Quantitative UTE MR Imaging: Sensitive Biomarkers for Osteoarthritis

定量 UTE MR 成像：骨关节炎的敏感生物标志物

• 批准号: 10361531
• 负责人: Jiang Du
• 金额: $ 44.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10361531
• 关键词: 3-Dimensional; Acceleration; Award; Biochemistry; Biological Markers; Biomechanics; Cadaver; Cartilage; Clinical; Collagen; Degenerative polyarthritis; Dependence; Development; Diagnosis; Disease; Disease Progression; Early Diagnosis; Evaluation; Fiber; Goals; Histopathology; Human; Image; Image Analysis; In Vitro; Joints; Knee; Knee joint; Ligaments; Magic; Magnetic Resonance Imaging; Measurement; Measures; Meniscus structure of joint; Methods; Modeling; Monitor; Morphology; Organ; Patients; Physiologic pulse; Polarization Microscopy; Preparation; Proteoglycan; Protons; Quantitative Evaluations; Research; Sampling; Sensitivity and Specificity; Signal Transduction; Specimen; Techniques; Tendon structure; Time; Tissues; Trypsin; Water; anterior cruciate ligament reconstruction; bone; collagenase; healthy volunteer; in vivo; joint destruction; macromolecule; novel; reconstruction; volunteer

7. Abstract Magnetic resonance imaging (MRI) is widely used for the diagnosis of advanced osteoarthritis (OA), but is less sensitive for the diagnosis of early OA. There are three major barriers to progress in evaluation of early OA. First, OA is a “whole organ disease” involving all the principal knee joint tissues. However, many tissues or tissue components such as the deep layers of cartilage, menisci, ligaments, tendons and bone have short T2s and show little or no signal with conventional clinical sequences. Second, distinct proton groups, namely water protons and macromolecular protons are present in most joint tissues. Macromolecular protons in many the knee joint tissues, especially the short T2 tissues have not been investigated with clinical sequences. Third, extensive research over the past two decades has focused on two particular biomarkers for OA: T2 and T1, with T2 sensitive to collagen degradation, and T1 sensitive to proteoglycan (PG) depletion. The main confounding factor is the magic angle effect, which may result in a several fold increase in T2 and T1 when the tissue fibers are oriented ~54 to the B0 field. This often far exceeds the change produced by disease. We have developed 3D ultrashort echo time (UTE) sequences with TEs as short as 8 µs that are 100-1000 times shorter than the TEs of clinical sequences. These allow us to directly image “MR invisible” joint tissues. Recently adiabatic spin-lock imaging has been proposed to measure T1. Magnetization transfer (MT) imaging has been introduced to assess macromolecular protons. Most importantly, the adiabatic T1 and MT biomarkers are magic angle insensitive. In this proposal, we will further develop a 3D adiabatic-UTE-T1 sequence for magic angle insensitive T1 measurement, and a UTE-MT sequence for magic angle insensitive biomarkers of MT ratio (MTR) and MT modeling of macromolecular fractions and exchange rates. We will further evaluate the 3D adiabatic-UTE-T1 and UTE-MT techniques for evaluation of macromolecules and water components in both short and long T2 tissues in normal knee joint specimens (Aim 1). We expect that the UTE-adiabatic-T1 biomarker will be sensitive to PG depletion, while the UTE MTR and MT modeling parameters will be sensitive to PG and collagen changes in the knee joint tissues. Then we will compare the novel 3D UTE and clinical sequences for quantitative evaluation of cadaveric human knee specimens with normal (n=20), mild (n=20) and moderate (n=20) OA (Aim 2). We expect that the UTE-adiabatic-T1 and UTE-MT sequences will be more sensitive to degeneration in the principal knee joint tissues than conventional clinical sequences. Finally, we will apply 3D UTE-adiabatic-T1 and UTE-MT techniques to evaluate knee joint degeneration in healthy volunteers (n=20) and patients (n=20) 6 months, 1 year, and 2 years after anterior cruciate ligament (ACL) reconstruction. We will correlate the MR measures with clinical scores (Aim 3). We expect the UTE measures will be more sensitive than clinical MRI measures to changes in the knee of patients after ACL reconstruction. The study is likely to have a major impact on making early OA diagnosis and monitoring disease progression.

7. 摘要 磁共振成像 (MRI) 广泛用于诊断晚期骨关节炎 (OA)，但 less sensitive for the diagnosis of early OA.早期评估进展存在三大障碍 办公自动化。首先，OA是一种涉及所有主要膝关节组织的“全器官疾病”。然而，许多组织 或组织成分如软骨、半月板、韧带、肌腱和骨骼的深层有短 T2s 和常规临床序列显示很少或没有信号。 Second, distinct proton groups, namely 大多数关节组织中都存在水质子和大分子质子。 Macromolecular protons in many 膝关节组织，特别是短T2组织尚未进行临床序列研究。 第三，过去二十年的广泛研究集中在 OA 的两个特定生物标志物上：T2 和 T1，T2 对胶原蛋白降解敏感，T1 对蛋白多糖 (PG) 消耗敏感。主要 混杂因素是魔角效应，当 组织纤维朝向 B0 场 ~54°。这往往远远超过疾病所产生的变化。 我们开发了 3D 超短回波时间 (UTE) 序列，TE 短至 8 µs，为 100-1000 比临床序列的 TE 短几倍。这些使我们能够直接对“MR 隐形”关节组织进行成像。 最近提出了绝热自旋锁成像来测量 T1。 Magnetization transfer (MT) imaging 已被引入评估大分子质子。最重要的是，绝热 T1 和 MT 生物标志物 are magic angle insensitive.在本提案中，我们将进一步开发 3D 绝热-UTE-T1 序列 魔角不敏感 T1 测量，以及用于魔角不敏感生物标志物的 UTE-MT 序列 MT 比率 (MTR) 以及大分子分数和汇率的 MT 建模。 We will further evaluate the 用于评估大分子和水成分的 3D 绝热-UTE-T1 和 UTE-MT 技术 正常膝关节标本中的短 T2 组织和长 T2 组织（目标 1）。 We expect that the UTE-adiabatic-T1 生物标志物将对 PG 消耗敏感，而 UTE MTR 和 MT 建模参数将对 PG 消耗敏感 膝关节组织中 PG 和胶原蛋白的变化。然后我们将比较新型 3D UTE 和临床 用于定量评估正常 (n=20)、轻度 (n=20) 人体膝关节标本的序列 and moderate (n=20) OA (Aim 2).我们预计 UTE-adiabatic-T1 和 UTE-MT 序列将更加 与传统的临床序列相比，对主要膝关节组织的退变敏感。最后，我们 将应用3D UTE-adiabatic-T1和UTE-MT技术来评估健康人的膝关节退变 前十字韧带 (ACL) 术后 6 个月、1 年和 2 年的志愿者 (n=20) 和患者 (n=20) 重建。我们将 MR 测量值与临床评分相关联（目标 3）。 We expect the UTE measures 对 ACL 重建后患者膝关节的变化比临床 MRI 测量更敏感。 这项研究可能会对早期 OA 诊断和监测疾病进展产生重大影响。

项目成果

Magnetic resonance imaging assessed cortical porosity is highly correlated with μCT porosity.

• DOI: 10.1016/j.bone.2014.06.004
• 发表时间: 2014-09
• 期刊: BONE
• 影响因子: 4.1
• 作者: Bae, Won C.;Patil, Shantanu;Biswas, Reni;Li, Shihong;Chang, Eric Y.;Statum, Sheronda;D'Lima, Darryl D.;Chung, Christine B.;Du, Jiang
• 通讯作者: Du, Jiang

Maximizing MR signal for 2D UTE slice selection in the presence of rapid transverse relaxation.

在存在快速横向弛豫的情况下最大化 MR 信号以进行 2D UTE 切片选择。

• DOI: 10.1016/j.mri.2014.05.001
• 发表时间: 2014
• 期刊: Magnetic resonance imaging
• 影响因子: 2.5
• 作者: Carl,Michael;Chiang,Jing-TzyhAlan;Du,Jiang
• 通讯作者: Du,Jiang