Investigating the Early Mr Biomarkers of the Brain Demyelination Using Myelin Water Imaging, Diffusion Kurtosis Imaging, and Chemical Exchange Saturation Transfer (Cest) Schemes: a Translational Study Ii

Demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica (NMO), affecting approximately 2.5 million people worldwide, could lead to a spectrum of neuropsychiatric impairments. Although the pathophysiological mechanisms remains elusive, demyelination process has been frequently characterized by loss of the myelin sheath associated with immune-mediated inflammation, microglial/macrophage activation, and so forth. MR FLAIR image, as the first line diagnostic tool, may be sensitive to the white matter lesions at chronic demyelination. However, there is no single conventional MR image can provide the pathologically specific information about the brain demyelination at the early phase. Recently, myelin water fraction (MWF) could have the potential to reflect the loss of myelin content, which is one of the most primary pathological features during brain demyelination. On the other hand, DKI, assessing the non-Gaussian water diffusion, could have the ability to provide more comprehensive information about microstructure changes in the brain as compared to the conventional diffusion tensor imaging (DTI). Additionally, glucose CEST or amide proton transfer (APT) methods may provide the capability of revealing the possible metabolic alterations during demyelinating process in the brain. This is a three-year translational study project. In the first year, the advanced MR imaging protocols including myelin water imaging, diffusion kurtosis imaging (DKI), and chemical exchange saturation transfer (CEST) scheme have been well established and optimized. Within the next two years, the proposed advanced MR imaging techniques will be performed on the rat demyelinating model at 7 T MRI in comparison with the pathophysiological features of brain demyelination to find surrogate MR biomarkers during early demyelination. Hopefully, the translational study of investigating the relationships between these advanced MR imaging approaches and immunohistochemical analysis in rats as well as assessment of neuropsychiatric functions in human will yield novel insights into the potential mechanism of cerebral demyelination. Specific aims: (1) To establish the demyelinating rat model (2) To validate the MR biomarkers, including, including myelin water imaging, diffusion kurtosis imaging (DKI), and chemical exchange saturation transfer (CEST), in rat demyelinating model in vivo (3) To translate the proposed MR imaging schemes from bench to bed (4) To validate the advanced MR biomarkers in early detection of the elderly subjects as well as patients with demyelinating diseases