Transosseous application of low-intensity ultrasound for the enhancement and monitoring of fracture healing process in a sheep osteotomy model
Transosseous application of low-intensity ultrasound for the enhancement and monitoring of fracture healing process in a sheep osteotomy model
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DOI：
10.1016/j.bone.2005.10.012
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发表时间：
2006-04-01
期刊：
影响因子：
4.1
通讯作者：
Fotiadis, DI
中科院分区：
文献类型：
--
作者：
Malizos, KN;Papachristos, AA;Fotiadis, DI
本研究的目的有两个：(A)研究低强度脉冲超声(LIUS)在促进骨折愈合方面的应用；(B)证实超声传播对骨折愈合过程的监测能力。40只成年绵羊采用胫骨中段截骨模型，应用外固定器保持截骨的复位和稳定。在骨折处植入两个超声换能器，使其与骨骼接触。为研究六味地黄汤的疗效，将动物随机分为两组：治疗组和对照组。LUU处理的动物接受200亩S脉冲重复频率为1 kHz，平均强度为30 mW/cm(2)的1 MHz正弦波，每天20分钟。为了监测的目的，构建了一个超声数据集，由从愈合的骨骼获得的一系列超声测量组成。术后第100天处死动物。通过X线片、破坏性三点弯曲试验和基于CT的骨密度(BMD)定量测量来评价LUS对骨折愈合的影响。Kaplan-Meier曲线生存分析显示，治疗组动物的放射学愈合概率显著高于对照组(P=0.009)。骨痂骨密度(P=0.003，Wilcoxon非参数检验)、断裂载荷(P=0.001)、外刚度(P=0.019)、杨氏模量(P=0.043)和极限强度(P=0.051)也有统计学意义。超声测量结果分析表明，愈合骨的传播速度是早期区分愈合和未愈合骨的重要特征(术后第80天和第100天，ROC曲线下面积分别为0.810和0.841)。LUS应用程序和超声测量都由集成的远程医疗系统支持，该系统还结合了超声可穿戴设备和患者管理系统。(C)2005 Elsevier Inc.保留所有权利。
The purpose of this study is twofold: (a) to investigate the application of transosseous low-intensity pulsed ultrasound (LiUS) on the enhancement of fracture healing and (b) to demonstrate the ability of transosseous ultrasound propagation to monitor the healing process. A midshaft tibial osteotomy model was used on 40 skeletally mature sheep, and an external fixator was applied to maintain the reduction and stabilization of the osteotomy. Two ultrasound transducers were implanted into the fracture site in contact with the bone. For investigating the efficacy of LiUS, the animals were randomly divided in two equal groups: the treatment group and the control group. The LiUS-treated animals received 200-mu s bursts of 1-MHz sine waves with a pulse repetition rate of 1 kHz and average intensity of 30 mW/cm(2), for 20 min daily. For monitoring purposes, an ultrasound dataset was constructed consisting of serial ultrasound measurements obtained from healing bones. Animals' sacrifice took place on the 100th postoperative day. The effect of LiUS on fracture healing was evaluated using radiographs, destructive three-point bending testing and quantitative CT-based bone mineral density (BMD) measurements. Survival analysis using Kaplan-Meier curves showed significantly higher probability of radiographic healing for the animals in the treatment group (P = 0.009). Statistical significance was also observed for callus BMD (P = 0.003, Wilcoxon nonparametric test), the breaking load (P = 0.001), extrinsic stiffness (P = 0.019), Young's modulus (P = 0.043) and ultimate strength (P = 0.051) in favor of the LiUS-treated limbs. Analysis of the obtained ultrasonic measurements showed that the propagation velocity across healing bones constitutes a significant feature able to early distinguish between healed and nonhealed bones (area under ROC curve was 0.810 and 0.841 on the 80th and 100th post-operative days, respectively). Both the LiUS application and the ultrasonic measurements are supported by an integrated telemedicine system which also incorporates an ultrasound wearable device and a patient management system. (c) 2005 Elsevier Inc. All rights reserved.