Continued Development of 4-dimensional Image Warping and Registration Software

描述（由申请人提供）：4维图像变形和配准软件的持续开发摘要：本项目旨在继续4维（4D）图像变形和配准算法的方法学开发、测试和评估，重点是测量大脑结构及其随时间的演变。医学成像的爆炸式增长产生了对开发用于分析医学图像的定量、高度自动化、准确和强大的软件工具的需求。图像配准吸引了特别的科学兴趣，因为它是必要的整合和比较的数据，从个人或群体，以及统计地图集的发展，反映解剖和功能的变化，在一组个人。此外，它还可用于测量结构和功能的时间演变，方法是对同一个体的连续扫描进行共配准，并最终使用它们构建4D统计图谱。尽管已经开发并广泛使用了过多的3D图像配准方法，但是目前缺乏用于鲁棒地测量细微纵向变化的方法，即，结构和功能随时间的变化。目前，纵向变化通常通过首先将标准3D配准方法应用于系列中的各个扫描，然后将某种回归应用于它们来测量。然而，由于3D配准方法的有限精度，并且更重要的是由于在将变化评估为两个独立3D测量之间的差异时放大的各种噪声，理论上和实验上已知估计的纵向变化与实际变化显著不同。我们已经开发了一种称为HAMMER的可变形配准算法，并且是率先将其扩展到完全4D可变形配准方法（4D-HAMMER）的第一组之一，用于同时将连续扫描与图谱配准，并且证明与测量连续扫描中形态变化的细微图案的类似3D配准相比有显著改进。该方法同时分析个体的所有序列扫描，因此它可以评估纵向变化并同时将序列扫描配准到图谱。有效地，该过程减少了噪声的有害影响，因此在测量纵向变化时更准确。显然，为4D-HAMMER设计一个易于使用、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-HAMMER对纵向数据的可变对比度和质量的鲁棒性，以及显著提高其速度，需要进一步开发算法。为了使计算机分析方法的非专家更容易使用，并将这一软件纳入ITK，还计划在软件工程方面作出重大努力。因此，在本项目中，我们将a）进行新的方法开发，以在单个框架内集成和优化4D组织分割和配准，使4D-HAMMER更加准确和稳健，并通过将计算时间从20多个小时减少到几个小时来显著加快4D-HAMMER（目标1）; B）进行一系列验证实验和比较研究，以优化新的4D-HAMMER中的参数，并通过将其与先前的方法以及与两种广泛使用的替代方法进行比较来证明其性能，例如，SPM和基于B样条的扭曲算法（目标2）; c）开发和传播便于用户使用和有良好记录的软件，并将其纳入ITK（目标3-4）。公共卫生相关性：该项目旨在继续四维（4D）图像变形和配准算法的方法学开发、测试和评估，重点是测量大脑结构及其随时间的演变。为了增加4D图像变形算法对纵向数据的可变对比度和质量的鲁棒性，并显著提高其速度，需要进一步的算法开发。还计划在软件工程方面作出重大努力，以提高计算机分析方法的非专家的易用性，并将该软件纳入ITK，使需要使用这种先进的图像分析方法进行纵向研究的广大最终用户受益。随着拟议的方法和软件开发，将向公众提供一个最后的用户友好和有良好记录的软件包，并将其纳入ITK。

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.