An MRI-Based Method for Measuring Bone Mineral and Matrix Densities in Humans

描述（由申请人提供）：骨质疏松症和骨脱矿物质疾病（例如骨软化症）是导致骨矿物质密度降低并降低骨机械能力的骨骼疾病，容易导致骨折。而骨质疏松症是一种结构性骨疾病，其中骨矿物质和基质都丢失，骨脱矿物质障碍仅涉及骨矿物质的不足。因此，骨成分密度比（RBCD），即骨矿物质密度与骨基质密度的比值，是区分这两组疾病的合适指标。RBCD与骨矿化度（DMB）密切相关，DMB表示为每体积基质的矿物质质量。目前的诊断方法，如双能X射线吸收法（DXA），只能测量骨密度，因此无法区分这两组疾病。二级诊断方法，如骨活检，有时可以区分这些疾病，但这种程序是侵入性的。由于这两种疾病经常在老年人中同时发生，因此此类患者经常被误诊为仅患有骨质疏松症，从而使他们的骨脱矿物质疾病得不到治疗。拟议的工作建立在申请人实验室最近进行的研究基础上。该项目旨在将基于MRI的骨基质和矿物质密度测量方法（在专用硬件中的动物标本上得到证明）调整为可以在人类身上进行的单一定量检查。假设是，拟议的检查将能够区分骨质疏松症和矿化受损的疾病，使用临床MRI设备，没有电离辐射相关的风险，如DXA或定量计算机断层扫描（QCT），或侵入性骨活检。拟议的工作将包括确定最佳的磁场强度为这一进程，从总骨质子池的骨基质相关的质子信号的隔离方法，调整MRI脉冲序列，以平衡图像分辨率与扫描时间，图像强度参考样本的设计，和用于计算密度从图像强度的算法的改进。然后将所得检查应用于正常和化学脱矿骨标本，以确认该方法的准确性和重现性。将通过重量分析法测量这些样本的真密度。最后一步将是在一项小型试点研究中将这种方法转化为临床，该研究涉及健康志愿者和患有这两种不同类型疾病的受试者，以证明该方法区分疾病状态的可行性。

DESCRIPTION (provided by applicant): Osteoporosis and bone-demineralizing disorders (e.g. osteomalacia) are skeletal diseases that cause decreased bone mineral density and reduce the mechanical competence of bone, predisposing to fractures. Whereas osteoporosis is a structural bone disease where both bone mineral and matrix are lost, bone- demineralizing disorders involve a deficit in bone mineral only. Therefore, the ratio of bone constituent densitie (RBCD), given as the ratio of bone mineral density to bone matrix density, would be a suitable metric by which to distinguish these two groups of diseases. The RBCD is closely related to the degree of mineralization of bone (DMB), which is expressed as mass of mineral per volume of matrix. Current diagnostic methods, such as dual-energy x-ray absorptiometry (DXA), measure only bone mineral density and, thus, are unable to distinguish between these two groups of diseases. Secondary diagnostic methods, such as bone biopsy, can sometimes discriminate between these diseases, but this procedure is invasive. Because these two disorders often co-occur in the elderly, such patients are often misdiagnosed as having only osteoporosis, leaving their bone-demineralizing disorder untreated. The proposed work builds on recent research conducted in the applicant's lab. This project seeks to adapt MRI-based methods for bone matrix and mineral density measurements, proven on animal specimens in specialized hardware, into a single quantitative examination that can be performed on humans. The hypothesis is that the proposed examination will be able to distinguish between osteoporosis and disorders of impaired mineralization using clinical MRI equipment and without the risks associated with ionizing radiation, as in DXA or quantitative computed tomography (QCT), or invasive bone biopsy. The proposed work will include determining the optimal magnetic field strength for this procedure, the method for isolation of bone matrix-associated proton signal from the total bone proton pool, the adjustment of the MRI pulse sequence to balance image resolution with scan time, the design of image intensity reference samples, and the improvement of algorithms used to calculate densities from image intensities. The resulting examination will then be applied to normal and chemically demineralized bone specimens in order to confirm the method's accuracy and reproducibility. The true densities of these specimens will be measured by gravimetry. The final step will be to translate this method to the clinic in a small pilot study involving healthy volunteers and subjects with these two different classes of disorders in order to demonstrate the method's feasibility to distinguish between disease states.