Magnetic Resonance Imaging of Bound and Free Water in Cortical Bone

描述(由申请人提供)：骨质疏松症(OP)的常规临床评估仅限于使用双能X射线骨密度仪(DEXA)和/或CT评估骨密度(BMD)。大多数骨、有机基质和水，它们加起来占骨体积的57%，这些技术是无法接触到的。BMD单独预测骨折的成功率只有30%-50%。缺失的因素可能是骨有机基质和水的贡献。骨水出现在不同的位置和不同的状态。它结合在有机基质上，或在哈弗氏和腔隙-小管系统中以“游离”的形式存在。结合水含量反映了有机基质的密度。游离水含量可以潜在地提供骨孔隙率的替代测量。然而，无论是DEXA还是CT都不能检测到皮质骨中的结合水和游离水。我们已经开发出超短回波时间(UTE)磁共振成像序列，最小TES为8？S，这使得从骨骼中检测水信号成为可能。通过比较来自骨骼的UTE信号和水模体，可以量化总的骨水量。结合水可以选择性地用单一绝热反转脉冲来反转和消除自由水磁化强度的SIR序列成像。游离水可以用DIR-UTE序列选择性地成像，这些序列饱和了结合水，而不影响自由水的磁化强度。束缚水的T2*比自由水短约10倍。可以用双分量拟合法将这两个分量分开。游离水具有短的T2*和长的T2，并且可以用FSE序列进行成像。UTE入路可检测皮质骨内Gd络合物的影响，并在高分辨率下研究其血流灌注。这为研究皮质骨的特性提供了一种新的方法。在这项建议中，我们假设骨水含量和骨灌注量可以通过新的MRI技术进行非侵入性评估，并可以作为骨质量的敏感生物标志物。我们的目标是开发新的UTE、SIR-UTE、DIR-UTE和FSE技术来测量皮质骨中的总水、结合水和游离水(目标1)，以评估两组女性身体胫骨标本MR测量的准确性，年轻组(60岁)和老年组(&gt；并将结果与MCT测定的皮质孔隙率和灰化测定的有机基质含量以及四点弯曲试验(目标2)确定的弹性特性(弹性系数、屈服应力和应变)和破坏特性(极限应力、破坏应变和能量)相关联，并开发平移MR技术来量化两组绝经后妇女的总水、结合水和自由水以及骨灌注量：60岁以下的OP组和80岁以上的OP组(目标3)。其目的是在组织研究和少数患者中开发和验证这些技术，为RO1拨款申请提供初步数据，以使用MR治疗弥漫性骨疾病，包括OP、肾性骨营养不良、Paget病和骨软化症。在这些情况下，骨骼的综合特征可能对它们的诊断和治疗产生深远的影响。

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.