Correlation of in vivo and ex vivo 1H-MRI with histology in two severities of mouse spinal cord injury

Spinal cord injury (SCI) is a debilitating neuropathology with no effective treatment. Magnetic resonance imaging (MRI) technology is the only method used to assess the impact of an injury on the structure and function of the human spinal cord. Moreover, in pre-clinical SCI research, MRI is a non-invasive method with great translational potential since it provides relevant longitudinal assessment of anatomical and structural alterations induced by an injury. It is only recently that MRI techniques have been effectively used for the follow-up of SCI in rodents. However, the vast majority of these studies have been carried out on rats and when conducted in mice, the contusion injury model was predominantly chosen. Due to the remarkable potential of transgenic mice for studying the pathophysiology of SCI, we examined the use of both in and ex vivo 1H-MRI (9.4 T) in two severities of the mouse SCI (hemisection and over-hemisection) and documented their correlation with histological assessments. We demonstrated that a clear distinction between the two injury severities is possible using in and ex vivo 1H-MRI and that ex vivo MR images closely correlate with histology. Moreover, tissue modifications at a remote location from the lesion epicenter were identified by conventional ex vivo MRI analysis. Therefore, in vivo MRI has the potential to accurately identify in mice the progression of tissue alterations induced by SCI and is successfully implemented by ex vivo MRI examination. This combination of in and ex vivo MRI follow-up associated with histopathological assessment provides a valuable approach for further studies intended to evaluate therapeutic strategies on SCI.

[1]  B. Ellingson,et al.  Ex vivo diffusion tensor imaging and quantitative tractography of the rat spinal cord during long‐term recovery from moderate spinal contusion , 2008, Journal of magnetic resonance imaging : JMRI.

[2]  Mehmet Bilgen,et al.  Evaluating regional blood spinal cord barrier dysfunction following spinal cord injury using longitudinal dynamic contrast-enhanced MRI , 2009, BMC Medical Imaging.

[3]  E. D. Schwartz,et al.  Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF , 2003, Experimental Neurology.

[4]  D. Hackney,et al.  Diffusion-weighted MRI and the evaluation of spinal cord axonal integrity following injury and treatment , 2003, Experimental Neurology.

[5]  Kathryn Trinkaus,et al.  Diffusion tensor imaging at 3 hours after traumatic spinal cord injury predicts long-term locomotor recovery. , 2010, Journal of neurotrauma.

[6]  O. Nalcioglu,et al.  Behavioral, histological, and ex vivo magnetic resonance imaging assessment of graded contusion spinal cord injury in mice. , 2007, Journal of neurotrauma.

[7]  Julien Cohen-Adad,et al.  The current state-of-the-art of spinal cord imaging: Methods , 2014, NeuroImage.

[8]  Jae K. Lee,et al.  Animal models of axon regeneration after spinal cord injury , 2013, Neuroscience Bulletin.

[9]  Mehmet Bilgen,et al.  Longitudinal magnetic resonance imaging of spinal cord injury in mouse: changes in signal patterns associated with the inflammatory response. , 2007, Magnetic resonance imaging.

[10]  R. Yezierski,et al.  Evaluation of the pathologic characteristics of excitotoxic spinal cord injury with MR imaging. , 2005, AJNR. American journal of neuroradiology.

[11]  P. W. Stroman,et al.  The current state-of-the-art of spinal cord imaging: Applications , 2014, NeuroImage.

[12]  J. Bonny,et al.  Time course of acute phase in mouse spinal cord injury monitored by ex vivo quantitative MRI , 2006, Neurobiology of Disease.

[13]  Nyoman D. Kurniawan,et al.  Longitudinal assessment of white matter pathology in the injured mouse spinal cord through ultra-high field (16.4T) in vivo diffusion tensor imaging , 2013, NeuroImage.

[14]  C. Hellerqvist,et al.  CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Bilgen,et al.  Magnetic resonance imaging of mouse spinal cord , 2005, Magnetic resonance in medicine.

[16]  R. Bhadelia,et al.  Magnetic resonance imaging of intramedullary spinal cord lesions: a pictorial review. , 2010, Current problems in diagnostic radiology.

[17]  F. Mohamed,et al.  Small mammal MRI imaging in spinal cord injury: A novel practical technique for using a 1.5T MRI , 2008, Journal of Neuroscience Methods.

[18]  P. Joseph,et al.  Hemorrhage and edema in acute spinal cord compression: demonstration by MR imaging. , 1986, Radiology.

[19]  C. Hellerqvist,et al.  CM 101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury , 1999 .

[20]  G. Cosnard,et al.  [MRI of closed head injury]. , 2003, Journal of neuroradiology. Journal de neuroradiologie.

[21]  A. Faden,et al.  Neuropathological differences between rats and mice after spinal cord injury , 2010, Journal of magnetic resonance imaging : JMRI.

[22]  J. Bonny,et al.  Nuclear magnetic resonance microimaging of mouse spinal cord in vivo , 2004, Neurobiology of Disease.

[23]  Charles Watson,et al.  Vertebral landmarks for the identification of spinal cord segments in the mouse , 2013, NeuroImage.

[24]  A. Rose The sensitivity performance of the human eye on an absolute scale. , 1948, Journal of the Optical Society of America.

[25]  P. Narayana,et al.  1.5 tesla magnetic resonance imaging of acute spinal trauma. , 1988, Radiographics : a review publication of the Radiological Society of North America, Inc.

[26]  P. Mishra,et al.  MRI in Rodent Models of Brain Disorders , 2011, Neurotherapeutics.

[27]  N. Harel,et al.  Functional MRI and other non-invasive imaging technologies: Providing visual biomarkers for spinal cord structure and function after injury , 2008, Experimental Neurology.

[28]  A. Privat,et al.  A remotely controlled model of spinal cord compression injury in mice: toward real-time analysis. , 2009, Journal of neurosurgery. Spine.