Assessment of metabolic bone disease of prematurity using an acoustic method

早产儿代谢性骨病或早产儿骨质减少症（OP），或新生儿佝偻病或 早产，是用来描述一个共同的和重要的问题，是指低矿化的术语 以骨矿化减少的放射学证据为特征的早产儿骨骼 并且经常导致长骨和肋骨骨折。为了最大限度地增加骨矿化， OP，临床医生使用血清钙，无机磷和碱性磷酸酶的生化测量 磷酸酶，以作出决定，优化婴儿营养，但仅限于放射学证据超过 有时间来观察这个过程。目前，还没有筛选试验显示出既提供敏感的， 早产儿在出生后的前几周内发生OP的具体证据。等 这些信息将极大地促进临床医生优化早产儿营养的努力， 最大限度地减少OP的风险。目前的骨评估工具包括平片X线摄影、双能X线 吸收（DXA）和定量超声（QUS）。由于使用电离辐射和笨重的 设备，前两种方法不适合婴儿，特别是低出生体重早产儿 新生儿是矿物质受损的特殊风险群体。QUS的设计是为了测量声速， 通过发射单频超声波来治疗四肢大骨。使该装置适应婴儿， 特别是早产儿非常贫困。传统QUS用于评估的最大缺点 婴儿骨骼的一个重要特征是，结果受皮下组织的影响很大，特别是皮下 脂肪层当前QUS技术的另一个缺点是系统在单个- 频率基础基于我们的调查，稍后将在本申请中描述， 在很宽的频率范围内，特别是在千赫范围内的数据，可以提供有关以下方面的有价值的信息： 骨的机械结构，并可能导致改善骨评估。建议的目标 一个项目是开发一种新的基于超声的技术，称为振动声学分析（VAA），这是基于 一种全新的机制，允许在宽频率范围内评估婴儿骨骼特性 没有皮下组织的干扰。在目标1中，优化用于定量分析的VAA方法。 评估，我们将优化和验证体内研究的技术。在目标2中，我们将确定 在一项初步研究中，VAA方法用于胫骨定量评估的有效性。 将在足月和早产儿中进行测试，以在纵向研究中检测和监测治疗。的 本项目开发的技术可为临床医生提供有价值的信息，以监测和治疗 在放射学证据尚不明显的阶段发展OP。此外，定量 使用改进的VAA技术随时间的测量可以促进治疗功效的评估， 从而进一步指导具有改善患者结果的强大潜力的临床干预。

Metabolic bone disease in preterm newborn or osteopenia of prematurity (OP), or neonatal rickets or rickets of prematurity, are terms used to describe a common and significant problem that refers to hypo-mineralized skeleton of premature infants that is hallmarked by radiographic evidence of decreased bone mineralization and often leads to fractures of long bone and ribs. In an effort to maximize bone mineralization and minimize OP, clinicians use biochemical measurements of serum calcium, inorganic phosphorus, and alkaline phosphatase to make decisions for optimizing infant nutrition, but are limited to radiographic evidence over time to monitor this progress. Currently, no screening test has been shown to provide both sensitive and specific evidence of developing OP over the first several weeks of life in the premature infants. Such information would greatly facilitate clinicians’ efforts to optimize nutrition for preterm infants in an effort to minimize the risk of OP. Current bone assessment tools include plain radiography, dual-energy X-ray absorption (DXA), and quantitative ultrasonography (QUS). Due to the use of ionizing radiation and bulky equipment, the first two methods are not suitable for infants and especially for the low-birth-weight pre-term neonates, a group at particular risk of mineral compromise. QUS is designed to measure the speed of sound in large extremity bones by transmitting a single-frequency ultrasound. Adaptation of this device to infants and especially premature infants is very poor. The most important shortcoming of conventional QUS for evaluation of infant bone is that the results are greatly affected by subcutaneous tissues, particularly by the subcutaneous fat layer. Another shortcoming of the current QUS technology is that the system operates on a single- frequency basis. Based on our investigations, to be described later in this application, acquiring ultrasound data in a wide range of frequencies, especially in the kilo-Hertz range, can provide valuable information about the mechanical structure of bone and may lead to improved bone assessment. The goal of the proposed project is to develop a new ultrasound based technology, called vibro-acoustic analysis (VAA), which is based on a fundamentally new mechanism that allows evaluation of infant bone properties in a wide frequency range without the interference from subcutaneous tissues. In Aim 1, optimization of the VAA method for quantitative assessment, we will optimize and validate the technique for in vivo study. In Aim 2, we will determine the efficacy of the VAA method for quantitative assessment of tibia bone in a pilot study.The proposed technique will be tested on term and preterm infants to detect and monitor the treatment in a longitudinal study. The technology to be developed in this project may provide clinicians with valuable information to monitor and treat developing OP at a stage where radiographic evidence is not yet apparent. Additionally, quantitative measurements over time using improved VAA technology may facilitate assessments of treatment efficacy, thus further guiding clinical interventions with the strong potential for improved patient outcomes.