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. In this three-year translational study, we aim to investigate the advanced MR imaging biomarkers using myelin water imaging, diffusion kurtosis imaging (DKI), and chemical exchange saturation transfer (CEST) schemes, in conjugation with the pathophysiological features of brain demyelination in preclinical animal model at 7T MRI and human subjects at 3T MRI to find surrogate MR biomarkers during early demyelination. More specifically, 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. 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 potential mechanism in the early demyelination. Specific aims: (1) To develop the proposed advanced MR imaging, including myelin water imaging, diffusion kurtosis imaging (DKI), and chemical exchange saturation transfer (CEST) schemes. (2) To establish the demyelinating rat model (3) To validate the MR biomarkers in the rats in vivo (4) To translate the proposed MR imaging schemes from bench to bed (5) To validate the advanced MR biomarkers in early detection of the elderly subjects as well as patients with demyelinating diseases
|Effective start/end date||8/1/16 → 7/31/17|
- MR physics
- diffusion kurtosis
- chemical exchange saturation transfer
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