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用于神经病理学中吞噬细胞的体内磁共振和计算机断层扫描成像的基于金属的对比剂的应用。

Use of metal-based contrast agents for in vivo MR and CT imaging of phagocytic cells in neurological pathologies.

机构信息

Univ. Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, 69003 Lyon, France; CNRS, Lyon, France.

Univ. Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, 69003 Lyon, France; Univ. Grenoble Alpes, INSERM UA7 STROBE, 38000 Grenoble, France.

出版信息

J Neurosci Methods. 2023 Jan 1;383:109729. doi: 10.1016/j.jneumeth.2022.109729. Epub 2022 Oct 19.

Abstract

The activation of phagocytic cells is a hallmark of many neurological diseases. Imaging them in their 3-dimensional cerebral environment over time is crucial to better understand their role in disease pathogenesis and to monitor their potential therapeutic effects. Phagocytic cells have the ability to internalize metal-based contrast agents both in vitro and in vivo and can thus be tracked by magnetic resonance imaging (MRI) or computed tomography (CT). In this review article, we summarize the different labelling strategies, contrast agents, and in vivo imaging modalities that can be used to monitor cells with phagocytic activity in the central nervous system using MRI and CT, with a focus on clinical applications. Metal-based nanoparticle contrast agents such as gadolinium, gold and iron are ideal candidates for these applications as they have favourable magnetic and/or radiopaque properties and can be fine-tuned for optimal uptake by phagocytic cells. However, they also come with downsides due to their potential toxicity, especially in the brain where they might accumulate. We therefore conclude our review by discussing the pitfalls, safety and potential for clinical translation of these metal-based neuroimaging techniques. Early results in patients with neuropathologies such as multiple sclerosis, stroke, trauma, cerebral aneurysm and glioblastoma are promising. If the challenges represented by safety issues are overcome, phagocytic cells imaging will be a very valuable tool for studying and understanding the inflammatory response and evaluating treatments that aim at mitigating this response in patients with neurological diseases.

摘要

吞噬细胞的激活是许多神经疾病的标志。在三维脑环境中随时间对其进行成像对于更好地了解它们在疾病发病机制中的作用以及监测它们的潜在治疗效果至关重要。吞噬细胞具有在体外和体内内化基于金属的对比剂的能力,因此可以通过磁共振成像 (MRI) 或计算机断层扫描 (CT) 进行跟踪。在这篇综述文章中,我们总结了不同的标记策略、对比剂和体内成像方式,这些方法可用于使用 MRI 和 CT 监测中枢神经系统中具有吞噬活性的细胞,重点介绍了临床应用。基于金属的纳米颗粒对比剂,如钆、金和铁,是这些应用的理想候选物,因为它们具有有利的磁性和/或不透射线特性,并且可以针对吞噬细胞的最佳摄取进行微调。然而,由于它们的潜在毒性,尤其是在大脑中可能会积累,它们也存在缺点。因此,我们在讨论这些基于金属的神经影像学技术的陷阱、安全性和临床转化潜力时得出结论。在多发性硬化症、中风、创伤、脑动脉瘤和胶质母细胞瘤等神经病理学患者中的早期结果很有希望。如果克服了安全问题所带来的挑战,吞噬细胞成像将成为研究和了解炎症反应以及评估旨在减轻神经疾病患者这种反应的治疗方法的非常有价值的工具。

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