Disease stage-dependent relationship between diffusion tensor imaging and electrophysiology of the visual system in a murine model of multiple sclerosis
Diffusion tensor imaging (DTI) is commonly used to evaluate white matter integrity in multiple sclerosis (MS), but the relationship between DTI measures and functional changes during disease remains ambiguous. Using a mouse model of MS, we tested the hypothesis that DTI measures would correlate to the visual evoked potential (VEPs) dynamically at different disease stages.
In vivo DTI, gadolinium-enhanced T1WI (Gd-T1WI) and VEPs were performed in 5 control and 25 mice after 2–12 weeks of experimental autoimmune encephalomyelitis (EAE). DTI indices, including fractional anisotropy (FA), axial and radial diffusivities (AD and RD), and Gd-T1WI enhancement, were measured in the optic nerve and tract (ON and OT), which were compared with measured VEPs.
Gd-T1WI showed a 3- to 4-fold enhancement over controls beginning after 2 weeks of EAE. Across the time course, we found progressive reductions in FA and increases in RD with increases in VEP latency and reductions in amplitude. Significant correlations between DTI (FA and RD) and VEP evolved; in control/early asymptomatic EAE mice, both FA and RD were highly correlated with VEP latency (but not amplitude), while in late EAE, both DTI indices were highly correlated with VEP amplitude (but not latency).
DTI measures FA and RD are associated to VEP latency in early stages of EAE but associated to VEP amplitude in later stages, suggesting that the patterns of DTI related to the functional decline may depend on the stage of disease progression.
KeywordsDiffusion tensor imaging (DTI) Visual evoked potential (VEP) Gd-enhanced T1WI (Gd-T1WI) Experimental autoimmune encephalomyelitis (EAE) Multiple sclerosis (MS)
Diffusion tensor imaging
Visual evoked potential
Gd-enhanced T1-weighted imaging
Experimental autoimmune encephalomyelitis
We thank Dr. Wei-Xing Shi, Pharmaceutical Science, Loma Linda University, for an insightful discussion.
Compliance with ethical standards
This work was funded in part by NIH R01 NS062830 and the National Space Biomedical Research Institute (RE03701) through the National Aeronautics and Space Administration NCC 9–58.
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
Statement of informed consent was not applicable since the manuscript does not contain any patient data.
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