Use of High Resolution 3D Diffusion Tensor Imaging to Study Brain White Matter Development in Live Neonatal Rats

High resolution diffusion tensor imaging (DTI) can provide important information on brain development, yet it is challenging in live neonatal rats due to the small size of neonatal brain and motion-sensitive nature of DTI. Imaging in live neonatal rats has clear advantages over fixed brain scans, as longitudinal and functional studies would be feasible to understand neuro-developmental abnormalities. In this study, we developed imaging strategies that can be used to obtain high resolution 3D DTI images in live neonatal rats at postnatal day 5 (PND5) and PND14, using only 3 h of imaging acquisition time. An optimized 3D DTI pulse sequence and appropriate animal setup to minimize physiological motion artifacts are the keys to successful high resolution 3D DTI imaging. Thus, a 3D rapid acquisition relaxation enhancement DTI sequence with twin navigator echoes was implemented to accelerate imaging acquisition time and minimize motion artifacts. It has been suggested that neonatal mammals possess a unique ability to tolerate mild-to-moderate hypothermia and hypoxia without long term impact. Thus, we additionally utilized this ability to minimize motion artifacts in magnetic resonance images by carefully suppressing the respiratory rate to around 15/min for PND5 and 30/min for PND14 using mild-to-moderate hypothermia. These imaging strategies have been successfully implemented to study how the effect of cocaine exposure in dams might affect brain development in their rat pups. Image quality resulting from this in vivo DTI study was comparable to ex vivo scans. fractional anisotropy values were also similar between the live and fixed brain scans. The capability of acquiring high quality in vivo DTI imaging offers a valuable opportunity to study many neurological disorders in brain development in an authentic living environment.

[1]  E. Adolph.  Tolerance to cold and anoxia in infant rats. , 1948, The American journal of physiology.

[2]  D Singer,et al.  Neonatal tolerance to hypoxia: a comparative-physiological approach. , 1999, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[3]  M. Moseley,et al.  Self‐navigated interleaved spiral (SNAILS): Application to high‐resolution diffusion tensor imaging , 2004, Magnetic resonance in medicine.

[4]  P. Hüppi,et al.  Diffusion tensor imaging of normal and injured developing human brain ‐ a technical review , 2002, NMR in biomedicine.

[5]  Christos Davatzikos,et al.  Spatiotemporal maturation patterns of murine brain quantified by diffusion tensor MRI and deformation-based morphometry , 2005, Proc. Natl. Acad. Sci. USA.

[6]  Lawrence R. Frank,et al.  High efficiency, low distortion 3D diffusion tensor imaging with variable density spiral fast spin echoes (3D DW VDS RARE) , 2010, NeuroImage.

[7]  Robin M Heidemann,et al.  High resolution diffusion‐weighted imaging using readout‐segmented echo‐planar imaging, parallel imaging and a two‐dimensional navigator‐based reacquisition , 2009, Magnetic resonance in medicine.

[8]  Robert Turner,et al.  Single-shot diffusion imaging at 2.0 tesla , 1990 .

[9]  E. Adolph.  Regulations during survival without oxygen in infant mammals. , 1969, Respiration physiology.

[10]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[11]  F. Schick.  SPLICE: Sub‐second diffusion‐sensitive MR imaging using a modified fast spin‐echo acquisition mode , 1997, Magnetic resonance in medicine.

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

[13]  Fahmeed Hyder,et al.  Hypoxic injury during neonatal development in murine brain: correlation between in vivo DTI findings and behavioral assessment. , 2009, Cerebral cortex.

[14]  Michael I. Miller,et al.  Mapping postnatal mouse brain development with diffusion tensor microimaging , 2005, NeuroImage.

[15]  Fahmeed Hyder,et al.  Neurodevelopment of C57B/L6 mouse brain assessed by in vivo diffusion tensor imaging , 2007, NMR in biomedicine.

[16]  N. Makris,et al.  High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity , 2002, Magnetic resonance in medicine.

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

[18]  Victor H. Denenberg,et al.  Corpus callosum: effects of neonatal hormones on sexual dimorphism in the rat , 1990, Brain Research.

[19]  M. Solaiyappan,et al.  Diffusion tensor imaging of the developing mouse brain , 2001, Magnetic resonance in medicine.

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

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

[22]  Susumu Mori,et al.  Quantitative Cortical Mapping of Fractional Anisotropy in Developing Rat Brains , 2008, The Journal of Neuroscience.

[23]  C. Pierpaoli,et al.  Diffusion‐weighted radial fast spin‐echo for high‐resolution diffusion tensor imaging at 3T , 2008, Magnetic resonance in medicine.

[24]  Wieslaw Lucjan Nowinski,et al.  Three-Dimensional Interactive and Stereotactic Human Brain Atlas of White Matter Tracts , 2011, Neuroinformatics.

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

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

[27]  Andre Obenaus,et al.  Magnetic resonance imaging and mathematical modeling of progressive formalin fixation of the human brain , 2005, Magnetic resonance in medicine.

[28]  M. Solaiyappan,et al.  In vivo three‐dimensional reconstruction of rat brain axonal projections by diffusion tensor imaging , 1999, Magnetic resonance in medicine.

[29]  James G Pipe,et al.  Multishot diffusion‐weighted FSE using PROPELLER MRI , 2002, Magnetic resonance in medicine.

[30]  Sheng-Kwei Song,et al.  Relative indices of water diffusion anisotropy are equivalent in live and formalin‐fixed mouse brains , 2003, Magnetic resonance in medicine.

[31]  Jie Deng,et al.  Multishot diffusion‐weighted SPLICE PROPELLER MRI of the abdomen , 2008, Magnetic resonance in medicine.

[32]  A. Stark,et al.  Hypothermia: A Neuroprotective Therapy for Neonatal Hypoxic-Ischemic Encephalopathy , 2006, Pediatrics.

[33]  Hao Huang,et al.  Three-dimensional anatomical characterization of the developing mouse brain by diffusion tensor microimaging , 2003, NeuroImage.

[34]  F. H. Lee,et al.  Diffusion tensor imaging (DTI) of rodent brains in vivo using a 1.5T clinical MR scanner , 2006, Journal of magnetic resonance imaging : JMRI.

[35]  A. Snyder,et al.  Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging. , 1998, Radiology.

[36]  B. Siewert,et al.  Abdominal diffusion mapping with use of a whole-body echo-planar system. , 1994, Radiology.

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

[38]  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.

[39]  Dae-Shik Kim,et al.  Spatial resolution dependence of DTI tractography in human occipito-callosal region , 2006, NeuroImage.

[40]  Terence W Nixon,et al.  High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo , 2006, Magnetic resonance in medicine.

[41]  Zhi-Pei Liang,et al.  Diffusion tensor imaging of mouse brain stem and cervical spinal cord , 2009, Journal of Neuroscience Methods.

[42]  P A Narayana,et al.  Early postnatal development of rat brain: In vivo diffusion tensor imaging , 2008, Journal of neuroscience research.

[43]  J. Michael Tyszka,et al.  Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant , 2006, NeuroImage.