Package: intensity-normalization
intensity-normalizationThis package contains various methods to normalize the intensity of various modalities of magnetic resonance (MR)
images, e.g., T1-weighted (T1-w), T2-weighted (T2-w), FLuid-Attenuated Inversion Recovery (FLAIR), and Proton
Density-weighted (PD-w).The basic functionality of this package can be summarized in the following image:where the left-hand side are the histograms of the intensities for a set ofunnormalizedimages (from the same scanner
with the same protocol!) and the right-hand side are the histograms after (FCM) normalization.We used this package to explore the impact of intensity normalization on a synthesis task (pre-printavailablehere).Note that while this release was carefully inspected, there may be bugs. Please submit an issue if you encounter a
problem.MethodsWe implement the following normalization methods (the names of the corresponding command-line interfaces are to the
right in parentheses):Individual time-point normalization methodsZ-score normalization (zscore-normalize)Fuzzy C-means (FCM)-based tissue-based mean normalization (fcm-normalize)Kernel Density Estimate (KDE) WM mode normalization (kde-normalize)WhiteStripe[1](ws-normalize)Sample-based normalization methodsLeast squares (LSQ) tissue mean normalization (lsq-normalize)Piecewise Linear Histogram Matching (Nyúl & Udupa)[2][3](nyul-normalize)RAVEL[4](ravel-normalize)Individual image-basedmethods normalize images based on one time-point of one subject.Sample-basedmethods normalize images based on asetof images of (usually) multiple subjects of the same
modality.Recommendation on where to start: If you are unsure which one to choose for your application, try FCM-based WM-based
normalization (assuming you have access to a T1-w image for all the time-points). If you are getting odd results in
non-WM tissues, try least squares tissue normalization (which minimizes the least squares distance between CSF, GM, and
WM tissue means within a set).Read about the methods and how they work.
If you have a non-standard modality, e.g., a contrast-enhanced image, read about how the methods work and
determine which method would work for your use case. Make sure you plot the foreground intensities (with
the-poption in the CLI or theHistogramPlotterin the Python API) to validate the normalization results.All algorithms except Z-score(zscore-normalize)and the Piecewise Linear Histogram Matching(nyul-normalize)are specific to images of the brain.MotivationIntensity normalization is an important pre-processing step in many image processing applications regarding MR images
since MR images have an inconsistent intensity scale across (and within) sites and scanners due to, e.g.,:the use of different equipment,different pulse sequences and scan parameters,and a different environment in which the machine is located.Importantly, the inconsistency in intensitiesisn’t a featureof the data (unless you want to classify the
scanner/site from which an image came)—it’s an artifact of the acquisition process. The inconsistency causes a problem
with machine learning-based image processing methods, which usually assume the data was gathered iid from some
distribution.InstallThe easiest way to install the package is through the following command:pip install intensity-normalizationTo install from the source directory, clone the repo and run:python setup.py installNote the packageantspyis required for the RAVEL normalization routine, the
preprocessing tool as well as the co-registration tool, but all other normalization and processing tools work without
it. To install the antspy package along with the RAVEL, preprocessing, and co-registration CLI, install with:pip install "intensity-normalization[ants]"Basic UsageSee the5 minute overviewfor a more detailed tutorial.In addition to the above small tutorial, here is consolidateddocumentation.Call any executable script with the-hflag to see more detailed instructions about the proper call.Note thatbrain masks(or already skull-stripped images) are required for most of the normalization methods. The
brain masks do not need to be perfect, but each mask needs to remove most of the tissue outside the brain. Assuming you
have T1-w images for each subject, an easy and robust method for skull-stripping
isROBEX[5].If the images are already skull-stripped, you don’t need to provide a brain mask. The foreground will be
automatically estimated and used.You can install ROBEX—and get python bindings for it at the same time–with the
packagepyrobex(installable viapip install pyrobex).Individual time-point normalization methodsExample call to a individual time-point normalization CLI:fcm-normalize t1w_image.nii -m brain_mask.niiSample-based normalization methodsExample call to a sample-based normalization CLI:nyul-normalize images/ -m masks/ -o nyul_normalized/ -vwhereimages/is a directory full of N MR images andmasks/is a directory full of N corresponding brain masks,nyul_normalizedis the output directory for the normalized images, and-vcontrols the verbosity of the output.The command line interface is standard across all sampled-based normalization routines (i.e., you should be able to run
all sample-based normalization routines with the same call as in the above example); however, each has unique
method-specific options.Potential PitfallsThis package was developed to processadult humanMR images; neonatal, pediatric, and animal MR imagesshouldalso work but—if the data has different proportions of tissues or differences in relative intensity among tissue
types compared with adults—the normalization may fail. Thenyul-normalizemethod, in particular, will fail hard if
you train it on adult data and test it on non-adult data (or vice versa). Please open an issue if you encounter a
problem with the package when normalizing non-adult human data.When we refer to any specific modality, it is referring to anon-contrastversion unless otherwise stated. Using
a contrast image as input to a method that assumes non-contrast will produce suboptimal results. One potential way to
normalize contrast images with this package is to 1) find a tissue that is not affected by the contrast (e.g., grey
matter) and normalize based on some summary statistic of that (where the tissue mask was found on a non-contrast
image); 2) use a simplistic (but non-robust) method like Z-score normalization.Read about the methodsand how they work
to decide which method would work best for your contrast-enhanced images.ContributingHelp wanted!SeeCONTRIBUTING.rstfor details and/or reach out to me if you’d like to contribute. Credit will be given!
If you want to add a method, I’ll be happy to add your reference to the citation
section below.Test PackageUnit tests can be run from the main directory as follows:pytest testsCitationIf you use theintensity-normalizationpackage in an academic paper, please cite the
correspondingpaper:@inproceedings{reinhold2019evaluating,
  title={Evaluating the impact of intensity normalization on {MR} image synthesis},
  author={Reinhold, Jacob C and Dewey, Blake E and Carass, Aaron and Prince, Jerry L},
  booktitle={Medical Imaging 2019: Image Processing},
  volume={10949},
  pages={109493H},
  year={2019},
  organization={International Society for Optics and Photonics}}References[1]R. T. Shinohara, E. M. Sweeney, J. Goldsmith, N. Shiee, F. J. Mateen, P. A. Calabresi, S. Jarso, D. L. Pham, D. S.
Reich, and C. M. Crainiceanu, “Statistical normalization techniques for magnetic resonance imaging,” NeuroImage Clin.,
vol. 6, pp. 9–19, 2014.[2]N. Laszlo G and J. K. Udupa, “On Standardizing the MR Image Intensity Scale,” Magn. Reson. Med., vol. 42, pp.
1072–1081, 1999.[3]M. Shah, Y. Xiao, N. Subbanna, S. Francis, D. L. Arnold, D. L. Collins, and T. Arbel, “Evaluating intensity
normalization on MRIs of human brain with multiple sclerosis,” Med. Image Anal., vol. 15, no. 2, pp. 267–282, 2011.[4]J. P. Fortin, E. M. Sweeney, J. Muschelli, C. M. Crainiceanu, and R. T. Shinohara, “Removing inter-subject technical
variability in magnetic resonance imaging studies,” NeuroImage, vol. 132, pp. 198–212, 2016.[5]Iglesias, Juan Eugenio, Cheng-Yi Liu, Paul M. Thompson, and Zhuowen Tu. “Robust brain extraction across datasets and
comparison with publicly available methods.” IEEE transactions on medical imaging 30, no. 9 (2011): 1617-1634.History2.2.4 (2023-05-31)Update to allow Python >=3.92.2.3 (2022-03-15)Revert error on different image shapes fromRavelNormalize; it is required!2.2.2 (2022-03-15)Remove plural fromModalityandTissueTypeenumerations.Update tutorials to use theModalityandTissueTypeenumerations.Remove error on different image shapes fromRavelNormalizewhen registration enabled.2.2.1 (2022-03-14)Update documentation to support modifications to Python APIUpdate dependenciesRemove incorrect warning from WhiteStripe normalization2.2.0 (2022-02-25)Change backend topymedioto support more medical image formats2.1.4 (2022-01-17)Fix testing bugs in 2.1.3 and cleanup some interfaces2.1.3 (2022-01-17)Cleanup Makefile and dependenciesAdd py.typed file2.1.2 (2022-01-03)Updates for security2.1.1 (2021-10-20)Fix warning about negative values when not passing in a maskRemove redundant word from Nyul normalize keyword arguments2.1.0 (2021-10-13)Restructure CLIs for faster startup and improve handling of missing antspyadd option to CLIs to print version2.0.3 (2021-10-11)Improve Nyul docs and argument/keyword names2.0.2 (2021-09-27)Fix and improve documentationAdd an escape-hatch “other” modalityAdd peak types as modalities in KDE & WS2.0.1 (2021-08-31)Save and load fit artifacts for LSQ and Nyul for both the CLIs and Python API2.0.0 (2021-08-22)Major refactor to reduce redundancy, make code more usable outside of the CLIs, and generally improve code quality.1.4.0 (2021-03-16)First release on PyPI.