Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone

骨超短回波时间 (UTE) 磁共振成像

• 批准号: 10132985
• 负责人: Jiang Du
• 金额: $ 64.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-17 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10132985
• 关键词: 3-Dimensional; Achievement; Affect; Age; Aging; American; Award; Biochemical Markers; Biological Markers; Biomechanics; Body mass index; Bone Density; Cadaver; Chemicals; Clinical; Collagen; Cone; Control Groups; Development; Diagnosis; Diagnostic; Disease; Dual-Energy X-Ray Absorptiometry; Elderly woman; Ethnic Origin; Etiology; Evaluation; Failure; Femur; Fracture; Goals; Gold; Head and neck structure; Human; Image; Individual; Magnetic Resonance Imaging; Maps; Measurement; Measures; Metabolic Bone Diseases; Minerals; Modality; Modeling; Morphologic artifacts; Osteomalacia; Osteopenia; Osteoporosis; Participant; Patients; Physiologic pulse; Porosity; Predisposition; Property; Protons; Raman Spectrum Analysis; Recording of previous events; Recovery; Reference Standards; Relaxation; Renal Osteodystrophy; Roentgen Rays; Signal Transduction; Specimen; Techniques; Testing; Time; Validation; Water; Woman; Work; World Health Organization; accurate diagnosis; age group; base; bone; bone imaging; clinical practice; cohort; cortical bone; cost; crosslink; crystallinity; insight; mechanical properties; millisecond; mineralization; novel; older women; research clinical testing; rib bone structure; substantia spongiosa

7. Abstract Metabolic bone diseases including osteoporosis (OP), osteopenia, osteomalacia and renal osteodystrophy (ROD) affect more than 55 million Americans with an annual cost of more than $17B. The gold standard, dual energy X-ray absorptiometry (DEXA) measures bone mineral density (BMD). However, the majority of bone, the organic matrix and water which together occupy ~60% of bone by volume, is inaccessible. A recent study of over 14,613 participants found that ~80% of all non-vertebral fractures occurred among individuals with BMD above the WHO definition of OP. Furthermore, the etiologies and treatments for OP/osteopenia (reduced bone content) and osteomalacia/ROD (reduced mineralization) are different, but DEXA cannot differentiate between these diseases. More comprehensive techniques are needed for the evaluation of cortical and trabecular bone quantity/quality with information not only about mineral, but about organic matrix and water. Bone is “invisible” with clinical MRI sequences due to its short T2*. Ultrashort echo time (UTE) sequences with minimal TEs of 8 µs make it possible to detect signal from bone. In the first four years of this award (1R01 AR068987, 09/2015 – 08/2019), we investigated 3D UTE Cones imaging of bound and pore water content as well as T1, T2* and magnetization transfer (MT) ratio. However, those biomarkers showed only low to moderate correlation with biomechanics, likely due to inaccurate measure of bound and pore water as well as incomplete assessment of organic matrix and mineral in bone. UTE with a soft-hard composite pulse suppresses chemical shift artifact, thus allowing more accurate measure of total water. Double adiabatic inversion recovery UTE (DIR-UTE) provides more complete suppression of pore water, thus allowing more accurate measure of bound water. UTE with MT (UTE-MT) modeling measures collagen proton fraction, exchange and relaxation. UTE with quantitative susceptibility mapping (UTE-QSM) maps bone susceptibility, providing information about BMD. Our goal is to develop a package for fast and accurate mapping of total, bound and pore water, collagen proton fraction, exchange, relaxation, and mineral, and to apply it to OP, osteopenia and ROD patients. Aim 1 targets UTE techniques for fast and accurate mapping of water, collagen and mineral in femur (midshaft, head and neck), using µCT, histomorphometry, Raman and gravimetry as reference standard. Aim 2 will evaluate UTE techniques for water, collagen and mineral in femur from donors with OP (n=20), osteopenia (n=20) and ROD (n=20), with UTE biomarkers correlated with µCT, histomorphometry, Raman and biomechanical testing. Aim 3 targets translational UTE sequences to measure water, collagen and mineral in femur of young (<40y, n=30) and older women (>70y) with (n=30) and without (n=30) OP, with osteopenia (n=30) and with ROD (n=30). UTE biomarkers in different groups will be compared, and correlated with BMD, biochemical markers and fracture history. This work will provide panels of 3D UTE biomarkers for more accurate assessment of bone quantity and quality, and may have a major impact on the diagnosis of various metabolic bone diseases.

7. 摘要 代谢性骨疾病，包括骨质疏松症 (OP)、骨质减少、骨软化症和肾性骨营养不良 (ROD) 影响超过 5500 万美国人，每年造成的费用超过 $17B。黄金标准，双重 能量 X 射线吸收测定法 (DEXA) 可测量骨矿物质密度 (BMD)。然而，大多数骨头， 有机基质和水合计占骨骼体积的约 60%，是无法接近的。最近的一项研究 超过 14,613 名参与者发现，约 80% 的非椎骨骨折发生在患有以下疾病的个体中： BMD 高于 WHO 对 OP 的定义。此外，OP/骨质减少症的病因和治疗（减少 骨含量）和骨软化/ROD（矿化减少）不同，但 DEXA 无法区分 这些疾病之间。需要更全面的技术来评估皮质和 小梁骨的数量/质量不仅包含有关矿物质的信息，还包含有关有机基质和水的信息。 由于 T2* 较短，骨骼在临床 MRI 序列中是“看不见的”。超短回波时间 (UTE) 序列 TE 最小为 8 µs，可以检测来自骨骼的信号。在该奖项的前四年（1R01 AR068987，09/2015 – 08/2019），我们研究了结合水和孔隙水含量的 3D UTE 锥体成像： 以及 T1、T2* 和磁化转移 (MT) 比率。然而，这些生物标志物仅表现出低至中度 与生物力学的相关性，可能是由于结合水和孔隙水的测量不准确以及不完整 骨中有机基质和矿物质的评估。具有软硬复合脉冲的 UTE 可抑制化学物质 位移伪影，从而可以更准确地测量总水量。双绝热反转恢复UTE (DIR-UTE) 可以更完全地抑制孔隙水，从而可以更准确地测量结合 水。 UTE 与 MT (UTE-MT) 建模可测量胶原质子分数、交换和松弛。 UTE 通过定量磁化率绘图 (UTE-QSM) 绘制骨磁化率图，提供有关 弹道导弹防御。我们的目标是开发一个软件包，用于快速准确地绘制总水、结合水和孔隙水、胶原蛋白 质子分数、交换、松弛和矿物质，并将其应用于 OP、骨质减少和 ROD 患者。目标1 目标 UTE 技术可快速准确地绘制股骨（中轴、头部）中的水、胶原蛋白和矿物质 和颈部），使用 µCT、组织形态测定、拉曼和重量测定作为参考标准。目标 2 将评估 UTE 技术对患有 OP (n=20)、骨质减少 (n=20) 和 ROD (n=20)，UTE 生物标志物与 µCT、组织形态计量学、拉曼和生物力学测试相关。 目标 3 以翻译 UTE 序列为目标，测量年轻人（<40 岁、 n=30) 和老年女性 (>70 岁)，有 (n=30) 和没有 (n=30) OP，有骨质减少 (n=30) 和 ROD (n=30)。比较不同组别UTE生物标志物，并与BMD、生化标志物相关 和骨折史。这项工作将提供 3D UTE 生物标记物组，以便更准确地评估 骨的数量和质量，可能对各种代谢性骨疾病的诊断产生重大影响。