Precise Cerebral Vascular Atlas in Stereotaxic Coordinates of Whole Mouse Brain

Understanding amazingly complex brain functions and pathologies requires a complete cerebral vascular atlas in stereotaxic coordinates. Making a precise atlas for cerebral arteries and veins has been a century-old objective in neuroscience and neuropathology. Using micro-optical sectioning tomography (MOST) with a modified Nissl staining method, we acquired five mouse brain data sets containing arteries, veins, and microvessels. Based on the brain-wide vascular spatial structures and brain regions indicated by cytoarchitecture in one and the same mouse brain, we reconstructed and annotated the vascular system atlas of both arteries and veins of the whole mouse brain for the first time. The distributing patterns of the vascular system within the brain regions were acquired and our results show that the patterns of individual vessels are different from each other. Reconstruction and statistical analysis of the microvascular network, including derivation of quantitative vascular densities, indicate significant differences mainly in vessels with diameters less than 8 μm and large than 20 μm across different brain regions. Our precise cerebral vascular atlas provides an important resource and approach for quantitative studies of brain functions and diseases.

[1]  Margaret J. Cook,et al.  The anatomy of the laboratory mouse , 1965 .

[2]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[3]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[4]  D. J. Knudsen,et al.  Mouse Strain Differences in Susceptibility to Cerebral Ischemia are Related to Cerebral Vascular Anatomy , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[6]  R. C Cannon,et al.  An on-line archive of reconstructed hippocampal neurons , 1998, Journal of Neuroscience Methods.

[7]  Håkan Johansson,et al.  Modern Techniques in Neuroscience Research , 1999, Springer Berlin Heidelberg.

[8]  R. Guillery,et al.  Exploring the Thalamus , 2000 .

[9]  A. Morita,et al.  The preservation and reconstruction of cerebral veins and sinuses , 2002, Journal of Clinical Neuroscience.

[10]  C. Iadecola Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[11]  Berislav V. Zlokovic,et al.  Neurovascular mechanisms of Alzheimer's neurodegeneration , 2005, Trends in Neurosciences.

[12]  Douglas B. Ehlenberger,et al.  New techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales , 2005, Neuroscience.

[13]  C. Batzios,et al.  Developmental changes in the vascular network of the rat visual areas 17, 18 and 18a , 2006, Brain Research.

[14]  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.

[15]  Philipp Schneider,et al.  Hierarchical microimaging for multiscale analysis of large vascular networks , 2006, NeuroImage.

[16]  John G. Sled,et al.  Three-dimensional cerebral vasculature of the CBA mouse brain: A magnetic resonance imaging and micro computed tomography study , 2007, NeuroImage.

[17]  G. Semenza,et al.  Vasculogenesis, angiogenesis, and arteriogenesis: Mechanisms of blood vessel formation and remodeling , 2007, Journal of cellular biochemistry.

[18]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[19]  Thomas Krucker,et al.  Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease , 2008, Proceedings of the National Academy of Sciences.

[20]  Jeroen van der Grond,et al.  Brain perfusion territory imaging: methods and clinical applications of selective arterial spin-labeling MR imaging. , 2008, Radiology.

[21]  R. Mark Henkelman,et al.  High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice , 2008, NeuroImage.

[22]  D Mayerich,et al.  Knife‐edge scanning microscopy for imaging and reconstruction of three‐dimensional anatomical structures of the mouse brain , 2008, Journal of microscopy.

[23]  John Keyser,et al.  Visualization of Cellular and Microvascular Relationships , 2008, IEEE Transactions on Visualization and Computer Graphics.

[24]  Franz Pfeiffer,et al.  High-resolution tomographic imaging of microvessels , 2008, Optical Engineering + Applications.

[25]  A. Foundas,et al.  The Cerebral Vascular System , 2008 .

[26]  D. Kleinfeld,et al.  'Where' and 'what' in the whisker sensorimotor system , 2008, Nature Reviews Neuroscience.

[27]  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.

[28]  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.

[29]  Jyh-Horng Chen,et al.  In vivo cerebromicrovasculatural visualization using 3D ΔR 2-based microscopy of magnetic resonance angiography (3DΔR 2-mMRA) , 2009, NeuroImage.

[30]  Alfredo Rodriguez,et al.  Three-dimensional neuron tracing by voxel scooping , 2009, Journal of Neuroscience Methods.

[31]  Patrick Jenny,et al.  Vascular Graph Model to Simulate the Cerebral Blood Flow in Realistic Vascular Networks , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  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.

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

[34]  Q. Luo,et al.  Micro-Optical Sectioning Tomography to Obtain a High-Resolution Atlas of the Mouse Brain , 2010, Science.

[35]  Hanchuan Peng,et al.  Automatic reconstruction of 3D neuron structures using a graph-augmented deformable model , 2010, Bioinform..

[36]  D. Attwell,et al.  Glial and neuronal control of brain blood flow , 2022 .

[37]  D. Selkoe Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[38]  I. Geudens,et al.  Coordinating cell behaviour during blood vessel formation , 2011, Development.

[39]  Yoonsuck Choe,et al.  Multiscale Exploration of Mouse Brain Microstructures Using the Knife-Edge Scanning Microscope Brain Atlas , 2011, Front. Neuroinform..

[40]  Yoonsuck Choe,et al.  Fast macro-scale transmission imaging of microvascular networks using KESM , 2011, Biomedical optics express.

[41]  B. Weber,et al.  Topology and hemodynamics of the cortical cerebrovascular system , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  Andre Obenaus,et al.  The vascular neural network—a new paradigm in stroke pathophysiology , 2012, Nature Reviews Neurology.

[43]  Peng Miao,et al.  Micro-Computed Tomography for Hemorrhage Disruption of Mouse Brain Vasculature , 2012, Translational Stroke Research.

[44]  Shaoqun Zeng,et al.  Rapid Reconstruction of 3D Neuronal Morphology from Light Microscopy Images with Augmented Rayburst Sampling , 2013, PloS one.

[45]  W Ding,et al.  Automatic macroscopic density artefact removal in a Nissl‐stained microscopic atlas of whole mouse brain , 2013, Journal of microscopy.

[46]  A. Linninger,et al.  Cerebral Microcirculation and Oxygen Tension in the Human Secondary Cortex , 2013, Annals of Biomedical Engineering.

[47]  Shaoqun Zeng,et al.  Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution , 2013, NeuroImage.

[48]  D. Kleinfeld,et al.  The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow , 2013, Nature Neuroscience.

[49]  Qingming Luo,et al.  An Automated Three-Dimensional Detection and Segmentation Method for Touching Cells by Integrating Concave Points Clustering and Random Walker Algorithm , 2014, PloS one.

[50]  Anan Li,et al.  Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain , 2014, PloS one.

[51]  John G. Sled,et al.  Automatic anatomical labeling of the complete cerebral vasculature in mouse models , 2014, NeuroImage.

[52]  Qingming Luo,et al.  3D BrainCV: Simultaneous visualization and analysis of cells and capillaries in a whole mouse brain with one-micron voxel resolution , 2014, NeuroImage.

[53]  F. Cassot,et al.  Tortuosity and other vessel attributes for arterioles and venules of the human cerebral cortex. , 2014, Microvascular research.

[54]  Shaoqun Zeng,et al.  Visible rodent brain-wide networks at single-neuron resolution , 2015, Front. Neuroanat..

[55]  Tao Jiang,et al.  Direct 3D Analyses Reveal Barrel-Specific Vascular Distribution and Cross-Barrel Branching in the Mouse Barrel Cortex. , 2016, Cerebral cortex.

[56]  T. Ragan,et al.  Whole Brain Imaging with Serial Two-Photon Tomography , 2016, Front. Neuroanat..

[58]  Kâmil Uludag,et al.  Linking brain vascular physiology to hemodynamic response in ultra-high field MRI , 2017, NeuroImage.