Automatic clustering of white matter fibers in brain diffusion MRI with an application to genetics

To understand factors that affect brain connectivity and integrity, it is beneficial to automatically cluster white matter (WM) fibers into anatomically recognizable tracts. Whole brain tractography, based on diffusion-weighted MRI, generates vast sets of fibers throughout the brain; clustering them into consistent and recognizable bundles can be difficult as there are wide individual variations in the trajectory and shape of WM pathways. Here we introduce a novel automated tract clustering algorithm based on label fusion--a concept from traditional intensity-based segmentation. Streamline tractography generates many incorrect fibers, so our top-down approach extracts tracts consistent with known anatomy, by mapping multiple hand-labeled atlases into a new dataset. We fuse clustering results from different atlases, using a mean distance fusion scheme. We reliably extracted the major tracts from 105-gradient high angular resolution diffusion images (HARDI) of 198 young normal twins. To compute population statistics, we use a pointwise correspondence method to match, compare, and average WM tracts across subjects. We illustrate our method in a genetic study of white matter tract heritability in twins.

[1]  John D. E. Gabrieli,et al.  Knowledge-Based Classification of Neuronal Fibers in Entire Brain , 2005, MICCAI.

[2]  Alex R. Smith,et al.  Sex differences in the structural connectome of the human brain , 2013, Proceedings of the National Academy of Sciences.

[3]  Torsten Rohlfing,et al.  Performance-based classifier combination in atlas-based image segmentation using expectation-maximization parameter estimation , 2004, IEEE Transactions on Medical Imaging.

[4]  Jean-Francois Mangin,et al.  Segmentation of Short Association Bundles in Massive Tractography Datasets Using a Multi-subject Bundle Atlas , 2011, CIARP.

[5]  Paul M. Thompson,et al.  Multivariate variance-components analysis in DTI , 2010, 2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[6]  Paul M. Thompson,et al.  Disrupted Brain Networks in the Aging HIV+ Population , 2012, Brain Connect..

[7]  Mara Cercignani,et al.  Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: An in vivo study with TBSS and VBM , 2009, Human brain mapping.

[8]  J. Thiran,et al.  Fiber tracts of high angular resolution diffusion MRI are easily segmented with spectral clustering. , 2005 .

[9]  C. Jack,et al.  Alzheimer's Disease Neuroimaging Initiative , 2008 .

[10]  R. Deriche,et al.  Regularized, fast, and robust analytical Q‐ball imaging , 2007, Magnetic resonance in medicine.

[11]  Alfred O. Hero,et al.  Fiber Tract Clustering on Manifolds With Dual Rooted-Graphs , 2007, 2007 IEEE Conference on Computer Vision and Pattern Recognition.

[12]  Carl-Fredrik Westin,et al.  Clustering Fiber Traces Using Normalized Cuts , 2004, MICCAI.

[13]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[14]  Dinggang Shen,et al.  Application of neuroanatomical features to tractography clustering , 2013, Human brain mapping.

[15]  Carl-Fredrik Westin,et al.  Automatic Tractography Segmentation Using a High-Dimensional White Matter Atlas , 2007, IEEE Transactions on Medical Imaging.

[16]  Tyrone D. Cannon,et al.  Genetic influences on brain structure , 2001, Nature Neuroscience.

[17]  Guido Gerig,et al.  Fiber tract-oriented statistics for quantitative diffusion tensor MRI analysis. , 2006, Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention.

[18]  Stephen T. C. Wong,et al.  A hybrid approach to automatic clustering of white matter fibers , 2010, NeuroImage.

[19]  Klaus-Dietmarmerboldt Self-Diffusion NMR Imaging Using Stimulated Echoes , 2004 .

[20]  Rachid Deriche,et al.  Unsupervised white matter fiber clustering and tract probability map generation: Applications of a Gaussian process framework for white matter fibers , 2010, NeuroImage.

[21]  Paul M. Thompson,et al.  Genetics of white matter development: A DTI study of 705 twins and their siblings aged 12 to 29 , 2011, NeuroImage.

[22]  Paul M. Thompson,et al.  3D elastic registration improves HARDI-derived fiber alignment and automated tract clustering , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[23]  H. Grüneberg,et al.  Introduction to quantitative genetics , 1960 .

[24]  Paul M. Thompson,et al.  Automated Ventricular Mapping with Multi-atlas Fluid Image Alignment Reveals Genetic Effects in Alzheimer's Disease , 2007 .

[25]  Mert R. Sabuncu,et al.  A Generative Model for Image Segmentation Based on Label Fusion , 2010, IEEE Transactions on Medical Imaging.

[26]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[27]  Randy L. Gollub,et al.  Reproducibility of quantitative tractography methods applied to cerebral white matter , 2007, NeuroImage.

[28]  Daniel Rueckert,et al.  Automatic anatomical brain MRI segmentation combining label propagation and decision fusion , 2006, NeuroImage.

[29]  W. Eric L. Grimson,et al.  A unified framework for clustering and quantitative analysis of white matter fiber tracts , 2008, Medical Image Anal..

[30]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Gareth J. Barker,et al.  White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus , 2008, NeuroImage.

[32]  A. Anderson,et al.  Classification and quantification of neuronal fiber pathways using diffusion tensor MRI , 2003, Magnetic resonance in medicine.

[33]  Paul M. Thompson,et al.  Heritability of White Matter Fiber Tract Shapes: A HARDI Study of 198 Twins , 2011, MBIA.

[34]  Derek K. Jones,et al.  Symmetries in human brain language pathways correlate with verbal recall , 2007, Proceedings of the National Academy of Sciences.

[35]  Matthew P. G. Allin,et al.  Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography , 2011, NeuroImage.

[36]  Juha Koikkalainen,et al.  Fast and robust multi-atlas segmentation of brain magnetic resonance images , 2010, NeuroImage.

[37]  Paul M. Thompson,et al.  Combining meta- and mega- analytic approaches for multi-site diffusion imaging based genetic studies: From the ENIGMA-DTI working group , 2014, 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI).

[38]  M C Bushell,et al.  PRELIMINARY COMMUNICATION: The spatial mapping of translational diffusion coefficients by the NMR imaging technique , 1985 .

[39]  Brian B. Avants,et al.  Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain , 2008, Medical Image Anal..

[40]  Paul M. Thompson,et al.  Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group , 2013, NeuroImage.

[41]  Geoffrey J M Parker,et al.  A framework for a streamline‐based probabilistic index of connectivity (PICo) using a structural interpretation of MRI diffusion measurements , 2003, Journal of magnetic resonance imaging : JMRI.

[42]  Rachid Deriche,et al.  Diffusion Maps Clustering for Magnetic Resonance Q-Ball Imaging Segmentation , 2008, Int. J. Biomed. Imaging.

[43]  Alan Connelly,et al.  Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution , 2004, NeuroImage.

[44]  John H. Gilmore,et al.  Fiber Tract-Oriented Statistics for Quantitative Diffusion Tensor MRI Analysis , 2005, MICCAI.

[45]  P. Thompson,et al.  Diffusion imaging, white matter, and psychopathology. , 2011, Annual review of clinical psychology.

[46]  Arthur W. Toga,et al.  Atlas-guided tract reconstruction for automated and comprehensive examination of the white matter anatomy , 2010, NeuroImage.

[47]  Arthur W. Toga,et al.  Atlas-based whole brain white matter analysis using large deformation diffeomorphic metric mapping: Application to normal elderly and Alzheimer's disease participants , 2009, NeuroImage.

[48]  Paul M. Thompson,et al.  Mapping genetic influences on ventricular structure in twins , 2009, NeuroImage.

[49]  Jens Frahm,et al.  Topography of the human corpus callosum revisited—Comprehensive fiber tractography using diffusion tensor magnetic resonance imaging , 2006, NeuroImage.

[50]  Essa Yacoub,et al.  A Hough transform global probabilistic approach to multiple-subject diffusion MRI tractography , 2011, Medical Image Anal..

[51]  C. Westin,et al.  A method for clustering white matter fiber tracts. , 2006, AJNR. American journal of neuroradiology.

[52]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[53]  Christophe Lenglet,et al.  Sex differences in the human connectome: 4-Tesla high angular resolution diffusion imaging (HARDI) tractography in 234 young adult twins , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[54]  Daniel C. Alexander,et al.  Probabilistic Monte Carlo Based Mapping of Cerebral Connections Utilising Whole-Brain Crossing Fibre Information , 2003, IPMI.

[55]  Jean-Francois Mangin,et al.  Automatic fiber bundle segmentation in massive tractography datasets using a multi-subject bundle atlas , 2012, NeuroImage.

[56]  I. Corouge,et al.  Analysis of brain white matter via fiber tract modeling , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[57]  Paul M. Thompson,et al.  Along-tract statistics allow for enhanced tractography analysis , 2012, NeuroImage.

[58]  Paul A. Yushkevich,et al.  Structure-specific statistical mapping of white matter tracts , 2007, NeuroImage.

[59]  Paul M. Thompson,et al.  Multi-atlas tensor-based morphometry and its application to a genetic study of 92 twins , 2008 .

[60]  Paul M. Thompson,et al.  Genetic Analysis of Cortical Thickness and Fractional Anisotropy of Water Diffusion in the Brain , 2011, Front. Neurosci..

[61]  Thomas E. Nichols,et al.  Acquisition and voxelwise analysis of multi-subject diffusion data with Tract-Based Spatial Statistics , 2007, Nature Protocols.

[62]  Michael Weiner,et al.  Breakdown of Brain Connectivity Between Normal Aging and Alzheimer's Disease: A Structural k-Core Network Analysis , 2013, Brain Connect..

[63]  Dorret I. Boomsma,et al.  Heritability of DTI and MTR in nine-year-old children , 2010, NeuroImage.

[64]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[65]  R. Poldrack,et al.  Microstructure of Temporo-Parietal White Matter as a Basis for Reading Ability Evidence from Diffusion Tensor Magnetic Resonance Imaging , 2000, Neuron.

[66]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[67]  A. Alexander,et al.  White matter tractography using diffusion tensor deflection , 2003, Human brain mapping.

[68]  D. Tuch Q‐ball imaging , 2004, Magnetic resonance in medicine.

[69]  Douglas L. Rosene,et al.  The Geometric Structure of the Brain Fiber Pathways , 2012, Science.

[70]  Christophe Lenglet,et al.  Atlas-based fiber clustering for multi-subject analysis of high angular resolution diffusion imaging tractography , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[71]  P. Hagmann,et al.  Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging , 2005, Magnetic resonance in medicine.

[72]  Alan C. Evans,et al.  Genetic Contributions to Human Brain Morphology and Intelligence , 2006, The Journal of Neuroscience.

[73]  Gareth J. Barker,et al.  Abnormal brain connectivity in first-episode psychosis: A diffusion MRI tractography study of the corpus callosum , 2007, NeuroImage.

[74]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[75]  Jan K. Buitelaar,et al.  Partition-based mass clustering of tractography streamlines , 2011, NeuroImage.

[76]  Essa Yacoub,et al.  Differential information content in staggered multiple shell hardi measured by the tensor distribution function , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.