Medical image registration is an important task in medical image processing. It refers to the process of aligning data sets, possibly from different modalities (e.g., magnetic resonance and computed tomography), different time points (e.g., follow-up scans), and/or different subjects (in case of population studies). A large number of methods for image registration are described in the literature. Unfortunately, there is not one method that works for all applications. We have therefore developed elastix, a publicly available computer program for intensity-based medical image registration. The software consists of a collection of algorithms that are commonly used to solve medical image registration problems. The modular design of elastix allows the user to quickly configure, test, and compare different registration methods for a specific application. The command-line interface enables automated processing of large numbers of data sets, by means of scripting. The usage of elastix for comparing different registration methods is illustrated with three example experiments, in which individual components of the registration method are varied.

Nonrigid image registration is an important, but time-consuming task in medical image analysis. In typical neuroimaging studies, multiple image registrations are performed, i.e., for atlas-based segmentation or template construction. Faster image registration routines would therefore be beneficial. In this paper we explore acceleration of the image registration package by a combination of several techniques: (i) parallelization on the CPU, to speed up the cost function derivative calculation; (ii) parallelization on the GPU building on and extending the OpenCL framework from ITKv4, to speed up the Gaussian pyramid computation and the image resampling step; (iii) exploitation of certain properties of the B-spline transformation model; (iv) further software optimizations. The accelerated registration tool is employed in a study on diagnostic classification of Alzheimer's disease and cognitively normal controls based on T1-weighted MRI. We selected 299 participants from the publicly available Alzheimer's Disease Neuroimaging Initiative database. Classification is performed with a support vector machine based on gray matter volumes as a marker for atrophy. We evaluated two types of strategies (voxel-wise and region-wise) that heavily rely on nonrigid image registration. Parallelization and optimization resulted in an acceleration factor of 4–5x on an 8-core machine. Using OpenCL a speedup factor of 2 was realized for computation of the Gaussian pyramids, and 15–60 for the resampling step, for larger images. The voxel-wise and the region-wise classification methods had an area under the receiver operator characteristic curve of 88 and 90%, respectively, both for standard and accelerated registration. We conclude that the image registration package was substantially accelerated, with nearly identical results to the non-optimized version. The new functionality will become available in the next release of as open source under the BSD license.

Image registration, the process of aligning two or more images, is the core technique of many (semi-)automatic medical image analysis tasks. Recent studies have shown that deep learning methods, notably convolutional neural networks (ConvNets), can be used for image registration. Thus far training of ConvNets for registration was supervised using predefined example registrations. However, obtaining example registrations is not trivial. To circumvent the need for predefined examples, and thereby to increase convenience of training ConvNets for image registration, we propose the Deep Learning Image Registration (DLIR) framework for unsupervised affine and deformable image registration. In the DLIR framework ConvNets are trained for image registration by exploiting image similarity analogous to conventional intensity-based image registration. After a ConvNet has been trained with the DLIR framework, it can be used to register pairs of unseen images in one shot. We propose flexible ConvNets designs for affine image registration and for deformable image registration. By stacking multiple of these ConvNets into a larger architecture, we are able to perform coarse-to-fine image registration. We show for registration of cardiac cine MRI and registration of chest CT that performance of the DLIR framework is comparable to conventional image registration while being several orders of magnitude faster.

An automatic method for delineating the prostate (including the seminal vesicles) in three-dimensional magnetic resonance scans is presented. The method is based on nonrigid registration of a set of prelabeled atlas images. Each atlas image is nonrigidly registered with the target patient image. Subsequently, the deformed atlas label images are fused to yield a single segmentation of the patient image. The proposed method is evaluated on 50 clinical scans, which were manually segmented by three experts. The Dice similarity coefficient (DSC) is used to quantify the overlap between the automatic and manual segmentations. We investigate the impact of several factors on the performance of the segmentation method. For the registration, two similarity measures are compared: Mutual information and a localized version of mutual information. The latter turns out to be superior (median DeltaDSC approximately equal 0.02, p < 0.01 with a paired two-sided Wilcoxon test) and comes at no added computational cost, thanks to the use of a novel stochastic optimization scheme. For the atlas fusion step we consider a majority voting rule and the "simultaneous truth and performance level estimation" algorithm, both with and without a preceding atlas selection stage. The differences between the various fusion methods appear to be small and mostly not statistically significant (p > 0.05). To assess the influence of the atlas composition, two atlas sets are compared. The first set consists of 38 scans of healthy volunteers. The second set is constructed by a leave-one-out approach using the 50 clinical scans that are used for evaluation. The second atlas set gives substantially better performance (DeltaDSC=0.04, p < 0.01), stressing the importance of a careful atlas definition. With the best settings, a median DSC of around 0.85 is achieved, which is close to the median interobserver DSC of 0.87. The segmentation quality is especially good at the prostate-rectum interface, where the segmentation error remains below 1 mm in 50% of the cases and below 1.5 mm in 75% of the cases.

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.

A novel atlas-based segmentation approach based on the combination of multiple registrations is presented. Multiple atlases are registered to a target image. To obtain a segmentation of the target, labels of the atlas images are propagated to it. The propagated labels are combined by spatially varying decision fusion weights. These weights are derived from local assessment of the registration success. Furthermore, an atlas selection procedure is proposed that is equivalent to sequential forward selection from statistical pattern recognition theory. The proposed method is compared to three existing atlas-based segmentation approaches, namely 1) single atlas-based segmentation, 2) average-shape atlas-based segmentation, and 3) multi-atlas-based segmentation with averaging as decision fusion. These methods were tested on the segmentation of the heart and the aorta in computed tomography scans of the thorax. The results show that the proposed method outperforms other methods and yields results very close to those of an independent human observer. Moreover, the additional atlas selection step led to a faster segmentation at a comparable performance.

A popular technique for nonrigid registration of medical images is based on the maximization of their mutual information, in combination with a deformation field parameterized by cubic B-splines. The coordinate mapping that relates the two images is found using an iterative optimization procedure. This work compares the performance of eight optimization methods: gradient descent (with two different step size selection algorithms), quasi-Newton, nonlinear conjugate gradient, Kiefer-Wolfowitz, simultaneous perturbation, Robbins-Monro, and evolution strategy. Special attention is paid to computation time reduction by using fewer voxels to calculate the cost function and its derivatives. The optimization methods are tested on manually deformed CT images of the heart, on follow-up CT chest scans, and on MR scans of the prostate acquired using a BFFE, T1, and T2 protocol. Registration accuracy is assessed by computing the overlap of segmented edges. Precision and convergence properties are studied by comparing deformation fields. The results show that the Robbins-Monro method is the best choice in most applications. With this approach, the computation time per iteration can be lowered approximately 500 times without affecting the rate of convergence by using a small subset of the image, randomly selected in every iteration, to compute the derivative of the mutual information. From the other methods the quasi-Newton and the nonlinear conjugate gradient method achieve a slightly higher precision, at the price of larger computation times.

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