以进行评估 全膝关节血友病患者体内组织中含铁血黄素、软骨和OCJ的变化 关节置换术(n=10)和正常身体膝关节移植(n=10)。我们将比较基于UTE的 形态和定量测量(组织磁化率、T1、T2*、脂肪分数、绝热-T1ρ、 磁化转移率、大分子分数)与临床MRI评价含铁血黄素、软骨、 和OCJ，我们将把UTE和临床MRI测量与组织病理学、生化和 生物力学。在目标3中，我们将应用优化的3DUTE和临床mri技术来评估结果。 轻度血友病患者(n=20)、中度血友病患者(n=20)和重度血友病患者(n=20)的预防效果 在两个时间点(基线和12个月)和一组年龄匹配的健康志愿者(n=20)进行一次。 横断面和纵向超声和临床MRI检查将与血友病关节相关 健康评分(HJHS)、Pettersson X线片评分和自我报告结果。我们期待着那次空降 序列对血友病关节的早期变化将比临床MRI更敏感。

PROJECT SUMMARY/ABSTRACT Hemophilia is an x-linked bleeding disorder characterized by deficiencies in clotting factor VIII or IX. Patients suffer from frequent joint bleeding, which may lead to debilitating hemophilic arthropathy (HA). Both symptomatic and silent bleeds, as well as unnoticed microhemorrhages, generate hemosiderin deposits, the primary etiology of joint degeneration in HA. Non-invasive imaging of both hemosiderin and the subsequent damage it causes to cartilage and subchondral bone is important for optimizing costly prophylactic treatment plans and monitoring disease progression. While magnetic resonance imaging (MRI) is the gold standard for evaluation of HA, it has significant limitations including imprecise, only semi-quantitative evaluation of hemosiderin deposition, and an inability to detect both early iron deposition and degeneration in cartilage and subchondral bone. Ultrashort echo time (UTE) MRI sequences, with TEs ~100 times shorter than those of clinical sequences, can overcome these limitations. Using targeted UTE sequences, fast transverse relaxation signals from hemosiderin and the osteochondral junction (OCJ) can be directly detected with high contrast. This study aims to develop a complete package of UTE MRI techniques for evaluation of HA, including 1) accurate quantification of hemosiderin through volumetric mapping of T1, T2*, and susceptibility; 2) assessment of early cartilage damage by monitoring proteoglycan and collagen; and 3) evaluation of the OCJ, and aims to apply this package in cross-sectional and longitudinal studies of three groups of HA patients (mild, moderate, and severe), as well as an age-matched control group. In Aim 1 we will further optimize the speed, contrast, resolution, and accuracy of a series of 3D UTE MRI techniques for morphological and quantitative evaluation of hemosiderin in synovium, and for assessment of articular cartilage health and OCJ changes using a clinical 3T MR scanner. In Aim 2 we will evaluate the optimized 3D UTE and clinical MRI sequences for assessment of hemosiderin, cartilage, and the OCJ in ex vivo tissues from hemophilia patients following total knee arthroplasty (n=10) and from normal cadaveric human knee joints (n=10). We will compare UTE-based morphological and quantitative measures (tissue magnetic susceptibility, T1, T2*, fat fraction, adiabatic-T1ρ, magnetization transfer ratio, macromolecular fraction) with clinical MRI evaluation of hemosiderin, cartilage, and the OCJ, and we will correlate UTE and clinical MRI measures with histopathology, biochemistry, and biomechanics. In Aim 3 we will apply the optimized 3D UTE and clinical MRI techniques to evaluate outcome of prophylaxis in three groups of hemophilia patients with mild (n=20), moderate (n=20), and severe (n=20) HA at two time points (baseline and 12 months), and a group of age-matched healthy volunteers (n=20) once. Cross-sectional and longitudinal UTE and clinical MRI measures will be correlated with Hemophilia Joint Health Scores (HJHSs), Pettersson radiograph scores, and self-reported outcomes. We expect that UTE sequences will be more sensitive to early changes in hemophiliac joints than clinical MRI.