31P/1H MRI Measurement of Bone Mineralization

描述(由申请人提供)： 2001年，美国国立卫生研究院的一个共识发展小组得出结论，仅在美国，就有1000万人患有骨质疏松症，还有1800万人患有低骨量。由于骨软化症导致的低骨量患者通常会被误诊为骨质疏松症，因为X光片加上血液和尿液测量经常无法区分这两种情况。骨软化症患者的骨矿化受损，可能还会有大量的骨组织减少，而骨质疏松症患者的正常矿化的骨量减少。目前，有创骨活检是唯一有把握地区分骨软化和骨质疏松症的方法。在个别患者中，混淆骨软化症和骨质疏松症会导致不适当的治疗。 所提出的31P/1H固态核磁共振成像(31P/1H)骨矿化测量的目的是提供关于骨矿物质和骨基质在给定体积的骨物质中的相对比例的迫切需要的信息，这是任何其他非侵入性方法(包括CT和高分辨率液态MRI)无法获得的。SMRI方法的目标是所谓的软固体区域。骨矿物的~(31)P核磁共振信号和部分固体骨基质的~(31)P核磁共振信号在此范围内。定量~(31)P核磁共振成像能很好地表示骨中的矿物质密度，定量水和脂肪抑制的核磁共振成像(WASPI)提供骨的基质密度的测量。这两种测量相结合得到骨矿化的程度。 在拟议的项目中，这项新的MRI技术将进一步开发并在全身MRI扫描仪中实现。它将首先在患有骨软化症的活猪和对照组中进行评估，然后在患有骨关节炎的人类受试者中进行评估，所有这些都是根据从动物身上采集的或在全膝关节置换过程中切除的相关骨样本的金标准化学和重量分析进行的。最后，建议的SMRI将在临床诊断为骨质疏松症和/或骨软化症的患者中进行评估。 如果这项技术成功，它将在低骨密度患者中非侵入性地识别骨软化症，并有利于他们的医疗保健，因为骨软化症的治疗非常有效，而且比任何现有的骨质疏松症治疗方法都更能提高骨密度和骨强度。

DESCRIPTION (provided by applicant): An NIH consensus development panel concluded in 2001 that in the United States alone, 10 million people already have osteoporosis, and 18 million more have low bone mass. Patients with low bone mass due to osteomalacia usually remain for many years misdiagnosed as only having osteoporosis, since radiographs plus blood and urine measurements frequently fail to distinguish the two conditions. Patients with osteomalacia have impaired bone mineralization, and may in addition have a reduced amount of bone tissue, whereas patients with osteoporosis have a reduced amount of bone which is normally-mineralized. At present an invasive bone biopsy is the only way to discriminate osteomalacia from osteoporosis with confidence. Confounding osteomalacia with osteoporosis in individual patients leads to inappropriate therapy. The purpose of the proposed 31P/1H solid state magnetic resonance imaging (SMRI) measurement of bone mineralization is to provide critically needed information about the relative proportions of bone mineral and bone matrix in a given volume of bone substance that is unattainable by any other noninvasive methods including CT and high resolution liquid state MRI. The SMRI method targets a so-called soft solid regime. The 31P NMR signals of bone mineral and some portion of the 'H NMR signals of solid bone matrix fall in this regime. Quantitative 31P SMRI yields a good representation of the mineral density in bone, and quantitative water and fat suppressed [H projection MRI (WASPI) provides the measurement of the matrix density of bone. Combining these two measurements yields the degree of bone mineralization. In the proposed project, this novel MRI technology will be further developed and implemented in a whole body MRI scanner. It will be evaluated first in live swine with osteomalacia and controls, then in human subjects with osteoarthritis, all against gold standard chemical and gravimetric analyses of the associated bone specimens harvested from the animals or resected during total knee replacement. Finally, the proposed SMRI will be evaluated in patients who have been clinically diagnosed with osteoporosis and/or osteomalacia. If this technology is successful, it would identify osteomalacia non-invasively in patients with low bone density and benefit their medical care, because treatment of osteomalacia is dramatically effective, and increases bone mineral density and bone strength much more than any available treatment for osteoporosis.