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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要血友病是一种 X 连锁出血性疾病，其特征是患者缺乏凝血因子 VIII 或 IX。经常关节出血，可能导致衰弱性血友病关节病 (HA)。有症状和无症状的出血，以及未被注意到的微出血，会产生含铁血黄素沉积， HA 关节退变的主要病因含铁血黄素及其后续的非侵入性成像。它对软骨和软骨下骨造成的损伤对于优化昂贵的预防性治疗非常重要计划和监测疾病进展，而磁共振成像 (MRI) 是黄金标准。 HA 的评估，它有很大的局限性，包括不精确，只能半定量评估含铁血黄素沉积，并且无法检测软骨和软骨中的早期铁沉积和变性软骨下骨。超短回波时间 (UTE) MRI 序列，TE 比软骨下骨短约 100 倍。临床序列，可以克服这些限制，使用靶向UTE序列，快速横向松弛。可以以高对比度直接检测来自含铁血黄素和骨软骨连接处 (OCJ) 的信号。本研究旨在开发一整套用于评估 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；3) 评估 OCJ，旨在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、用于形态学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，并使用临床评估关节软骨健康和 OCJ 变化在目标 2 中，我们将评估优化的 3D UTE 和临床 MRI 序列以进行评估。全膝关节置换术后血友病患者离体组织中含铁血黄素、软骨和 OCJ 的变化我们将比较基于 UTE 的关节成形术 (n=10) 和正常尸体膝关节 (n=10)。形态学和定量测量（组织磁化率、T1、T2*、脂肪分数、绝热-T1ρ、磁化转移率、大分子分数）以及含铁血黄素、软骨、和 OCJ，我们会将 UTE 和临床 MRI 测量与组织病理学、生物化学和在目标 3 中，我们将应用优化的 3D UTE 和临床 MRI 技术来评估结果。三组轻度 (n=20)、中度 (n=20) 和重度 (n=20) HA 血友病患者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 UTE 以及临床 MRI 测量将与血友病关节相关我们期望健康评分 (HJHS)、Pettersson X 光片评分和自我报告结果。序列对血友病关节的早期变化比临床 MRI 更敏感。