Abstract：
Cholesterol is a vital component of the central nervous system and tissues, and understanding its spatial distribution is crucial for biology, pathophysiology, and diagnostics. However, direct imaging of cholesterol using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) remains challenging and time-consuming due to the difficulty in ionizing the sterol molecule. To tackle this issue, a MALDI-MSI method is established for direct and rapid analysis of the spatial distribution of cholesterol in Alzheimer\'s disease (AD), different cancer tissues and organs via MALDI-MSI. This excellent imaging performance depends on the study and systemic optimization of various conditions that affect the imaging of MALDI-MSI. In this case, we report the distribution and levels of cholesterol across specific structures of the AD mouse brain and different tumor tissue and organs. According to the results, the content of cholesterol in the AD mouse cerebellum, especially in the arborvitae, was significantly higher than that in the wild type (WT) model. Furthermore, we successfully visualize the distribution of cholesterol in other organs, such as the heart, liver, spleen, kidney, pancreas, as well as tumor tissues parenchyma and interstitium using MALDI-MSI. Notably, the attribution of cholesterol MS/MS hydrocarbon fragments was systematically investigated. Our presented optimization strategy and established MALDI-MSI method can be easily generalized for different animal tissues or live samples, thereby facilitating the potential for applications of MALDI-MSI in clinical, medical and biological research.
摘要：
胆固醇是中枢神经系统和组织的重要组成部分，了解它的空间分布对生物学至关重要，病理生理学,和诊断。然而,使用基质辅助激光解吸/电离质谱成像（MALDI-MSI）对胆固醇进行直接成像仍然具有挑战性且耗时，因为难以电离甾醇分子。为了解决这个问题，建立了MALDI-MSI方法，用于直接和快速分析阿尔茨海默病（AD）中胆固醇的空间分布，通过MALDI-MSI不同的癌组织和器官。这种优异的成像性能取决于影响MALDI-MSI成像的各种条件的研究和系统优化。在这种情况下,我们报告了胆固醇在AD小鼠大脑和不同肿瘤组织和器官的特定结构中的分布和水平。根据结果,AD小鼠小脑中的胆固醇含量，尤其是在侧柏中，显著高于野生型(WT)模型。此外，我们成功地可视化了胆固醇在其他器官中的分布，比如心脏，肝脏,脾,脾肾,胰腺,以及使用MALDI-MSI的肿瘤组织实质和间质。值得注意的是,系统研究了胆固醇MS/MS烃碎片的归属。我们提出的优化策略和建立的MALDI-MSI方法可以很容易地推广到不同的动物组织或活样品，从而促进MALDI-MSI在临床上的应用潜力，医学和生物学研究。
