The Maastricht MultiModal Molecular Imaging (M4I) institute, Division of Imaging Mass Spectrometry (IMS), Maastricht University, 6229 ER Maastricht, The Netherlands.
Central Analytical Research Facility, Queensland University of Technology, Brisbane, Queensland 4001, Australia.
Anal Chem. 2021 Jul 20;93(28):9826-9834. doi: 10.1021/acs.analchem.1c01377. Epub 2021 Jul 6.
Mass spectrometry imaging (MSI) of lipids within tissues has significant potential for both biomolecular discovery and histopathological applications. Conventional MSI technologies are, however, challenged by the prevalence of phospholipid regioisomers that differ only in the location(s) of carbon-carbon double bonds and/or the relative position of fatty acyl attachment to the glycerol backbone (., position). The inability to resolve isomeric lipids within imaging experiments masks underlying complexity, resulting in a critical loss of metabolic information. Herein, ozone-induced dissociation (OzID) is implemented on a mobility-enabled quadrupole time-of-flight (Q-TOF) mass spectrometer capable of matrix-assisted laser desorption/ionization (MALDI). Exploiting the ion mobility region in the Q-TOF, high number densities of ozone were accessed, leading to ∼1000-fold enhancement in the abundance of OzID product ions compared to earlier MALDI-OzID implementations. Translation of this uplift into imaging resulted in a 50-fold improvement in acquisition rate, facilitating large-area mapping with resolution of phospholipid isomers. Mapping isomer distributions across rat brain sections revealed distinct distributions of lipid isomer populations with region-specific associations of isomers differing in double bond and positions. Moreover, product ions arising from sequential ozone- and collision-induced dissociation enabled double bond assignments in unsaturated fatty acyl chains esterified at the noncanonical -1 position.
组织内脂质的质谱成像（MSI）在生物分子发现和组织病理学应用方面具有重要的潜力。然而，传统的 MSI 技术受到磷脂区域异构体的普遍性的挑战，这些异构体仅在碳-碳双键的位置（s）和/或脂肪酸与甘油主链的相对位置（即， 位置）上有所不同。在成像实验中无法分辨异构体脂质掩盖了潜在的复杂性，导致代谢信息的严重丢失。在此，臭氧诱导解离（OzID）在能够进行基质辅助激光解吸/电离（MALDI）的可移动四极杆飞行时间（Q-TOF）质谱仪上实施。利用 Q-TOF 中的离子迁移区，可以获得高浓度的臭氧，与早期的 MALDI-OzID 实施相比，OzID 产物离子的丰度增加了约 1000 倍。将这种提升转化为成像，导致采集速率提高了 50 倍，从而可以以分辨率为磷脂异构体的大面积映射。在大鼠脑切片上进行的异构体分布映射揭示了脂质异构体群体的不同分布，双键和 位置的异构体具有特定的区域关联。此外，由连续的臭氧和碰撞诱导解离产生的产物离子能够对酯化在非规范 -1 位置的不饱和脂肪酸链中的双键进行分配。
