Skip to main content

Advertisement

Log in

An Open Source Multivariate Framework for n-Tissue Segmentation with Evaluation on Public Data

  • Original Article
  • Published:
Neuroinformatics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Listing 1
Fig. b
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Notes

  1. Atropos is one of the three Fates from Greek mythology characterized by her dreaded shears used to decide the destiny of each mortal. Also, consistent with the entomological motif of our ANTs, Acherontia atropos is a species of large moth known for the skull-like pattern visible on its thorax.

  2. In the classic 3-tissue segmentation case, each voxel in the brain region is assigned a label of ‘cerebrospinal fluid (csf)’, ‘gray matter (gm)’, or ‘white matter (wm)’.

  3. Using a more expansive definition of U(x),

    $$ U(\mathbf{x}) = \sum\limits_{i = 1}^N \left( V_i(x_i) + \beta \sum\limits_{j \in \mathcal{N}_i} V_{ij}( x_i, x_j ) \right) $$

    would permit casting the other prior terms inside the definition of U(x) in the form of the external field V i (x i ) but, for clarity purposes, we consider them separately.

  4. Due to the lack of parameters in the non-parametric approach, it is not technically an EM algorithm (as described in Wells et al. (1996)). However, the same iterative maximization is applicable and is quite robust in practice as evidenced by the number of researchers employing non-parametric models (see the Introduction).

  5. Consider N sites each with a possible K labels for a total of N K possible labeling configurations. For large K ≫ 3, exact optimization is even more intractable than for the traditional 3-tissue scenario.

  6. http://www.itk.org/Doxygen/html/classitk_1_1N4MRIBiasFieldCorrectionImageFilter.html

  7. A comprehensive evaluation of N4 reported in Tustison et al. (2010a) used the BrainWeb data set to compare performance with the original N3 algorithm (Sled et al. 1998).

References

  • Ashburner, J., & Friston, K. J. (2005). Unified segmentation. Neuroimage, 26, 839–851.

    Article  PubMed  Google Scholar 

  • Aubert-Broche, B., Griffin, M., Pike, G. B., Evans, A. C., & Collins, D. L. (2006). Twenty new digital brain phantoms for creation of validation image data bases. IEEE Transactions on Medical Imaging, 25, 1410–1416.

    Article  PubMed  Google Scholar 

  • Avants, B. B., Yushkevich, P., Pluta, J., Minkoff, D., Korczykowski, M., Detre, J., et al. (2010a). The optimal template effect in hippocampus studies of diseased populations. Neuroimage, 49, 2457–2466.

    Article  PubMed  Google Scholar 

  • Avants, B., Klein, A., Tustison, N., Woo, J., & Gee, J. C. (2010b). Evaluation of open-access, automated brain extraction methods on multi-site multi-disorder data. In 16th annual meeting for the Organization of Human Brain Mapping.

  • Avants, B., Cook, P. A., McMillan, C., Grossman, M., Tustison, N. J., Zheng, Y., et al. (2010c). Sparse unbiased analysis of anatomical variance in longitudinal imaging. In Proceedings of the 13th international conference on medical image computing and computer-assisted intervention (MICCAI) (Vol. 13, pp. 324–331).

  • Avants, B. B., Tustison, N. J., Song, G., Cook, P. A., Klein, A., & Gee, J. C. (2011). A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage, 54, 2033–2044.

    Article  PubMed  Google Scholar 

  • Awate, S. P., Tasdizen, T., Foster, N., & Whitaker, R. T. (2006). Adaptive Markov modeling for mutual-information-based, unsupervised MRI brain-tissue classification. Medical Image Analysis, 10, 726–739.

    Article  PubMed  Google Scholar 

  • Balafar, M. A., Ramli, A. R., Saripan, M. I., & Mashohor, S. (2010). Review of brain MRI image segmentation methods. Artificial Intelligence Review, 33, 261–274.

    Article  Google Scholar 

  • Ballester, M. A. G., Zisserman, A. P., & Brady, M. (2002). Estimation of the partial volume effect in MRI. Medical Image Analysis, 6, 389–405.

    Article  Google Scholar 

  • Battaglini, M., Smith, S. M., Brogi, S., & Stefano, N. D. (2008). Enhanced brain extraction improves the accuracy of brain atrophy estimation. Neuroimage, 40, 583–589.

    Article  PubMed  Google Scholar 

  • Bazin, P. L., & Pham, D. L. (2007). Topology-preserving tissue classification of magnetic resonance brain images. IEEE Transactions on Medical Imaging, 26, 487–496.

    Article  PubMed  Google Scholar 

  • Besag, J. (1974). Spatial interaction and the statistical analysis of lattice systems. Journal of the Royal Royal Statistical Society B, 36, 192–236.

    Google Scholar 

  • Besag, J. (1986). On the statistical analysis of dirty pictures. Journal of the Royal Royal Statistical Society, Series B, 48, 259–302.

    Google Scholar 

  • Bezdek, J. C., Hall, L. O., & Clarke, L. P. (1993). Review of MR image segmentation techniques using pattern recognition. Medical Physics, 20, 1033–1048.

    Article  PubMed  CAS  Google Scholar 

  • Boyes, R. G., Gunter, J. L., Frost, C., Janke, A. L., Yeatman, T., Hill, D. L. G., et al. (2008). Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils. Neuroimage, 39, 1752–1762.

    Article  PubMed  Google Scholar 

  • Boykov, Y. Y., & Jolly, M. P. (2001). Interactive graph cuts for optimal boundary & region segmentation of objects in N-D images. In Proc. eighth IEEE int. conf. computer vision ICCV 2001 (Vol. 1, pp. 105–112).

  • Boykov, Y., & Kolmogorov, V. (2004). An experimental comparison of min-cut/max-flow algorithms for energy minimization in vision. IEEE Transactions on Pattern Analysis amd Machine Intelligence, 26, 1124–1137.

    Article  Google Scholar 

  • Chou, Y. Y., Leporã, N., Avedissian, C., Madsen, S. K., Parikshak, N., Hua, X., et al. (2009). Mapping correlations between ventricular expansion and CSF amyloid and tau biomarkers in 240 subjects with Alzheimer’s disease, mild cognitive impairment and elderly controls. Neuroimage, 46, 394–410.

    Article  PubMed  Google Scholar 

  • Clarke, L. P., Velthuizen, R. P., Camacho, M. A., Heine, J. J., Vaidyanathan, M., Hall, L. O., et al. (1995). MRI segmentation: Methods and applications. Magnetic Resonance Imaging, 13, 343–368.

    Article  PubMed  CAS  Google Scholar 

  • Cline, H. E., Lorensen, W. E., Kikinis, R., & Jolesz, F. (1990). Three-dimensional segmentation of MR images of the head using probability and connectivity. Journal of Computer Assisted Tomography, 14, 1037–1045.

    Article  PubMed  CAS  Google Scholar 

  • Cuadra, M. B., Cammoun, L., Butz, T., Cuisenaire, O., & Thiran, J. P. (2005). Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images. IEEE Transactions on Medical Imaging, 24, 1548–1565.

    Article  PubMed  Google Scholar 

  • Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage, 9, 179–194.

    Article  PubMed  CAS  Google Scholar 

  • de Boer, R., Vrooman, H. A., Ikram, M. A., Vernooij, M. W., Breteler, M. M. B., van der Lugt, A., et al. (2010). Accuracy and reproducibility study of automatic MRI brain tissue segmentation methods. Neuroimage, 51, 1047–1056.

    Article  PubMed  Google Scholar 

  • de Bresser, J., Portegies, M. P., Leemans, A., Biessels, G. J., Kappelle, L. J., & Viergever, M. A. (2011). A comparison of MR based segmentation methods for measuring brain atrophy progression. Neuroimage, 54, 760–768.

    Article  PubMed  Google Scholar 

  • Dempster, A., Laird, N., & Rubin, D. (1977). Maximum likelihood estimation from incomplete data using the EM algorithms. Journal of the Royal Statistical Society, 39, 1–38.

    Google Scholar 

  • Destrieux, C., Fischl, B., Dale, A., & Halgren, E. (2010). Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. Neuroimage, 53, 1–15.

    Article  PubMed  Google Scholar 

  • Duncan, J. S., Papademetris, X., Yang, J., Jackowski, M., Zeng, X., & Staib, L. H. (2004). Geometric strategies for neuroanatomic analysis from MRI. Neuroimage, 23(Suppl 1), S34–S45.

    Article  Google Scholar 

  • Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage, 9, 195–207.

    Article  PubMed  CAS  Google Scholar 

  • Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Ségonne, F., Salat, D. H., et al. (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14, 11–22.

    Article  PubMed  Google Scholar 

  • Freeborough, P. A., & Fox, N. C. (1997). The boundary shift integral: An accurate and robust measure of cerebral volume changes from registered repeat MRI. IEEE Transactions on Medical Imaging, 16, 623–629.

    Article  PubMed  CAS  Google Scholar 

  • Freeborough, P. A., Fox, N. C., & Kitney, R. I. (1997). Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Computer Methods and Programs in Biomedicine, 53, 15–25.

    Article  PubMed  CAS  Google Scholar 

  • Friston, K. J., Frith, C. D., Liddle, P. F., Dolan, R. J., Lammertsma, A. A., & Frackowiak, R. S. (1990). The relationship between global and local changes in PET scans. Journal of Cerebral Blood Flow and Metabolism, 10, 458–466.

    Article  PubMed  CAS  Google Scholar 

  • Geman, S., & Geman, D. (1984). Stochastic relaxation, Gibbs distributions, and the Bayesian restoration of images. IEEE Transactions on Pattern Analysis and Machine Intelligence, 6, 721–741.

    Article  Google Scholar 

  • Goualher, G. L., Procyk, E., Collins, D. L., Venugopal, R., Barillot, C., & Evans, A. C. (1999). Automated extraction and variability analysis of sulcal neuroanatomy. IEEE Transactions on Medical Imaging, 18, 206–217.

    Article  PubMed  Google Scholar 

  • Greenspan, H., Ruf, A., & Goldberger, J. (2006). Constrained Gaussian mixture model framework for automatic segmentation of MR brain images. IEEE Transactions on Medical Imaging, 25, 1233–1245.

    Article  PubMed  Google Scholar 

  • Hammers, A., Allom, R., Koepp, M. J., Free, S. L., Myers, R., Lemieux, L., et al. (2003). Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Human Brain Mapping, 19, 224–247.

    Article  PubMed  Google Scholar 

  • Heckemann, R. A., Hajnal, J. V., Aljabar, P., Rueckert, D., & Hammers, A. (2006). Automatic anatomical brain MRI segmentation combining label propagation and decision fusion. Neuroimage, 33, 115–126.

    Article  PubMed  Google Scholar 

  • Heckemann, R. A., Keihaninejad, S., Aljabar, P., Rueckert, D., Hajnal, J. V., Hammers, A., et al. (2010). Improving intersubject image registration using tissue-class information benefits robustness and accuracy of multi-atlas based anatomical segmentation. Neuroimage, 51, 221–227.

    Article  PubMed  Google Scholar 

  • Held, K., Kops, E. R., Krause, B. J., Wells, W. M., Kikinis, R., & Müller-Gärtner, H. W. (1997). Markov random field segmentation of brain MR images. IEEE Transactions on Medical Imaging, 16, 878–886.

    Article  PubMed  CAS  Google Scholar 

  • Julin, P., Melin, T., Andersen, C., Isberg, B., Svensson, L., & Wahlund, L. O. (1997). Reliability of interactive three-dimensional brain volumetry using MP-RAGE magnetic resonance imaging. Psychiatry Research, 76, 41–49.

    Article  PubMed  CAS  Google Scholar 

  • Kikinis, R., Shenton, M. E., Gerig, G., Martin, J., Anderson, M., Metcalf, D., et al. (1992). Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging. Journal of Magnetic Resonance Imaging, 2, 619–629.

    Article  PubMed  CAS  Google Scholar 

  • Klauschen, F., Goldman, A., Barra, V., Meyer-Lindenberg, A., & Lundervold, A. (2009). Evaluation of automated brain MR image segmentation and volumetry methods. Human Brain Mapping, 30, 1310–1327.

    Article  PubMed  Google Scholar 

  • Klein, A., & Hirsch, J. (2005). Mindboggle: A scatterbrained approach to automate brain labeling. Neuroimage, 24, 261–280.

    Article  PubMed  Google Scholar 

  • Leemput, K. V., Maes, F., Vandermeulen, D., & Suetens, P. (1999a). Automated model-based bias field correction of MR images of the brain. IEEE Transactions on Medical Imaging, 18, 885–896.

    Article  PubMed  Google Scholar 

  • Leemput, K. V., Maes, F., Vandermeulen, D., & Suetens, P. (1999b). Automated model-based tissue classification of MR images of the brain. IEEE Transactions on Medical Imaging, 18, 897–908.

    Article  PubMed  Google Scholar 

  • Leemput, K. V., Maes, F., Vandermeulen, D., & Suetens, P. (2003). A unifying framework for partial volume segmentation of brain MR images. IEEE Transactions on Medical Imaging, 22, 105–119.

    Article  PubMed  Google Scholar 

  • Li, S. Z. (2001). Markov random field modeling in computer vision. London: Springer.

    Google Scholar 

  • Lim, K. O., & Pfefferbaum, A. (1989). Segmentation of MR brain images into cerebrospinal fluid spaces, white and gray matter. Journal of Computer Assisted Tomography, 13, 588–593.

    Article  PubMed  CAS  Google Scholar 

  • Marroquin, J. L., Vemuri, B. C., Botello, S., Calderon, F., & Fernandez-Bouzas, A. (2002). An accurate and efficient Bayesian method for automatic segmentation of brain MRI. IEEE Transactions on Medical Imaging, 21, 934–945.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, K., & Fisher, E. (2009). Segmentation of brain magnetic resonance images for measurement of gray matter atrophy in multiple sclerosis patients. Neuroimage, 44, 769–776.

    Article  PubMed  Google Scholar 

  • Noe, A., & Gee, J. C. (2001). Partial volume segmentation of cerebral MRI scans with mixture model clustering. In M. Insana, & R. Leahy (Eds.), Information processing in medical imaging. Lecture notes in computer science (Vol. 2082, pp. 423–430). Berlin: Springer.

    Chapter  Google Scholar 

  • Pal, N. R., & Pal, S. K. (1993). A review on image segmentation techniques. Pattern Recognition, 26, 1277–1294.

    Article  Google Scholar 

  • Pappas, T. N. (1992). An adaptive clustering algorithm for image segmentation. IEEE Transactions on Signal Processing, 40, 901–914.

    Article  Google Scholar 

  • Pham, D. L., Xu, C., & Prince, J. L. (2000). Current methods in medical image segmentation. Annual Review of Biomedical Engineering, 2, 315–337.

    Article  PubMed  CAS  Google Scholar 

  • Pieper, S., Lorensen, B., Schroeder, W., & Kikinis, R. (2006). The NA-MIC kit: ITK, VTK, pipelines, grids and 3D Slicer as an open platform for the medical image computing community. In Proceedings of the 3rd IEEE international symposium on biomedical imaging: From nano to macro (Vol. 1, pp. 698–701).

  • Pohl, K. M., Bouix, S., Nakamura, M., Rohlfing, T., McCarley, R. W., Kikinis, R., et al. (2007). A hierarchical algorithm for MR brain image parcellation. IEEE Transactions on Medical Imaging, 26, 1201–1212.

    Article  PubMed  Google Scholar 

  • Pohl, K. M., Fisher, J., Grimson, W. E. L., Kikinis, R., & Wells, W. M. (2006). A Bayesian model for joint segmentation and registration. Neuroimage, 31, 228–239.

    Article  PubMed  Google Scholar 

  • Prastawa, M., Gilmore, J. H., Lin, W., & Gerig, G. (2005). Automatic segmentation of MR images of the developing newborn brain. Medical Image Analysis, 9, 457–466.

    Article  PubMed  Google Scholar 

  • Ruan, S., Jaggi, C., Xue, J., Fadili, J., & Bloyet, D. (2000). Brain tissue classification of magnetic resonance images using partial volume modeling. IEEE Transactions on Medical Imaging, 19, 1179–1187.

    Article  PubMed  CAS  Google Scholar 

  • Sanjay-Gopal, S., & Hebert, T. J. (1998). Bayesian pixel classification using spatially variant finite mixtures and the generalized em algorithm. IEEE Transactions on Image Processing, 7, 1014–1028.

    Article  PubMed  CAS  Google Scholar 

  • Sánchez-Benavides, G., Gómez-Ansón, B., Sainz, A., Vives, Y., Delfino, M., & Peña-Casanova, J. (2010). Manual validation of Freesurfer’s automated hippocampal segmentation in normal aging, mild cognitive impairment, and Alzheimer disease subjects. Psychiatry Research, 181, 219–225.

    Article  PubMed  Google Scholar 

  • Scherrer, B., Forbes, F., Garbay, C., & Dojat, M. (2009). Distributed local MRF models for tissue and structure brain segmentation. IEEE Transactions on Medical Imaging, 28, 1278–1295.

    Article  PubMed  Google Scholar 

  • Shiee, N., Bazin, P. L., Ozturk, A., Reich, D. S., Calabresi, P. A., & Pham, D. L. (2010). A topology-preserving approach to the segmentation of brain images with multiple sclerosis lesions. Neuroimage, 49, 1524–1535.

    Article  PubMed  Google Scholar 

  • Sled, J. G., Zijdenbos, A. P., & Evans, A. C. (1998). A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Transactions on Medical Imaging, 17, 87–97.

    Article  PubMed  CAS  Google Scholar 

  • Smith, S. M., Rao, A., Stefano, N. D., Jenkinson, M., Schott, J. M., Matthews, P. M., et al. (2007). Longitudinal and cross-sectional analysis of atrophy in alzheimer’s disease: Cross-validation of BSI, SIENA and SIENAX. Neuroimage, 36, 1200–1206.

    Article  PubMed  Google Scholar 

  • Suri, J. S., Singh, S., & Reden, L. (2002). Computer vision and pattern recognition techniques for 2-D and 3-D MR cerebral cortical segmentation (part I): A state-of-the-art review. Pattern Analysis & Applications, 5, 46–76. doi:10.1007/s100440200005.

    Article  Google Scholar 

  • Tustison, N. J., Avants, B. B., Cook, P. A., Zheng, Y., Egan, A., Yushkevich, P. A., et al. (2010a). N4ITK: Improved N3 bias correction. IEEE Transactions on Medical Imaging, 29, 1310–1320.

    Article  PubMed  Google Scholar 

  • Tustison, N., Avants, B., Altes, T., de Lange, E., Mugler, J., & Gee, J. (2010b). Automatic segmentation of ventilation defects in hyperpolarized 3He MRI. In Proceedings of the biomedical engineering society annual meeting.

  • Tustison, N., Avants, B., Siqueira, M., & Gee, J. (2010c). Topological well-composedness and Glamorous Glue: A digital gluing algorithm for topologically constrained front propagation. IEEE Transactions on Image Processing, accepted.

  • Vannier, M. W., Butterfield, R. L., Jordan, D., Murphy, W. A., Levitt, R. G., & Gado, M. (1985). Multispectral analysis of magnetic resonance images. Radiology, 154, 221–224.

    PubMed  CAS  Google Scholar 

  • Viergever, M. A., Maintz, J. B., Niessen, W. J., Noordmans, H. J., Pluim, J. P., Stokking, R., et al. (2001). Registration, segmentation, and visualization of multimodal brain images. Computerized Medical Imaging and Graphics, 25, 147–151.

    Article  PubMed  CAS  Google Scholar 

  • Weisenfeld, N. I., & Warfield, S. K. (2009). Automatic segmentation of newborn brain MRI. Neuroimage, 47, 564–572.

    Article  PubMed  Google Scholar 

  • Wells, W. M., Grimson, W. L., Kikinis, R., & Jolesz, F. A. (1996). Adaptive segmentation of MRI data. IEEE Transactions on Medical Imaging, 15, 429–442.

    Article  PubMed  CAS  Google Scholar 

  • Westlye, L. T., Walhovd, K. B., Dale, A. M., Espeseth, T., Reinvang, I., Raz, N., et al. (2009). Increased sensitivity to effects of normal aging and Alzheimer’s disease on cortical thickness by adjustment for local variability in gray/white contrast: A multi-sample MRI study. Neuroimage, 47, 1545–1557.

    Article  PubMed  Google Scholar 

  • Wolpert, D. H., & Macready, W. G. (1997). No free lunch theorems for optimization. IEEE Transactions on Evolutionary Computation, 1, 67–82.

    Article  Google Scholar 

  • Yushkevich, P. A., Piven, J., Hazlett, H. C., Smith, R. G., Ho, S., Gee, J. C., et al. (2006). User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability. Neuroimage, 31, 1116–1128.

    Article  PubMed  Google Scholar 

  • Zaidi, H., Ruest, T., Schoenahl, F., & Montandon, M. L. (2006). Comparative assessment of statistical brain MR image segmentation algorithms and their impact on partial volume correction in PET. Neuroimage, 32, 1591–1607.

    Article  PubMed  Google Scholar 

  • Zhang, Y., Brady, M., & Smith, S. (2001). Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Transactions on Medical Imaging, 20, 45–57.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported in part by NIH (AG17586, AG15116, NS44266, and NS53488).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brian B. Avants.

Additional information

The first two authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avants, B.B., Tustison, N.J., Wu, J. et al. An Open Source Multivariate Framework for n-Tissue Segmentation with Evaluation on Public Data. Neuroinform 9, 381–400 (2011). https://doi.org/10.1007/s12021-011-9109-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12021-011-9109-y

Keywords

Navigation