Advanced Normalization Tools Quick Reference

Brian B. Avants
2016-08-08

Introduction

Advanced Normalization Tools1 is software for biomedical 1

http://stnava.github.io/ANTs/

image analysis with a focus on registration, segmentation, geomet-

ric quantification and statistics. Statistical methods are available in
ANTsR 2 which tightly integrates ANTs with the R statistical comput- 2
http://stnava.github.io/ANTsR/

ing language. This document briefly highlights ANTs features.

Provenance and Testing

Much core functionality in ANTs lives in ITK, a project to which we

contribute regularly. This core is tested on many platforms via ctest
and the results are on the ITK dashboard3 . ANTs is also tested with 3
https://open.cdash.org/index.php?
project=Insight
every commit via codeship 4 and Travis 5 . Many (not all) ANTs pro- 4
https://codeship.com
grams support programName --version. Our github commit hashes 5
https://travis-ci.org/stnava/ANTs
give the best way to track code versions by identifying core and de-
pendency versions. See the ANTs website for current testing results
and installation instructions.

In conjunction with other analysis systems

ANTs and ITK work synergistically within a well-defined I/O and

world coordinate system. Using FSL, SPM or other pre-processing in
conjunction with ITK and ANTs must be done with extreme care. The
physical spaces (or interpretation of image headers) may not be the
same in different systems. Such inconsistencies may lead to severe
misinterpretation of results. WARNING!

Data types

Images
Images are the core data type in ANTs. Valid extensions are deter-
mined by ITK 6 image input/output libraries 7 . ITK images can be of 6
www.itk.org
arbitrary dimensionality and pixel type, but in ANTs we instantiate 7
NiftiImageIO, NrrdImageIO, GiplIm-
ageIO, HDF5ImageIO, JPEGImageIO,
float pixel type in 2, 3 or 4 dimensions.
GDCMImageIO, BMPImageIO, LSMIm-
ageIO, PNGImageIO, TIFFImageIO,
VTKImageIO, StimulateImageIO, BIO-
RadImageIO, MetaImageIO, MRCIm-
ageIO, GE4ImageIO, GE5ImageIO,
MGHImageIO
 advanced normalization tools quick reference 2

CSV files and point sets

CSV (comma separated value) files are useful for storing tabular
data. We may also use them to store point sets. It is critical when
using point sets with ANTs to ensure that the physical space of the
points matches that of the images. It is best to start with our standard
example of registering images and applying the results to points 8 . 8
https://github.com/stnava/chicken

Point sets may also be stored in the binary format provided by the
Meta I/O library 9 . This format allows much faster I/O for large 9
http://www.itk.org/Wiki/ITK/
MetaIO/Documentation
datasets.

Registration

The most well-known components of ANTs relate to mapping be-

tween coordinate systems 10 . Briefly, these maps may relate to: 10
Registration: targeting of points in
one coordinate system onto another
• statistical image similarity: image difference, correlation or mutual
information

• translation, rotation, affine, B-spline or various diffeomorphic

models 11 Diffeomorphism: differentiable map
11

with differentiable inverse

• spatial or spatiotemporal maps
• dense or sparse transformation models, the latter being similar to
SIFT or HOGG
• applying composite transformations to images, labels or point sets.

These components all exist within an integrated framework which

is nearly always capable of incorporating many features or applying
to multiple different modalities.12 12
http://journal.frontiersin.org/
article/10.3389/fninf.2014.00044/
abstract
Evaluation history
ANTs became well known because it performed well in a variety
of open competitions related to image registration. Most of these
successes occurred in the days before the community had many such
competitions. 13 Highlights include: Klein 2009, Murphy 2011, SATA 201*,
13

BRATS 2013, etc.

• finishing in the top rank in the Klein 2009 evaluation on brain MRI

• finishing in the top rank in the Murphy 2011 lung CT evaluation

• top SATA 2012 and 2013 finishers used ANTs

• performing well in a cardiac motion estimation competition

• well-known robust performance on large datasets

 advanced normalization tools quick reference 3

Although ANTs has often performed well without using domain

knowledge, it is still valuable to use problem-specific solutions when
feasible.

Quick start
ANTsR gives some quick registration options. One can achieve simi-
lar performance with antsRegistrationSyNQuick.sh.

fi <- antsImageRead(getANTsRData("r16"))
mi <- antsImageRead(getANTsRData("r64"))
mytxr <- antsRegistration(fixed = fi, moving = mi,
typeofTransform = c("Rigid"))
mywarpedimager <- antsApplyTransforms(fixed = fi,
moving = mi, transformlist = mytxr$fwdtransforms)
mytx <- antsRegistration(fixed = fi, moving = mi,
typeofTransform = c("SyN"))
mywarpedimage <- antsApplyTransforms(fixed = fi,
moving = mi, transformlist = mytx$fwdtransforms)

invisible(plot(fi, mi %>% iMath("Canny", 1, 5,

12)))

invisible(plot(fi, mywarpedimager %>% iMath("Canny",

1, 5, 12)))

invisible(plot(fi, mywarpedimage %>% iMath("Canny",

1, 5, 12)))

Low-dimensional
translation, rigid, affine - optional multi-start exploration of the trans-
formation space (antsAI)

High-dimensional
transformations with many parameters - primarily SyN and B-spline
SyN as well as time-varying diffeomorphic models.

Parameter choices and testing

We wrote a paper that details procedures for evaluating analysis
software 14 . We wrote this paper in order to help those who want to 14
http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3766821/
use or evaluate ANTs make more informed choices on how to pro-
ceed. Briefly: (1) ask developers questions; (2) leverage biologically
motivated testing metrics that are independent of registration.
advanced normalization tools quick reference 4

Figure 1: initial relative image positions

advanced normalization tools quick reference 5

Figure 2: rigidly aligned image posi-

tions
advanced normalization tools quick reference 6

Figure 3: quick deformable registration

 advanced normalization tools quick reference 7

Segmentation, geometry and labeling

This category of methods relates to labeling and quantifying images.

These methods may require data of reasonable quality to perform
well. WARNING!

N4
Nick’s N3 15 improves the original N3 inhomogeneity correction 15
http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3071855/
method.

ficorrupt = as.antsImage(as.array(fi) * 1:length(fi[fi >=

0]))
fifixed = n4BiasFieldCorrection(ficorrupt)

invisible(plot(ficorrupt))

Figure 4: corrupted image

invisible(plot(fifixed))
advanced normalization tools quick reference 8

Figure 5: n4 repair
 advanced normalization tools quick reference 9

Atropos
Expecation maximization segmentation with a variety of likelihood
models and initialization strategies. Incorporates multiple modalities
and allows control of prior strength. The finite mixture modeling
(FMM) segmentation approach is the most popular. Prior constraints
include the specification of a prior label image, prior probability
images (one for each class), and/or an MRF prior to enforce spatial
smoothing of the labels.

img <- antsImageRead(getANTsRData("r16"))

mask <- getMask(img)
segs1 <- kmeansSegmentation(img, 3, mask)

# Use probabilities from k-means seg as priors

feats <- list(img, iMath(img, "Laplacian"), iMath(img,
"Grad"))
segs2 <- atropos(d = 2, a = feats, m = "[0.2,1x1]",
c = "[2,0]", i = segs1$probabilityimages,
x = mask)

invisible(plot(fi, segs1$segmentation))

invisible(plot(fi, segs2$segmentation))

Weingarten map-based surface curvature and area

The shape operator provides a beautiful way to compute the mean or
Gaussian curvature (or related values) in any three-dimensional im-
age 16 . The ANTs program that implements this is called SurfaceCurvature16. http://www.ncbi.nlm.nih.gov/
pubmed/15344450

fi <- antsImageRead(getANTsRData("mni"))
fiseg = kmeansSegmentation(fi, 3)
fik <- weingartenImageCurvature(fi)

invisible(plot(fik, axis = 3))

fisulc = antsImageClone(fik) * 0
selector = (fiseg$segmentation == 2 & fik < 0)
fisulc[selector] = fik[selector]
invisible(plot(fi, fisulc, axis = 3))
advanced normalization tools quick reference 10

Figure 6: kmeans result

advanced normalization tools quick reference 11

Figure 7: prior probability result with 2

feature channels

Figure 8: shape operator in 3D

 advanced normalization tools quick reference 12

Figure 9: shape operator selects sulci

Cortical thickness pipeline

You can use antsCorticalThickness.sh to reproduce our lifespan

thickness analysis from the Freesurfer evaluation paper 17 . 17
http://www.ncbi.nlm.nih.gov/
pubmed/24879923

img <- antsImageRead(getANTsRData("r16"), 2)

mask <- getMask(img)
segs <- kmeansSegmentation(img, k = 3, kmask = mask)
thk <- kellyKapowski(s = segs$segmentation, g = segs$probabilityimages[[2]],
w = segs$probabilityimages[[3]], its = 45,
r = 0.5, m = 1)

invisible(plot(img, thk, window.overlay = c(0.1,

max(thk))))

Multiple modality pipeline

You can use our neurobattery to reproduce our adolescent multiple

modality analysis from the paper 18 . The neurobattery is online and 18
http://www.nature.com/articles/
sdata20153
administered by Jeffrey T. Duda 19 . 19
https://github.com/jeffduda/
NeuroBattery

Brain mapping in the presence of lesions or other obstructions

Our fully automated registration and segmentation approach for the

lesioned or occluded brain uses machine learning to identify and
down-weight missing data. One may also use pre-identified inclusive
masks to focus registration on healthy tissue 20 . 20
antsRegistration -d 3
... etcetera ... -x
healthyTissueMask.nii.gz
advanced normalization tools quick reference 13

Figure 10: thickness calculation

 advanced normalization tools quick reference 14

Statistical pipelines

ANTs-based statistical pipelines are best accessed through ANTsR. We

use these pipelines for:

• estimating cerebral blood flow with robust and data-driven meth-

ods

• performing structural and functional connectivity measurements

• employing biologically-regularized dimensionality reduction for

hypothesis testing

• implementing exploratory multivariate analysis tools such as

sparse canonical correlation analysis for neuroimaging 21 21
http://www.sciencedirect.
com/science/article/pii/
• performing prediction studies 22
S1053811913009841
22
http://www.sciencedirect.
• associating modalities 23 com/science/article/pii/
S1046202314003338
and more basic studies such as mass univariate regression. 23
http://www.sciencedirect.
com/science/article/pii/
S105381191400891X
Overview of ANTs programs

ANTs executables come in either binary ( compiled from C++ ) or

script form ( usually bash or R ). Here, we summarize the relevant
programs.

Table 1: ANTs transformation programs

program description
4 ANTSIntegrateVectorField ode integration of vector field
5 ANTSIntegrateVelocityField ode integration of velocity field
8 ANTSUseLandmarkImagesToGetAffineTransform fit affine tx to landmarks
12 AverageAffineTransform average affine transformations
13 AverageAffineTransformNoRigid average affine transformations without rigid part
19 CompositeTransformUtil dis/assembles composite transform files
25 ConvertTransformFile convert mat to txt, for example
30 CreateJacobianDeterminantImage compute deformation gradient from displacement
38 FitBSplineToPoints fit bspline to point set
64 ReorientTensorImage reorient tensors by transformation
85 antsAI multi-start low-dimensional registration
88 antsAffineInitializer see antsAI
89 antsAlignOrigin basic origin alignment
90 antsApplyTransforms apply (multiple) transformations to image types
91 antsApplyTransformsToPoints apply (multiple) transformations to points
96 antsIntermodalityIntrasubject.sh example of how to map within subject
 advanced normalization tools quick reference 15

program description
103 antsMotionCorr time series motion correction
104 antsMotionCorrDiffusionDirection DWI specific motion correction
106 antsMotionCorrStats summarize antsMotionCorr output
107 antsMultivariateTemplateConstruction.sh multiple modality templates
108 antsMultivariateTemplateConstruction2.sh multiple modality templates
111 antsRegistration standard registration algorithms
112 antsRegistrationSpaceTime.sh spatiotemporal registration methods
113 antsRegistrationSyN.sh default decent quality registration
114 antsRegistrationSyNQuick.sh default fast registration
115 antsSliceRegularizedRegistration see spinal cord toolbox
132 geodesicinterpolation.sh shape-based interpolate two images
133 guidedregistration.sh example of landmark based registration
137 landmarkmatch.sh example of landmark based registration

Table 2: ANTs segmentation programs

program description
11 Atropos EM segmentation framework and tools
49 LabelClustersUniquely label each isolated region
77 ThresholdImage simple image thresholding
92 antsAtroposN4.sh joint segmentation and bias correction
94 antsBrainExtraction.sh brain extraction via registration and segmentation
98 antsJointFusion better JLF implementation
99 antsJointLabelFusion.sh better JLF script
150 skel.sh topological skeleton of segmentation
163 mrvnrf machine learning segmentation - see ANTsR

Table 3: ANTs processing programs

program description
14 AverageImages average list of images
15 AverageTensorImages average list of tensor images
21 ConvertImagePixelType change pixel type
34 DenoiseImage non-local denoising
39 GetConnectedComponentsFeatureImages ?
45 ImageMath basic processing operations on images
47 KellyKapowski image-based thickness estimator
50 LabelGeometryMeasures measure geometry of labeled regions
58 N3BiasFieldCorrection ancient bias corrector
59 N4BiasFieldCorrection better bias corrector
 advanced normalization tools quick reference 16

program description
63 RebaseTensorImage map tensor into new basis
71 SmoothImage smooth in given units
73 SurfaceBasedSmoothing smoothing restricted to segmentation
74 SurfaceCurvature shape operator curvature
75 TextureCooccurrenceFeatures texture based statistics
76 TextureRunLengthFeatures texture based statistics
86 antsASLProcessing.R BMKandel ASL processing
87 antsASLProcessing.sh BMKandel ASL processing
95 antsCorticalThickness.sh brain thickness pipeline
101 antsLongitudinalCorticalThickness.sh longitudinal brain thickness pipeline
110 antsNeuroimagingBattery align MR modalities to common space

Table 4: ANTs statistics programs

program description
27 CreateDTICohort simulate DTI population
44 ImageIntensityStatistics simple summary stats for image +/- ROIs
46 ImageSetStatistics compute mean, median, etc of images
51 LabelOverlapMeasures compute overlaps
54 MeasureImageSimilarity similarity between image pairs
55 MeasureMinMaxMean basic stats on an image
79 TimeSCCAN cca for temporal images
146 sccan utility for sparse decomposition - see ANTsR

Table 5: ANTs visualization programs

program description
23 ConvertScalarImageToRGB use lookup table to make RBG from gray
31 CreateTiledMosaic tile images for viewing
32 CreateWarpedGridImage make a warped grid from displacement
72 StackSlices stack up a population of image slices
78 TileImages collect images in tile form for viewing
116 antsSurf surface rendering and other operations

Table 6: ANTs utility programs

program description
10 ANTSpexec.sh helper for parallel execution
 advanced normalization tools quick reference 17

program description
26 CopyImageHeaderInformation copy header from one image to another
28 CreateDisplacementField make vector field from component images
29 CreateImage make an image
35 ExtractRegionFromImage get subset of image using indices
36 ExtractRegionFromImageByMask get subset of image using mask
37 ExtractSliceFromImage get slice from image
41 ITK_bld_internal_H5detect ?
42 ITK_bld_internal_H5make_libsettings ?
43 ImageCompare see if images are nearly the same
56 MemoryTest memory profiler
57 MultiplyImages multiply image1 by x
60 PasteImageIntoImage put one image in another
61 PermuteFlipImageOrientationAxes flip or permute image
62 PrintHeader image header information
65 ResampleImage change image resolution
66 ResampleImageBySpacing change image resolution
67 ResetDirection change image direction to identity
68 SetDirectionByMatrix change image direction
69 SetOrigin set origin in image
70 SetSpacing set spacing in image
117 antsTransformInfo investigate a transformation
118 antsUtilitiesTesting see how metric changes with tx
130 compareTwoTransforms as described
157 waitForPBSQJobs.pl utility
158 waitForSGEQJobs.pl utility
159 waitForXGridJobs.pl utility