Magnetic Resonance Imaging of Bound and Free Water in Cortical Bone

皮质骨中结合水和游离水的磁共振成像

• 批准号: 8582497
• 负责人: Jiang Du
• 金额: $ 19.76万
• 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: 2013-08-16 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8582497
• 关键词: Affect; Age; Aged, 80 and over; Applications Grants; Binding; Biological Markers; Biomechanics; Bone Density; Bone Diseases; Bone Matrix; Clinical; Data; Diagnosis; Diffuse; Dual-Energy X-Ray Absorptiometry; Failure; Fracture; Gadolinium; Human; Image; Imaging Techniques; Intention; Left; Location; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Microscopic; Minerals; Modeling; Osteomalacia; Osteoporosis; Paget' s Disease; Patients; Perfusion; Phase; Physiologic pulse; Porosity; Postmenopause; Property; Protocols documentation; Radioisotopes; Recovery; Reference Standards; Relative (related person); Relaxation; Renal Osteodystrophy; Resolution; Risk; Risk Assessment; Sampling; Signal Transduction; Specimen; Stress; System; Techniques; Testing; Time; Tissue Sample; Tissues; Validation; Viscosity; Water; Woman; Women' s Group; Work; X-Ray Computed Tomography; bone; bone quality; data acquisition; density; gadolinium oxide; improved; interest; millisecond; novel; public health relevance; research clinical testing; research study; soft tissue; success; tibia; tool; two-dimensional

DESCRIPTION (provided by applicant): Routine clinical evaluation of osteoporosis (OP) has been limited to the assessment of bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) and/or CT. The majority of bone, the organic matrix and water, which together represent ~57% of bone by volume, are not accessible with these techniques. BMD alone predicts fractures with only a 30-50% success rate. The missing factor may be the contribution of bone organic matrix and water. Bone water occurs at various locations and in different states. It is bound to the organic matrix or in 'free' form in the Haversian and the lacunar-canalicular systems. The bound water content reflects organic matrix density. The free water content can potentially provide a surrogate measure of bone porosity. However, neither DEXA nor CT can detect either bound or free water in cortical bone. We have developed Ultrashort Time-to-Echo (UTE) magnetic resonance imaging (MRI) sequences with minimum TEs of 8 ¿s, and this makes it possible to detect water signal from bone. Total bone water can be quantified by comparing UTE signal from bone and a water phantom. Bound water can be selectively imaged with SIR-UTE sequences which use a single adiabatic inversion pulse to invert and null the free water magnetization. Free water can be selectively imaged with DIR-UTE sequences which saturate bound water while leave free water magnetization unaffected. Bound water has ~10 times shorter T2* than free water. The two components may be separated with bi-component fitting. Free water has a short T2* but long T2, and may be imaged with FSE sequences. The UTE approach may detect the effect of Gadolinium chelates within cortical bone and study its perfusion at high resolution. This provides a new way to characterize cortical bone. In this proposal we hypothesize that bone water content and bone perfusion can be non-invasively assessed by novel MRI techniques, and can serve as sensitive biomarkers of bone quality. We aim to develop novel UTE, SIR-UTE, DIR-UTE and FSE techniques to measure total, bound and free water in cortical bone (Aim 1), to evaluate the accuracy of MR measures of two groups of women cadaveric human tibia specimens, the younger group (< 60 years old) and the older group (> 80 years old), and correlate the results with cortical porosity determined by mCT and organic matrix content determined by ashing, as well as elastic properties (modulus, yield stress and strain) and failure properties (ultimate stress, failure strain and energy) determined by 4-point bending test (Aim 2), and to develop translational MR techniques to quantify total, bound and free water as well as bone perfusion in two groups of postmenopausal women: i.e., below 60 without OP and above 80 with OP (Aim 3). The intention is to develop and validate these techniques in tissue studies and a small number of patients to provide preliminary data for an RO1 grant application on the use of MR in diffuse bone disease including OP, renal osteodystrophy, paget disease and osteomalacia. The comprehensive characterization of bone in these conditions could have a profound impact in their diagnosis and treatment.

描述（由申请方提供）：骨质疏松症（OP）的常规临床评价仅限于使用双能X线吸收测定法（DEXA）和/或CT评估骨矿物质密度（BMD）。大部分骨、有机基质和水（按体积计约占骨的57%）无法通过这些技术获取。仅BMD预测骨折的成功率仅为30-50%。缺失的因素可能是骨有机基质和水的贡献。骨水发生在不同的位置和不同的状态。它与有机基质结合，或在哈弗氏系统和腔隙-小管系统中以“自由”形式存在。束缚水含量反映有机基质密度。游离水含量可潜在地提供骨孔隙度的替代测量。然而，无论是DEXA还是CT都不能检测到皮质骨中的结合水或自由水。我们已经开发了超短回波时间（UTE）磁共振成像（MRI）序列，最小TE为8 μ s，这使得检测骨骼中的水信号成为可能。可以通过比较来自骨和水体模的UTE信号来量化总骨水。结合水可以有选择地成像SIR-UTE序列，使用一个单一的绝热反转脉冲反转和零的自由水磁化。自由水可以选择性地成像与饱和结合水，而离开自由水磁化不受影响的DIR-UTE序列。结合水的T2* 比自由水短约10倍。这两个组件可以用双组件配件分离。自由水具有短T2* 但长T2，并且可以用FSE序列成像。UTE方法可以检测皮质骨内钆螯合物的作用，并以高分辨率研究其灌注。这提供了一种新的方法来表征皮质骨。在这个提议中，我们假设骨含水量和骨灌注可以通过新的MRI技术进行无创评估，并且可以作为骨质量的敏感生物标志物。我们的目的是开发新的UTE、SIR-UTE、DIR-UTE和FSE技术来测量皮质骨中的总水、结合水和自由水（目标1），以评价两组女性尸体胫骨标本（年轻组）MR测量的准确性。（< 60岁）和老年组（> 80岁），并将结果与通过mCT测定的皮质孔隙度和通过灰化测定的有机基质含量以及弹性性质相关联（模量、屈服应力和应变）和失效特性（极限应力、失效应变和能量），并开发平移MR技术来量化两组绝经后妇女的总水、结合水和游离水以及骨灌注：即，60以下无OP，80以上有OP（目标3）。目的是在组织研究和少量患者中开发和验证这些技术，为MR在弥漫性骨病（包括OP、肾性骨营养不良、佩吉特病和骨软化症）中的应用提供RO 1资助申请的初步数据。在这些情况下，骨的综合表征可能对其诊断和治疗产生深远的影响。