Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone

7.摘要 代谢性骨病，包括骨质疏松症（OP）、骨量减少、骨软化和肾性骨营养不良 (ROD)影响了超过5500万美国人，每年花费超过170亿美元。金本位，双重 能量X射线吸收测定法（DEXA）测量骨矿物质密度（BMD）。然而，大部分的骨头， 有机基质和水共占骨体积的约60%，是不可接近的。最近的一项研究 在超过14，613名参与者中发现，约80%的非椎骨骨折发生在患有 此外，OP/骨量减少（减少）的病因和治疗 骨含量）和骨软化/ROD（矿化减少）是不同的，但DEXA不能区分 这些疾病之间。需要更全面的技术来评估皮质和 松质骨的数量/质量不仅与矿物质有关，而且与有机基质和水有关。 由于T2* 较短，骨在临床MRI序列中“不可见”。超短回波时间序列 最小TE为8 µs，因此可以检测来自骨骼的信号。在该奖项的前四年（1 R 01 AR 068987，09/2015 - 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* 和磁化传递（MT）比。然而，这些生物标志物仅显示低至中度， 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抑制化学物质 偏移伪影，从而允许更准确地测量总水量。双绝热反转恢复 （DIR-UTE）提供了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）建模测量胶原蛋白质子分数、交换和松弛。UTE 利用定量磁化率绘图（UTE-QSM）绘制骨磁化率，提供以下信息： BMD。我们的目标是开发一个软件包，用于快速准确地绘制总，结合和孔隙水，胶原蛋白 质子分数、交换、松弛和矿物质，并将其应用于OP、骨量减少和ROD患者。要求1 目标：通过UTE技术快速准确地绘制股骨（中段、头部）中的水、胶原蛋白和矿物质 和颈部），使用µCT、组织形态学、拉曼和重量分析法作为参考标准。目标2将评估 UTE技术用于OP（n=20）、骨量减少（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。 目的3用翻译后的UTE序列测定青年人（<40岁， n=30）和老年女性（> 70岁），有（n=30）和无（n=30）OP，骨质减少（n=30）和ROD （n=30）。比较各组的UTE生物标志物，并与BMD、生化指标进行相关性分析 和骨折史这项工作将提供3D UTE生物标志物的面板，用于更准确地评估 骨的数量和质量，并可能对各种代谢性骨疾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.