Clinical and Imaging Cohort of Neuroinflammation Diseases in China (CLUE)

The study is an observational study of multi-model imaging to determine structural and functional changes of the brain, spinal cord and optic nerve as well as the inflammatory environment inflammatory environment in patients with neuroinflammatory and demyelination disease. Brain, spinal cord and optic nerve involvement are common in neuroinflammatory and demyelination disease including clinical isolated syndrome (CIS), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody - associated disorders (MOGAD). The pathophysiology in neuroinflammatory disease involves the intensive autoimmune inflammatory response, resulting in demyelination and neuroaxonal injury and loss. Some cerebrospinal fluid (CSF) biomarkers have been reported to indicate the pathology and reflect disease activity, especially during the acute stage. However, they couldn't directly reflect the macroscopic and microscopic neuroaxonal change in the brain and spinal cord, which seem to be important determinants of long-term severe disability in chronic neuroinflammatory disease.

Finally, new MRI techniques are the most reliable and non-invasive method to assess the structure and function of brain and spinal cord, plus to monitor disease activity in clinical practice. Double inversion recovery (DIR) imaging allows better detection of cortical and white matter lesion, which has highlighted the role in MS. Diffusion kurtosis imaging (DKI) which has been proposed to characterize the deviation of water diffusion in neural tissues from Gaussian diffusion, is promising to provide information of demyelination and subsequent inflammatory processes in brain or spinal cord. Quantitative susceptibility mapping (QSM) has enabled MRI of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM better depicts spatial susceptibility patterns in MS lesions compared to phase-based imaging. Besides, resting-state functional imaging(Rs-fMRI) has the potential to map the intrinsic functional brain networks and to detect early functional brain changes in neuroinflammatory disease. Metabolic SPICE sequence enables simultaneous mapping of multiple brain metabolites such as Glx, tNAA, and Cho, offering complementary information on neuronal injury and neuroinflammation. 7T MRI provides ultra-high-field imaging with superior signal-to-noise ratio, allowing visualization of subtle cortical lesions, central veins within plaques, and microbleeds not discernible at lower field strengths. PET-MRI integrates molecular imaging using radiotracers like TSPO ligands to quantify microglial activation and neuroinflammation, while coregistered MRI provides anatomical localization of corresponding lesions. In addition, our 3T MRI protocol includes other immune-mediated diseases such as autoimmune encephalitis (AE) and primary angiitis of the central nervous system (PACNS), as well as healthy controls, to further explore differences between diseases and between patients and healthy individuals.

This study will be a prospective cohort study of patients with neuroinflammatory and demyelination disease. Subjects will undertake MR scans at the acute stage and required follow-up visits after 3 month, 6 months, and 1 year. The MR scans are necessary at each visit.

This study does not limit treatment methods. Patients commonly use high-dose intravenous steroid therapy (HD-S) during the acute stage. The HD-S treatment course referred to intravenous administration of 1 g of glucocorticoid daily for 3 consecutive days and continuous dose 240 mg reduction for 60mg oral administration. Immunomodulatory therapies are necessary for the remission stage. The treatment methods include: Azathioprine (start at 50 mg per day, add 50 mg per week to 2 mg/kg*d); Mycophenolate Mofetil (The initial dose was 0.25g bid, add 0.5g per week to 0.75g bid); and Rituximab (500 mg on the 1st day, the 15th day, then 500mg per half year).