Continued Development of 4-dimensional Image Warping and Registration Software

描述(申请人提供)：4维图像扭曲和配准软件的继续开发摘要：本项目旨在继续4维(4D)图像扭曲和配准算法的方法开发、测试和评估，重点是测量大脑结构及其随时间的演变。医学成像的爆炸性增长产生了对用于分析医学图像的定量、高度自动化、准确和健壮的软件工具的需求。图像配准引起了特别的科学兴趣，因为它对于整合和比较来自个人或群体的数据以及编制反映一组个人内部解剖和功能差异的统计地图集是必要的。此外，它还可以用来测量结构和功能的时间演变，方法是对来自同一个体的连续扫描进行联合配准，并最终使用它们来构建4D统计图谱。虽然已经开发和广泛使用了大量的3D图像配准方法，但目前还缺乏稳健地测量细微的纵向变化的方法，即结构和功能随时间的变化。目前，纵向变化通常是通过首先对系列中的单个扫描应用标准3D配准方法，然后对它们应用某种回归来测量的。然而，由于3D配准方法的精度有限，并且更重要的是，当将变化评估为两个独立的3D测量之间的差异时，估计的纵向变化被放大的各种噪声在理论和实验上都已知与实际的变化显著不同。我们开发了一种名为HAMER的可变形配准算法，并是首批将其扩展到全4D可变形配准方法(4D-HAMER)的小组之一，用于同时将连续扫描与图集共同配准，并展示了与类似的3D配准相比，在测量连续扫描中形态变化的细微模式方面的显著改进。该方法同时分析一个个体的所有序列扫描，从而可以评估纵向变化并同时将序列扫描注册到图谱。这一过程有效地减少了噪声的有害影响，因此在测量纵向变化方面更加准确。显然，为4D-HAMMER设计一个易于使用的、强大的软件包并将其纳入ITK将使需要使用这种先进的图像分析方法进行纵向研究的大量最终用户受益。为了提高4D锤子对不同对比度和纵向数据质量的稳健性，以及显著提高其速度，需要进一步的算法开发。为了提高非计算机分析方法专家的易用性，并将该软件纳入国际交易日志，还计划进行大量的软件工程工作。因此，在这个项目中，我们将a)开展新的方法开发，以便在单一框架内集成和优化4D组织分割和配准，以使4D-HAMER更准确和更健壮，并通过将计算时间从20多小时减少到几个小时来显著提高4D-HAME的速度(目标1)；b)进行一系列验证实验和比较研究，以优化新的4D-HAMER中的参数，并通过与以前的方法以及与两种广泛使用的替代方法，例如基于SPM和B-Spline的WARCHING算法的比较来展示其性能(目标2)；C)开发和传播方便用户的、文件齐全的软件，并将其纳入信息技术转让中心(目标3-4)。与公共卫生相关：该项目旨在继续开发、测试和评估4维(4D)图像扭曲和配准算法的方法学，重点是测量大脑结构及其随时间的演变。为了提高4D图像扭曲算法对不同对比度和纵向数据质量的稳健性，并显著提高其速度，需要进一步的算法开发。还计划进行大量的软件工程工作，以提高非计算机分析方法专家的易用性，并将该软件整合到国际交易日志中，使需要使用这一先进图像分析方法进行纵向研究的大量终端用户受益。随着拟议的方法和软件开发，将向公众提供一个最后的、方便用户的、文件齐全的软件包，并纳入国际交易日志。

DESCRIPTION (provided by applicant): Continued Development of 4-dimensional Image Warping and Registration Software Abstract: This project aims to continue the methodological development, testing and evaluation of a 4-dimensional (4D) image warping and registration algorithm, with emphasis on measurement of brain structure and its evolution over time. The explosive growth of medical imaging has created the need for the development of quantitative, highly automated, accurate, and robust software tools for analysis of medical imagery. Image registration has attracted particular scientific interest, since it is necessary for integration and comparison of data from individuals or groups, as well as for the development of statistical atlases that reflect anatomical and functional variability within a group of individuals. Moreover, it can be used to measure the temporal evolution of structure and function by co-registering serial scans from the same individual, and ultimately using them to construct 4D statistical atlases. Although a plethora of 3D image registration methods has been developed and used extensively, there is currently a scarcity of methods for robustly measuring subtle longitudinal change, i.e., change of structure and function with time. Currently, longitudinal change is typically measured by first applying a standard 3D registration method to individual scans in a series and then applying some sort of regression to them. However, the estimated longitudinal change is known both theoretically and experimentally to be significantly different from the actual one, due to the limited accuracy of the 3D registration methods, and more importantly to all sorts of noises that are amplified when evaluating change as a difference between two independent 3D measurements. We have developed a deformable registration algorithm, called HAMMER, and was among the first groups to pioneer its extension to a fully 4D deformable registration method (4D-HAMMER) for co- registering serial scans to an atlas simultaneously, and to demonstrate the significant improvement compared to analogous 3D registration in measuring subtle patterns of morphological change in serial scans. This approach analyzes all serial scans of an individual at the same time, thus it can assess longitudinal change and register serial scans to the atlas simultaneously. Effectively, this process reduces the detrimental effects of noise, and therefore is more accurate in measuring longitudinal changes. Clearly, designing an easy-to-use, robust software package for 4D-HAMMER and incorporating it into the ITK will benefit a large community of end-users that need access to this advanced image analysis method for longitudinal study. To increase the robustness of the 4D-HAMMER to the variable contrast and quality of longitudinal data, as well as to significantly improve its speed, further algorithm development is necessary. To increase ease of use by non-experts in computer analysis methods and to integrate this software into the ITK, significant software engineering efforts are also planned. Therefore, in this project, we will a) carry out novel methodological developments to integrate and optimize the 4D tissue segmentation and registration within a single framework for rendering the 4D-HAMMER more accurate and robust, and to significantly speed up the 4D-HAMMER by reducing the computational time from over 20 hours to several hours (Aim 1); b) perform a series of validation experiments and comparative studies, to optimize parameters in the new 4D-HAMMER and demonstrate its performance by comparing it with previous one, as well as with the two widely used alternative methods, e.g., SPM and B-spline based warping algorithms (Aim 2); c) develop and disseminate user-friendly and well-documented software, and also incorporate it into ITK (Aims 3-4). PUBLIC HEALTH RELEVANCE: This project aims to continue the methodological development, testing and evaluation of a 4-dimensional (4D) image warping and registration algorithm, with emphasis on measurement of brain structure and its evolution over time. To increase the robustness of the 4D image warping algorithm to the variable contrast and quality of longitudinal data, and to significantly improve its speed, further algorithm development is necessary. Significant software engineering efforts are also planned to increase ease of use by non-experts in computer analysis methods, and to integrate this software into the ITK to benefit a large community of end-users that need access to this advanced image analysis method for longitudinal study. With proposed methodological and software developments, a final user-friendly and well- documented software package, with incorporation into the ITK, will be available to the public.