Vectorization of optically sectioned brain microvasculature: Learning aids completion of vascular graphs by connecting gaps and deleting open-ended segments

A graph of tissue vasculature is an essential requirement to model the exchange of gasses and nutriments between the blood and cells in the brain. Such a graph is derived from a vectorized representation of anatomical data, provides a map of all vessels as vertices and segments, and may include the location of nonvascular components, such as neuronal and glial somata. Yet vectorized data sets typically contain erroneous gaps, spurious endpoints, and spuriously merged strands. Current methods to correct such defects only address the issue of connecting gaps and further require manual tuning of parameters in a high dimensional algorithm. To address these shortcomings, we introduce a supervised machine learning method that (1) connects vessel gaps by "learned threshold relaxation"; (2) removes spurious segments by "learning to eliminate deletion candidate strands"; and (3) enforces consistency in the joint space of learned vascular graph corrections through "consistency learning." Human operators are only required to label individual objects they recognize in a training set and are not burdened with tuning parameters. The supervised learning procedure examines the geometry and topology of features in the neighborhood of each vessel segment under consideration. We demonstrate the effectiveness of these methods on four sets of microvascular data, each with >800(3) voxels, obtained with all optical histology of mouse tissue and vectorization by state-of-the-art techniques in image segmentation. Through statistically validated sampling and analysis in terms of precision recall curves, we find that learning with bagged boosted decision trees reduces equal-error error rates for threshold relaxation by 5-21% and strand elimination performance by 18-57%. We benchmark generalization performance across datasets; while improvements vary between data sets, learning always leads to a useful reduction in error rates. Overall, learning is shown to more than halve the total error rate, and therefore, human time spent manually correcting such vectorizations.

[1]  Ronen Basri,et al.  Completion Energies and Scale , 2000, IEEE Trans. Pattern Anal. Mach. Intell..

[2]  Wei-Yin Loh,et al.  Classification and regression trees , 2011, WIREs Data Mining Knowl. Discov..

[3]  Ghassan Hamarneh,et al.  Vessel Crawlers: 3D Physically-based Deformable Organisms for Vasculature Segmentation and Analysis , 2006, 2006 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'06).

[4]  Cassot Francis,et al.  Scaling Laws for Branching Vessels of Human Cerebral Cortex , 2009 .

[5]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[6]  J. Mundy,et al.  Driving vision by topology , 1995, Proceedings of International Symposium on Computer Vision - ISCV.

[7]  Tom Fawcett,et al.  ROC Graphs: Notes and Practical Considerations for Researchers , 2007 .

[8]  Yoav Freund,et al.  A decision-theoretic generalization of on-line learning and an application to boosting , 1995, EuroCOLT.

[9]  Laurent Risser,et al.  Gap filling in 3D vessel like patterns with tensor fields - application to high resolution computed tomography images of vessel networks , 2007, VISAPP.

[10]  Srinivas C. Turaga,et al.  Machines that learn to segment images: a crucial technology for connectomics , 2010, Current Opinion in Neurobiology.

[11]  Kevin L. Briggman,et al.  3D structural imaging of the brain with photons and electrons , 2008, Current Opinion in Neurobiology.

[12]  Nicholas Ayache,et al.  Model-based multiscale detection of 3D vessels , 1998, Proceedings. 1998 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (Cat. No.98CB36231).

[13]  H. Sebastian Seung,et al.  Boundary Learning by Optimization with Topological Constraints , 2010, 2010 IEEE Computer Society Conference on Computer Vision and Pattern Recognition.

[14]  Ron Kohavi,et al.  A Study of Cross-Validation and Bootstrap for Accuracy Estimation and Model Selection , 1995, IJCAI.

[15]  Seong-Gi Kim,et al.  Mapping Iso-Orientation Columns by Contrast Agent-Enhanced Functional Magnetic Resonance Imaging: Reproducibility, Specificity, and Evaluation by Optical Imaging of Intrinsic Signal , 2006, The Journal of Neuroscience.

[16]  Adam Tauman Kalai,et al.  Analysis of Perceptron-Based Active Learning , 2009, COLT.

[17]  Rich Caruana,et al.  An empirical comparison of supervised learning algorithms , 2006, ICML.

[18]  Anthony Hoogs,et al.  Learning to segment images using region-based perceptual features , 2004, Proceedings of the 2004 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2004. CVPR 2004..

[19]  D. Kleinfeld,et al.  Correlations of Neuronal and Microvascular Densities in Murine Cortex Revealed by Direct Counting and Colocalization of Nuclei and Vessels , 2009, The Journal of Neuroscience.

[20]  Leo Breiman,et al.  Bagging Predictors , 1996, Machine Learning.

[21]  Badrinath Roysam,et al.  Robust 3-D modeling of tumor microvasculature using superellipsoids , 2006, 3rd IEEE International Symposium on Biomedical Imaging: Nano to Macro, 2006..

[22]  D. Kleinfeld,et al.  Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion , 2006, PLoS biology.

[23]  David Kleinfeld,et al.  Threshold Relaxation is an Effective Means to Connect Gaps in 3 D Images of Complex Microvascular Networks , 2022 .

[24]  Ali Shahrokni,et al.  Three-dimensional analysis of complex branching vessels in confocal microscopy images. , 2005, Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society.

[25]  D. Kleinfeld,et al.  Topological basis for the robust distribution of blood to rodent neocortex , 2010, Proceedings of the National Academy of Sciences.

[26]  Laurent Risser,et al.  From Homogeneous to Fractal Normal and Tumorous Microvascular Networks in the Brain , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  A. Grinvald,et al.  Non-invasive visualization of cortical columns by fMRI , 2000, Nature Neuroscience.

[28]  Isabelle Bloch,et al.  A review of 3D vessel lumen segmentation techniques: Models, features and extraction schemes , 2009, Medical Image Anal..

[29]  Yuan Liu,et al.  DIADEMchallenge.Org: A Compendium of Resources Fostering the Continuous Development of Automated Neuronal Reconstruction , 2011, Neuroinformatics.

[30]  Yousef Al-Kofahi,et al.  Associative image analysis: A method for automated quantification of 3D multi-parameter images of brain tissue , 2008, Journal of Neuroscience Methods.

[31]  Konstantin Mischaikow,et al.  Coronary vessel cores from 3D imagery: a topological approach , 2005, SPIE Medical Imaging.

[32]  Eugene W. Myers,et al.  Proof-editing is the Bottleneck Of 3D Neuron Reconstruction: The Problem and Solutions , 2011, Neuroinformatics.

[33]  Steffen Prohaska,et al.  Large-Scale Automated Histology in the Pursuit of Connectomes , 2011, The Journal of Neuroscience.

[34]  John F. Canny,et al.  A Computational Approach to Edge Detection , 1986, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[35]  Jinbo Bi,et al.  Hierarchical learning for tubular structure parsing in medical imaging: A study on coronary arteries using 3D CT Angiography , 2009, 2009 IEEE 12th International Conference on Computer Vision.

[36]  D. Kleinfeld,et al.  All-Optical Histology Using Ultrashort Laser Pulses , 2003, Neuron.

[37]  Céline Fouard,et al.  A Novel Three‐Dimensional Computer‐Assisted Method for a Quantitative Study of Microvascular Networks of the Human Cerebral Cortex , 2006, Microcirculation.

[38]  Kaleem Siddiqi,et al.  Flux driven automatic centerline extraction , 2005, Medical Image Anal..

[39]  H. Sebastian Seung,et al.  Learning to Agglomerate Superpixel Hierarchies , 2011, NIPS.

[40]  Horst Bischof,et al.  Multiscale Medialness for Robust Segmentation of 3 D Tubular Structures ∗ , 2005 .

[41]  H. Sebastian Seung,et al.  Maximin affinity learning of image segmentation , 2009, NIPS.

[42]  Laurent Risser,et al.  Gap Filling of 3-D Microvascular Networks by Tensor Voting , 2008, IEEE Transactions on Medical Imaging.

[43]  Heinz-Otto Peitgen,et al.  Multiple hypothesis template tracking of small 3D vessel structures , 2010, Medical Image Anal..

[44]  Ralph Müller,et al.  Novel three-dimensional analysis tool for vascular trees indicates complete micro-networks, not single capillaries, as the angiogenic endpoint in mice overexpressing human VEGF(165) in the brain. , 2008, NeuroImage.

[45]  Suya You,et al.  A Vision-Based System For Automatic Detection and Extraction Of Road Networks , 2008, 2008 IEEE Workshop on Applications of Computer Vision.

[46]  Max A. Viergever,et al.  Vessel enhancing diffusion: A scale space representation of vessel structures , 2006, Medical Image Anal..

[47]  H. Duvernoy,et al.  Scaling Laws for Branching Vessels of Human Cerebral Cortex , 2009, Microcirculation.

[48]  Heikki Mannila,et al.  Principles of Data Mining , 2001, Undergraduate Topics in Computer Science.

[49]  Johannes Reichold,et al.  The microvascular system of the striate and extrastriate visual cortex of the macaque. , 2008, Cerebral cortex.

[50]  Wiro J. Niessen,et al.  Level set based cerebral vasculature segmentation and diameter quantification in CT angiography , 2006, Medical Image Anal..

[51]  H. Sebastian Seung,et al.  Selective Sampling Using the Query by Committee Algorithm , 1997, Machine Learning.

[52]  Jitendra Malik,et al.  Learning Probabilistic Models for Contour Completion in Natural Images , 2008, International Journal of Computer Vision.

[53]  J. Ross Quinlan,et al.  C4.5: Programs for Machine Learning , 1992 .

[54]  D. Kleinfeld,et al.  Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-Dependent Signal , 2007, The Journal of Neuroscience.

[55]  Sanjoy K. Mitter,et al.  Hierarchical Curve Reconstruction. Part I: Bifurcation analysis and Recovery of Smooth Curves , 1996, ECCV.

[56]  Moritz Helmstaedter,et al.  High-accuracy neurite reconstruction for high-throughput neuroanatomy , 2011, Nature Neuroscience.

[57]  Stephan Saalfeld,et al.  Globally optimal stitching of tiled 3D microscopic image acquisitions , 2009, Bioinform..

[58]  Francis K. H. Quek,et al.  A review of vessel extraction techniques and algorithms , 2004, CSUR.

[59]  Ralph Müller,et al.  Novel three-dimensional analysis tool for vascular trees indicates complete micro-networks, not single capillaries, as the angiogenic endpoint in mice overexpressing human VEGF165 in the brain , 2008, NeuroImage.

[60]  Benjamin B. Kimia,et al.  Towards surface regularization via medial axis transitions , 2004, Proceedings of the 17th International Conference on Pattern Recognition, 2004. ICPR 2004..

[61]  Alejandro F. Frangi,et al.  Muliscale Vessel Enhancement Filtering , 1998, MICCAI.