31P/1H MRI Measurement of Bone Mineralization

描述（由申请人提供）： 2001年，NIH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1800万人骨质疏松。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多年，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。患有骨软化症的患者具有受损的骨矿化，并且可能另外具有减少量的骨组织，而患有骨质疏松症的患者具有减少量的正常矿化的骨。目前，有创性骨活检是唯一有把握区分骨软化症和骨质疏松症的方法。在个体患者中混淆骨软化症和骨质疏松症导致不适当的治疗。 拟定的骨矿化31 P/1H固态磁共振成像（SMRI）测量的目的是提供关于给定体积骨物质中骨矿物质和骨基质相对比例的急需信息，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状态。骨矿物质的31 P NMR信号和固体骨基质的一部分1H NMR信号落入该区域。定量31 P SMRI能很好地反映骨矿物质密度，定量水和脂肪抑制的[H]投影MRI（WASPI）能提供骨基质密度的测量。结合这两种测量结果得出骨矿化程度。 在拟议的项目中，这种新的MRI技术将进一步发展，并在全身MRI扫描仪中实施。将首先在患有骨软化症的活猪和对照组中进行评价，然后在患有骨关节炎的人类受试者中进行评价，所有评价均针对从动物中采集或在全膝关节置换术期间切除的相关骨样本的金标准化学和重量分析。最后，将在临床诊断为骨质疏松症和/或骨软化症的患者中评价拟定的SMRI。 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，并使他们的医疗护理受益，因为骨软化症的治疗非常有效，并且比任何可用的骨质疏松症治疗方法都更能增加骨矿物质密度和骨强度。

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.