Normal Chinese Lifespan Brain Charts Initiative (NCLBCI)

Overview

Major brain diseases (including neuroimmune diseases, neurodegenerative diseases, and cerebrovascular diseases) are leading causes of death and disability in humans. This research will gather brain imaging data from more than 10,000 participants across multiple age groups from multiple centers nationwide. Using standardized modeling methods, the investigators aim to establish normal brain imaging reference values for the Chinese population. (1) The study will reveal population-level patterns of brain structure changes and determine normal reference values for brain structure at different ages. (2) Non-invasive imaging methods will be applied to evaluate blood-brain barrier changes without the need for invasive procedures, establishing age-related permeability patterns and normal values in healthy populations. Additionally, functional magnetic resonance imaging (fMRI) will be combined to provide brain function indicators at various scales, creating comprehensive multi-dimensional function charts. (3) These brain structure and function charts will be applied to the individualized diagnosis and treatment of major brain diseases, including neuroimmune diseases (Multiple Sclerosis \[MS\], Neuromyelitis Optica Spectrum Disorders \[NMOSD\]), neurodegenerative diseases (Alzheimer's disease \[AD\], Parkinson's disease \[PD\]), and cerebrovascular diseases (Cerebral Small Vessel Diseases \[cSVD\]). This approach will facilitate early disease diagnosis and provide precise, individualized assessments of treatment efficacy and prognosis prediction. The established brain structure and function charts will be accessible via interactive websites or software, enabling real-time online data updates and individualized percentile outputs for brain structure and function. By inputting the target data, users can obtain individualized evaluation metrics for brain structure and function. The project's implementation and application hold great potential for broad use, promotion, and high translational potential.

In 2022, the World Health Organization (WHO) issued a policy document calling for attention to brain health and neurological diseases. In China's "14th Five-Year Plan," brain science research is designated as one of the key research areas, with the development goal of promoting the understanding of fundamental brain mechanisms and meeting the needs for improving brain health in the population. Understanding brain development and aging in healthy individuals is a prerequisite for comprehending neurological diseases. The function of the blood-brain barrier is crucial to maintaining brain health and plays a central role in the occurrence and development of major brain diseases. However, there is currently a lack of standardized reference values for brain structural imaging evaluation, and even less is known about the changes in blood-brain barrier function in healthy populations. This significantly hinders the understanding of brain health, the pathology of major brain diseases, and the ability to make early individualized diagnoses and treatments. Additionally, although functional Magnetic Resonance Imaging (fMRI) has become an essential research tool in neuroscience, its clinical application is still fraught with difficulties, primarily due to the lack of standardized quantitative evaluation methods. In 2022, international datasets covering the human lifespan were established, and the constructed percentile curves revealed population patterns of brain development and individualized differences, offering a promising standardized tool for evaluating brain health and diseases. Nevertheless, existing brain imaging characterizations still have some limitations: (1) the lack of normal reference values for brain imaging structures in the Chinese population; (2) the absence of brain function indicator charts, such as functional connectivity and cerebral blood flow perfusion, especially with regard to the critical role of blood-brain barrier changes in major brain disease transformation; (3) The application value of brain charts in the diagnosis and treatment of major brain diseases lacks systematic research. Therefore, constructing brain structure and function imaging charts (normal reference values) for the Chinese population is imperative and represents a pressing scientific and clinical issue that needs to be addressed. Establishment of the Chinese Normal Population Neuroimaging Database: The investigators aim to establish the largest neuroimaging research cohort in China, consisting of 10,000 participants, with a wide age range (6-90 years), balanced gender distribution, and representation from more than 30 centers nationwide, ensuring a balanced distribution of scanning devices. Using federated machine learning methods, the study will address data privacy and security concerns. This project primarily includes: ① Retrospective collection of neuroimaging data from 5,000 participants nationwide, focusing mainly on 3DT1WI and 3DFLAIR imaging, and also collecting basic demographic information, health status, and neuropsychological assessments. ② A prospective neuroimaging cohort of 5,000 participants from the Chinese normal population, including multimodal imaging sequences (3DT1WI, 3DFLAIR, DKI, ASL, VEXI, MRA, and resting-state fMRI), along with detailed demographic information, neuropsychological assessments, standardized questionnaires, and basic physical examinations. Multimodal neuroimaging data and neuropsychological assessments will be collected at two follow-ups (1-year and 2-year intervals). Among the multimodal brain imaging collected, the method reflecting blood-brain barrier permeability is vascular water exchange MRI (VEXI), which uses water molecules as natural internal tracers to measure blood-brain barrier function. Establishment of Brain Structure and Function Charts for the Chinese Normal Population: Based on retrospective and prospective neuroimaging data from the Chinese normal population, standardized modeling methods (including Generalized Additive Mixed Models \[GAMLSS\] and Gaussian Process Regression \[GPR\]) will be used to create structural brain charts. These charts will include: ① Whole brain volumes (Gray Matter Volume \[GMV\], White Matter Volume \[WMV\], Total Intracranial Volume \[TIV\], etc.), the volumes of 148 brain regions, and subcortical nuclei volumes. ② White matter fiber tracts (48 white matter fiber tracts and diffusion metrics, including Fractional Anisotropy \[FA\], Mean Kurtosis \[MK\], Mean Diffusivity \[MD\], etc.) and functional brain charts, which include: ① Blood-brain barrier permeability; ② Cerebral blood flow (CBF); ③ Local brain activity indicators (Regional Homogeneity \[ReHo\], Amplitude of Low-Frequency Fluctuations \[ALFF\], etc.); ④ Global functional connectivity; and ⑤ Brain network analysis (local and global efficiency), among others.