Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone

7.摘要 代谢性骨病包括骨质疏松症、骨量减少、骨软化和肾性骨营养不良 (Rod)影响着超过5500万美国人，每年的成本超过170亿美元。黄金标准，双重标准 能量X射线吸收法(DEXA)测量骨密度(BMD)。然而，大部分的骨头， 有机基质和水共占骨体积的60%，是无法接触到的。最近的一项研究 超过14,613名参与者发现，约80%的非脊椎骨折发生在患有 骨密度高于世界卫生组织对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)是不同的，但DEXA无法区分 在这些疾病之间。需要更全面的技术来评估皮质和 骨小梁数量/质量不仅包含矿物质信息，还包含有机基质和水的信息。 由于其短T2*，骨在临床MRI序列中是“看不见的”。超短回波时间(UTE)序列 S的最低TES为8微米，使从骨骼中检测信号成为可能。在该奖项的前四年(01年第1季度 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。然而，这些生物标志物只显示出低到中等的水平。 与生物力学的相关性，可能是由于结合水和孔隙水测量不准确以及不完整所致 骨中有机基质和矿物质的评估。采用软硬复合脉冲的UTE抑制化学物质 移动伪影，从而可以更准确地测量总水量。双绝热反转恢复管 (直接)提供更完全的孔隙水抑制，从而允许更准确地测量结合 水。UTE与MT(UTE-MT)模型测量胶原质子分数、交换和松弛。UTE 使用定量磁化率图(UTE-QSM)映射骨骼磁化率，提供以下信息 骨密度。我们的目标是开发一套快速、准确的总水、结合水和孔隙水、胶原蛋白的测绘程序 质子组分、交换、松弛和矿物质，并将其应用于OP、骨量减少和Rod患者。目标1 快速准确地绘制股骨(中干、头部)中水、胶原蛋白和矿物质图的目标技术 和颈部)，使用µCT、组织形态计量学、拉曼和重量法作为参考标准。AIM 2将评估 骨质疏松症、骨质疏松症和骨质疏松症供者股骨中水分、胶原和矿物质的UTE技术 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。 目的3以翻译UUT序列为靶点，测量年轻人股骨中的水分、胶原和矿物质。 30名)和70岁的老年妇女(70岁)，有(n=30)有和没有(n=30)OP，有骨量减少(n=30)和有Rod (n=30)。将不同组别的UTE生物标志物进行比较，并与BMD、生化标志物进行相关分析 和骨折史。这项工作将提供3D UTE生物标志物面板，以便更准确地评估 骨骼的数量和质量，并可能对各种代谢性骨病的诊断产生重大影响。

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.