Department of Electronic Engineering, City University of Hong Kong, Hong Kong.
Phys Med Biol. 2013 Sep 7;58(17):5959-82. doi: 10.1088/0031-9155/58/17/5959. Epub 2013 Aug 12.
With the advent of new therapies and management strategies for carotid atherosclerosis, there is a parallel need for measurement tools or biomarkers to evaluate the efficacy of these new strategies. 3D ultrasound has been shown to provide reproducible measurements of plaque area/volume and vessel wall volume. However, since carotid atherosclerosis is a focal disease that predominantly occurs at bifurcations, biomarkers based on local plaque change may be more sensitive than global volumetric measurements in demonstrating efficacy of new therapies. The ultimate goal of this paper is to develop a biomarker that is based on the local distribution of vessel-wall-plus-plaque thickness change (VWT-Change) that has occurred during the course of a clinical study. To allow comparison between different treatment groups, the VWT-Change distribution of each subject must first be mapped to a standardized domain. In this study, we developed a technique to map the 3D VWT-Change distribution to a 2D standardized template. We then applied a feature selection technique to identify regions on the 2D standardized map on which subjects in different treatment groups exhibit greater difference in VWT-Change. The proposed algorithm was applied to analyse the VWT-Change of 20 subjects in a placebo-controlled study of the effect of atorvastatin (Lipitor). The average VWT-Change for each subject was computed (i) over all points in the 2D map and (ii) over feature points only. For the average computed over all points, 97 subjects per group would be required to detect an effect size of 25% that of atorvastatin in a six-month study. The sample size is reduced to 25 subjects if the average were computed over feature points only. The introduction of this sensitive quantification technique for carotid atherosclerosis progression/regression would allow many proof-of-principle studies to be performed before a more costly and longer study involving a larger population is held to confirm the treatment efficacy.
随着颈动脉粥样硬化新疗法和管理策略的出现，需要有测量工具或生物标志物来评估这些新策略的疗效。三维超声已被证明可提供斑块面积/体积和血管壁体积的可重复测量。然而，由于颈动脉粥样硬化是一种局灶性疾病，主要发生在分叉处，因此基于局部斑块变化的生物标志物在证明新疗法的疗效方面可能比整体容积测量更敏感。本文的最终目标是开发一种基于血管壁加斑块厚度变化（VWT-Change）的局部分布的生物标志物，该生物标志物在临床研究过程中发生。为了能够在不同的治疗组之间进行比较，必须首先将每个受试者的 VWT-Change 分布映射到标准化域。在本研究中，我们开发了一种将 3D VWT-Change 分布映射到 2D 标准化模板的技术。然后，我们应用特征选择技术来识别 2D 标准化图上的区域，在这些区域中，不同治疗组的受试者在 VWT-Change 上表现出更大的差异。将所提出的算法应用于阿托伐他汀（立普妥）对安慰剂对照研究中 20 例受试者的 VWT-Change 进行分析。为每个受试者计算（i）在 2D 图中的所有点上和（ii）仅在特征点上的平均 VWT-Change。对于在所有点上计算的平均值，如果在 6 个月的研究中要检测阿托伐他汀 25%的效果大小，则每组需要 97 例受试者。如果仅计算特征点上的平均值，则样本量减少到 25 例。这种用于颈动脉粥样硬化进展/消退的敏感定量技术的引入将允许在进行涉及更大人群的更昂贵和更长的研究以确认治疗效果之前，进行许多原理验证研究。
