Nicholas J. Tustison

A reproducible evaluation of ANTs similarity metric performance in brain image registration.

The United States National Institutes of Health (NIH) commit significant support to open-source data and software resources in order to foment reproducibility in the biomedical imaging sciences. Here, we report and evaluate a recent product of this commitment: Advanced Neuroimaging Tools (ANTs), which is approaching its 2.0 release. The ANTs open source software library consists of a suite of state-of-the-art image registration, segmentation and template building tools for quantitative morphometric analysis. In this work, we use ANTs to quantify, for the first time, the impact of similarity metrics on the affine and deformable components of a template-based normalization study. We detail the ANTs implementation of three similarity metrics: squared intensity difference, a new and faster cross-correlation, and voxel-wise mutual information. We then use two-fold cross-validation to compare their performance on openly available, manually labeled, T1-weighted MRI brain image data of 40 subjects (UCLAs LPBA40 dataset). We report evaluation results on cortical and whole brain labels for both the affine and deformable components of the registration. Results indicate that the best ANTs methods are competitive with existing brain extraction results (Jaccard=0.958) and cortical labeling approaches. Mutual information affine mapping combined with cross-correlation diffeomorphic mapping gave the best cortical labeling results (Jaccard=0.669±0.022). Furthermore, our two-fold cross-validation allows us to quantify the similarity of templates derived from different subgroups. Our open code, data and evaluation scripts set performance benchmark parameters for this state-of-the-art toolkit. This is the first study to use a consistent transformation framework to provide a reproducible evaluation of the isolated effect of the similarity metric on optimal template construction and brain labeling.

N4ITK: Improved N3 Bias Correction

A variant of the popular nonparametric nonuniform intensity normalization (N3) algorithm is proposed for bias field correction. Given the superb performance of N3 and its public availability, it has been the subject of several evaluation studies. These studies have demonstrated the importance of certain parameters associated with the B-spline least-squares fitting. We propose the substitution of a recently developed fast and robust B-spline approximation routine and a modified hierarchical optimization scheme for improved bias field correction over the original N3 algorithm. Similar to the N3 algorithm, we also make the source code, testing, and technical documentation of our contribution, which we denote as ¿N4ITK,¿ available to the public through the Insight Toolkit of the National Institutes of Health. Performance assessment is demonstrated using simulated data from the publicly available Brainweb database, hyperpolarized 3He lung image data, and 9.4T postmortem hippocampus data.

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients - manually annotated by up to four raters - and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

Evaluation of Registration Methods on Thoracic CT: The EMPIRE10 Challenge

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 intra patient 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 con figuration 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.

An open source multivariate framework for n-tissue segmentation with evaluation on public data.

We introduce Atropos, an ITK-based multivariate n-class open source segmentation algorithm distributed with ANTs (http://www.picsl.upenn.edu/ANTs). The Bayesian formulation of the segmentation problem is solved using the Expectation Maximization (EM) algorithm with the modeling of the class intensities based on either parametric or non-parametric finite mixtures. Atropos is capable of incorporating spatial prior probability maps (sparse), prior label maps and/or Markov Random Field (MRF) modeling. Atropos has also been efficiently implemented to handle large quantities of possible labelings (in the experimental section, we use up to 69 classes) with a minimal memory footprint. This work describes the technical and implementation aspects of Atropos and evaluates its performance on two different ground-truth datasets. First, we use the BrainWeb dataset from Montreal Neurological Institute to evaluate three-tissue segmentation performance via (1) K-means segmentation without use of template data; (2) MRF segmentation with initialization by prior probability maps derived from a group template; (3) Prior-based segmentation with use of spatial prior probability maps derived from a group template. We also evaluate Atropos performance by using spatial priors to drive a 69-class EM segmentation problem derived from the Hammers atlas from University College London. These evaluation studies, combined with illustrative examples that exercise Atropos options, demonstrate both performance and wide applicability of this new platform-independent open source segmentation tool.

Large-scale evaluation of ANTs and FreeSurfer cortical thickness measurements.

Many studies of the human brain have explored the relationship between cortical thickness and cognition, phenotype, or disease. Due to the subjectivity and time requirements in manual measurement of cortical thickness, scientists have relied on robust software tools for automation which facilitate the testing and refinement of neuroscientific hypotheses. The most widely used tool for cortical thickness studies is the publicly available, surface-based FreeSurfer package. Critical to the adoption of such tools is a demonstration of their reproducibility, validity, and the documentation of specific implementations that are robust across large, diverse imaging datasets. To this end, we have developed the automated, volume-based Advanced Normalization Tools (ANTs) cortical thickness pipeline comprising well-vetted components such as SyGN (multivariate template construction), SyN (image registration), N4 (bias correction), Atropos (n-tissue segmentation), and DiReCT (cortical thickness estimation). In this work, we have conducted the largest evaluation of automated cortical thickness measures in publicly available data, comparing FreeSurfer and ANTs measures computed on 1205 images from four open data sets (IXI, MMRR, NKI, and OASIS), with parcellation based on the recently proposed Desikan-Killiany-Tourville (DKT) cortical labeling protocol. We found good scan-rescan repeatability with both FreeSurfer and ANTs measures. Given that such assessments of precision do not necessarily reflect accuracy or an ability to make statistical inferences, we further tested the neurobiological validity of these approaches by evaluating thickness-based prediction of age and gender. ANTs is shown to have a higher predictive performance than FreeSurfer for both of these measures. In promotion of open science, we make all of our scripts, data, and results publicly available which complements the use of open image data sets and the open source availability of the proposed ANTs cortical thickness pipeline.

The Insight ToolKit image registration framework.

Publicly available scientific resources help establish evaluation standards, provide a platform for teaching and improve reproducibility. Version 4 of the Insight ToolKit (ITK4) seeks to establish new standards in publicly available image registration methodology. ITK4 makes several advances in comparison to previous versions of ITK. ITK4 supports both multivariate images and objective functions; it also unifies high-dimensional (deformation field) and low-dimensional (affine) transformations with metrics that are reusable across transform types and with composite transforms that allow arbitrary series of geometric mappings to be chained together seamlessly. Metrics and optimizers take advantage of multi-core resources, when available. Furthermore, ITK4 reduces the parameter optimization burden via principled heuristics that automatically set scaling across disparate parameter types (rotations vs. translations). A related approach also constrains steps sizes for gradient-based optimizers. The result is that tuning for different metrics and/or image pairs is rarely necessary allowing the researcher to more easily focus on design/comparison of registration strategies. In total, the ITK4 contribution is intended as a structure to support reproducible research practices, will provide a more extensive foundation against which to evaluate new work in image registration and also enable application level programmers a broad suite of tools on which to build. Finally, we contextualize this work with a reference registration evaluation study with application to pediatric brain labeling.1

Optimal Symmetric Multimodal Templates and Concatenated Random Forests for Supervised Brain Tumor Segmentation (Simplified) with ANTsR.

Segmenting and quantifying gliomas from MRI is an important task for diagnosis, planning intervention, and for tracking tumor changes over time. However, this task is complicated by the lack of prior knowledge concerning tumor location, spatial extent, shape, possible displacement of normal tissue, and intensity signature. To accommodate such complications, we introduce a framework for supervised segmentation based on multiple modality intensity, geometry, and asymmetry feature sets. These features drive a supervised whole-brain and tumor segmentation approach based on random forest-derived probabilities. The asymmetry-related features (based on optimal symmetric multimodal templates) demonstrate excellent discriminative properties within this framework. We also gain performance by generating probability maps from random forest models and using these maps for a refining Markov random field regularized probabilistic segmentation. This strategy allows us to interface the supervised learning capabilities of the random forest model with regularized probabilistic segmentation using the recently developed ANTsR package—a comprehensive statistical and visualization interface between the popular Advanced Normalization Tools (ANTs) and the R statistical project. The reported algorithmic framework was the top-performing entry in the MICCAI 2013 Multimodal Brain Tumor Segmentation challenge. The challenge data were widely varying consisting of both high-grade and low-grade glioma tumor four-modality MRI from five different institutions. Average Dice overlap measures for the final algorithmic assessment were 0.87, 0.78, and 0.74 for “complete”, “core”, and “enhanced” tumor components, respectively.

Directly Manipulated Free-Form Deformation Image Registration

Previous contributions to both the research and open source software communities detailed a generalization of a fast scalar field fitting technique for cubic B-splines based on the work originally proposed by Lee . One advantage of our proposed generalized B-spline fitting approach is its immediate application to a class of nonrigid registration techniques frequently employed in medical image analysis. Specifically, these registration techniques fall under the rubric of free-form deformation (FFD) approaches in which the object to be registered is embedded within a B-spline object. The deformation of the B-spline object describes the transformation of the image registration solution. Representative of this class of techniques, and often cited within the relevant community, is the formulation of Rueckert who employed cubic splines with normalized mutual information to study breast deformation. Similar techniques from various groups provided incremental novelty in the form of disparate explicit regularization terms, as well as the employment of various image metrics and tailored optimization methods. For several algorithms, the underlying gradient-based optimization retained the essential characteristics of Rueckerts original contribution. The contribution which we provide in this paper is two-fold: 1) the observation that the generic FFD framework is intrinsically susceptible to problematic energy topographies and 2) that the standard gradient used in FFD image registration can be modified to a well-understood preconditioned form which substantially improves performance. This is demonstrated with theoretical discussion and comparative evaluation experimentation.

Biventricular myocardial strains via nonrigid registration of AnFigatomical NURBS models

We present research in which both left and right ventricular deformation is estimated from tagged cardiac magnetic resonance imaging using volumetric deformable models constructed from nonuniform rational B-splines (NURBS). The four model types considered and compared for the left ventricle include two Cartesian NURBS models-one with a cylindrical parameter assignment and one with a prolate spheroidal parameter assignment. The remaining two are non-Cartesian, i.e., prolate spheroidal and cylindrical each with their respective prolate spheroidal and cylindrical parameter assignment regimes. These choices were made based on the typical shape of the left ventricle. For each frame starting with end-diastole, a NURBS model is constructed by fitting two surfaces with the same parameterization to the corresponding set of epicardial and endocardial contours from which a volumetric model is created. Using normal displacements of the three sets of orthogonal tag planes as well as displacements of contour/tag line intersection points and tag plane intersection points, one can solve for the optimal homogeneous coordinates, in a weighted least squares sense, of the control points of the deformed NURBS model at end-diastole using quadratic programming. This allows for subsequent nonrigid registration of the biventricular model at end-diastole to all later time frames. After registration of the model to all later time points, the registered NURBS models are temporally lofted in order to create a comprehensive four-dimensional NURBS model. From the lofted model, we can extract three-dimensional myocardial deformation fields and corresponding Lagrangian and Eulerian strain maps which are local measures of nonrigid deformation. The results show that, in the case of simulated data, the quadratic Cartesian NURBS models with the cylindrical and prolate spheroidal parameter assignments outperform their counterparts in predicting normal strain. The decreased complexity associated with the Cartesian model with the cylindrical parameter assignment prompted its use for subsequent calculations. Lagrangian strains in three canine data, a normal human, and a patient with history of myocardial infarction are presented. Eulerian strains for the normal human data are also included.