Localized diffusion magnetic resonance micro-imaging of the live mouse brain

High-resolution diffusion MRI (dMRI) is useful for resolving complex microstructures in the mouse brain, but technically challenging for in vivo studies due to the long scan time. In this study, selective excitation and a three-dimensional fast imaging sequence were used to achieve in vivo high-resolution dMRI of the mouse brain at 11.7Tesla. By reducing the field of view using spatially selective radio frequency pulses, we were able to focus on targeted brain structures and acquire high angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 0.1mm and 30 diffusion encoding directions in approximately 1h. We investigated the complex tissue microstructures of the mouse hippocampus, cerebellum, and several cortical areas using this localized dMRI approach, and compared the results with histological sections stained with several axonal and dendritic markers. In the mouse visual cortex, the results showed predominately radially arranged structures in an outer layer and tangentially arranged structures in an inner layer, similar to observations from postmortem human brain specimens.

[1]  Jürgen Hennig,et al.  Inner‐volume imaging in vivo using three‐dimensional parallel spatially selective excitation , 2013, Magnetic resonance in medicine.

[2]  S. Mori,et al.  Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience Research , 2006, Neuron.

[3]  P. Basser,et al.  In vivo measurement of axon diameter distribution in the corpus callosum of rat brain. , 2009, Brain : a journal of neurology.

[4]  Thomas H. Mareci,et al.  Experimental study of optimal selective 180° radiofrequency pulses , 1988 .

[5]  R. Turner,et al.  Layer-Specific Intracortical Connectivity Revealed with Diffusion MRI , 2012, Cerebral cortex.

[6]  Kerstin Pannek,et al.  Comparative mouse brain tractography of diffusion magnetic resonance imaging , 2010, NeuroImage.

[7]  Alan Connelly,et al.  MRtrix: Diffusion tractography in crossing fiber regions , 2012, Int. J. Imaging Syst. Technol..

[8]  Silun Wang,et al.  Characterization of White Matter Injury in a Hypoxic-Ischemic Neonatal Rat Model by Diffusion Tensor MRI , 2008, Stroke.

[9]  Geoffrey J. M. Parker,et al.  Probabilistic quantification of regional cortical microstructural complexity , 2010 .

[10]  Alan Connelly,et al.  Track-density imaging (TDI): Super-resolution white matter imaging using whole-brain track-density mapping , 2010, NeuroImage.

[11]  Robert Turner,et al.  Diffusion imaging in humans at 7T using readout‐segmented EPI and GRAPPA , 2010, Magnetic resonance in medicine.

[12]  L. Frank.  Anisotropy in high angular resolution diffusion‐weighted MRI , 2001, Magnetic resonance in medicine.

[13]  Michael A. King,et al.  Diffusion tensor microscopy in human nervous tissue with quantitative correlation based on direct histological comparison , 2011, NeuroImage.

[14]  Shu-Wei Sun,et al.  Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia , 2006, NeuroImage.

[15]  Susumu Mori,et al.  Three‐dimensional diffusion tensor microimaging for anatomical characterization of the mouse brain , 2010, Magnetic resonance in medicine.

[16]  W. Baaré,et al.  An ex vivo imaging pipeline for producing high‐quality and high‐resolution diffusion‐weighted imaging datasets , 2011, Human brain mapping.

[17]  Denis Le Bihan,et al.  Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature Reviews Neuroscience.

[18]  J. Finsterbusch.  Fast‐spin‐echo imaging of inner fields‐of‐view with 2D‐selective RF excitations , 2010, Journal of magnetic resonance imaging : JMRI.

[19]  Susumu Mori,et al.  Three-Dimensional Diffusion Tensor Magnetic Resonance Microimaging of Adult Mouse Brain and Hippocampus , 2002, NeuroImage.

[20]  Jürgen Finsterbusch,et al.  Functional neuroimaging of inner fields-of-view with 2D-selective RF excitations. , 2013, Magnetic resonance imaging.

[21]  D. Le Bihan,et al.  Double-sampled echo-planar imaging at 3 tesla. , 1996, Journal of magnetic resonance. Series B.

[22]  A. Snyder,et al.  Radial organization of developing preterm human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI. , 2002, Cerebral cortex.

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

[24]  V. Wedeen,et al.  Diffusion MRI of Complex Neural Architecture , 2003, Neuron.

[25]  M. Horsfield,et al.  Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging , 1999, Magnetic resonance in medicine.

[26]  Julien Cohen-Adad,et al.  Pushing the limits of in vivo diffusion MRI for the Human Connectome Project , 2013, NeuroImage.

[27]  Douglas C Noll,et al.  Spatial domain method for the design of RF pulses in multicoil parallel excitation , 2006, Magnetic resonance in medicine.

[28]  J. Reichenbach,et al.  Diffusion Weighted ZOOM Imaging in the Lumbar Spine Based on Single-Shot STEAM , 2009 .

[29]  Derek K. Jones,et al.  Diffusion tensor imaging. , 2011, Methods in molecular biology.

[30]  Douglas C Noll,et al.  Iterative RF pulse design for multidimensional, small‐tip‐angle selective excitation , 2005, Magnetic resonance in medicine.

[31]  J. Pauly,et al.  Saturated double‐angle method for rapid B1+ mapping , 2006, Magnetic resonance in medicine.

[32]  Alan Connelly,et al.  Super-resolution track-density imaging studies of mouse brain: Comparison to histology , 2012, NeuroImage.

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

[34]  Sheng-Kwei Song,et al.  Axial Diffusivity Is the Primary Correlate of Axonal Injury in the Experimental Autoimmune Encephalomyelitis Spinal Cord: A Quantitative Pixelwise Analysis , 2009, The Journal of Neuroscience.

[35]  Stephen J Blackband,et al.  Aldehyde fixative solutions alter the water relaxation and diffusion properties of nervous tissue , 2009, Magnetic resonance in medicine.

[36]  Hsiao-Fang Liang,et al.  Formalin fixation alters water diffusion coefficient magnitude but not anisotropy in infarcted brain , 2005, Magnetic resonance in medicine.

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

[38]  A. Dale,et al.  Quantitative Histological Validation of Diffusion MRI Fiber Orientation Distributions in the Rat Brain , 2010, PloS one.

[39]  H. Wen,et al.  An in vivo automated shimming method taking into account shim current constraints , 1995, Magnetic resonance in medicine.

[40]  J. Staiger,et al.  Mapping remodeling of thalamocortical projections in the living reeler mouse brain by diffusion tractography , 2013, Proceedings of the National Academy of Sciences.

[41]  Susumu Mori,et al.  Structural insights into the rodent CNS via diffusion tensor imaging , 2012, Trends in Neurosciences.

[42]  David L. Thomas,et al.  Using High Angular Resolution Diffusion Imaging Data to Discriminate Cortical Regions , 2013, PloS one.

[43]  D. Holtzman,et al.  Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury , 2007, Experimental Neurology.

[44]  Michael A. King,et al.  Cellular-level diffusion tensor microscopy and fiber tracking in mammalian nervous tissue with direct histological correlation , 2010, NeuroImage.

[45]  S. Mori,et al.  In vivo and ex vivo diffusion tensor imaging of cuprizone‐induced demyelination in the mouse corpus callosum , 2012, Magnetic resonance in medicine.

[46]  J. DeFelipe,et al.  Microstructure of the neocortex: Comparative aspects , 2002, Journal of neurocytology.

[47]  R. Meuli,et al.  Diffusion Spectrum Imaging Shows the Structural Basis of Functional Cerebellar Circuits in the Human Cerebellum In Vivo , 2009, PloS one.

[48]  D. Feinberg,et al.  GRASE (Gradient‐and Spin‐Echo) imaging: A novel fast MRI technique , 1991, Magnetic resonance in medicine.

[49]  Yaniv Assaf,et al.  Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the human brain , 2005, NeuroImage.

[50]  Hsiao-Fang Liang,et al.  Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum , 2006, Magnetic resonance in medicine.

[51]  G. Glover,et al.  Rapid in vivo proton shimming , 1991, Magnetic resonance in medicine.

[52]  Alan Connelly,et al.  Track density imaging (TDI): Validation of super resolution property , 2011, NeuroImage.

[53]  Zhi-Pei Liang,et al.  A noniterative method to design large‐tip‐angle multidimensional spatially‐selective radio frequency pulses for parallel transmission , 2007, Magnetic resonance in medicine.

[54]  K. Trinkaus,et al.  Quantification of increased cellularity during inflammatory demyelination. , 2011, Brain : a journal of neurology.

[55]  P. V. van Zijl,et al.  A motion correction scheme by twin‐echo navigation for diffusion‐weighted magnetic resonance imaging with multiple RF echo acquisition , 1998, Magnetic resonance in medicine.

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

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

[58]  Susumu Mori,et al.  Image contrast using the secondary and tertiary eigenvectors in diffusion tensor imaging , 2006, Magnetic resonance in medicine.

[59]  Lawrence L. Wald,et al.  Surface based analysis of diffusion orientation for identifying architectonic domains in the in vivo human cortex , 2013, NeuroImage.

[60]  Xin Xu,et al.  An MRI-based atlas and database of the developing mouse brain , 2011, NeuroImage.

[61]  Albert Macovski,et al.  A linear class of large-tip-angle selective excitation pulses , 1989 .

[62]  E. Kholmovski,et al.  High‐resolution DTI with 2D interleaved multislice reduced FOV single‐shot diffusion‐weighted EPI (2D ss‐rFOV‐DWEPI) , 2005, Magnetic resonance in medicine.

[63]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

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

[65]  Jiangyang Zhang,et al.  Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: A case study at 11.7T , 2013, NeuroImage.

[66]  Jeremy D. Schmahmann,et al.  Detection of postmortem human cerebellar cortex and white matter pathways using high angular resolution diffusion tractography: A feasibility study , 2013, NeuroImage.

[67]  Daniel C. Alexander,et al.  NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain , 2012, NeuroImage.

[68]  Timothy Verstynen,et al.  In vivo mapping of microstructural somatotopies in the human corticospinal pathways. , 2011, Journal of neurophysiology.

[69]  R. Hurd,et al.  Optimized Shimming for High-Resolution NMR Using Three-Dimensional Image-Based Field Mapping , 1994 .