Imaging whole-brain cytoarchitecture of mouse with MRI-based quantitative susceptibility mapping

The proper microstructural arrangement of complex neural structures is essential for establishing the functional circuitry of the brain. We present an MRI method to resolve tissue microstructure and infer brain cytoarchitecture by mapping the magnetic susceptibility in the brain at high resolution. This is possible because of the heterogeneous magnetic susceptibility created by varying concentrations of lipids, proteins and irons from the cell membrane to cytoplasm. We demonstrate magnetic susceptibility maps at a nominal resolution of 10-μm isotropic, approaching the average cell size of a mouse brain. The maps reveal many detailed structures including the retina cell layers, olfactory sensory neurons, barrel cortex, cortical layers, axonal fibers in white and gray matter. Olfactory glomerulus density is calculated and structural connectivity is traced in the optic nerve, striatal neurons, and brainstem nerves. The method is robust and can be readily applied on MRI scanners at or above 7T.

[1]  Jeff Duyn,et al.  MR susceptibility imaging. , 2013, Journal of magnetic resonance.

[2]  G Allan Johnson,et al.  Susceptibility tensor imaging of the kidney and its microstructural underpinnings , 2015, Magnetic resonance in medicine.

[3]  G. Allan Johnson,et al.  Quantitative magnetic susceptibility of the developing mouse brain reveals microstructural changes in the white matter , 2014, NeuroImage.

[4]  Chunlei Liu,et al.  Whole brain susceptibility mapping using compressed sensing , 2012, Magnetic resonance in medicine.

[5]  A Mogro-Campero,et al.  A high-temperature superconducting receiver for nuclear magnetic resonance microscopy. , 1993, Science.

[6]  Bing Wu,et al.  Quantitative susceptibility mapping of human brain reflects spatial variation in tissue composition , 2011, NeuroImage.

[7]  P Boesiger,et al.  Influence of SENSE on image properties in high‐resolution single‐shot echo‐planar DTI , 2006, Magnetic resonance in medicine.

[8]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

[9]  Blair R. Leavitt,et al.  Induction of neurogenesis in the neocortex of adult mice , 2000, Nature.

[10]  Hellmut Merkle,et al.  Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. , 2011, Brain : a journal of neurology.

[11]  Bing Wu,et al.  Magnetic susceptibility of brain iron is associated with childhood spatial IQ , 2016, NeuroImage.

[12]  Khadar Abdi,et al.  Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4 , 2013, Nature.

[13]  Wei Li,et al.  Susceptibility‐weighted imaging and quantitative susceptibility mapping in the brain , 2015, Journal of magnetic resonance imaging : JMRI.

[14]  Robert W. Williams,et al.  Complex trait analysis of the mouse striatum: independent QTLs modulate volume and neuron number , 2001, BMC Neuroscience.

[15]  George Paxinos,et al.  Atlas of the developing mouse brain , 2007 .

[16]  Robert W. Williams,et al.  Increased brain size and glial cell number in CD81‐null mice , 2002, The Journal of comparative neurology.

[17]  Jianrong Xu,et al.  Streaking artifact reduction for quantitative susceptibility mapping of sources with large dynamic range , 2015, NMR in biomedicine.

[18]  H. Steinbusch,et al.  Distribution of serotonin-immunoreactivity in the central nervous system of the rat—Cell bodies and terminals , 1981, Neuroscience.

[19]  Wei Li,et al.  Microstructural origins of gadolinium‐enhanced susceptibility contrast and anisotropy , 2014, Magnetic resonance in medicine.

[20]  D. Yablonskiy,et al.  Biophysical mechanisms of phase contrast in gradient echo MRI , 2009, Proceedings of the National Academy of Sciences.

[21]  Karen O. Egiazarian,et al.  Nonlocal Transform-Domain Filter for Volumetric Data Denoising and Reconstruction , 2013, IEEE Transactions on Image Processing.

[22]  A. Schierloh,et al.  Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain , 2007, Nature Methods.

[23]  Hongjiang Wei,et al.  Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications , 2015, Tomography.

[24]  Satyandra K. Gupta,et al.  Algorithms for On-Line Monitoring of Micro Spheres in an Optical Tweezers-Based Assembly Cell , 2007, J. Comput. Inf. Sci. Eng..

[25]  H. C. Cook Manual of histological demonstration techniques , 1974 .

[26]  Alessandro Foi,et al.  Image Denoising by Sparse 3-D Transform-Domain Collaborative Filtering , 2007, IEEE Transactions on Image Processing.

[27]  Wei Li,et al.  3D fiber tractography with susceptibility tensor imaging , 2012, NeuroImage.

[28]  Xu Li,et al.  Mean magnetic susceptibility regularized susceptibility tensor imaging (MMSR‐STI) for estimating orientations of white matter fibers in human brain , 2014, Magnetic resonance in medicine.

[29]  Dan Wu,et al.  In vivo high-resolution diffusion tensor imaging of the mouse brain , 2013, NeuroImage.

[30]  Yuyao Zhang,et al.  Joint 2D and 3D phase processing for quantitative susceptibility mapping: application to 2D echo‐planar imaging , 2017, NMR in biomedicine.

[31]  Rolf Gruetter,et al.  On the origin of the MR image phase contrast: An in vivo MR microscopy study of the rat brain at 14.1 T , 2009, NeuroImage.

[32]  Jean-Michel Deniau,et al.  Striatal Medium-Sized Spiny Neurons: Identification by Nuclear Staining and Study of Neuronal Subpopulations in BAC Transgenic Mice , 2009, PloS one.

[33]  Yi Jiang,et al.  Microscopic diffusion tensor imaging of the mouse brain , 2010, NeuroImage.

[34]  C. Petersen The Functional Organization of the Barrel Cortex , 2007, Neuron.

[35]  Jeff H. Duyn,et al.  High-field MRI of brain cortical substructure based on signal phase , 2007, Proceedings of the National Academy of Sciences.

[36]  Wei Cao,et al.  A method for estimating and removing streaking artifacts in quantitative susceptibility mapping , 2015, NeuroImage.

[37]  N. Spruston Pyramidal neurons: dendritic structure and synaptic integration , 2008, Nature Reviews Neuroscience.

[38]  Peter J. Basser,et al.  Glial Regulation of the Neuronal Connectome through Local and Long-Distant Communication , 2015, Neuron.

[39]  L. Hedlund,et al.  Morphologic phenotyping with MR microscopy: the visible mouse. , 2002, Radiology.

[40]  J. Reichenbach,et al.  Magnetic susceptibility-weighted MR phase imaging of the human brain. , 2005, AJNR. American journal of neuroradiology.

[41]  Pascal Spincemaille,et al.  Nonlinear formulation of the magnetic field to source relationship for robust quantitative susceptibility mapping , 2013, Magnetic resonance in medicine.

[42]  J. Reichenbach,et al.  Differentiation between diamagnetic and paramagnetic cerebral lesions based on magnetic susceptibility mapping. , 2010, Medical physics.

[43]  Petra Schmalbrock,et al.  Enhanced gray and white matter contrast of phase susceptibility‐weighted images in ultra‐high‐field magnetic resonance imaging , 2003, Journal of magnetic resonance imaging : JMRI.

[44]  Yi Wang,et al.  Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker , 2014, Magnetic resonance in medicine.

[45]  Luke Xie,et al.  Magnetic Resonance Histology of Age-Related Nephropathy in the Sprague Dawley Rat , 2012, Toxicologic pathology.

[46]  Chunlei Liu Susceptibility tensor imaging , 2010, Magnetic resonance in medicine.

[47]  Wei Li,et al.  Quantitative Magnetic Susceptibility Mapping of the developing mouse brain , 2011 .

[48]  Torsten Rohlfing,et al.  MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping , 2011, NeuroImage.

[49]  J. Royet,et al.  Morphometric study of the glomerular population in the mouse olfactory bulb: Numerical density and size distribution along the rostrocaudal axis , 1988, The Journal of comparative neurology.

[50]  Fernando Calamante,et al.  Visualization of mouse barrel cortex using ex-vivo track density imaging , 2014, NeuroImage.

[51]  Jeff H. Duyn,et al.  The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain , 2012, NeuroImage.

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