Assessment of metabolic bone disease of prematurity using an acoustic method

早产儿代谢性骨病或早产儿骨量减少(OP)，或新生儿软骨病或软骨病 早熟，是用来描述一种常见而重要的问题的术语，指的是矿化不足 以骨骼矿化减少为特征的早产儿骨骼 并经常导致长骨和肋骨骨折。为了最大限度地增加骨骼矿化并尽量减少 OP，临床医生使用血清钙、无机磷和碱性的生化测量 磷酸酶为优化婴儿营养做出决定，但仅限于放射证据。 是时候监测这一进展了。目前，还没有任何筛查试验被证明同时提供敏感和 早产儿在出生后头几周发生OP的具体证据。是这样的 信息将极大地促进临床医生努力优化早产儿的营养，努力 将OP的风险降至最低。目前的骨骼评估工具包括平片、双能X射线 吸收(DXA)和定量超声(QUS)。由于使用了电离辐射和体积 仪器，前两种方法不适合婴儿，特别是低出生体重的早产儿 新生儿，这是一个特别容易受到矿物质危害的群体。QUS是用来测量声速的 通过发射单频超声波获得大块四肢骨骼。该装置适用于婴幼儿和 尤其是早产儿很差。传统量化评价方法的最大缺陷 婴幼儿骨骼受皮下组织，尤其是皮下组织的影响很大。 肥胖层。当前QUS技术的另一个缺点是该系统运行在单一的- 频率基准。基于我们的研究，稍后将在本申请中描述，获取超声波 各种频率范围内的数据，特别是千赫兹范围内的数据，可以提供有关 改善骨骼的机械结构，并可能导致改进骨骼评估。建议的目标是 项目是开发一种基于超声波的新技术，称为振动-声学分析(VAA)，它基于 关于一种全新的机制，允许在广泛的频率范围内评估婴儿的骨骼特性 没有皮下组织的干扰。在目标1中，对VAA方法进行了优化 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 VAA方法在一项先导性研究中对胫骨定量评估的有效性 将在一项纵向研究中对足月儿和早产儿进行测试，以检测和监测治疗情况。这个 该项目将开发的技术可能为临床医生提供有价值的监测和治疗信息 在放射证据尚不明显的阶段发展OP。此外，量化 使用改进的VAA技术随着时间的推移进行测量可以促进对治疗效果的评估， 从而进一步指导临床干预，具有改善患者结局的强大潜力。

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.