Unlocking the Hidden Depths: Multi-Modal Integration of Imaging Mass Spectrometry-Based and Molecular Imaging Techniques

Multimodal imaging (MMI) has emerged as a powerful tool in clinical research, combining different imaging modes to acquire comprehensive information and enabling scientists and surgeons to study tissue identification, localization, metabolic activity, and molecular discovery, thus aiding in disease progression analysis. While multimodal instruments are gaining popularity, challenges such as non-standardized characteristics, custom software, inadequate commercial support, and integration issues with other instruments need to be addressed. The field of multimodal imaging or multiplexed imaging allows for simultaneous signal reproduction from multiple imaging strategies. Intraoperatively, MMI can be integrated into frameless stereotactic surgery. Recent developments in medical imaging modalities such as magnetic resonance imaging (MRI), and Positron Emission Topography (PET) have brought new perspectives to multimodal imaging, enabling early cancer detection, molecular tracking, and real-time progression monitoring. Despite the evidence supporting the role of MMI in surgical decision-making, there is a need for comprehensive studies to validate and perform integration at the intersection of multiple imaging technologies. They were integrating mass spectrometry-based technologies (e.g., imaging mass spectrometry (IMS), imaging mass cytometry (IMC), and Ion mobility mass spectrometry ((IM-IM) with medical imaging modalities, offering promising avenues for molecular discovery and clinical applications. This review emphasizes the potential of multi-omics approaches in tissue mapping using MMI integrated into desorption electrospray ionization (DESI) and matrix-assisted laser desorption ionization (MALDI), allowing for sequential analyses of the same section. By addressing existing knowledge gaps, this review encourages future research endeavors toward multi-omics approaches, providing a roadmap for future research and enhancing the value of MMI in molecular pathology for diagnosis.

多模态成像（Multimodal Imaging，MMI）已成为临床研究中的强力工具，通过整合多种成像模式获取全面信息，助力科研人员与外科医生开展组织识别、定位、代谢活性研究及分子发现，从而辅助疾病进展分析。尽管多模态仪器日渐普及，但仍存在诸多亟待解决的挑战，包括非标准化特征、定制化软件、商业支持不足，以及与其他仪器的集成问题。多模态成像或多重成像领域支持同时复现多种成像策略下的信号。在术中场景下，MMI可集成至无框架立体定向手术中。近年来，磁共振成像（Magnetic Resonance Imaging，MRI）与正电子发射断层扫描（Positron Emission Topography，PET）等医学成像模式的最新进展为多模态成像带来了新视角，可实现癌症早期检测、分子追踪及实时进展监测。尽管已有证据证实MMI在外科决策中的作用，但仍需开展全面研究以验证并实现多种成像技术交叉场景下的集成方案。当前研究人员正将基于质谱的技术（例如成像质谱（imaging mass spectrometry，IMS）、成像质谱流式（imaging mass cytometry，IMC）及离子迁移质谱（Ion mobility mass spectrometry，IM-IM））与医学成像模式相集成，为分子发现与临床应用开辟了极具前景的路径。本综述着重探讨了集成了解吸电喷雾电离（Desorption Electrospray Ionization，DESI）与基质辅助激光解吸电离（Matrix-Assisted Laser Desorption Ionization，MALDI）的MMI在组织绘图中的多组学方法潜力，可实现同一切片的序贯分析。通过填补现有知识空白，本综述呼吁未来围绕多组学方法开展研究，为后续研究提供路线图，并提升MMI在分子病理诊断中的应用价值。