title: Validating myelin water imaging with transmission electron microscopy in a rat spinal cord injury model.
abstract: Myelin content is an important marker for neuropathology and MRI generated myelin water fraction (MWF) has been shown to correlate well with myelin content. However, because MWF is based on the amount of signal from myelin water, that is, the water trapped between the myelin lipid bilayers, the reading may depend heavily on myelin morphology. This is of special concern when there is a mix of intact myelin and myelin debris, as in the case of injury. To investigate what MWF measures in the presence of debris, we compared MWF to transmission electron microscopy (TEM) derived myelin fraction that measures the amount of compact appearing myelin. A rat spinal cord injury model was used with time points at normal (normal myelin), 3 weeks post-injury (myelin debris), and 8 weeks post-injury (myelin debris, partially cleared). The myelin period between normal and 3 or 8 weeks post-injury cords did not differ significantly, suggesting that as long as the bilayer structure is intact, myelin debris has the same water content as intact myelin. The MWF also correlated strongly with the TEM-derived myelin fraction, suggesting that MWF measures the amount of compact appearing myelin in both intact myelin and myelin debris. From the TEM images, it appears that as myelin degenerates, it tends to form large watery spaces within the myelin sheaths that are not classified as myelin water. The results presented in this study improve our understanding and allows for better interpretation of MWF in the presence of myelin debris.
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, Canada; University of British Columbia MRI Research Centre, Vancouver, Canada. Electronic address: szumeng@phas.ubc.ca.
authors.forename: Henry Szu-Meng
authors.initials: HS
authors.lastname: Chen
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), Vancouver, Canada; Department of Zoology, University of British Columbia, Vancouver, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Holmes
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), Vancouver, Canada. Electronic address: jliu@icord.org.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), Vancouver, Canada; Department of Zoology, University of British Columbia, Vancouver, Canada. Electronic address: tetzlaff@icord.org.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tetzlaff
authors.affiliation: University of British Columbia MRI Research Centre, Vancouver, Canada; International Collaboration on Repair Discoveries (ICORD), Vancouver, Canada; Department of Radiology, University of British Columbia, Vancouver, Canada. Electronic address: piotr.kozlowski@ubc.ca.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D045604:Extracellular Fluid / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000737:chemistry* / Q000648:ultrastructure*; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000473:pathology*; D014867:Water / Q000032:analysis
chemical_list: D014867:Water
keywords: Electron microscopy; Magnetic resonance imaging; Myelin; Myelin debris; Myelin water imaging; Spinal cord injury