Ultrashort Echo Time Magnetic Resonance Imaging of Hemophilic Arthropathy

血友病关节病的超短回波时间磁共振成像

• 批准号: 10385820
• 负责人: Hyungseok Jang
• 金额: $ 53.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-06 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10385820
• 关键词: 3-Dimensional; Achievement; Age; Area; Biochemistry; Biological Markers; Biomechanics; Blood Coagulation Disorders; Blood Coagulation Factor; Cadaver; Cartilage; Clinical; Collagen; Control Groups; Cross-Sectional Studies; Cyst; Data; Deposition; Deterioration; Diagnosis; Disease Management; Disease Progression; Etiology; Evaluation; Factor IX; Factor VIII; Fatty acid glycerol esters; Goals; Gold; Health; Hemophilia A; Hemophilic Arthritis; Hemorrhage; Hemosiderin; Histopathology; Human; Image; Image Analysis; Imaging Techniques; Iron; Joints; Knee joint; Lead; Lesion; Ligaments; Link; Longitudinal Studies; Magic; Magnetic Resonance Imaging; Magnetism; Maps; Measures; Meniscus structure of joint; Modeling; Monitor; Morphology; Normal tissue morphology; Outcome; Patient Self-Report; Patients; Predisposition; Prophylactic treatment; Proteoglycan; Quantitative Evaluations; Recovery; Recurrence; Relaxation; Resolution; Sampling; Scanning; Series; Signal Transduction; Speed; Synovial Membrane; Synovitis; Techniques; Tendon structure; Time; Tissues; Treatment Cost; age group; articular cartilage; base; contrast imaging; cost; density; healthy volunteer; in vivo; joint destruction; knee replacement arthroplasty; non-invasive imaging; osteochondral tissue; precision medicine; prevent; prophylactic; subchondral bone; treatment planning; ultrasound; validation studies

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.

项目摘要/摘要 血友病是一种X连锁的出血障碍，其特征是闭合因子VIII或IX中的缺陷。患者 经常出血，可能导致衰弱的血友人关节病（HA）。两个都 有症状的和无声的出血，以及未忽视的微毛发，会产生头皮蛋白沉积物， HA中关节变性的主要病因。脱皮成像和随后的侵入性成像 它会导致软骨和软骨下骨造成的损害对于优化昂贵的预防治疗很重要 计划和监测疾病进展。而磁共振成像（MRI）是金标准 评估HA，它具有重大局限性，包括暗示，仅半定量评估 黄昏蛋白沉积，无法检测软骨的早期铁沉积和变性 软骨下骨。 Ultrashort回声时间（UTE）MRI序列，TES比 临床序列可以克服这些局限性。使用靶向的UTE序列，快速横向松弛 可以用高对比度直接检测到头鼻蛋白和骨软骨结（OCJ）的信号。 这项研究旨在开发完整的UTE MRI技术，以评估HA，包括1） 通过T1，T2*和易感性的体积映射准确地定量缓压蛋白； 2）评估 通过监测蛋白聚糖和胶原蛋白的早期软骨损伤； 3）OCJ的评估，目的是 将此包装应用于三组HA患者的横断面和纵向研究（轻度，中度， 和严重的）以及年龄匹配的对照组。在AIM 1中，我们将进一步优化速度，对比度， 一系列3D UTE MRI技术的分辨率和准确性，用于形态和定量评估 临床上的临床，临床上的炎症性蛋白质和关节软骨健康和OCJ变化的评估 3T先生Scanner。在AIM 2中，我们将评估优化的3D UTE和临床MRI序列进行评估 总膝盖后，血友病患者的体内组织中的血压，软骨和OCJ 关节置换术（n = 10）和正常的尸体人膝关节（n = 10）。我们将比较基于UTE的 形态和定量测量（组织磁化易感性，T1，T2*，脂肪分数，绝热T1ρ， 磁化转移率，大分子分数），临床MRI评估，软骨，软骨，软骨的临床MRI评估 OCJ，我们将将UTE和临床MRI测量与组织病理学，生物化学和 生物力学。在AIM 3中，我们将应用优化的3D UTE和临床MRI技术来评估结果 三组血友病患者（n = 20），中度（n = 20）和严重（n = 20）ha 在两个时间点（基线和12个月），一组年龄匹配的健康志愿者（n = 20）。 横截面和纵向UTE以及临床MRI测量将与血友病关节相关 健康分数（HJHSS），Pettersson X光片分数和自我报告的结果。我们希望那个 序列比临床MRI对血友病关节的早期变化更敏感。